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The Catastrophic Effects of Polypharmacy and Medical Incompetence

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Polypharmacy and Iatrogenic Injury: More Common Than Recognized

My life should never have taken the catastrophic negative turns that it did. I am well educated, was a minivan driving soccer mom and a devoted wife. I enjoyed a successful career as a pediatric audiologist working in a variety of fast-paced medical settings. I was well liked, a loyal friend to many and an active member of my community. My very vibrant and blessed life was obliterated by a perverse cascade of errors from a broken medical system. This affected my loved one’s lives as profoundly as mine. Had medical providers looked for, and addressed root causes, I’d still be driving that minivan.

It has taken me a long time and immense research to piece together and understand what happened to me. I would like to share my story for whatever understanding can do to ease the pain, and for whatever help it could give to prevent others from experiencing what our family did. First and foremost, however, I want my husband and children to understand the truth of what happened to me.

I did not suddenly develop perverse mental illness out of thin air. I was a victim of repeated misdiagnoses, unrecognized adverse drug reactions/drug toxicity and profound polypharmacy.

This is described in the literature as “medication induced iatrogenic chronic health syndrome, or iatrogenic injury.” It is more common than one would think and it unnecessarily destroys lives.

The First Hit: Toxic Mold Effects Misdiagnosed as Depression

The circumstances which led to my catastrophic outcome are cumulative. It was no one thing, but several hits to my system.

In the late 1990’s, my husband and I were a happy, newly married couple enjoying a carefree dual income lifestyle. We had successful and fulfilling careers, great friends, and loved life; the world was our oyster. Despite all this, however, we both found ourselves incredibly tired all the time and experienced frequent brain fog. My husband also began having recurrent sinus infections. I developed unrelenting headaches, fibromyalgia, dry eyes, vision issues, G.I. disturbance, frequent urination, skin rashes, excessive thirst, irregular menstruation, and disorientation – I was getting lost going to familiar places.

When seeking medical attention for this cluster of symptoms, we were both told we were suffering from mild depression and were prescribed an anti-depressant (SSRI). Neither one of us actually felt “depressed,” though. Yet, we trusted our doctors knew best and so took the anti-depressant medication as prescribed.

It’s absurd that we were given a psychiatric diagnosis given the physiologic symptoms we were experiencing. More unbelievable is that we did not even question the doctor. I would later learn that the constellation of symptoms we had is consistent with toxic mold illness, a subcategory of biotoxin illness known as Chronic Inflammatory Reactive Syndrome (CIRS). I was, in fact, subsequently diagnosed with CIRS.

We unknowingly lived in a home with hidden toxic mold, where up to two feet of water collected in the crawlspace underneath the home seasonally every winter. The root cause of our symptoms which doctors diagnosed as “depression” was completely missed. We did not need antidepressant medication. We needed out of our water damaged home and treatment for mold illness/CIRS. Instead, we got put on an unnecessary neurotoxic medication with serious adverse health risks including the effects “medication spellbinding.”

The Second Hit: IVF Treatments Lupron and Synarel

When we decided to start our family, I experienced infertility. My husband and I utilized in vitro fertilization (IVF) to conceive our two children. During this process many different pharmaceuticals are prescribed for women. The doctors assured us the medications were all “safe”.

I was given Lupron and Synarel as part of my IVF treatment protocols. Both are antineoplastic agents, meaning they are cancer chemotherapy drugs, used off label for fertility treatment. Like all antineoplastics, they are harmful to both cancerous and non-cancerous cells — particularly to pregnant women and developing fetuses. It’s incredibly scary that it is actually used for conception, isn’t it? They are neurotoxic and can induce systemic damage-CNS, connective tissue, mitochondrial, immune, etc.; damage that unfolds over time.

Equally disturbing is that I was advised to stay on an antidepressant throughout pregnancy for a depressive disorder, it turns out, I never had. When I requested to be tapered off of the SSRI before attempting to achieve pregnancy, I was told that the risk of harm to the baby of a mother with untreated depression was greater than any potential adverse effects of in utero exposure to an anti-depressant medication. Really? This made absolutely no sense to me in my circumstance; the only qualifier for my diagnosis of mild depression was unrelenting fatigue. Yet, the doctor instilled such terror in me that I would be irrevocably harming my child if I did not not stay on an antidepressant during pregnancy, I reluctantly followed his advice. Prenatal exposure to an SSRI can be damaging to a developing brain and nervous system. Both my children were born with severe nervous system dysregulation and have developmental and immunological issues.

Toxic mold exposure and SSRIs can both cause various hormonal issues. My infertility was due to anovulatory cycles likely induced by the antidepressants that were inappropriately prescribed for the toxic mold. I had also been on hormonal birth control for many years prior to our attempts at conception. Suffice it to say, I was not healthy. Despite my compromised health, the fertility doctors added more toxic chemicals to my body to initiate conception.

The Third Hit: Fluoroquinolones

My children were both born via Cesarean section-my daughter due to vasa previa, my son due to failed VBAC, failure to descend. In each instance, IV Cipro (drug class fluoroquinolone) was given prophylactically.

“Fluoroquinolones are associated with prolonged (up to months or years), serious, disabling and potentially irreversible drug reactions affecting several, sometimes multiple, systems, organ classes and senses”. Fluoroquinolone toxicity can lead to a subsequent systemic health cascade.

Within a couple days after receiving IV Cipro, I experienced acute onset of significant arm weakness and severe wrist pain, requiring the use of wrist guards for several months. I had difficulty physically caring for my children after their birth because of this. I also experienced photosensitivity, hyperacusis, drenching night sweats, constipation/G.I., hair loss, hyperactivity, brain fog, short term memory issues and fatigue. Additionally, I had irritability, emotional blunting, and personality changes after my son’s C-section. All of these symptoms were much more severe after my son’s delivery and they did not ever resolve completely.

After my son’s birth, I was prescribed multiple consecutive courses of oral Levaquin plus steroids for persistent pneumonia I developed during the second trimester of my pregnancy with him. The concomitant use of steroids with fluoroquinolones exponentially magnifies the damage to the body.

Levaquin and Cipro belong to the class of medication known as fluoroquinolones. They are essentially chemotherapy drugs, that negatively impact the immune system, CNS/ANS/PNS, alter DNA, cause mitochondrial and connective tissue damage as well as severe neuropsychiatric/cognitive issues.

“Fluoroquinolone adverse-reactions are categorically different from allergic reactions, rather, fluoroquinolone toxicity is a syndrome of multi-symptom, chronic illness that does not go away when administration of the drug has stopped. Fluoroquinolone adverse-reactions are similar in symptoms and scope to autoimmune diseases, fibromyalgia, ME/CFS, POTS, psychiatric illnesses, neurodegenerative diseases (like ALS and Parkinson’s), and other chronic, multi-symptom, illnesses that involve multiple bodily symptoms. Like many of those diseases, fluoroquinolones adversely affect gut health, mitochondrial health, liver health, neurotransmitter balance, mineral homeostasis, hormones, and more. Fluoroquinolone toxicity is a multi-symptom, chronic, syndrome, that, for many, is incurable.”

Following the fluoroquinolone exposures, my health declined significantly and systemically over the next several years. Extreme fatigue, fibromyalgia, persistent headache, head pressure, G.I. issues, recurrent infections, cognitive issues, muscle wasting and visual disturbances. I also began to develop multiple chemical sensitivities, food sensitivities and electro-hypersensitivity. I have been told by physicians and researchers this is all consistent with fluoroquinolone toxicity which can lead to a progressive health cascade. However, this went unrecognized and, instead I was given large doses of antidepressants which only exacerbated my declining status.

The Fourth Hit: Multiple Viral and Fungal Infections and More Medications

Next, I was diagnosed via lab testing with neurological Lyme disease, bartonella, erichliosis, parasitosis, babesia, CIRS, systemic fungal infections, Epstein Barr and other chronic viral infections (2010). As my health had been decreasing for many years, I was relieved to finally have what doctors thought was the “root,” and I was eager to address it. I was a compliant patient and followed their complex protocols. An utterly insane amount of pharmaceuticals were given over the next six years (listed at the bottom of this post) for treatment, including more rounds of fluoroquinolones (Levaquin, Avelox) and their “second cousins” -Mepron, Malarone, Flagyl. The years of aggressive treatment proved disastrous.

Very well-intentioned doctors missed the pre-existing fluoroquinolone and SSRI toxicity. No regard was taken for the growing burden on organs, most notably the liver and brain. My G.I. system was decimated by dozens of antibiotics. Aggressive “Lyme” treatment involving years of polypharmacy only served to poison me more, further impairing my CNS and immune system. My health status continued to decline.

The Fifth Hit: Sedatives and Anticonvulsants to Quiet the Immune System

After years of Lyme treatment and with medication toxicity already through the roof, the next approach was to add Ativan, a benzodiazepine, and Gabapentin, an anticonvulsant. This was to calm mast cell activation and aide intractable insomnia that had developed. Both were used for off label purposes. Fluoroquinolone exposure can trigger mast cell activation. Toxic mold exposure can also trigger mast cell activation.

I suffered an immediate adverse drug reaction to Gabapentin in February 2015. Within the first day of beginning this medication my handwriting changed. I could not walk straight and began dropping things. I had an obvious and immediate decrease in executive function and short-term memory, along with hyperactivity, twiddling my fingers and other symptoms that I would later learn fall under the umbrella condition called akathisia. According to the Akathisia Alliance for Research and Advocacy:

“[Akathisia] …is an extremely distressing neuropsychiatric syndrome with symptoms including severe agitation, inability to remain still and an overwhelming sense of terror implicated in many suicides and acts of violence. It is a medication side effect.”

I reported all this to my doctor who instructed me to stay on the medication and that my body would “adjust with time”. These were not harmless “side effects” that would fade. This was a serious adverse drug reaction which went unrecognized as such and led to more polypharmacy.

Progressing Neurotoxicity: Let’s Up the Doses of the Contributing Medications

Over the next several months, my cognition and proprioception continued to rapidly decline. Additionally, I experienced the onset of deeply troubling new symptoms – an extreme fear to be alone, intense inner restlessness, confusion, blurry vision, severe headache, hand tremor, worsening insomnia, terror, and derealization/ depersonalization. Repeated changes were made to my Lyme treatment protocol with the assumption that these new symptoms and decline were related to that chronic health condition. The gabapentin and ativan doses were also increased. Changes were made to the SSRI. The adverse drug reaction and increasing toxicity was missed completely and, in fact, additional pharmacy worsened it.

Something was very, very wrong; I just kept declining. In no way did this feel like it was simply an exacerbation of Lyme. By the fall of 2015, things had deteriorated to the point to where I had to stop driving for safety reasons as my vision and motor skills had become too impaired. We had to hire household help and childcare because I had become essentially non-functional. I was acutely aware that my decline was negatively impacting my children and I wanted to make sure there was a capable adult in the home at all times with them. I tried hiding in the bedroom away from their view because my presentation and behavior had become very disturbing…and, I knew it. I would later come to understand that all the new symptoms beginning with the adverse reaction to gabapentin were consistent with medication induced akathisia.

Confirmation: It Was the Medications All Along

In December 2015, after ten months of searching for answers to my abrupt and progressive decline, I finally got confirmation from my doctor and own research that indeed I was experiencing numerous, severe negative medication effects and not solely an exacerbation of Lyme disease.

“In summary, the benzodiazepines can produce a wide variety of abnormal mental responses and hazardous behavioral abnormalities, including rebound anxiety and insomnia, psychosis, paranoia, violence, antisocial acts, depression, and suicide.” Dr Peter Breggin

I also learned that a supervised slow taper off of these psychotropic medications was required for my safety. I was referred by my doctor to a psychiatrist for a guided taper.

I was not “addicted” to the medications, rather my brain had become dependent on them and cessation had to be gradual and monitored.

The psychiatrist advised me to crossover from Ativan to Valium because it has a longer half-life to reduce inter-dose withdrawal effects. Then, once stable on an equivalent dose of Valium, taper slowly off of that. She also wanted to add in other medications to counter the negative side effects of the withdrawal process.

Crossing over to Valium was extremely problematic for me. I experienced an immediate adverse reaction to it with increased agitation and pacing on the very first dose. (It turns out I cannot metabolize Valium properly). Upon reporting this to my physician, she told me just to “go slower” with the process and things would “even out” over time. Despite following her instructions to slow down the crossover, nothing “evened out”. I experienced ever-increasing negative and disturbing symptoms. I now I understand that I suffered multiple drug-to-drug interactions and adverse drug reactions, drug toxicity that went unrecognized for what it was. I had developed medication induced akathisia.

Even So, Let’s Add More Medications

To counter these growing negative effects, the doctors continually changed dosages of existing drugs and added many new ones, all trial and error, with no discernible rationale. This only worsened things, causing even more frightening and violent new symptoms – rapid pacing, twisting dystonia, severe depersonalization, disinhibition, myoclonic jerking, derealization, panic, agitation, aggression, severe insomnia, paranoia, vocal tics including profanity, mono-phobia, agoraphobia, rage, stuttering, disequilibrium, severe confusion, heart palpitations, visual disturbances, air hunger, motor slowing, oppositional behavior and more. My environmental sensitivities also escalated.

The tapering protocol involved adding Valium to cross taper Ativan according to the Ashton Method recommended by my physician. I had a severe adverse drug reaction to Valium which the doctor failed to recognize, escalation of negative symptoms increased. At one point low-dose Seroquel, an antipsychotic, was prescribed to me in an off label use for the extreme insomnia that developed on this cocktail of drugs. Off label use of low dose antipsychotics for insomnia is NOT recommended.

After Seroquel was added, I developed vocal tics, suicidal ideation, extreme terror, delirium, the pacing and other movements increased dramatically. Despite reporting this immediate negative side effect of feeling intense agitation and rage, the doctor denied that a low dose of Seroquel could cause this and told me it must be underlying or emerging psychiatric illness. They continued to add and abruptly remove many other medications.

I lost my sense of human connection and self. I felt completely lobotomized. The collateral damage on my children and husband was and is INHUMANE.

Despite my reporting the immediate negative side effects with the addition of Seroquel, doctors denied that a low dose could cause them and told me it must instead be symptoms of an underlying or emerging psychiatric illness. Really? How do you suddenly develop severe psychiatric illness out of nowhere?

Prior to being put on Ativan and Gabapentin and the subsequent polypharmacy, I had NEVER before experienced suicidal ideation or the other extreme negative behavioral and cognitive changes. I was repeatedly told that my very classic symptoms of akathisia were not akathisia and not related to medications. The Barnes Scale, a standardized tool to assess drug induced akathisia, was never administered.

The very behaviors that were unfolding right before the physicians’ eyes and that I was reporting are known and dangerous medication side effects, included on manufacturers’ warnings. So why then did so many doctors fail to recognize this?

Spinning Out: Let’s Go Cold Turkey. What Could Possibly Go Wrong?

My physical/cognitive/mental health continued to spin out of control with the medication merry-go-round. In August 2016, I was admitted to a psychiatric unit from the ER due to severe confusion, pacing akathisia, and dystonia. The uninformed doctor there forced an abrupt discontinuation of the polypharmacy cocktail I had wound up being put on (in the name of “safe” tapering). Cold turkey off of four psychotropic medications overnight. This severely shocked my CNS. Over the next few weeks, I experienced what I felt were seizures, difficulty forming words, severe vertigo, worsening cognitive function, visual disturbances, racing heart, auditory hallucinations etc. Fearing for my life, as I spiraled into mania, psychosis and suicidality from this abrupt cessation, I sought reinstatement of some of the medications six weeks later. I was accused of “drug seeking” for this decision. It’s not that I wanted to be on any of these poisons ever again; I was simply trying not to die.

The partial reinstatement did stabilize me a bit.

