Lupron - Page 2

Lupron, Surrogacy, and Multiple Sclerosis White Matter Lesions

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I decided to be a surrogate after watching a birth story on TV. I felt like it would be a meaningful way to give back. I was adopted as an infant and I wanted to help another couple have a baby of their own. I did some research, found an agency, met a couple, and went through reproductive screening at a fertility clinic. They explained to me that they would give me hormone injections to artificially stop my body from releasing an egg. I was a gestational surrogate, meaning I only carried the embryo. The embryo was made from a donor egg. Once they confirmed that I had not ovulated they would begin giving me estrogen to produce a uterine lining. After two weeks, it was time for the big day, the transfer of the embryo to my uterus. The embryo transfer was successful and so for twelve weeks following I took a daily injection of progesterone.

I am ashamed to say that I did not do my research and I did not know exactly what I was taking, other than “hormones”. I recall the potential side effects being listed as headache, fatigue and hot flashes and that these side effects were temporary and would dissipate after I stopped taking the medication. I remember glancing over the package insert for the leuprolide acetate (Lupron) noticing nothing was too alarming.

Post Lupron Symptoms

I went on to deliver a healthy baby boy in May of 2013, his parents were thrilled and it was time to focus on me again, get my body back in shape and move on with my life. It was August when I had my first “attack”. I was feeling extremely dizzy and had tingling in my left hand so I went to my primary care provider. She could not tell exactly what was going on but felt that the dizziness was caused by allergies and the numbness in my left arm caused by carpel tunnel. She sent me home with an antihistamine and a brace for my left arm. Eventually my symptoms subsided and I felt perfectly normal.

In January of 2014, I began feeling dizzy again, I tried an antihistamine and it just made me tired. The tingling and numbness came back in my left hand. I went to a different doctor who told me I had vertigo. The doctor tried a few tricks, such as hanging upside down and flipping up really quickly to try to “reset” my equilibrium (that didn’t work). The tingling in my arm was thought to be a pinched nerve in my neck because I lifted weights. Several days went by and I was still feeling terrible, the numbness was also occurring in my face. I was convinced I was having a stroke or that I had brain tumor. I went back to the doctor, insisting on an MRI. I was relieved when I was told that I did not have a tumor. The doctor said that I had signs of a demyelinating disease, such as multiple sclerosis. There are six lesions on my brain.

Multiple Sclerosis or Something Else?

Obtaining the actual diagnosis was a very long process which involved a lumbar puncture to check my cerebrospinal fluid for elevated levels of antibodies and a specific group of proteins called oligoclonal bands.  The findings indicated I did have elevated levels of the antibodies but that the group of proteins were not present. Still the neurologist felt that it was enough for a diagnosis for multiple sclerosis and prescribed a disease modifying drug, a three times a week injection. Multiple sclerosis cannot be cured but there are drugs designed to try to prevent the immune system from attacking the myelin sheath (protective nerve coating). I sought the opinion of another neurologist who had a specialty in multiple sclerosis. She agreed with the diagnosis of Relapsing Remitting Multiple Sclerosis, which is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks are followed by periods of partial or complete recovery. During remissions, all symptoms may disappear, or some symptoms may continue and become permanent. However, there is no apparent progression of the disease during the periods of remission.

Another Surrogacy and Another Round of Lupron

During this process, I knew that I was going to be gestational surrogate again. I had already committed to the couple to carry a second child for them. I stopped taking my disease modifying drug and began the gestational surrogacy protocol again of Lupron, estrogen and progesterone. Thankfully we were successful on the first round as we were with the first baby. Many surrogates are not successful on the first round and go through the protocol over and over again.

I was advised by my neurologist that many women have an exacerbation of MS after birth, as it is very stressful on the body. He advised that I begin taking steroids immediately following the birth to prevent a relapse. I had a very traumatic birth, resulting in surgery and I decided I did not want to take steroids. I would take my chances with the relapse – nothing happened, I felt perfectly normal again.