Then, only one month later, I was again rapidly tapered off the polypharmacy cocktail at an outpatient facility. Originally, I understood, the program was completed over 15 days. I have since learned from my medical records that my rapid detox was longer and more intense than the prescribed protocol. According to my records, I received 23 days of treatment with the administration of daily six hour infusions of IV NAD+ with B complex and amino acids (December 2016). My dose was significantly greater than the maximum standard dose of 250 mg, provided at too fast a drip rate and over a treatment course that was many times longer than is typical. I also learned that it was done without proper methylation support.

From what I have learned, this treatment is purported to protect the brain and ease medication withdrawal syndrome. However, this was not at all what happened for me. I had a severe negative response to it, utterly catastrophic, inducing permanent profound physical disability. During the IV administration, I experienced extreme brain burning, increased heart rate/blood pressure, auditory hallucinations, seizures, extreme agitation, terror, tremors, fever, hypomania, worsened akathisia with pacing, violent dystonia, hand clawing, delirium, jerking and twitching, homicidal and suicidal ideation. Most horrifically, the severe adverse reaction caused an impulsive akathisia induced suicide attempt.

With pre-existing mitochondrial issues, a suspected underlying connective tissue disorder and years of cumulative toxicity (medication and environmental), it has been suggested by physicians and researchers that NAD+ would increase the cytotoxic effects through reactive oxygenation species. This seems to have accelerated my mitochondrial dysfunction leading to catastrophic connective tissue damage and a progressive musculoskeletal collapse.

There is a genetic/epigenetic researcher, Bob Miller, whose work focuses on Lyme patients and others with complex chronic diseases. He discusses NAD+ in an interview where he mentions that while for some it can be a miraculous molecule, improving many things metabolically, for others it can have serious adverse effects. He believes this could be caused by something he coins the “NADPH-steal”, where NADPH starts acting like a free radical due to other compromised enzymes stealing away the NADPH (excess of sulfites, glutamate, histamine, things like that). With the compromised methylation and Kreb’s cycle that I have, treating all those things prior would be necessary to not to overload the system and cause serious damage. No provider recognized this serious contraindication with their recommendation of NAD+.  In fact, they blindly touted the opposite claiming it to be neuroprotective for all. An interview with Bob Miller’s latest research and perspective can be seen here and here. Another researcher, who specializes in drug neurotoxicity, confirmed the negative effects of NAD+.

The Results of Polypharmacy and Failed Treatments

I have experienced profound progressive connective tissue destruction since the IV NAD+. At the age of only 54, I am now non-ambulatory, bed-bound requiring full physical care in an assisted living facility. This has left me unable to bathe or dress myself. I have difficulty feeding and swallowing. I have very limited use of my hands; my manual dexterity is poor. I have profound autonomic nervous system dysfunction and cannot tolerate even supported sitting. It feels as though my entire spine has collapsed, bone on bone-discs and other supportive connective tissue severely compromised. My tendons and ligaments feel too lax systemically throughout my body, head to toe-my feet now literally curl and bend in ways that they should not. My upper palate has fallen and my lower jaw swings so much so that it often feels like I’m being choked. Speech articulation is difficult because of the laxity in my oral cavity. Systemic collagen and cartilage loss. My internal organs don’t feel supported and I’m experiencing prolapse.  I am right side lying 24/7, propped up at an angle and need assistance repositioning my body. Toileting is difficult. My vascular and lymphatic system have been severely affected. I have full body tissue swelling, like an exploded baby diaper.

It feels as if the structural integrity of my connective tissues, the glue that holds *everything* together, is gone…like chewing gum on hot pavement or stretched out pantyhose. I quite literally feel as if I’m melting from the inside out. Additionally, I have constant severe acid burning sensation throughout my body and deep bone pain, head pressure, central vision and auditory processing issues.

And Yet They Insist It Was All In My Head

It has been a grueling 35 months since that IV NAD and rapid taper of toxic medications. During this time period, my mental and cognitive state has steadily and dramatically improved. I no longer have any psychiatric symptoms and my personality has fully returned. I am once again gentle, kind, funny thoughtful and empathetic. Doctors kept insisting that the extreme cognitive and behavioral changes I experienced, beginning with that original adverse reaction to Gabapentin, was an emerging, intrinsic psychiatric illness. It most definitely was not. Rather, it was severe psychogenic effects of drug toxicity that they failed to recognize as such.

They wanted me to continue on various psychotropic medications and strongly recommended I seek treatment in a long-term inpatient psychiatric facility for the severe mental illness they thought I had. If they had been correct in their assessment, I would not have experienced the dramatic return to a healthy mental and cognitive state that I have despite declining their medication/treatment.

I NEVER had emerging severe psychiatric illness that the doctors said I had. Rather, the perverse neuropsychiatric manifestations were actually CAUSED by repeated misdiagnosis and careless polypharmacy. The medications caused these problems.

Misinformed doctors told my family I became perversely mentally ill versus I suffered extreme adverse drug reactions and toxicity. Because of their ignorance, my family believes I abruptly lost my mind at the age of fifty. When I rejected the false diagnoses of emergent psychiatric illness and refused further treatment (i.e., re-starting psychotropic medication), I was labeled non-compliant. This caused my family to believe I didn’t care enough about them to seek “treatment”. In fact, it is because I love them so deeply that I refused treatment. I knew my decision would appear non-compliant, but had I gone back on the poisons that induced this catastrophe in the first palace, I would not have regained my mental and cognitive health. I may have lost my life.

Without an authentic understanding of what happened to me, how are my children supposed to process this trauma? I absolutely did not just lose my mind one day. I was successively and cumulatively poisoned.

In today’s modern world, physicians are grossly misinformed regarding the very real dangers of pharmaceuticals, especially the grave dangers of polypharmacy and adverse drug reactions. Our medical system does not look for root cause. The healthcare system is dangerously broken. Patients are dismissed and gas-lighted when reporting negative side effects and misdiagnosed with psychiatric illnesses instead of recognizing medication toxicity.

I was systematically poisoned into oblivion by modern medicine and labeled with perverse psychiatric illness that did not exist prior. My children deserve to know the truth of what happened. This absolutely never should have happened to me, to my husband, nor to my children.

Over the last 6-12 months, I have had multiple objective tests completed that verified my cognitive, psychological and physical status. As a result, four separate doctors concluded that my past decline was due medical error and polypharmacy. While this is validating, it does not change the fact that my family is now gone and I am left permanently physically disabled due to a fatally flawed medical system and its love affair with prescription drugs.

What They Prescribed

These are most of the medications I was prescribed for the complex umbrella of Lyme disease, co-infections, CIRS, etc. with no regard for toxicity to the liver, brain or organs. Many of these were extended courses, long-term, and given concurrently. Looking back, I cannot believe that I survived. This is what medical polypharmacy looks like. It is not one or two drugs, it is dozens.

  • Macrobid (nitrofurantoin)
  • Ceftin (cefuroxime)
  • Cephalexin
  • Moxatag (amoxicillin)
  • Cefdinir
  • Minocylcline
  • Doryx (doxycycline)
  • Cedax (ceftibuten)
  • Tindamax (tindazole)
  • Minocycline
  • Clindamycin
  • Biaxin (clarithromycin)
  • Rifampin (rifampicin)
  • Augmentin (amoxicillin and clavulanate potassium)
  • Deplin/Duleek-DP (l-methylfolate)
  • Fluconazole
  • Ketoconazole
  • Itraconazole
  • Voriconazole
  • Rocephin (ceftriaxone ) – IV via Hickman catheter
  • Azithromycin – IV via Hickman catheter
  • Mepron(atovaquone)
  • Alinia (nitazoxanide)
  • Malarone (atovaquone/proguanil)
  • Biltricide (praziquantel)
  • Nystatin
  • Bicillian (penicillin G benzathine) – IM injection
  • Albendazole
  • Mebendazole
  • Stromectol (ivermectin)
  • Bactrim/Septra (sulfamethoxazole/trimethoprim)
  • Vancomycin – IV peripheral
  • Cortef (hydrocortisone)
  • Testosterone/progesterone (BHRT)
  • NAD/B complex – IV
  • Meyers cocktails – IV
  • Glutathione – IV
  • Phosphatidylcholine – IV
  • Cholestyramine (CSM)
  • Ketotifen
  • Hydroxyzine
  • Vitamin B12 – Subcutaneous Injection
  • Low-dose naltrexone (LDN)
  • Cipro (ciprofloxacin) – IV
  • Levaquin (levofloxacin) – Repeated and extended courses
  • Avelox (moxifloxacin) – Repeated and extended courses
  • Valtrex (valaciclovir)
  • Medrol (methylprednisolone) – Given concurrently with fluoroquinolones
  • Symbicort (budesonide/formoterol)
  • Synarel (nafarelin acetate)
  • Lupron (leuprorelin)
  • Vioxx (rofecoxib)
  • VSL-3 (bifidobacterium, lactobacillus, and streptococcus probiotics)
  • Singulair (montelukast)
  • ProAir (albuterol)
  • Xopenex (levalbuterol)
  • DuoNeb (ipratropium/albuterol)
  • Alvesco (ciclesonide)
  • Prednisone
  • Promethazine/codeine
  • Chloestyramine
  • Probalan (probenecid)
  • Ursodiol – Given because of rocephin
  • Ferrous gluconate (iron)
  • Nexium (esomeprazole magnesium)
  • Xyzal (levocetirizine)
  • Allegra (fexofenadine)

…And HUNDREDS of oral herbal medicines and supplements

The cascade into unnecessary and catastrophic psychotropic polypharmacy:

  • Celexa (citalopram)
  • Lexapro (escitalopram)
  • Zoloft (sertraline)
  • Remeron (mirtazapine)
  • Buspar (buspirone)
  • Benzodiazepines
  • Ativan (lorazepam)
  • Valium (diazepam)
  • Clonazepam
  • Antipsychotics
  • Seroquel (quetiapine)
  • Risperidone
  • Zyprexa (olanzapine)
  • Antihistamines
  • Benadryl (diphenhydramine)
  • Hydroxyzine
  • Anticonvulsants
  • Gabapentin
  • Lyrica (pregabalin)
  • Baclofen

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This article was published originally on: November 13, 2019. 

 

Related posts:

thinking about side effectsThinking About Side Effects Recovering from chronic illnessRecovering From Medically Induced Chronic Illness postpartum anxietySevere Postpartum Anxiety, Suicidality, and Polypharmacy Endometriosis, Lupron, Fluoroquinolones and DysautonomiaEndometriosis, Lupron, and Fluoroquinolones: A Recipe for Autonomic Disintegration

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They Say Lupron Is Safe

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lupron lies

In addition to the adverse event of dizziness reported during and post Lupron use, just reading and trying to understand Lupron’s literature can also be dizzying. So much of the research and information about this drug is utterly baffling; some circumstances have been manipulated by slick design, with information hidden or suppressed, other Lupron information can be readily disproved by known facts, and all this is admixed with conflicts of interest. In the process, decades of victims have accumulated and are without any real medical or legal advocacy. All the while, the powers that be have essentially appeared inert.

The contradictions found within Lupron documentation are indeed baffling and Lupron’s history is littered with instances of nefarious machinations. In prior installments of this series, the conflicting information about Lupron’s metabolism has been explored (part 4), as well as addressing the fact that Lupron is categorized as a hazardous, Pregnancy Category X drug (meaning it should be avoided by any woman who is or who may become pregnant), yet Lupron is prescribed to women in IVF, egg donation and surrogacy (part 3).  Since there are numerous other examples of puzzling – just plain wacky (inexplicable and unacceptable) – ‘circumstances’ surrounding Lupron, this final installment will look at a number of these head-scratchers, as well as reviewing some of the more notorious slick maneuvers associated with Lupron. (The other installments in this series were Part 1, Part 2, and Part 5.)

Why has Lupron’s manufacturer made statements that can be proven inaccurate?

Oral Lupron:  No — Yes — Maybe so?

Lupron’s labels and the literature ubiquitously proclaim that Lupron “is not active when given orally” – yet early investigation shows information to the contrary. None other than Andrew Schally, who is responsible for the isolation of the GnRH molecule (allowing the subsequent manufacturing of its analogs), and who won the 1977 Nobel Prize in Medicine for doing so, co-authored a 1975 article on the oral administration of Lupron. Thirteen healthy men were given Lupron (known only chemically, at the time, as “D-Leu-6 des-Gly-NH2-10”) by mouth, and within 45 minutes “the analogue had produced a statistically significant increase in mean plasma LH concentration”, and “the times of maximum LH activity noted … by mouth were not much different from those observed after parenteral injection”.

While the majority of men in this study did not have raised FSH concentrations, the remaining subjects had a significantly different mean change in plasma FSH concentrations “24 hours after the oral dose”. The article notes that “[a]lthough [Lupron] seemed to have little effect on FSH release, the interpretation depends upon how the results are expressed.” Discussion of Lupron’s parenteral effects decades later noted “the lack of long-term suppression of FSH observed in some patients” (American Hospital Formulary Service, Drug Information, 1994; p. 644). So it would appear that both oral and parenteral routes of Lupron have induced similar LH and FSH responses.

Andrew Schally stated 42 years ago that “oral administration [of Lupron] can now be added to the previously established effective methods [of intravenous, subcutaneous, and intramuscular administration].” Yet Lupron’s labels continue to state that it is “not active when given orally”.

Lupron Induces Menopause – NOT

In Lupron brochures for its use in endometriosis, the manufacturer states: “GnRH … acts on the pituitary to stimulate two other hormones, LH and FSH. … When LUPRON DEPOT is administered monthly, production of these hormones is reduced to the very low levels found after menopause” (emphasis mine). Yet, any medical textbook describes menopause as “FSH and LH (mainly FSH) are produced thereafter in large and continuous quantities” (emphasis mine) (‘Textbook of Medical Physiology’, A.C. Guyton.  1981.  6th Edition.  W.B Saunders Co. Philadelphia; p. 1016).

And most astoundingly, the hormonal profile of a menopausal woman – increased FSH/LH, decreased estrogen (“hypergonadotropic hypogonadism”) does not match the hormonal profile of a woman on Lupron – decreased FSH/LH, decreased {sometimes} estrogen (“hypogonadotropic hypogonadism”).  (See ‘Chart 1″ on page 2 here.)  Yet women are repeatedly told Lupron will put them into a temporary “menopause”.

Endometriosis Clinical Trials’ Data versus Claim in Lupron’s Label

Lupron’s female labels state the drug’s hypoestrogenic effect “is reversible on discontinuation of therapy”. However, an independent analysis of the endometriosis clinical trials’ raw data conducted during a product liability litigation revealed “62.5% of study subjects had failed to return to baseline ovarian function one year after stopping Lupron.” (Issue discussed in further detail below.)

Lupron-induced Impotence 

Initial 1980s clinical trials for FDA approval of Lupron for use in palliative treatment of prostate cancer found that 2 out of 98 subjects experienced the adverse event of impotence. More than a decade later, it was reported that Lupron “strongly suppresses erectile function and sexual activity” and “sexual desire, sexual interest and sexual intercourse were totally annulled.”  Large scale studies have revealed “80%” of subjects using GnRHas reported being impotent, and a “267% increase in impotence was observed after one year of treatment”

A decrease in sex drive (reported by both sexes) and impotence are such well-known, expected, adverse effects of Lupron that the drug has for some time been used (court ordered at times) as ‘treatment’ for sex offenders (see here, here, and here).

It should be found curious that what has become accepted as a near-universal adverse event to Lupron (impotence) was claimed, in the initial clinical trials, to affect a mere “2 out of 98” subjects.

Infamous Fraudulent Marketing Schemes and Unlawful Off-label Promotion of Lupron

There is quite a history of Lupron being unlawfully promoted for off-label indications, including the company receiving “Notices of Adverse Findings” from the FDA about the company’s Lupron symposiums (deemed ‘indoctrinations‘ by the FDA).

In 2001, Lupron’s manufacturer paid $875 million, the then-highest criminal and civil fine in U.S. history, for its fraudulent marketing scheme to promote sales of Lupron, involving violations of the False Claims Act, 31 U.S.C. §§ 3729.  The landmark case highlighted the company’s monetary incentive schemes to physicians to boost Lupron sales. Internal confidential company memos detailed how urologists could earn $105,011.40 annually by prescribing Lupron to just 65 patients.  The U.S. government’s investigation revealed that the company provided many sales incentives, such as products, cash prizes, and trips, including a vacation referred to as the “Excalibur” – and the “Excalibur party was awarded annually to the top 30% of the [] sales force. …  At times in the 1990s, the annual budget for the Excalibur party exceeded $4,000,000” (see page 9 here).

More recent ideation can be gleaned from anonymous postings in a pharmaceutical ‘sales rep chat room’;  i.e., a few noteworthy 2010 posts state: “ABBOTT PAYS MILLIONS UNDER THE TABLE SO DOCS USE LUPRON” (emphasis in original) (posted 3/27/10 @ 7:45 PM);  and “the docs know who has buttered their bread, and we [Abbott] got very deep pockets” (posted 3/27/10 @ 9:41 AM)

Why was the preservative in daily Lupron given only to humans, and not given to the “study rats”?

The daily formulation of Lupron is prescribed to both the pediatric and adult population, and was the very first FDA approval Lupron received, in 1985.  This initial, approved formulation contains the preservative “benzyl alcohol”.  But curiously, the animal toxicology studies required for Lupron’s initial FDA approval were not done using Lupron and benzyl alcohol, but were done using Lupron and “normal saline” (NDA 19-010).  Shouldn’t these animal toxicology studies reflect the exact injection intended for humans?

The National Institute for Occupational Safety and Health (NIOSH) lists pages of toxicity data for benzyl alcohol, while the Material Safety Data Sheet (MSDS) for benzyl alcohol identifies that there is “no information available” for numerous areas (such as teratogenicity, neurotoxicity, reproductive effects – See ‘Section 11’ here). Why were rats spared the exposure to benzyl alcohol in their Lupron injections, when humans were and are exposed to the benzyl alcohol day after day in their daily Lupron injections?

Funny Business with Bones

In this discussion, it is important to note that human bones contain 2 different types of bone – cortical (or compact) bone and trabecular (or cancellous or spongy) bone (see here and here).

While there are studies which claim no adverse effect of Lupron/GnRHas on the bones of treated children (i.e., here), other published reports on treated children note leuprolide/GnRHas “may have an adverse effect upon bone health“. As early as 1991, “a small but significant decrease in bone mass” was noted in a small Italian study using another GnRH analog (triptorelin) in children with precocious puberty. Another small Italian study in 1995 using leuprolide to treat precocious puberty found a “reduction of trabecular bone mass”. In a small Taiwanese follow-up study of girls treated with either leuprolide or triptorelin, “45% of patients had lumbar bone mineral density less than 1 SD below that of normal young Taipei adults”, evidencing “45% of patients had decreased bone accretion during therapy“. And recently a small study in Turkey using leuprolide in children concluded “GnRHas may have an adverse effect on bone health” perhaps via an impact upon vitamin D levels.

As early as 1991, in gynecological uses of GnRHas, evidence indicated that there was little or no change in cortical bone density, however “[t]he great majority of studies of trabecular bone show a significant reduction in bone mass in both spine and distal radius during 6 months of agonist therapy … between 5-10% of baseline”. Another early study in treatment of endometriosis found “bone loss induced by GnRH analogs may be associated with adverse effects on cancellous [trabecular] microstructure which are unlikely to be reversed following cessation of therapy.”  (An increased rate of bone loss in men receiving Lupron and other GnRHas has also been reported, i.e. here.)

It is important to note that most of the bone mineral testing done using Lupron or other GnRHas in adults have been done using DEXA (Dual-energy X-ray absorptiometry) or DPA (Dual-photon absorptiometry) scans; and there have been GnRHa studies using DEXA in precocious puberty bone mineral density assessments. Another study, using triptorelin in precocious puberty subjects, evaluated bone mineral density by assessment with DEXA and concluded that while bone mineral density was significantly lower at discontinuation of GnRHa, later DEXA scans showed values “not significantly different from controls.”  (But what would QCT [quantitated computerized tomography] scans have revealed?)

Bone density scans such as DEXA/DXA and DPA assess both cortical and trabecular bone – and studies using DEXA and DPA scans have revealed adverse effects from GnRHas  (i.e. bone mineral density “decreased significantly [6 months: -6.0%, 12 months: -8.0%]”).  However, QCT scans assess only trabecular bone and are most effective at detecting “the significant trabecular bone loss of the vertebrae and hip [associated] with GnRH agonists”.  (See also here.)

GnRHas appear to have “a significant negative impact on trabecular bone mass.  … Initial studies [in women] with dual-photon absorptiometry [DPA] were unable to detect any appreciable bone loss with GnRH agonists.  … Quantitated computerized tomography [QCT] always shows significant trabecular bone loss of the vertebrae and hip with GnRH agonists. Depot preparations appear to produce more marked loss than daily intranasal sprays.”  (emphasis mine).

Early investigations of leuprolide and buserelin’s effect upon cortical and trabecular bone mineral content in women with endometriosis identified that “[b]ecause QCT of the spine measures only the trabecular bone … any significant change affecting mainly the trabecular bone is more readily detected earlier by the QCT”, and “[b]ecause DPA measures both trabecular and cortical bone, a significant reduction in true trabecular bone mass actually may be diluted … thus giving a lack of significant change.”

In further illustration of this point, note that Lupron’s label for endometriosis from 1991 through 1996 stated “after 6 months the vertebral trabecular bone density as measured by QCT was decreased by an average of 13.5%”, however in 1996 Lupron’s endometriosis label was changed to read the “vertebral bone density as measured by DEXA was decreased by an average of 3.9%” (1991 – 1995 Physicians Desk Reference, Lupron Depot 3.75 mg).  By using data only from DEXA scans, the significant bone density loss previously detected by QCT was eliminated.  Current Lupron Depot 3.75 mg label states “vertebral bone density as measured by dual energy x-ray absorptiometry (DEXA) decreased by an average of 3.2%”.   By continuing to use data only from DEXA scans, the “significant” bone density loss detectable by QCT is ensured to remain undetected.

In a 2000 study of bone markers and bone mineral density during growth hormone treatment in children with growth hormone deficiency, it was noted that future research should be carried out “by the direct measurement of bone density using quantitative computer tomography [QCT]. Mineralization is only one facet of bone strength, however; other important components (e.g. bone structure and geometry) should be addressed in future paediatric studies.”  (See also here.)  A PubMed literature search of ‘QCT bone pediatric GnRHa’ produced zero results for humans, but one result was found for a report on rats  (in which bone mineral density was “significantly decreased in GnRHa-treated rats” and concluded “a delay in the onset of sexual maturation may cause prolonged, possibly irreversible defect in bone mineralization”).

In a 1995 study, bone biopsies and microscopic analyses (histomorphometric analysis) were done on women treated with GnRHas and the “results suggest that bone loss induced by GnRH analogs may be associated with adverse effects on cancellous [trabecular] microstructure which are unlikely to be reversed following cessation of therapy.”  Microscopic scan photographs of a 28 year old woman treated with GnRHa for 6 months show “severe disruption of the cancellous microstructure in the post-treatment biopsy” – see photo on page 6 here.

It would appear that without a body of data specific for QCT results, appropriate conclusions cannot be reached about the effects of GnRHas upon the type of bone (trabecular) that is most impacted by GnRHas. All the above points to the need to assess Lupron/GnRHas effect upon trabecular bone through QCT scans – and it would seem that to do otherwise would hinder data collection.

Yet many Lupron studies and follow-up studies have been designed using non-QCT bone density scans, and often it is wrist (and not hip or vertebral) scans that are performed. A perverse analogy comes to mind, relating to the heinous act of sick individuals who hide dangerous items (i.e., needles, razor blades) into the center of Halloween candy – and the community safeguards that have been enacted to X-Ray the candy in order to assess and ensure safety (i.e., here and here): What if these community resources were not offering to X-Ray the candy but instead were offering to merely photograph the candy in attempts to ‘assess and ensure safety’?

Tricks in the Courtroom Yield Treats for Lupron’s Manufacturer

The only lawsuit to make it to trial (in 2011), the case of Karin Klein v. TAP, Abbott, stemmed from Karin’s prescription of Lupron Depot 3.75 mg in 2005 as a 17 year old for endometriosis – and resulted in the development of (among others) a thyroid disorder. Pre-2005 Lupron Depot 3.75 mg labels, and post-2005 Lupron Depot 3.75 mg labels (domestic and foreign), warned of thyroid adverse events, but the company removed this warning for the 2005 label – the year of Karin’s prescription.

At trial, Karin was prevented from presenting to the jury any pre-2005 or post-2005 Lupron Depot 3.75 mg labels acknowledging thyroid adverse events, and the trial judge only allowed the jury to consider the 2005 label which lacked the warning. Lupron manufacturer’s principal medical expert, Dr. Richard Blackwell, under oath falsely stated “the thyroid gland … There are no receptors for GnRH. So there is no basic key on the thyroid gland for Lupron. Therefore, it is absolutely biologically impossible for Lupron to affect the thyroid gland. No textbook, no article has ever supported that contention. It’s simply biologically impossible” (emphasis mine) – see page 20 here.

Of note, Dr. Richard Blackwell has a history of receiving monies to study Lupron in women – see ‘Birmingham Center’ in this ‘Multicenter Lupron Study Group’. Also note that the latter study’s lead investigator, Dr. Andrew Friedman, was found guilty of fabricating and falsifying approximately 80% of data in 4 Lupron studies.

When the Klein jury heard Lupron’s expert medical witness proclaim it was “biologically impossible” for Lupron to affect the thyroid gland, they could not possibly know this physician was committing perjury. (Perjury is a felony, and if convicted involves fines and/or imprisonment up to 5 years – see here and here). If only the jury had known that evidence of this misinformation was just a keyboard away – a simple PubMed search (up to, and including, 2005) reveals the following published medical journal articles that evidence it is absolutely biologically possible for Lupron to affect the thyroid gland’:

“The first report to demonstrate the association of thyroid disorder with leuprolide [Lupron] injections” (2000), “Possible induction of Grave’s disease & painless thyroiditis by GnRHa’s” (2003), “The role of leuprolide acetate therapy in triggering auto-immune thyroiditis” (2005).

Serving as an “expert”, this is information that must certainly have been known, yet as a ‘hired gun’ for the drug company, the existence of this information was emphatically denied – leading the jury to believe it was impossible for Lupron to cause Karin’s thyroid disorder, and resulted in the jury finding in favor of the drug company. And thus the queue of Lupron litigation that was forming in anticipation of a Klein victory suddenly evaporated in the face of unmitigated, unethical, unlawful, unseemly, unchallenged ‘expert’ machinations.

To quote a ‘friend of the court’ brief filed on behalf of Klein by the organization “Consumer Attorneys of California”:

“[Klein was] entirely shackled in the evidence she was allowed to present. It is particularly galling to have qualified (and expensive) expert witnesses on hand to testify [on behalf of Klein], only for them to be shut down before the jury and precluded from offering competing expert opinions. The pattern shown by the record is deeply disturbing. Virtually every discovery and evidentiary ruling, and other orders of significance, went for one party [Lupron’s manufacturer]. Klein was not entitled to a perfect trial, but at least an evenhanded one. Such a one-sided proceeding was not the fair trial our system demands” (emphasis mine) – see page 6 here.

Klein ultimately petitioned the U.S. Supreme Court which refused to hear the case – great news for Lupron’s manufacturer, terrible news for young, disabled Klein, and chilling repercussions for society at large and Lupron victims in particular. Apparently, perjury under oath by paid medical experts, grossly misleading a jury, and the denial of a right to fair trial are issues deemed not significant by the U.S. Supreme Court.  For further information on the Klein matter, see here, here and here.

Obscuring the Drug’s Hazardous Status

Lupron is categorized by the FDA as a “Pregnancy Category X drug” (page 20, “leuprolide” – meaning any woman who is or who may become pregnant should avoid exposure), yet it became a staple of ovulation induction medication regimens in infertility, egg donation, and surrogacy. Lupron’s labels do state there is “a potential hazard to a fetus” (and oddly the most wording is found within the male Lupron Depot label). Lupron is classified by the National Institute for Occupational Safety and Health (NIOSH) as a “hazardous drug” (page 20, “leuprolide”), however nowhere in any of Lupron’s labels is there identification that Lupron is classified as a “hazardous drug” (i.e., pediatric, female, male);  nor does the label advise that as a result of this classification by NIOSH, special requirements apply for the handling, preparation, and administration of “hazardous drugs” (see here and here).

Around 2008, curious changes took place within Lupron labels (multiple indications) whereby it appears that cleverly, as if hiding evidence in plain sight, the “References” section of the labels now contained 4 citations – yet there are no corresponding footnotes within the label’s text for any one of these 4 citations. These 4 new “References” are as follows: (#1) NIOSH Alert, Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings; 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, NIOSH Publication No. 2004-165;  (#2) 1999 OSHA Technical Manual on Hazardous Drugs; (#3) 2006 ASHP guidelines on hazardous drugs; and (#4) 2005 Oncology Nursing guidelines on hazardous drugs (see pages 6, 14, 25, 36, and 47). Again, most curiously, not one of these 4 citations/”References” — or the information the citation source contains — were referred to, mentioned, identified, or discussed, at all, within the Lupron labels.

And presently, revised labels no longer contain the 4 citations mentioned above (see pediatric, female, male); and the labels continue to omit any identification of Lupron as a “hazardous drug”.

Measures Undertaken to Silence Critics

The Cardiac Stent Internal Memo

When Lupron’s manufacturer was under investigation for potential fraud related to its cardiac stents, numerous critical articles were written by a Baltimore Sun news columnist – and the drug company apparently targeted this columnist. As reported in a 2010 Senate Committee on Finance (examining a “clear example of potential fraud, waste and abuse”), “one Abbott official suggested that local connections or the “Philly mob” should intervene to silence Baltimore Sun columnist Jay Hancock for his coverage of the scandal, saying “someone needs to take this writer outside and kick his ass!”

Not a ‘seal of approval’ – the Hidden Lupron Endometriosis Clinical Trials’ Data

To the best of my knowledge, no one other than Dr. Redwine has independently analyzed the thousands of pages of raw data from the 1980s clinical trials for Lupron’s initial use in adult females (Lupron Depot 3.75 mg, for endometriosis). The conclusion from this independent analysis was that fraudulent data and misleading outcomes were found within these trials’ raw data. In one example, the raw data showed that “62.5%” of subjects had failed to return to baseline ovarian function one year after stop of study – yet Lupron’s label states Lupron’s hypoestrogenic effect “is reversible on discontinuation of drug therapy.” (For further information, see Part 3 of this series; the FDA’s response to Dr. Redwine’s request for an investigation into this serious matter; and here.)

It certainty appears that Lupron’s manufacturer intends to keep this raw data hidden from public view. Years ago the company sought and obtained a court-ordered seal on the raw data from these endometriosis clinical trials (see page 6 here), ensuring that this data will remain concealed from the public and any inquiring eyes.

Several years ago, when my assistance was sought by a Lupron victim whose attorney had retired in the middle of her case, the opportunity was used to file a motion to request the Court remove this seal (see “Reply Motion … and a Request that Court Seal on Defendants’ Clinical Trial Data Be Lifted”, Document # 135, Case 1:11-cv-04860, filed 2-20-14,  Paulsen v. Abbott, Takeda, TAP, US District Court, Northern District of Illinois, Eastern Division). No response from the Court was ever forthcoming from this request to unseal the raw data. The Paulsen case remains pending (see also here). A request to Lupron’s manufacturer to lift their seal also was unsuccessful (personal correspondence, 2015).