I am currently not treating myself with the medication prescribed for MS. I have not had any new or worsening symptoms in three years and each MRI shows no new lesions, although I live daily with existing symptoms. I have damage to my trigeminal nerve causing constant pain and numbness in the left side of my face, I also have occasional numbness and tingling in my left arm and leg.

When I was first diagnosed, I searched for nearly every cause I could think of. There is no one in my family history with MS. I didn’t have a vitamin D deficiency. I didn’t have the Epstein-Barr virus or any of the other things thought to be linked to multiple sclerosis. I started searching though my life for anything unusual, which is when I finally researched Lupron. There have been less than 5% of adverse effects reported; however, neuromuscular conditions are listed. I have since learned that there are no clinical studies on the safety of Lupron for IVF and it is being used as an “off label” medication. This allows for it to be used for medical purposes that were not originally specified in the FDA’s approval of the drug and it is not on the labeling. I have reached out to many women online and have heard similar stories of MS, or MS like symptoms or other autoimmune conditions and the use of Lupron.

I feel that I was lucky, I only took Lupron for a short amount of time, many women take it for much longer and at higher doses, possibly causing more damage. I want women, potential surrogates, reproductive endocrinologists and fertility clinics to be aware of this. I want more research to be done on the hazards of the drug. I want to prevent the off-label use of medications.

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If you have experience with Lupron and/or with surrogacy would like to share your story, send us a note.

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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 published originally on February 13, 2018. 

Lupron Induced Osteoporosis?

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Women who suffer with endometriosis do not have many options for treatment. As a result, many women try Lupron because they are desperate to be pain and symptom free. I was one of these women. In 2011 and 2013, I tried Lupron for a total of three doses and wish I knew then what I know now.

In 2010, I was diagnosed with endometriosis laparoscopically. After that, I tried everything from many different types of birth controls and pain medications to depression medications that can also be used to treat pain. Nothing worked. My doctor at the time suggested Lupron to me and I was desperate. I felt like I had already put my life on hold long enough because of this disease and just wanted to be out of pain. However, now I feel like I am suffering the consequences and it didn’t even get rid of my pain.

In 2015, I was diagnosed with osteoporosis. Prior to this, I had never had a bone scan done, not even before being administered Lupron. In 2009, I was diagnosed with Vitamin D deficiency and have been taking a supplement ever since. Three months before being diagnosed with osteoporosis, I stress fractured my knee and was told at my age, it should not have happened. In 2014, I had a hysterectomy because of endometriosis; I couldn’t take the pain anymore and had disease on both ovaries.

Before this, I had never had bone problems or been told that I could. I blame Lupron and strongly believe using it as a treatment for endometriosis led to me having osteoporosis. At 27 years old, I am still trying to work with doctors to determine if there are any treatments I can do because people my age having osteoporosis is rare. Many medications women use for osteoporosis could negatively impact my bones even more because of my age. If I don’t use any treatment, I could suffer from even more fractures or bone breaks the older I get. Right now, my average T-score for my left hip is -3.6 and was -3.3 when I was first diagnosed. I have no idea when my bones became so brittle. In my case, I wish I would have never tried Lupron as now I know this is one of the many side effects of this terrible treatment for endometriosis and something I will have to deal with for the rest of my life.

There are not studies done on medications for osteoporosis in my age group because there are not enough people with the disease to study. The medications my current doctor wants me to try would be a daily injection I would give myself in the abdomen for two years. They are known to possibly cause osteosarcoma, a bone cancer. Based on my history, I don’t like my odds. At this time, I don’t know how I will try to treat osteoporosis. I am planning on looking into natural ways of treating the disease and see how that goes.

As a result from my knee injury two years ago, I had to have an arthroscopic surgery. My doctor repaired my torn meniscus and removed scar tissue. It is taking me longer to heal than I anticipated and I wonder if it is because I have osteoporosis.