Suppression of Lupron’s Risks in Physician Continuing Medical Education

Renowned endometriosis surgeon Dr. Redwine became an outspoken critic of the use of Lupron in gynecology, and his opinion was reinforced by more than 700 women in his surgical practice who relayed harm from prior Lupron exposure. Dr. Redwine had most honorably refused the Lupron sales representative’s offer of $100,000 if he would prescribe Lupron to his patients. In 1994, Dr. Redwine wrote a ‘letter to editor’ in a fertility journal stating

“Inclusion of patients with a poor response to GnRHa therapy has not always occurred in outcome analysis in the published medical literature” (Letters:  Pros and Cons of “Add-Back” Therapy. 1994. Fertility and Sterility, 61:2:404).

According to Dr. Redwine’s expert medical testimony in the Klein case (in which he describes Lupron as being “unsafe and harmful in addition to being ineffective”), the following incident from the 1990s is described: Dr. Redwine was scheduled to be a speaker at a continuing medical education forum but was prevented from doing so by Lupron’s manufacturer because of his opposition to the use of Lupron. The drug manufacturer “interfered in the continuing medical education of physicians in order to enhance the sales of Lupron Depot” (see other excerpts of Dr. Redwine’s testimony here).

Peculiar Omission of Lupron/GnRHa Data in Studies of Health Disorders in Women With Endometriosis

Bone Density Loss

In 1989, a leading Lupron/GnRHa investigator in precocious puberty and gynecology concluded in a study that reduced bone mass (“significantly decreased cortical and trabecular bone mass”) was associated with the disease endometriosis. However, another study which found contrasting findings reported that “women with endometriosis do not have reduced bone density … One explanation for the difference between the results of this study and those of Comite et al. is that they included women who previously had been treated with GnRH agonists and these agonists are associated with bone loss.” (For further elaboration on these studies, see here.)

In my opinion, claims that the disease of endometriosis is associated with bone density loss, while appearing to deliberately omit the endometriosis patients’ common history of prior use of Lupron (which is known to causes bone density loss), is a treacherous concept and a slick maneuver — seeming to shield and manipulate iatrogenic, adverse drug effects into an ‘endometriosis-disease-related’ (and non-tort) phenomenon. This is something that deserves attention.

Autoimmune and Endocrine Disorders, Fibromyalgia, Chronic Fatigue Syndrome and Atopic Diseases

A 2002 publication (“High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis”) also failed to make any mention of Lupron or other GnRHas as treatment for endometriosis. This survey analysis, co-authored by the President of the Endometriosis Association (which has received hundreds of thousands of dollars from Lupron and other GnRHa manufacturers) also failed to identify the reported adverse events to Lupron (the most commonly prescribed medical therapy for endometriosis) – which have included autoimmune and endocrine disorders, fibromyalgia-like syndrome, chronic fatigue syndrome, and atopic diseases.

Yet, the survey upon which this analysis drew its conclusion does contain reference to Lupron/GnRHa use in the survey participants. In fact, of the 4000 surveys tabulated, 59% of survey respondents reported a history of Lupron/GnRHa use (‘Key Results from North American Membership Survey’, Endometriosis Association, 1998.  Presented at VI World Congress on Endometriosis). Given that the majority of the endometriosis respondents reported a history of Lupron/GnRHa use, how could this fact and highly significant confounding factor be ignored?

In my opinion, claims that the disease of endometriosis is associated with autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases, while appearing to deliberately omit the endometriosis patients’ common history of prior use of Lupron (which is known to cause autoimmune and endocrine disorders, fibromyalgia-like symptoms, chronic fatigue syndrome and atopic diseases), is a treacherous concept and a slick maneuver — seeming to shield and manipulate iatrogenic, adverse drug effects into an ‘endometriosis-disease-related’ (and non-tort) phenomenon.  This is something that deserves attention.

Coronary Heart Disease

Upon initial FDA approval for men in 1985, Lupron was alleged to have ‘insignificant cardiac adverse events’. (For further details on cardiac adverse events provided to and withheld from FDA by the manufacturer prior to approval, see page 4 here.) Subsequently, Lupron became the most prescribed GnRH analog. Decades later, a large study would show that the use of Lupron (and other GnRH analogs) for androgen deprivation therapy in management of prostate cancer was associated with a “10 – 50% increase” in the risks of coronary heart disease, myocardial infarction and sudden cardiac death (as well as fractures, strokes, and diabetes).

As a result of this and similar studies, the FDA issued a warning in 2010 concerning an increased risk of developing cardiovascular problems in men prescribed Lupron/GnRHas. The FDA acknowledged that there are no studies evaluating the cardiovascular risks of Lupron/GnRHas in children or women.  (To the best of my knowledge, there remains today no studies looking at Lupron/GnRHas cardiovascular risks in pediatric or female use; however there is presently an FDA “specific review” of nervous system and psychiatric events in children, and the NIH is in the midst of a study of long-term outcomes in transgender youth’s use of Lupron/GnRHas, evaluating “physiological and psychosocial impact, as well as safety”.)

In 2016, a cardiology journal published a study based on survey responses from the large-scale ‘Nurses’ Health Study II’ database, and this study associated endometriosis with an increased risk of coronary heart disease. Can you guess which drug was not queried in this ‘Nurses’ Health Study II’ survey? This survey sought information on the woman’s use of alcohol, cigarettes, post-menopausal hormones, oral contraceptives, multivitamins, analgesics (including acetaminophen, aspirin, ibuprofen, indometacin, naproxen, nabumetone, ketoprofen, celecoxib, rofecoxib, and valdecoxib), but omitted any questions about the woman’s exposure to the most frequently prescribed treatment for endometriosis – Lupron/GnRHas.

My response to this inexcusable omission of Lupron/GnRHa exposure data was published in the journal – see “Article’s conclusions seriously flawed without data on Lupron/GnRHa use”.  The authors of the study responded with inaccurate information on Lupron (see May 11, 2016 response), prompting me to submit a reply addressing this incorrect information. The journal failed to publish this corrective information, therefore I’ve published my reply on my own website.

In my opinion, claims that the disease of endometriosis is associated with coronary heart disease, while appearing to deliberately omit the endometriosis patients’ common history of  prior use of Lupron (which is known to cause numerous cardiovascular adverse effects in women – see ‘Cardiovascular Effects’, Left column here; and here), is a treacherous concept and a slick maneuver — seeming to shield and manipulate iatrogenic, adverse drug effects into an ‘endometriosis-disease-related’ (and non-tort) phenomenon. This trend is very troubling, and is something that deserves significant attention and investigation.

Conclusions

The above information, as well as information found within this series, the Kaiser Report, and other media sources (see here) should be more than sufficient indication that numerous investigations into the effects of Lupron (and all GnRHas) are warranted.

That there are large numbers of Lupron victims cannot be disputed – one need only have computer access to verify this sad fact. (For links to a large sampling of Lupron reviews, stories, posts and comments in various medication and legal websites, see here.) The petitions to Congress requesting an investigation into Lupron appear to have fallen on deaf ears; one petition started in 2009 states more than 21,000 messages have been sent to date. (Links to multiple petitions, in the U.S. and France, containing more Lupron horror stories, can be found here.)  There are more than ample numbers of Lupron victims complaining, the problem has been identified – what is needed is action.

Investigative reporters, the FDA, Congress, public health authorities, and the medical and legal community need to do their job and focus multiple spotlights on all the aspects of this drug, its effects, its associated harms, and the lack of medicolegal advocacy for its victims.

In my opinion, this drug should have been withdrawn from the market a long time ago – just how many more victims will it take?

Someone needs to be held responsible for all the suffering, and the ruined health, and careers, and lives of so many Lupron victims and their families. The devastation that Lupron has wrought ought to be criminal. People need to go to jail.

Or perhaps, they should just get a Lupron injection themselves.

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This article was published originally on May 31, 2017. 

Image by Peter Timmerhues from Pixabay.

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The Lupron Money Trail

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Lupron - follow the money

Recent attention in a dual Reveal and Kaiser Health News Report (‘Kaiser Report’) to the risks of Lupron’s use in children with central precocious puberty (PP) or growth issues, and to Lupron’s risks in general, presents an opportunity to continue the disclosures on the risks of Lupron. This is the fifth part in a 6-part series exploring numerous areas addressing the use of Lupron in the pediatric and teen population. The series began with the voices of the mothers of harmed children and the now-adult suffering children. This was followed by articles on the regulatory issues that surround Lupron’s approval and continued use, the possible reproductive injuries associated with this and other drugs within its class, and issues surrounding Lupron’s metabolism and clearance from the body. Here we will take a look at some of what is known about the Lupron money trail.

Ignoring and Dismissing Side Effects: Follow the Money

WebMD, a highly ranked and promoted consumer ‘go-to’ site for health information, ‘informs’ the public about precocious puberty:  “[t]here’s no evidence that these [GnRHa] drugs cause any long-term problems”. Common neurological and musculoskeletal complaints from Lupron, such as joint and muscle pain, and mood changes are listed as “infrequent” and decreased density of bone as a “rare” side effect. WebMDs “Fertility Drugs” page fails to identify Lupron as a ‘Pregnancy Category X’ drug (as designated by FDA), but states “as many as 50% [with successful ovulation] are able to get pregnant. Most side effects are mild.” Another high-ranking consumer information website, Medscape, tells of a number of clinics “all very experienced in treating gender dysphoric youth … This [GnRHa] treatment is fully reversible.” (See ‘Lupron and reproductive injury’.)

While unrelated to Lupron, the following news story from 2009 was nonetheless thought-provoking: Medscape and WebMD were accused in a whistleblower lawsuit (involving 17 states) of being “part of an illegal conspiracy to promote the off-label use of two [drugs]” – and the details of the charges were “a mystery” due to major redactions by the judge.

Lupron is no stranger to whistleblower lawsuits (here , here, and here) or to charges of promoting off-label uses. The drug’s manufacturer has received ‘Notices of Adverse Findings’ due to its promotion (“indoctrination“) of Lupron for unapproved gynecological indications, and warnings for misleading claims in its prostate indication. The company’s schemes of fraudulent drug pricing and bribing doctors are well known and documented.

CafePharma, an anonymous industry insider message board for pharmaceutical sales reps, had a few postings in 2010 that summed the scenario up succinctly.

“[T]he docs know who has buttered their bread, and we [drug company/sales force] got very deep pockets” (see post of March 20, 2010 @ 12:25 pm here).  And “YOU DUMMY ABBOTT PAYS MILLIONS UNDER THE TABLE SO DOCS USE LUPRON (emphasis in original)” (see post of March 27, 2010 @ 7:45 pm here).

How Lucrative is Lupron Use in Precocious Puberty?

The Kaiser Report identified that in a 2 year period of time Lupron’s manufacturer, AbbVie, had paid $157,066 to the lead investigator of Lupron’s precocious puberty clinical trials, Dr. Peter Lee (a pediatric endocrinologist). According to ProPublica’s “Dollars for Docs”, for the years 2015, 2014, and 2013, Lee received from AbbVie a total of $102,325 for “Promotional Speaking/Other” for Lupron.  (Payments by AbbVie to Lee for Lupron related “Consulting”, “Travel and Lodging” and “Food and Beverage” were not tallied, but figures are available at ‘Dollars for Docs’/ProPublica for each of those 3 years.)

The Kaiser Report also identified that both AbbVie and investigator Lee did not answer specific questions about the omission of serious adverse events (a bone disorder and a pathological fracture) in a key pediatric clinical trial of Lupron. How is this acceptable? If the drug company and lead clinical trial investigator will not answer questions about adverse events in the trial – who will?

In the drug company’s campaign to promote Lupron for precocious puberty (entitled “Too Soon”), they claimed (in 2003) “[t]here are almost 5,200 children who have central precocious puberty and grow up too soon” (see Question/Answer # 10). Lee was a member of the editorial board of “Too Soon”, and Lee is a consultant  for AbbVie, and “has received payment for the development of educational materials by AbbVie”.

It goes without saying that during a promotion of something (especially if one is being monetarily compensated for doing so), such promotion usually results in a loyalty to, and liking for, ‘the thing’.  And especially so if ‘the thing’ is a “cash cow” (stated in a ‘CafePharma’ post of August 8, 2011 @ 3:47 pm).

In 28 months (August 2013 through December 2015), AbbVie made 69,173 payments related to Lupron for a sum of $16.9 million to 24,910 doctors, and Lee came in second place in ‘top doctors receiving payments related to Lupron’.

How objective can Lee and the other 24,909 who are paid by the drug company to promote Lupron be? What would happen if any one of the 24,910 paid Lupron spokesmouths were to say “Hey, wait just a minute … there’s some pretty sick kids (or men and women) out there after using this drug – we need to take a serious look at this”?

Simple logic should tell you that a pharmaceutical company does not spend $16.9 million over a 28-month period to almost 25,000 doctors to hear a negative (bad) message about its product. In fact, I have seen signed consultant and scientific advisor agreements by a rheumatologist with this drug company, and there was a pledge taken to defend the company’s products at all times in all ways (documents presently unavailable, but reference to them was made in my 2003 congressional testimony, p. 12).

It seems peculiar that the #2 recipient of payments for the promotion of Lupron (the use of which spans multiple adult male and female indications that number in the millions) would involve a specialty that serves not quite 5,200 children.

Lupron’s use in the pediatric population is not limited to precocious puberty, and extends to youths and teens with gender dysphoria. Estimates from a federal database in 2016 place the numbers of adults who identify as transgender at 1.4 million (with states ranging from 0.30% to 0.75% of population), but there are no national surveys of youths; small-scale high school surveys have shown about 1.5% of surveyed students identified as transgender.

Pain and Agony of Adverse Effects Is Not a Lucrative Message

In an “ethical dilemma of choosing [between] wrongly suppressing puberty in kids who will grow out of their gender variance or refusing treatment [Dr.] Peter Lee … who had [by 2007] treated three young transgender teens with Lupron, knows on which side he’d rather err” – and that is to administer Lupron/GnRHas. Dr. Lee described one transgender adolescent 20 years ago “in so much pain and agony” that she later committed suicide. (A different perspective has been offered from a psychiatrist who has called this “Lupron treatment [for transgenders] a modern form of child abuse“.)

Where is the discussion on the pain and agony of pediatric (and adult) Lupron victims, and the psychological and psychosocial effects upon the child after development of medication adverse events?  (See Part 1 of this series for excerpts of heart-wrenching pain and agony voiced by parents and victims.) The sudden onset of migraines, weight gain, joint and bone pain, muscular pain, weakness, mobility limitations, mobility impairments, mood changes, irritable bowel, lethargy, difficulties with concentration and memory, anxiety, depression, suicidal ideation, etc., following treatment would indeed have a profound impact upon the child, their relationship to peers, and academic participation.

Given the flood of complaints about Lupron injury that is posted at various online sites, the $64,000 question remains ‘why has the pain and agony experienced by Lupron victims (of all ages and all genders) been so marginalized and often dismissed’? What causes the reported anger and defensiveness doctors have displayed when queried about the medication adverse effects? (See petitions and medication review site links – the web collectively provides millions of posted complaints, with daily additions.)

Marketing Indoctrination and Coercion

In March 1990 the FDA sent Lupron’s manufacturer a ‘Notice of Adverse Findings’, concerning its “deliberate campaign to promote this product for a wide range of unapproved uses.” A follow-up memo further detailed the FDA’s “concerns” about an upcoming drug company sponsored program at “Walt Disney World Swan”: the FDA said “it appears to be a program to indoctrinate physicians in unapproved uses of Lupron, and to specifically encourage administration of Lupron for these unapproved uses.” These unapproved uses involved gynecology and fertility. (In October 1990, Lupron received FDA approval for the indication of pain management in endometriosis; no FDA approval for fertility treatment has ever been obtained – and note that Lupron’s initial patent was for ovulation induction.)

As an IVF patient in 1990, my fertility clinic’s brochure stated “Lupron is only prescribed to persons with certain diagnoses”, but in 1991 this changed to “Lupron is widely prescribed”. What would cause the sudden universal use of Lupron at this (and just about every other) IVF clinic?  A 1992 study, which asked in its title whether there was any medical advantage for using GnRHa’s for all patients undergoing IVF, concluded:

“The routine use of GnRH-a for all patients undergoing IVF has practical but no significant medical advantages … there have been very few prospective randomized  studies comparing the use of GnRH-a with conventional stimulation regimens”.

My IVF clinic’s doctors had become indoctrinated to use Lupron in ovulation induction in the same manner as IVF clinics throughout the country. A 1989 US Subcommittee mailed a detailed survey to 224 US fertility clinics to obtain a wide variety of IVF data, and in the process many clinics self-reported their new ‘Lupron protocol’.  These survey responses, and transcripts of an accompanying hearing, were  published in a document titled “Serial No. 101-5” (101st Congress; March 9, 1989).  Here are a few pertinent excerpts illustrating the abrupt change to using Lupron by the survey respondents:

“Changing to Lupron stimulation for all patients” (p. 333. ART Program, Birmingham AL), “us[ing] Lupron for all patients” (p.408. Fertility and Reproductive Health Institute of Northern California, San Jose, CA.), “seventy percent of all patients are administered leuprolide” (p. 417. Century City Hospital, Los Angeles, CA.); “in 1988 we initiated the use of GnRH agonist for all patients” (p. 490. Hoag Fertility Services, Newport Beach, CA.).

Of the hundreds of fertility clinics responding to the Subcommittee survey, only one clinic raised a word of caution:

“Promoting the Use of GnRHa (Lupron) … it remains entirely unclear that all patients need this costly and often painful [and “experimental”] approach” (p.852.  University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ.).

Men, told they otherwise would face treatment for prostate cancer by either castration or DES (and potentially experience gynecomastia and adverse cardiovascular effects) were ‘encouraged’ to use this drug. A survey of urologists revealed that 53% did not believe in the efficacy of GnRHa treatment but still prescribed it.

My 2003 congressional testimony  identifies (p. 7) “the badgering, and coercion, and manipulation, and threats used to convince women into taking Lupron for a variety of indications – many refer to their doctor as trying to “shove it down [their] throat”.

Women were threatened with a hysterectomy (endometriosis), the specter of bleeding to death (fibroids), or refusal to undergo IVF. My 1993 testimony  to the MA. Health Care Committee (an attempt to enact legislation which would mandate fertility clinics provide, among others, accurate information on the risks of Lupron) states:  “… nearly every IVF clinic has mandated that women take Lupron – or they will not be allowed to cycle.”

Parents of children with precocious puberty are ‘encouraged’ to use this drug to prevent the child from ‘enduring psychological distress from their precocious development’ and to ensure achievement of ‘appropriate’ height.  In the transgender population, a similar psychological premise is offered for the normal – but ‘unwanted’ – sexual development, and the specter of anxiety, depression and suicide is raised for the untreated dysphoric youth/teen.

History of Fraudulent Data

In a review of the endometriosis clinical trials’ raw data, Dr. David Redwine discovered that the raw data did not support the claims by the company. In one example, Redwine’s analysis revealed that

“62.5% of women had not regained baseline estrogen levels one year after stopping Lupron … This is definitive evidence of long-term damage to ovarian function.”

Yet, contrary to this raw data, Lupron’s endometriosis label states the effects of Lupron “are reversible upon discontinuation”.  (See p. 26 in amicus curiae for US Supreme Court.) If 62.5% of subjects one year after Lupron discontinuation evidenced long-term damage to ovarian function, then what data did the company provide to the FDA for its 1990 Lupron approval which ‘demonstrated’ its effects “are reversible upon discontinuation”?

In 2010, Dr. Redwine provided a 300-page report to the FDA concerning these instances of apparent data fabrication. The essence of his report, titled “Leuprolide – the ‘D’ is Silent”, can be seen in a somewhat redacted power point presentation here.  Years after receiving the report, the FDA decided “no regulatory action is needed”  – all the while ignoring and failing to address the issue of fraudulent data and altered outcomes delineated in this report.  ‘Lupron Victims Hub’ sent an Open Letter to FDA in 2014 with specific questions – those questions remain unanswered.

During the lawsuit ‘Klein v. TAP, Abbott’, Redwine served as an expert medical witness, and in his expert statement he describes Lupron’s “medical fraud” as being “the most egregious example of Big Pharma controlling the practice of medicine”. Dr. Redwine concludes that Lupron is “unsafe and harmful in addition to being ineffective”.

For further information on retraction of Lupron studies and other instances of problems with the data in Lupron studies, see here,  here , here , here, and here.

Considered Not Related to Study Drug by the Investigator

In the Phase 3 and Phase 4 clinical trials by Dr. Lee for 1 month Lupron Depot-PED, one subject died from respiratory infection and heart arrest. In typical Lupron clinical trials’ language, this adverse event was “considered not related to study drug by the investigator”.  Of the 7 subjects for which serious adverse events were reported, 5 of those 7 subject’s adverse events were “considered not related to study drug by the investigator”.

In another precocious puberty study, the only serious adverse event reported was increased intracranial pressure, and this also was “considered not related to treatment by the investigator”.  While this subject did have a ventricular-peritoneal shunt, it should be noted that Lupron is known to be a cause of increased intracranial pressure. And so it would be interesting to learn how long – prior to Lupron – this subject had a shunt in place without any increased intracranial pressure.  Inclusion criteria for entrance into this study require “general good health with no uncontrolled, clinically significant disease”, and exclusion criteria preventing entrance into this study were “any concomitant medical condition that, in the opinion of the investigator, may expose a subject to an unacceptable level of safety risk”.  (And note  an unrelated post by a 24 year old woman who developed pseudotumor cerebri “as a result of the poison Lupron”, and who requires a shunt: see July 25, 2011 entry @ 10:38 am here.)

I suppose there could be a number of different reasons for an investigator to consider an adverse event as “unrelated” to a drug, but unless specific questions about the adverse events from these pediatric trials are actually answered — knowing the history of this drug — I can only assume the worst.

Questionable Data Found in Adult Male and Adult Female Studies

MEN: In the mid-1990s, after scouring FDA documents related to Lupron’s initial approval for prostate cancer, it appeared there was curious and questionable data related to Lupron’s cardiovascular effects. At the time, I questioned the validity of the claim Lupron had a safer cardiovascular profile than alternative treatment – a mantra that became a selling point for the drug. (See ‘Was Lupron’s Initial FDA Approval Based Upon Safety & Efficacy’, p. 4-10 here). In 2010 the FDA would issue warnings for Lupron/GnRHa use in men concerning the potential increased risk for cardiovascular problems, heart attack, sudden cardiac death, and stroke (and diabetes).

WOMEN: In my 1995 testimony to the MA. Health Care Committee, I identified “manipulated figures” (p. 8 here) in a female Lupron study – fourteen months before the Federal Register posted a Notice of Scientific Misconduct about the same Lupron investigator/author who had been found guilty of falsifying and fabricating 80% of data in 4 other Lupron studies (2 of which had been published and required retraction).

Illegal Marketing Schemes in Gynecology and Urology

Years ago I was aware of a gynecologist approached by the drug company’s sales force that indicated he could clear $98,000 to his income by prescribing Lupron” (see page 8), and would also find an internal confidential company memo unearthed during Oversight Hearings which detailed for urologists the annual $105,011.40 doctors could earn when they prescribed Lupron.

Bloomberg News summed up the impact drug money had in urology (‘Prostate Patients Suffer as Money Overwhelms Best Therapy’, November 6, 2012.  Bloomberg News;  article snippet  here):

“[In the past] Urologists could make $5,000 per patient dispensing Lupron in their offices, thanks to secret discounts and kickbacks from drug makers.  … In 1997 the 25 top-prescribing Lupron urologists each averaged $1.6 million in Medicare payments. … Two of every five patients who received hormone therapy didn’t need it, the [New England Journal of Medicine] study found. In 2005, after Medicare cut Lupron and Zoladex payment rates by over half, inappropriate use plummeted 44 percent. … Hundreds of thousands of men were chemically castrated for no reason; that’s the biggest scandal of all. … The money was too irresistible.”

There were reports of bribes from Lupron’s sales force in both urology and gynecology, and ultimately

“the company pleaded guilty to participating in a criminal conspiracy by providing doctors with free Lupron samples for which doctors then billed Medicare [with] the company inflat[ing] the list price of Lupron to ensure that doctors who prescribed it would make a sizable profit when the government reimbursed them.”

The company paid the then-highest fine in US history – $875 million.

In addition to my multiple  attempts to encourage the US investigation to expand its investigation from financial fraud and into the health risks posed by Lupron, it appears others were also making similar requests: “A call to the U.S, Attorneys Office inquiring whether financial fraud in the marketing of Lupron might indicate that FDA studies may also have been fabricated brought no answer. They are simply not interested.”

Paying the Patient Support Groups

In the past, “[i]n addition to offering inducements to hospitals and doctors, [Lupron’s manufacturer] was encouraging its salespeople to approach patients in support groups” (see here, here, and here ). It is known that the manufacturer of this drug and other GnRHas contributed hundreds of thousands of dollars to an endometriosis support association , and Lupron’s manufacturer also contributed thousands and thousands of dollars to a fertility support group (at a time when Lupron was only FDA approved for men). It is only logical to question whether any pediatric support group(s) experience(d) ‘infiltration’ of Lupron money.

One pediatric group dedicated to growth disorders, the Magic Foundation, is known to have received money from growth hormone manufacturers. According to publicly available documents from Guidestar, this foundation has reported 2014 contributions of $949,348 (contributors’ identity not provided). Appearing prominently (and to me, appearing promotionally), the Foundation’s website discusses and displays Lupron Depot-PED information, as well as providing the web address for AbbVie’s Lupron Depot-PED product information. (Until recently, no other GnRHa was identified, discussed, or linked on the Foundation’s website, and presently one other 12-month injectable, non-Lupron, GnRHa drug is mentioned.)

The information posted on the Foundation’s website of risks from Lupron Depot-PED is quite sparse: there is mention of temporary mood changes, injection site redness and pain, and rarely a sterile abscess, concluding “[r]esearch to date indicates that when treatment is stopped, puberty should resume and advance normally.” “Only as a convenience” does an AbbVie “Puberty Too Soon” website provide a web link to the Magic Foundation. It should be noted that AbbVie’s lead Lupron precocious puberty investigator Dr. Peter Lee, is on the Medical Advisory Board of the Magic Foundation.

Transgender Use of Lupron Noted as Lucrative for Some Providers

A 2013 ‘GenderTrender’ article noted for years “a cluster of extremely well-funded physician providers” have been prescribing to children off-label drugs for transgender use. This article states Lupron is “so toxic” adult transgenders are advised against its use. The article includes a statement by Lee: “Suppression … can be effectively and safely accomplished using GnRHa – an intervention that is both temporary and reversible.”

Benefits of Orphan Drug Status

Lupron for use in precocious puberty (a rare ‘orphan’ disease‘ which by definition affects less than 200,000 in the US) has the designation of “Orphan Drug” status, allowing the drug company tax credits (under 26 USC 45C) for related clinical testing expenses (see here and here). It should be determined if expenses from non-precocious puberty pediatric uses (which would be ineligible for orphan status/tax credits) have been filed, i.e., transgender and acne (which affects approximately 1.4 million and 50 million people, respectively). How many off-label, unpublished studies have been conducted in the pediatric and teen population?

Lupron is Lucrative

Based upon the information provided here (and this is not an all-inclusive list), in my opinion it seems little wonder that Lupron became the most prescribed GnRHa, became prescribed for men, women, and children (and animals, fish, chickens, etc.). And it’s no surprise why Lupron has been prescribed for A – Z off-label indications, nor why its victims have met with extreme difficulty in having their adverse events acknowledged and addressed.

Lupron has not only been lucrative for a number of its opinion leaders, spokesdoctors, and prescribers – it has also resulted in a cottage industry born from Lupron-induced iatrogenic injury, requiring acute and chronic office visits and hospitalizations for virtually every practice in medicine (neurology, rheumatology, cardiology, endocrinology, oncology, gastroenterology, psychiatry, pulmonary, dermatology, etc.).  This drug isn’t just a “cash cow” – it’s a “cash pig”.

Postscript: Correction

April 25, 2017 – The above is an edited version of an article that was originally published on April 18, 2017.  In this edited version, information pertaining to adverse events in one particular pediatric clinical trial has been removed from the original article because this information has been learned to be inaccurate. In the original article, I cited adverse event numbers as found listed within this pediatric study’s results. However, in looking at this study’s list of adverse events, I read (and cited) the reported numbers that followed any particular adverse event – when, in fact, the correct reported numbers were those that preceded any particular adverse event. This list’s reverse order of coding resulted in my (erroneous) conclusion that the numbers of adverse events reported for this trial were in error. (And the list, when read in reverse, provides reported adverse event numbers that exactly match those reported in this trial, indicating no error had occurred.) I have emailed the author of this pediatric study an apologetic note, describing the confusion that resulted from this list’s atypical coding methods, and have acknowledged that the reported adverse event numbers for this trial are indeed “valid”. I apologize to anyone else who may have been inconvenienced by this error.

The original (and now known to be erroneous) text removed from this edited version is included here for your information:

Original Text

CHILDREN: And now, after looking closely at one pediatric clinical trial, there appears to be clear evidence that larger numbers of adverse events were experienced by these children which were not recorded or identified in the final results of this study.

In this pediatric trial, my review counted six adverse events which did not contain the correct number of reported adverse events in the final study results. For purposes here, one adverse event – vomiting – will be used as an example to describe this inexplicable disappearing act of adverse events.

The medical journal publication of this clinical trial, and the ‘study results’ of this trial (housed at ‘ClinicalTrials.gov’) both claim there were “0” reports of “vomiting” in Group 1 (3-month Lupron Depot 11.25 mg) and “4” reports of vomiting in Group 2 (3-month Lupron Depot 30 mg). However, in looking at the history of this trial at ClinicalTrials.gov, which identifies the changes and additions made to this trial, it can readily be seen that the changes made on December 9, 2013 (the additions of reported adverse event numbers) display that for the adverse event of vomiting, Group 1 had “10” reports of vomiting, and Group 2 had “9” reports of vomiting. That is a significant difference in numbers of reported vomiting than is found in the journal publication and in ClinicalTrials.gov study results. And when these documented (but not counted) adverse event reports of vomiting are properly tallied, the claimed incidence of vomiting changes from the published 5.6% to an actual incidence of 26.4%.

In emails to the lead author in attempts to learn the explanation(s) for these missing, untallied adverse events, I was informed that the data as published in the medical journal “is valid” and he is “not the responsible person for this data.” Numerous attempts to learn exactly who is responsible for the data in this clinical trial have proved fruitless to date. How can the lead author not be responsible for the validity of the data from his own study?

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This article was published originally on April 18, 2017.

Photo by Pepi Stojanovski on Unsplash.

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Lupron and Reproductive Injury

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lupron and reproductive injury

Recent attention in a dual Reveal and Kaiser Health News Report (‘Kaiser Report’) to the risks of Lupron’s use in children with central precocious puberty or growth issues, and to Lupron’s risks in general, presents an opportunity to continue the disclosures on the risks of Lupron. This is the third part in a 6-week series exploring numerous areas addressing the use of Lupron in the pediatric and teen population (part 1, part 2).

Lupron and Reproductive Injury

The original patent for Lupron (leuprolide), granted in 1977, was for ovulation induction. Because of Lupron’s hazardous drug status and its categorization by the FDA as a Pregnancy Category X drug (any woman who is or who may become pregnant should avoid because of risk to fetus), it could not gain FDA approval for the indication of ovulation induction. Therefore, Lupron’s manufacturer sought, and gained, FDA approval for use in palliative treatment of prostate cancer. This then allowed the drug to be prescribed off-label for ovulation induction and many other unapproved indications. Over the next several decades, Lupron’s use has expanded into multiple areas of pediatric and women’s health.  There are three FDA approved indications (‘precocious puberty’ in children, ‘pain management in endometriosis’ and ‘the hematologic management of anemia associated with fibroids when iron therapy alone is ineffective’), and many off-label uses of Lupron (see Incomplete A-Z List of Off-Label Uses here).