If doctors use Lupron for patients, they should be required to give these patients bone scans before their first dose and do follow ups yearly. It is a known fact that Lupron should not be administered in more than 12 doses over a patient’s LIFETIME. I wonder why this is?

I hope my story helps someone make a decision that is best for their body and raise awareness about Lupron. I am not a doctor, nor do I claim to be, but I am a patient that continues to live with the outcomes of having endometriosis.

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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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Share Your Story

If you have experience with Lupron or other GnRH altering drugs, please share your story.

Image credit: Laboratoires Servier, CC BY-SA 3.0, via Wikimedia Commons.

This article was published originally on December 13, 2017. 

Healing From Lupron and Endometriosis With Thiamine

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I was diagnosed with stage 4 endometriosis in 1996. In 2017, I was ready for a hysterectomy. I had two children and was finished with childbirth. I was having a lot of pain on my left side where my ovary was located. My Veterans Administration GYN refused to do a hysterectomy without first giving me Lupron shots assuming that my pain was due to the endometriosis. I was trying to hold down a very demanding government job and missing a lot of work from the pain. I had two laparoscopic surgeries in 1996 and 2001, respectively. Both were to excise the endometriosis. At the time, I was required to take Lupron in order to have a hysterectomy, I was 46 years old. I was denied a hysterectomy after my son was born in 2000 because I was considered too young at 30 years old to have a hysterectomy.

Endometriosis in the Colon and Lupron

After the injections of Lupron, a colonoscopy confirmed a diverticula pocket in that spot that was painful and others on my large intestine. The laparoscopy and excision in 1996 confirmed that my endometriosis extended to my large intestine. The colonoscopy found that I have so many pockets of diverticulosis, a resection surgery was not possible. Basically, if I were to become septic due to an endometriosis/diverticulosis flare, they would need to remove all of my large intestine. My options were very limited. My GYN wouldn’t perform a hysterectomy and laparoscopy under the assumption that the pain I was having was due to endometriosis. He convinced me to start the shots to see if they would help the pain because he assumed the pain was due to endo. I didn’t research the Lupron injections much prior to receiving them. I fully trusted my GYN. He mentioned hot flashes and suppression of symptoms with estradiol.

Immediately I noticed a difference. I don’t take prescription drugs of any kind unless I am really sick. I had nothing for any preexisting conditions. I could not tolerate the injections and function at work. I had severe hot flashes every few seconds 24/7 for three months even with add back estradiol. Worse, the estradiol made my migraines flare and so I was a hot mess. After stopping estradiol, my migraines continued to flare and still do without supplementation. I was also having diverticulosis flares every month sometimes twice a month. I had terrible gas and severe IBS symptoms. My work leave, FMLA and advanced sick leave were dwindling from all the visits to the various doctors. Within three months of my last Lupron injection, I was forced to retire or be fired for not being able to work. I never fully recovered from the Lupron.

Finally, a Hysterectomy

My GYN finally agreed to the hysterectomy in 2018 where they found my left ovary and left fallopian tube in one mass of adhesion scarring with my large intestine. The GYN removed the left polycystic ovary, left and right fallopian tubes along with my uterus, which had fibroids, and cervix leaving me with just my right ovary. Prior to the hysterectomy, I began noticing some numbness and cramping or burning in my feet at work that was much worse at night. I had the same kind of cramping and burning in my lower back too. I would later learn that these are symptoms of thiamine deficiency. Trying to keep it together at work with all of this was a nightmare.

Around this time, I also began having severe nausea and pain in my stomach. The GI doctors did an upper GI scope to confirm duodenal ulcers. The digestive issues, especially the diverticulosis should disqualify anyone from having Lupron as Lupron causes major digestive upset according to the FDA fact sheet. My digestive tract was inflamed from mouth to anus post Lupron. I had an inflamed esophagus and ulcers, diverticulosis flares, IBS with constipation and diarrhea and hemorrhoids that I couldn’t heal with meds. The low FODMAP diet helped though.