In 1983, ten years before Lupron received FDA approval for precocious puberty (PP), GnRHas were being tested extensively in a variety of indications, including “as a new treatment for idiopathic precocious puberty”, and for male and female contraception. Eleven years later a pilot study using Lupron plus low-dose estrogen as a preventative for breast cancer was deemed “an adventure into the unknown”, and the FDA determined that this treatment “should not move into larger clinical trials” (The Pink Sheet 1994; 56(27):13.  ‘GnRH/low-dose Steroids Not Appropriate for Study in Breast Cancer High Risks’). The FDA Committee Chairman said at the time:

“It would be better to recommend a study of the drugs in a high-risk population as a chemopreventative for a long time, find out what its long-term effects were, and then consider it for a larger population.”

In 1993, the year of Lupron’s FDA approval for PP, a study was published of 10 girls who had been followed up to 5 years, and while concluding Lupron was safe and effective, it noted:

“[l]onger-term studies, including reproductive history, will be needed before the potential effects of treatment on fertility can be assessed.”

The following year, in 1994, the FDA recommended nonclinical safety studies of GnRH analogs be conducted. And while it is not clear whether these nonclinical safety studies were conducted, one FDA Medical Office stated at the time:

“the possibility exists that some germ cells may have been permanently affected by drug treatment. It is therefore important to investigate the effects on fetal morphology (teratogenicity) and on postnatal development of the offspring.”

In a long-term clinical study in 1999 examining GnRHa treated girls with PP (Lupron being the most frequently prescribed GnRHa), it was identified that:

“Ovarian volumes tend to increase progressively over the first 3 posttreatment years and were often larger than normal by 3 year post-therapy [and these findings] suggest that recovery of the suppressed gonad of girls treated for longer periods of time may be a more gradual process, and that a complete picture of the effects of therapy may only emerge after several years have passed.”

Similarly, the original rat studies provided to the FDA for its initial 1985 approval in prostate cancer identified that

“[t]he severity of the lesions were greater in testes of rats sacrificed 7 days after cessation of [Lupron] indicating that the effects continued after drug withdrawal (emphasis mine)”.  (“Review and Evaluation of Pharmacology and Toxicology Data‟, NDA [New Drug Application] 19-010, March 1, 1984.)

Lupron Depot-PED’s label states “[f]ollowing subcutaneous administration of LUPRON DEPOT to male and female rats before mating there was atrophy of the reproductive organs and suppression of reproductive performance.”  The label also states “[f]ollowing a study with leuprolide acetate, immature male rats demonstrated tubular degeneration in the testes even after a recovery period.”  (Even though these rats failed to recover histologically, the label claims they were as fertile as the controls.”)

Precocious Puberty, Lupron, and PCOS

In a 2010, Italian study of girls with early puberty treated with GnRHas, the prevalence of polycystic ovary syndrome (PCOS) and hyperandrogenemia  “was significantly higher” than those untreated, and “this study represented the first evidence of an independent effect of GNRHa treatment in increasing the risk for PCOS during adolescence in girls with early puberty.”  At least one earlier study noted “very large ovaries” when GnRHa treatment was stopped, and subjects “had an increased prevalence of ovaries with a polycystic appearance.”  PCOS has been associated with increased risk of metabolic syndrome, diabetes, and dyslipidemia – conditions which may increase risk of cardiovascular disease. PCOS is also associated with infertility, which can result in the need for assisted reproductive technologies which often involve the use of Lupron.

Lupron and Torsion

In a Brazilian case report of a girl with McCune Albright syndrome (which, though rare, accounts for about 10% of PP cases), a salpingo-oophorectomy (surgical removal of fallopian tube and ovary) was required after the 3rd leuprolide dose due to complete torsion of right adnexa and a necrotic, cystic right ovary.  This case report also notes that:

“treatment [for McCune Allbright syndrome] with a GnRH analog can result[] in ovarian stimulation, cyst formation, increase of [ovarian] volume and adnexal torsion” requiring surgical removal of gonads.   (See photo of this girl’s enlarged, cystic, necrotic ovary in case report’s “Figure 2”.)

In a review of FDA’s adverse event reports (“AERS”), data valid through June 2016, for “Lupron Depot-PED”, “Lupron (leuprolide; daily injection), and “Lupron Depot”, there were no reports found for “salpingo-oophorectomy”.   The above published case of a pediatric salpingo-oophorectomy should have been reported, both to the drug company and subsequently to the FDA.  The case of ovarian torsion and of ovarian necrosis that appears in a ‘Lupron Depot-PED’ search at RxISK.org  (for 1 to 13 years old) likely represents the Brazilian case, but it is baffling why this case report cannot be found within the FDA’s AERS database. In addition, the latter RxISK search engine yields a report of ovarian enlargement in a search of 1 to 13 years old, which is also not found within the FDA’s AERS database.

In a search of AERS for adult women who experienced oophorectomy post-Lupron, 42 reports were found, and all but three reports were expedited, 15-day reports (which are provided in cases of serious adverse drug reactions). In a search of the “Lupron Depot-PED” AERS, 3 cases of ovarian cyst were reported. It is well known only 1% – 10% of all serious adverse events are ever reported to the FDA – meaning 90-99% of adverse events to Lupron are not reported [see page 7 here].)

Off-Label Use for Gender Dysphoria

In the off-label use of Lupron for ‘pausing puberty’ in the transgender population, it should be understood that Lupron is rarely identified as “Lupron”, but is called a “puberty-blocker”, “hormone blocker”, or “a puberty-suppressing drug”.  No doubt this language shift is an attempt to prevent an association with the ‘dreaded Lupron’.  It should also be noted that a reproductive biologist has stated ‘puberty suppressing treatment’ “impairs the children’s reproductive capacity” and:

“[s]ome trans boys (i.e. girls) receive puberty-suppressing treatment and never produce mature ovarian follicles … the problem is accentuated with trans girls (i.e. boys) because their spermatozoa are still developing.”

Additional alarming acknowledgments within the transgender population’s off-label use of Lupron are that:

“[p]otential long-term effects can include other abnormalities of hormones, vascular complications and even potential cancer.”

According to UnitedHealthcare policy, “pubertal suppression therapy is considered unsafe in managing children and adolescents with gender identity dysphoria and is, therefore, not covered.”  Other insurers do cover treatment of gender dysphoria with Lupron. One Canadian consent form for Lupron treatment of natal females with gender dysphoria identifies a number of risks, and twice repeats the warning that “there may be long-term side effects we do not yet know about”.

In 2015, the NIH awarded $5.7 million for a 5-year multi-center study which

“will be the first in the U.S. to evaluate the long-term outcomes of medical treatment for transgender youth“, seeking data on the “physiological and psychosocial impact, as well as safety, of hormone blockers.”

Reproductive and Developmental Toxicant

Lupron is known as a “recognized reproductive and developmental toxicant“.  The manufacturer’s ‘Material Safety Data Sheet’ (MSDS) identifies that Lupron-PED “may impair fertility” and “may damage fertility”.  The product label states the effects are “reversible on discontinuation of drug therapy” and “normal pituitary-gonadal function is usually restored within six months after treatment with LUPRON DEPOT-PED is discontinued” (emphasis mine). The label also identifies that rats “demonstrated tubular degeneration in the testes even after a recovery period.”  Past product labels state “no clinical studies have been completed in children to assess the full reversibility of fertility suppression”, but in 2013 follow-up data from previous pediatric clinical trials identify that post-study surveys of 20 trial participants found 80% had normal menstrual cycles – which indicates 20% had abnormal menstrual cycles.

Lupron, Endometriosis, and Hypoestrogenism

It is pertinent to address here the findings of an independent analysis by Dr. David Redwine of the raw data from Lupron’s endometriosis clinical trials: this analysis evidenced, among others,

“62.5% of [Lupron Depot 3.75 mg.-treated endometriosis] patients had not regained baseline estrogen levels by one year after stop of study … [indicating] definitive evidence of long-term damage to ovarian function” (see ‘Alarming Facts About Lupron’s Risks’ on pg. 26 here).

In a stark and most troubling contrast, Lupron Depot’s product label states the Lupron-induced hypoestrogenism “is reversible upon discontinuation of therapy”. Lupron’s manufacturer sought and obtained a court seal (see page 6 here) upon its endometriosis clinical trial data (and my attempts to unseal this data were unsuccessful). Without access to this raw data, further independent validation is not possible. To this day, these studies remain in the published literature without any retraction or comment. And cumulatively, as of this writing, these published clinical trials have been cited – as fact – within 23 PubMed Central articles (as recently as 2016), and they have also been cited in three Cochrane Systematic Reviews.  The four published studies containing the questionable endometriosis clinical trials’ data are studies “M84-042“, “M86-031“, “M86-039“, and “M92-878“.

The alarming contradiction in data and outcomes (raw endometriosis data showing “62.5% experienced long-term damage to ovarian function” vs. Lupron’s label and published studies’ claim of “reversible upon discontinuation”), as well as the perplexing paralysis on the part of the FDA and medical journals to act on behalf of public health, begs for a high beam investigative spotlight by the media, and medicine. See FDA response  which completely ignores the issue of discovered fraudulent data in Lupron’s endometriosis clinical trials, and see 2014 letter to FDA by Lupron Victims Hub which remains unanswered.

Somebody needs to answer these questions. If the FDA is not able or willing to be in charge, then who is the responsible authority? Inaction in this matter is totally unacceptable on multiple levels.

What Does the Future Hold?

Lupron has been administered to children for 30+ years, yet no definitive conclusions about its effects upon  reproductive health can be made due to lack of data?

The NIH transgender study, which should include assessment of “hormone blockers” upon the reproductive system, won’t be completed until 2020. But even if study results were available today, would it be claimed the data from the transgender population is not transferable to the precocious puberty population?

If various medical boards can classify Lupron’s use in children with autism as “dangerous, abusive and exploitative”, then Lupron’s use in children (period) is dangerous, abusive, and exploitative.

Share your Story

If you have a Lupron story, please consider sharing it on Hormones Matter.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was originally published on March 15,  2017.

Photo by Jasmin Egger on Unsplash.

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Tank Estradiol and Lose Metabolic Flexibility: Pitfalls of Lupron and Oophorectomy

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Lupron mitochondrial damage

Over the last several weeks, I have been looking at the role of estradiol in mitochondrial health. In the first post Hormones, Hysterectomy and the Aging Brain, we learned that estradiol depletion wreaks havoc on brain mitochondria turning them into misshapen donuts and blobs. Digging a little deeper, the next post (Lupron, Estradiol and the Mitochondria) pondered the connection between estradiol-depleting drugs such as Lupron, other Lupron-like drugs, and the devastating side effects that often follow suit. Could Lupron-mediated mitochondrial damage be at the root of these side effects? Quite possibly?  A question that remains is how. In this post, I will be digging even deeper into the role of estradiol in mitochondrial functioning, especially its role in something called metabolic flexibility.

A note of caution, while I focus on estradiol, the mitochondria, and what happens to health when we remove estradiol pharmaceutically via Lupron or surgically via oophorectomy, it is important to remember that estradiol is not the only hormone synthesized in the ovaries nor are the ovaries the only hormone-producing tissues. Moreover, the chemical castration induced by Lupron and other medications or via ovary removal disrupts and diminishes the synthesis of a myriad of hormones. Estradiol is simply where most of the research is focused, and so, it is where I too must focus, at least for the time being.

Steroid Hormones and Metabolic Flexibility: A Critical Factor in Post Lupron and Post Oophorectomy Ill Health

Steroid hormones regulate metabolic flexibility at the level of the mitochondria. Estradiol, the most frequently studied among the steroid hormones, plays a pivotal role in determining how food fuel is converted into cellular fuel or ATP.  When we eliminate estradiol with medications such as Lupron and other GnRH agonists or antagonists, or when we remove a woman’s ovaries, depleting her primary source for estrogen synthesis, metabolic flexibility diminishes significantly.  With the lack of metabolic flexibility comes several health issues, some noticeable, like weight gain, and others less noticeable, at least initially, like cardiac and neurodegenerative diseases. A common component of each of these conditions is mitochondrial dysfunction. Mitochondrial dysfunction can be initiated and accumulated via a number of mechanisms and over time, so estradiol is not the only variable, but it is a key factor that is often ignored.

Mitochondria

Mitochondria are the cellular powerhouses that consume oxygen and transform the foods we eat into a currency that cells can use (ATP) to perform all of the intricate tasks needed for survival and health. Mitochondria are also the site of steroidogenesis (steroid synthesis), immune signaling, and all sorts of other functions that determine cellular life and death. When you think about it, how well the mitochondria perform these tasks affects health at every level of organismal physiology. Without the appropriate amount of mitochondrial energy/ ATP, cell function becomes deranged, and ultimately, grinds to a halt. When that happens, disease is imminent. Indeed, genetic perturbations of mitochondrial function are some of the most devastating diseases known to medicine.

One has to wonder, what happens when we perturb mitochondrial function from the outside in – via toxicant exposure or by eliminating critical hormones or other co-factors such as nutrients that are necessary to mitochondrial operations? Worse yet, what if an individual with unrecognized genetic defects in mitochondrial functioning faces additional mitotoxicant exposures; what then? Complex, multi-system disease – that’s what. I would argue that mitochondrial dysfunction represents the final common pathway, a convergence point, connecting an array of seemingly disparate disease processes. Mitochondrial metabolism, and specifically, metabolic flexibility, may be at the heart of the derangement, with estradiol, and likely other hormones, in the driver’s seat.

Metabolic Flexibility: Adapt and Survive

When we think of stress and flexibility in general terms, it is easy to recognize that the more flexible one is in his/her behaviors or coping mechanisms, the easier it is for one to respond to, and survive stressors. Flexibility means that options exist for when everything hits the fan. Imagine if there were no options or if you had to respond to each and every stressful event in your life using exactly the same behaviors or response patterns. You would not get very far. The same holds true for cell behavior, and more specifically, mitochondrial behavior. The mitochondria need options to respond to the differing needs of the cells that they supply with energy. If those options become limited in any way, the mitochondria become less effective. They produce less energy, scavenge fewer oxidants (toxicants), and when stressors present, cannot easily adapt. In fact, the more inflexible the mitochondria are forced to become, the less likely they, and the cells, tissues, organs, and organism within which they reside, will survive. Estradiol is integral to mitochondrial flexibility. Remove the estradiol and the mitochondria become less metabolically flexible and less able to respond to the demands of a changing environment.

Estradiol Equals Increased Mitochondrial Efficiency and Decreased ROS

Estradiol maintains metabolic flexibility via two important mechanisms: increased mitochondrial efficiency and ROS management. With the former, estradiol regulates metabolic flexibility by altering the expression of genes that control the enzymes within the fuel conversion pathways. It is a complex algorithm of responses, with some proteins upregulated and others downregulated. The net result, however, favors increased efficiency in ATP production by maximizing metabolic flexibility or adaptability to the environment.

With the latter, estradiol, along with progesterone, manage the clean-up tasks inherent to any energy production process. In effect, estradiol manages ROS both on the front end and the back end of mitochondrial ATP production. On the front end, increased metabolic efficiency and flexibility equals fewer ROS byproducts. On the backend, estradiol cleans up the byproducts of processing -ROS – and tempers the damage these byproducts can cause.

Estradiol, Pyruvate, and ATP

Of particular interest to our work here at Hormones Matter, estradiol upregulates a set of enzymes called the pyruvate dehydrogenase complex, PDC. The PDC, responsible for converting glucose into pyruvate, is the first step in the long process that nets multiple units of mitochondrial ATP. The PDC is key to carbohydrate metabolism and more recently has been linked to fatty acid metabolism, making this enzyme complex central to mitochondrial energy production. Diminished PDC derails mitochondrial functioning, producing serious diseases. Children born with genetic pyruvate dehydrogenase deficiency suffer serious neurological consequences and rarely live to adulthood.