No More Pharmaceuticals

In 2019, I finally stopped taking all pharmaceuticals. No pharmaceutical made me feel better. Every medication I took for GI issues and neuropathy made me worse. I only took one for one or two weeks at a time to log all my side effects from each so I could have them added to my growing list of allergic reactions. I did have some sensitivity issues with prescription drugs prior to Lupron, just not as bad. I have the MC1R redhead gene. Redheads are more sensitive to pharmaceuticals and have more adverse reactions. I struggle with topical solutions as well. I couldn’t use estradiol patches because I’m allergic to the adhesive. Thankfully, my primary care physician also has endometriosis and suggested herbal supplements and remedies. All of this ,surprisingly, is from the veteran’s hospital. I was ordered by her to stop working. This was a final attempt to heal my ulcers, as they would eventually kill me if I could not find relief.

How I Healed Myself With Thiamine and Diet

I decided to try high dose thiamine after researching it via Drs. Lonsdale and Marrs and Elliot Overton. I started with 100mg daily for 6 months. Then 500mg for 3 months and currently 1000mg (500mg 2x daily). The thiamine works as well as the acupuncture with EMS. I also take Alpha Lipoic Acid and Dandelion root daily. The increases in thiamine are proving to be a significant factor in recovery. If I miss one day of supplements I’m sick for several days so I’m convinced that it is working.

To help myself heal, I no longer work a 9 to 5 job. I follow a low FODMAP diet with modification for diverticulosis and supplement with elderberry or dandelion for inflammation and immunity, turmeric, prebiotic + probiotics, magnesium for bone loss, palpations, anxiety, alpha lipoic acid for neuropathy, high dose thiamine for neuropathy, fatigue anxiety and brain fog, b vitamins and D3+K2 for b1 uptake regulation and delta 8 CBD for fibromyalgia pain and fatigue. I have regular chiropractor adjustments of my neck and lower back. Acupuncture and light therapy on my feet helped with the burning and cramping.

Where I Am Now

Currently, I have no endometriosis pain, only some lingering PMDD. I have no ovarian cysts and the migraines are not as frequent. Now only a couple a month versus weekly. I still have some burning and cramping in my legs and feet, but it is tolerable. Before thiamine, I was bedridden. The back and neck pain I had previously has improved with thiamine along with physical therapy/yoga and regular chiropractic care. I no longer experience diverticulosis flares with the new diet and supplements for inflammation like dandelion root, turmeric, and elderberry. I switch out the dandelion and elderberry because they work about the same. Depends on what is on sale.

I am able to stand for longer periods of time. My anxiety is significantly reduced, my palpations are gone, I can remember things, and my ADHD flare ups are minimal. In 2022, I only had two mild diverticulosis flares. Prior to the diet changes and supplements, I was having them once a month. I went from being bedridden completely to cooking (I still need to sit some), cleaning with short breaks, gardening with a sit on garden cart, and walking about a half mile every few days. I still have numbness in both feet. I am hopeful that lowering my A1C will resolve this. It may be permanent. Only time will tell. I’m going to the VA this week for a checkup and requesting more PT to see if it will help. They did an EMP on both legs with normal results. That was pretty painful but I felt nothing in my 3 little toes on both feet. Overall, I am doing much better with the higher dose thiamine and have much more energy.

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. 

Photo by Erol Ahmed on Unsplash.

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 healthmitochondrial healthliver healthneurotransmitter balancemineral homeostasishormones, 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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The Lupron Money Trail

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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 pressureInclusion 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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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 published originally on April 18, 2017.

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Lupron and Reproductive Injury

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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.

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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.

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Puberty Blocking Drugs

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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.

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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.

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Why Lupron is a Poor Diagnostic Tool for Endometriosis

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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.