Importantly, the PDC (like all of the enzymes within these cascades) is highly dependent upon nutrient co-factors to function properly. Thiamine and magnesium, are critical to the PDC complex. Since PDC function demands thiamine, children and adults with thiamine deficiency also suffer significant ill-health, ranging from fatigue and muscle pain, to disturbed cognitive function, disrupted autonomic function affecting multiple organs, psychosis, and even death if not identified. Thiamine deficiency is most well known as a disease associated with chronic alcoholism but has recently begun re-emerging in non-alcoholic populations relative to medication and vaccine reactions.  Many medications and environmental variables deplete thiamine and magnesium, diminishing mitochondrial function significantly, by way of pyruvate.

Along with nutrient co-factors, estradiol is critical for pyruvate. Estradiol upregulates the expression of the enzymes that make up the PDC (in the brain). If estradiol is reduced or blocked, mitochondrial ATP production will take a hit. If estradiol is blocked in an already nutrient-depleted woman, the first step in mitochondrial fuel conversion would take a double hit. One can imagine the consequences.

In light of the direct role that thiamine, magnesium, and other nutrients play in the cascade of reactions required to produce ATP, can we maximize mitochondrial functioning with nutrients to compensate for the mitochondrial damage or deficiencies likely to occur post oophorectomy or as a result of GnRH agonist or antagonist drugs, like Lupron? I can find no research on the subject, but it is certainly a topic to explore given the millions of women already suffering from the mitochondrial damage induced by Lupron and/or pre-menopausal ovary removal. Even without the necessary research, correcting nutrient deficiencies and dietary issues should be undertaken for general health.

Another question in need of exploration, if we maximize mitochondrial functioning, does that then increase steroidogenesis in other endocrine glands? A section of the adrenal glands called the zona reticularus, for example, produces a complement of hormones similar to those of the ovaries. In postmenopausal women androgens, precursors for estradiol, produced by the adrenals account for a large percentage of total estradiol production. Could we take advantage of that to help stabilize circulating hormones?

Finally, beyond the nutrient requirements for mitochondrial ATP production, enzymes throughout the body, even those involved in post-mitochondrial steroid metabolism, require nutrient co-factors to function properly. Could we maximize those enzymes for more efficient steroid metabolism to net sufficient estradiol to maintain mitochondrial function?

What about Natural Declines in Estradiol?

It is not clear how menstrual cycle changes in estradiol affect mitochondrial functioning or how the postpartum decline in pregnancy hormones affects mitochondria. One would suspect there are compensatory reactions to prevent damage, but this has not been investigated. In natural menopause, however, researchers have noted that some form of compensation occurs as estradiol declines and, at least for a time, and in rodents, mitochondria maintain efficient production of ATP. In contrast, no such changes are noted with premature menopause or oophorectomy.

Also not investigated sufficiently, is the impact of chronic synthetic estrogen exposure on mitochondrial functioning. In other words, what are the effects of oral contraceptives, HRT, and the growing list of environmental endocrine disruptors, on mitochondrial ATP production? Since these compounds bind to estrogen receptors and displace the endogenous estrogens like estradiol, some evidence suggests endogenous production of estradiol is reduced. Do the mitochondria respond also by downregulating estrogen receptors or by some other mechanism?  Short-term, animal research suggests that supplementing 17B estradiol post oophorectomy reduces mitochondrial damage. In research in humans, where synthetic estrogens are used, results are less clear and longer-term studies do not exist beyond the broad brush strokes of epidemiology.

Metabolic Flexibility and Tissue Type

One of the more interesting aspects of estradiol’s role in metabolic flexibility is that it is site or tissue-specific and may point to novel therapeutic opportunities. Since different cell types, in different parts of the body, prefer different fuels for power to survive, when we eliminate estradiol from the equation, mitochondria from different tissues or organs respond differently to the lack of flexibility. Perhaps, we can utilize the information about fuel requirements to design diets that compensate for diminished metabolic flexibility.

Heart Cells. I’ve written about this research previously, not fully understanding the implications. Estradiol allows cardiomyocytes (heart cells) to switch from their preferred fuel of fatty acids to glucose during stressors such as heart attacks (and theoretically during any stressor like exercise). That ability to switch fuel types is protective and allows the cells to survive and heal. It may explain why women are more susceptible to heart damage post-menopause when endogenous estradiol declines. This may also point to a pathway for post oophorectomy and post Lupron declines in normal heart function.

Brain Health. Declining estradiol affects brain mitochondria differently. As I noted in a previous post, without estradiol, brain mitochondria become progressively less functional and misshapen. These structural changes impair mitochondrial ATP production. Unlike the heart, however, the brain prefers glucose as its primary fuel source. Estradiol appears to enhance glucose uptake from the periphery and across the blood-brain barrier. When estradiol is absent, brain glucose uptake diminishes significantly (in rodent studies), leaving the brain perpetually starved for glucose.

We know from brain cancer research, that with declining brain glucose, secondary fuels can kick in, but only when the mitochondria have sufficient flexibility to switch. For example, mitochondrial fuel flexibility is critical to battling brain tumors. Under conditions of stress and when brain glucose concentrations are low, healthy mitochondria can readily transition to ketone bodies for energy, at least in vivo. The transition from glucose to ketone bodies is believed to be an evolutionary adaptation to food deprivation allowing the survival of healthy cells during severe shifts in the nutritional environment. Estradiol appears to be key in maintaining that flexibility.

Weight Gain and Fat Accumulation. Post-menopausal, post-hysterectomy, and oophorectomy weight gain are well established research findings. Anecdotal complaints of Lupron weight gain are also common. These findings may be related to derangements in metabolic flexibility mediated by the relationship between estradiol and mitochondrial functioning. The increased lipid or fat accumulation in skeletal muscle though associated with impaired insulin-stimulated glucose metabolism may be related to the reduced capacity to adjust to a changing fuel environment. More specifically, weight gain may represent a declining ability to utilize fats effectively as a mitochondrial fuel source, possibly via a derangement in a mitochondrial channel responsible for shuttling fats and cholesterol into the mitochondria for processing. When the mitochondria become less flexible, a channel called the TSPO, shuts down, disallowing fats that would normally be shuttled into the mitochondria and processed for ATP (and steroid hormones), from entering. Instead, they are stored peripherally in adipocytes. I wrote about this in detail here: It’s All about the Diet: Obesity and Mitochondrial Dysfunction. It is possible in estradiol-depleted women that TSPO downregulation is a compensatory reaction to diminished metabolic flexibility.

It is also conceivable that the lack of brain glucose, as discussed above, leads to overeating and, more specifically, cravings for sugary foods. This would be a logical compensatory reaction to bring more fuel to the brain; one likely meant only for the short term and that when held chronically begins the cascade of other metabolic reactions known as obesity, diabetes, and heart disease. Perhaps, just as fat storage becomes a survival mechanism when mitochondria can longer process it effectively, the craving for sugar in estradiol-deprived women is also a survival mechanism.

Finally, adipocytes can synthesize estradiol. It is conceivable that in response to declining estradiol concentrations, the body stores fat to produce more estradiol.

Final Thoughts

Central to mitochondrial dysfunction, whether by genetic predisposition or environmental influence, is the inability to efficiently produce ATP (the fuel that all cells need to survive) and to effectively manage the by-products of fuel production and other toxicants. Estradiol plays a huge role in both of these processes. Eliminate estradiol and mitochondrial functioning becomes less efficient and less flexible initiating cascades of chronic and life-altering conditions. This suggests the ready application of medications like Lupron that deplete estradiol or the prophylactic removal of women’s ovaries is misguided at best, and dangerous at worst.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter. 

Image by Triggermouse from Pixabay.

This post was published originally on Hormones Matter on February 11, 2015. 

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Puberty Blocking Drugs

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puberty blocking drugs

On Twitter I came across a post from a physician suggesting that 1) puberty-blocking drugs were completely safe and reversible and 2) that for one to believe otherwise suggested a bias in that individual. Having studied these drugs when they were used across various women’s health modalities, long before they were used so broadly for this current application, I can say without a doubt that these drugs are neither safe nor are their effects completely reversible. As far as the bias argument goes, while it is true that many individuals use these and other hormone-modulating drugs as cudgels in various culture wars, to foreclose upon a discussion of drug safety a priori for fear of being aligned with a particular viewpoint is medical negligence pure and simple. Every drug, no matter its cultural or political significance carries with it certain risks. Those risks are not minimized because we want them to be or because we choose not to recognize them. That is not how pharmacology works. Heck, that is not how life works.

We see this type of behavior with hormonal birth control. If one dares to question the safety of these drugs, one is accused of being anti-women’s rights. We see this in discussions of vaccine safety. If one dares to question the safety of vaccines, one is accused of being anti-vax, or more recently, anti-science. We now see it with the puberty-blocking drugs where if one dares to question the safety of these drugs, one is accused of being anti-trans. In all cases, the ‘anti – [fill in the blank]’ label serves the manufacturers of these drugs well. So long as we bicker amongst ourselves, so long as the drug itself can signal some sort of inherent virtue or lack thereof, the safety of these drugs can never be impugned.

What many in the current battle fail to recognize, is that these drugs have been on the market for decades, first as a treatment for prostate cancer, then and currently as ‘treatments’ for endometriosis, fibroids, ovarian cysts, precocious puberty, and with in vitro fertilization. In every case, those who take these drugs are rendered chronically ill. These are drugs neither new nor safe, or even specifically designed for their current application. They have simply been rebranded to take advantage of a new market.

What do these drugs do? Technically, they override the hypothalamic-pituitary-gonadal or ovarian feedback loops that control the synthesis of the androgens and estrogens, the sex hormones. They do so at the level of the hypothalamus in the brain by overriding the production of something called gonadotropin-releasing hormone (GnRH). This then prevents signals to and from the pituitary gland and the testes and ovaries from fully cycling, effectively blocking the synthesis of testosterone, estradiol, and some of the other metabolites. Non-technically, and more accurately, they chemically castrate the user, by severely and immediately blocking the synthesis of the reproductive hormones, testosterone, and estradiol.

This begs the question, why would anyone think this type of drug would be a safe option for anyone, let alone children? Compartmentalization.

Within the current medical framework, reproductive hormones are believed to affect only the reproductive organs and nothing more. So if we block them, we needn’t worry about anything but their direct effect on reproductive tissues. This framework allows one to see only what one wants to see. It is the framework that buys into such silliness that we can fundamentally alter the regulation of these hormones without so much as affecting anything else in the body or the brain. Nothing. Nada. Nil. Reproductive hormones control reproduction and that is it. If one buys into this nonsense, well of course we can postpone puberty by using some of these drugs, and when ready reverse course, open the spigot and let puberty flow. Easy peasy.

Not only is this framework completely ignorant of how the body works, but blatantly negligent. The body is connected to itself. Its individual parts are not separate entities. Its systems do not work in isolation from each other, especially not hormones. Steroid hormones are synthesized and metabolized from each other and into other steroid hormones. They are part of extensive pathways that are constantly reconfiguring based on all sorts of endogenous and exogenous signals. Steroid hormones organize and activate critical systems relative to sex and development but are not limited to just those related to sex and reproduction. They modulate every cell in the body. There are steroid hormone receptors on the neurons in the brain that modulate neurotransmission (and vice versa), on the cardiomyocytes that influence heart rate, rhythm, and pressure, on muscle and bone cells that regulate growth and stability, on immune cells that influence inflammation and other patterns, and on the mitochondria, where cellular energy and all sorts of other processes, including steroidogenesis, are managed.

Estrogen receptors, for example, are all over the brain and are responsible for upregulating hundreds of genes involved in all sorts of brain activity, not just those involved in the development of sex characteristics or reproduction. These hormones are so important to brain function, that the brain not only allows them to cross the blood-brain barrier but also synthesizes these hormones de novo – from scratch. On the mitochondria, the estrogen receptor influences the shape of the mitochondria, such that in the absence of estradiol, a hormone blocked by these drugs, the mitochondria become misshapen, only to die a messy, necrotic death.

This begs the question, if these hormones are so important to general functioning, what do we think happens when we block their production, especially during a critical phase of development when the totality of the organism is poised for a huge growth and development spurt? Do we think somehow that magically only reproductive function is affected? That all of those other hormone-influenced cells will not be affected? Or that the other hormone pathways will not be affected. Or that the mitochondria, the energy engines of the cells, will somehow function just as well absent a critical substrate? Apparently, we do.

While there are people for whom these drugs represent an existential threat to their narrow ideologies, for most of us, questioning the safety of these compounds has nothing to do with ideology or bias and everything to do with the chemistry.

For more information on mechanisms, ill effects, and the long history of unethical marketing of this class of drugs, please read the various articles on Lupron. That is the name under which this type of drug is used in women’s health. This study illustrates the scope of injury.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

Photo by Markus Spiske on Unsplash.

Related posts:

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Endometriosis, Lupron, and Fluoroquinolones: A Recipe for Autonomic Disintegration

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Endometriosis, Lupron, Fluoroquinolones and Dysautonomia

I am sharing my health story in the hopes that someone can offer assistance. I had stage 4 endometriosis for years before it was diagnosed. On top of that, I have had reactions in antibiotics, including fluoroquinolones and was given Lupron. Each drug destroyed more of my health. I am currently bedridden, in pain and unable to function. I have lost hearing in my right ear, have Sjögren’s syndrome, Hashimoto’s, adrenal insufficiency, hypokalemia, electrolyte imbalances, IBS, MCS, Ocular migraines and recently, have been diagnosed with dysautonomia. My body feels like it is disintegrating. We believe that everything is related, that I have mitochondrial issues at the root of these illnesses, but to date, no one has been able to put the pieces together. With the help of my husband, I have put together my health history. We are looking for input.

Early Warning Signs

1985: late summer, I was hit by car while riding bicycle. I was banged up really bad and definitely had head injury.

1998: started feeling off, not sure yet at this point still very young

2001: birth of my first daughter. I developed severe preeclampsia and had an emergency C-section three days later. My daughter was 6 weeks early and spent two weeks in the intensive care unit.

2002-2003: I felt off at times and did go to GP on several occasions. I had pain shot to my back. I am not sure what it was but it took the pain away. I also kept saying just didn’t feel well. I felt off but nothing was found.

2005: the birth of our son and second C-section. I was on bed rest last three months of the pregnancy. I was given an antibiotic for some reason. I do not remember. I had a reaction to it and turned orange. The doctor gave me something else to counter the effects of the antibiotic and my color returned to normal. It was a normal birth.

2006-2007: I was still in pain. The pain moved to the abdominal area. I developed bowel issues, had and ovarian cyst. I saw gastrointestinal physician who did scans and found a thickening of the lining of uterus. He referred us back to the gynecologist who did D&C in 2007 and said I had very minuscule amount of endometriosis.

2008- 2009: still seeing OB for pelvic pain, also seeing multiple other doctors including a neurologist, internist, and surgeon. Everyone kept saying same thing: ‘Your fine. It’s in your head.” They wanted to put me on mood enhancers. I tried lorazepam and felt terrible on it, so I stopped after two weeks.

The Lupron Disaster

September 2009: I started doing Lupron injections from gynecologist. She was very forceful with me and stated “if you don’t do these injections I can’t help you.” She said it was the only way they could know if the pain was below the belly or above. I agreed reluctantly, but at that time still thought my doctors had their best interests in me. After the first injection, my doctor called at home on a Saturday to see how I was feeling. I responded I was already in pain, but it has now quadrupled and I feel like an old person. Every bone in my body hurt.  I couldn’t believe the amount of pain I was in. She said I had to get all 6 injections if it were to be able to help me.

At that time, my husband because of work only went to a few of my appointments. I soon began to have him go with me because I felt I was getting the run around.

Hearing Loss Post-Lupron: Let’s Add Fluoroquinolones and Steroids to the Mix

2010: the last injection was in February. I began to lose my hair. I had memory loss, stabbing and taser sensations in head. I was still getting pains in abdomen area. In September, I went in for ear pain. The ENT said it looked like a scratch, so he gave me fluoroquinolone drops. I had also taken other fluoroquinolone antibiotics for yeast infections earlier in the year. In October, I had sudden sensorineural hearing loss in the right ear. Within an hour, I called my husband told him my hearing was acting weird. I went totally deaf in my right ear, 8 months after my last injection of Lupron. My local ENT immediately gave me a shot of cortisone (I was able to still walk and drive). It all went crazy when my ENT put me on a large dose of oral prednisone for 14 days. Everything in my body went nuts. I was rolling out of bed, holding on to the walls to help me walk. I totally lost my balance. The oral prednisone really did a number on my head.  I had done genetic testing through 23andMe and our doctor upload the report to a reader called Opus23. It said that I should never take prednisone.

I went to Stanford Medical and saw top ENT and received three cortisone injections into the right ear drum. Had a 50/50 chance for recovery and for me it didn’t work. I left Stanford with them telling me they still don’t have all the answers yet when it comes to sudden hearing loss. They thought it was some sort of viral infection that attacked the ear drum and deafened the ear. After the hearing loss. I had three ER visits. This is when I first started having low potassium. I felt like I was about to pass out. I was still driving at this time, I didn’t know what to think.

2011 -2012: I began seeing a naturopathic physician. I also did a trip down to LA to the House Ear clinic to see some specialist regarding her hearing loss. They couldn’t help either. I left my current OB and started seeing the physician who was filling in. I ended up doing a partial hysterectomy with her after finding a growth at one of my numerous ER visits that year. I was still working and a full-time mommy, while dealing with massive pain in my lower abdomen and now starting to deal with multiple autoimmune diseases including: Sjögren’s syndrome, Hashimoto’s, adrenal insufficiency. In addition, a lot of my minerals and vitamins were off at that time. I suspect this was beginning of my dysautonomia. I also began seeing an endometriosis specialist at Stanford.

Was it Endometriosis All Along?

2013: On January 31st, I had laparoscopic surgery to clear the endometriosis. I had stage 4 endometriosis which took my appendix. The physician said my body was littered with endometriosis. He even checked up in my heart cavity to make sure no endometriosis had made its way up to the heart. Before the surgery, I was talking with the anesthesiologist and telling him about my hearing loss and my low potassium. That is when he stopped the surgery and I had to take a stress test. We left and went to Palo Alto heart center and did a stress test I fasted for 24 hours and then they had me go do a stress test on a treadmill on an empty stomach. I did it no problem and went back to the surgery center. That is when they did the laparoscopic surgery and found stage 4 endometriosis.

Also, I want to point out that we didn’t find out until much later that during the course of the endometriosis surgery, they had left surgical clips and suturing material in me. We discovered this at one of our many ER visits. The OR report from our doctor says nothing about these things being left inside of me. I believe this is an additional pain I have on top of the other complications in my abdomen area. Nothing like having a wad of surgical clips throughout my abdomen and suturing material left inside my already struggling body. We are trying to get these removed, but no surgeon will take my case.

Mitochondrial Damage and Autonomic Disintegration

April that year, I had another ER visit. I lost all bodily functions. My potassium was severely low. I would go to the ER in 2013 many more times.

2014: I had to stop working totally this year. I tried to come back and assist a friend of mine just being her loan officer assistant but the neurological pains and crazy foggy brain I was experiencing was just too much. Something that was so easy for me years earlier, I was now having trouble just doing basic loan officer task at this point. Strange neurological pains were becoming a normal. I stopped driving this year also. It was just getting to scary for me to continue. I continued to go to ER for multiple visits

2014- 2017: I went to the ER over 50 times for various reasons: heart pains, chest pains, shooting stabbing pains throughout my entire body. I almost always had low potassium. Over these years, we spent our life savings and pulled out a $100,000 from my husband’s 401k, which we spent on various treatment plans. We have traveled as far away to Philadelphia looking for answers. We even gutted our house when we were told at one time it must be mold that is killing me. We lived in a borrowed 5th wheel while my husband put our house back together. There have been numerous days where I felt I couldn’t go on one more minute. I felt like death was right around the corner.

In 2015 one of our doctors after reading my genetic report thought he found a breakthrough with a patient that had hypokalemia and Sjogren’s syndrome. He provided me a copy of the study they did on a girl with very similar symptoms to mine. He had our local compounding pharmacy mix a solution called Shohl’s. I took the solution after my doctor assured me I would be ok. Well, I tried it almost within in minutes I was convulsing and went into tachycardia. My husband called 911 ambulance took me to the ER. In route to hospital paramedic gave me nitroglycerin. I was monitored for several hours and eventually went home. During this time had been staying at my mother-in-law’s house for about 6 months because we weren’t sure at this point if something in our house was making me so sick. This was a very stressful time for me at this point we have no idea what’s going on and what’s causing this.

We did have some relief in 2017 when our local naturopathic doctor was able to get a new treatment called UBL or ultraviolet blood irradiation. I had about 6 months where I was feeling off, but having somewhat good days where I could semi-function. My viral count has been very high during these years, EBV, CMV, HHV6, etc., and possibly Lyme. If I push myself, I will crash for hours sometimes days until I start to get any strength back just to walk to the restroom.

Next, I went in for a completely different treatment called prolotherapy. I got one injection into my shoulder, and just like that my body reverted back to like I was before the UBL treatments. I was worse again. It was very strange my body reacted like that.

2016: I was diagnosed with dysautonomia by another specialist, an electrophysiologist cardiologist. I have several of the sub symptoms of dysautonomia including: postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), dizziness, vertigo, fainting, fast, slow or irregular heartbeat, chest pain, low blood pressure, problems with gastrointestinal system, nausea, disturbances in visual field, weakness, breathing difficulties, mood swings, anxiety, fatigue and intolerance to exercise, migraines, disrupted sleep patterns, temperature regulation problems, concentration and memory problem, poor appetite and overactive sense, especially when exposed to noise and light. We also met with a dozen or so other specialists. None were able to help.

I have multiple tears in both hips worse on right side. Multiple torn areas in the pelvic floor also.  Surgery is out of pocket and we have not been able to fly back and have surgery to repair those tears and hips yet as of 2019.

2018- 2019: I went to the ER only three times in 2018 and so far only three times in 2019. We try not to go because we know they never find much. I only go to be reassured that my vitals are still strong when I’m feeling at my worst. I have been denied disability. I had a neurocardiogenic seizure in the courtroom with judge and she still denied me. I have one last appeal that I am waiting on. I am not very hopeful that will go through. At this point, the dysautonomia, fibromyalgia/ chronic neurological pain and the low potassium are what are the hardest things for me to deal with. As of right now, we are concentrating on rebuilding my mitochondrial cells in hoping I can reverse some or most of the damage I think was a direct cause from the Lupron injections.

I was also on bio-identical progesterone creme from around 2012 to 2018. Then, in middle of 2018, my ND wanted me to try the bio-identical that went off the lunar moon cycle. It was a separate estrogen and progesterone creme in a plastic push-up type applicator. She said she was looking into it and thought it might help. Well, I tried it and had terrible side effects, I think most likely from the adding in the estrogen. After second month, I was having terrible stomach pains. I looked four months pregnant and was begging my husband to take me to the ER. The pain was worst at the part of the cycle where I took the estrogen only. I felt like she was going to die. In the past, I was always high in estrogen. I am not sure, but as soon as I introduced in that estrogen, it threw me out of whack terribly. I stopped that in November of 2018.

This is where I am now: in pain, unable to work or care for my children. My husband is my full-time caregiver. He takes care of our kids, shops cooks, does everything I used to do plus works his full-time job. I couldn’t do this without him. The doctors have run out answers. I believe it was the endometriosis all along, made infinitely worse by Lupron and the various rounds of antibiotics, including fluoroquinolones. The only way I can maintain my potassium levels is through huge daily doses. Otherwise, I slide into hypokalemia. We have a standing order at our local hospital to measure my potassium whenever I suspect it is low. We have sought treatment from dozens of specialists and spent our entire life savings and I am no better than I was 10 years ago. In fact, I am worse. Over the last 8 years, we have been supplementing with vitamins and minerals to try and repair the damage done to my mitochondria by the Lupron and the fluoroquinolones. Some things help and others do not. We are at wits end and do not know where to turn for help. Below is a list of supplements that I currently take.

Supplement List

Upon waking:

  • 600mg potassium,
  • 1 1/4 grain Naturethroid

Breakfast:

  • 3 200mg potassium. Daily total 1200mg
  • 1 Chewable Hydroxo B-12
  • 1 COQ10 100MG
  • 1 Biotin 10,000mcg chewable
  • 1 Chromium picolinate 200mcg chewable
  • 1 Desiccated adrenal from Standard process
  • 1 magnesium malate 100mg
  • 1 Thiamin 50mg
  • 1 Mitocore – it is like a multiple vitamin
  • 5 grams vitamin C, mixed with juice, plus I add Lugol’s iodine, colloidal silver, lymph drain and trace mineral mix.

Mid-morning:

  • 3 200mg potassium again – daily total 1800mg
  • B12 shot, a 100iu syringe

Lunch:

  • 3 200mg potassium, daily total 2400mg
  • 1 vitamin A 10.000iu
  • 1 vitamin K 90mcg
  • 1 Lugol’s iodine plus
  • 1 nettle leaf cap 400mg
  • 1 Monolaurin 600mg
  • 2 L-lysine 1000mg
  • 1 thiamin 50mg
  • 1 magnesium malate 100mg
  • 1 more Hydroxo B12

Diner:

  • 3 200mg potassium, daily total 3000mg
  • 1 thiamin 50mg
  • 1 milk thistle 150mg
  • 2 L-lysine 1000mg
  • 1 DHEA 25mg
  • 1 magnolia bark 450mg
  • 1 Digestive enzymes
  • 1 Dr. Berg Hair formula.
  • 1 L-carnitine 250mg

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Image: Maximum Speed of Raphael’s Madonna, Salvador Dali, 1954.

Posted originally on Aug 20, 2019.

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Why Lupron is a Poor Diagnostic Tool for Endometriosis

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stop using lupron as a diagnostic tool

In my work with The Endometriosis Network Canada, I have heard many women say that their doctors told them that if their pain does not go away on Lupron, then the pain must not be from endometriosis. Lupron never has and never will be an effective tool for diagnosing whether pain is due to endometriosis. Not only does Lupron have the potential for significant side effects, which alone should abrogate its use as a diagnostic tool, but it also is not at all effective at diagnosing endometriosis and distinguishing it from other conditions.

Lupron is a synthetic version of a naturally occurring hormone called gonadotropin-releasing hormone, and its action is actually stronger than the naturally occurring GnRH. It is a long-acting medication that initially stimulates hormones in the pituitary gland that control the menstrual cycle, and then suppresses these functions. It is typically given as a 1 month or 3 month injection.

Lupron Side Effects

Lupron therapy is associated with a significant potential for side effects. One of the biggest problems with Lupron is its effect on bone density (it can decrease bone density), and this effect is not always completely reversible after Lupron is discontinued. Lupron can also cause joint pain, which in some cases is permanent. Other potential side effects include hot flashes, vaginal dryness, headaches, mood swings, decreased interest in sex, depression (in some cases severe), cognitive problems, fatigue, acne, headaches, and upset stomach. Personal stories of women’s experiences of the downside of Lupron can be found here, here, here, here, and here.

Given all of these side effects, you might be wondering: why would anyone subject themselves to the potential for at best, a month of these side effects, and at worst, a lifetime of some of them, for the purpose of diagnosis? Even from the side effect perspective, using Lupron to try to diagnose endometriosis seems like a bad idea. But now we come to the more technical part of the discussion, which will address whether Lupron could even work as a diagnostic tool for endometriosis.

How to Evaluate a Diagnostic Tool

To evaluate the effectiveness of a diagnostic tool, the two measures that are used are called sensitivity and specificity. Sensitivity addresses the question of how often the diagnostic tool will pick up the disease, in people who have that disease. Specificity addresses the question of how often the test will be positive in people who actually do not have the disease (but may have conditions other than the one you are testing for). A good diagnostic test will pick up the presence of the condition in most people who have it, while not testing positive in people who may have similar symptoms but have a different disease. In other words, a good diagnostic test will have fairly high sensitivity and specificity.

All devices or tests that are approved by regulatory agencies as diagnostics have to undergo testing to demonstrate sufficient sensitivity and specificity. Lupron has not undergone such testing, because it was not developed as a diagnostic, and is not meant to be used as one. However, given the clinical trials that were done looking at the effectiveness of Lupron as a drug therapy, it is clear that the sensitivity and specificity of it as a diagnostic would not support its use in that way.

Lupron as a Diagnostic?

The clinical trial data published by the manufacturer in its prescribing information can be illuminating when considering its sensitivity and specificity for diagnosing endometriosis. The clinical trials used several measures to assess response to the drug, such as pelvic pain, dyspareunia (pain with intercourse), dysmenorrhea (pain with periods), and pelvic tenderness. The results showed that Lupron was by far the most effective at treating dysmenorrhea, compared to the other symptoms. Almost 90 percent of study participants had dysmenorrhea before taking Lupron, and after 6 months of treatment, fewer than 10 percent still had dysmenorrhea. (Not surprisingly, within 6 months after completing treatment, about 80 percent had dysmenorrhea again.) Looking at endometriosis symptoms other than pelvic pain, about 75 percent of study participants had pelvic pain at the start of the study, and 45 percent still had pelvic pain at the end. Lupron was similarly less effective at treating other symptoms of endometriosis.

From these results, we can get an idea of what the sensitivity of Lupron as a diagnostic would be. Imagine giving Lupron to a group of women with endometriosis, whose symptoms will vary from primarily dysmenorrhea, to all different types of pelvic pain at different times (or in some cases, all times) of the menstrual cycle. Those who have primarily dysmenorrhea will feel that their pain has been treated, whereas, because it is less effective on all other types of pain and symptoms, some women may feel that their pain did not decrease at all (remember, 45 percent of women still had pelvic pain after 6 months of Lupron). This is why it is completely incorrect for any doctor to say that if a woman’s pain did not decrease on Lupron, the pain cannot be from endometriosis. Therefore, the sensitivity of Lupron as a diagnostic for endometriosis is predicted to be poor, because in a significant number of women who actually do have endometriosis, it will not treat their pain substantially.

The specificity of Lupron as a diagnostic would be even worse. Clearly Lupron is effective at treating dysmenorrhea, because by its very mechanism of action it puts a woman into chemically-induced menopause, and you cannot have dysmenorrhea when you are not having periods. However, there are many causes of dysmenorrhea other than endometriosis. So even if Lupron does work to treat a woman’s pain (by preventing periods), this does not ensure that the cause of the pain was endometriosis.

A Call for More Research

There is no doubt that women would benefit greatly from a non-invasive diagnostic test for endometriosis, given that surgery is currently the only way to definitively diagnose it. However, Lupron is not sensitive or specific enough to be useful diagnostically. New diagnostic tests have been developed for many other diseases using recent advances in technology such as imaging methods, blood biomarkers, next generation sequencing, and others. A sensitive and specific diagnostic test for endometriosis is desperately needed. However, with so little funding going to basic and applied research into endometriosis, it is unlikely that this need will be met until this funding situation improves. As Siddhartha Mukherjee said about cancer in his book The Emperor of All Maladies:

“A disease needed to be transformed politically before it could be transformed scientifically.”

This is the situation that cancer research was in, during the 1940s, and sadly this is where we are at now, with endometriosis, a disease that affects one in ten women and has for centuries, in 2016.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

Image by Triggermouse from Pixabay.

This article was published originally on March 14, 2016. 

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