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Hormonal Contraceptives: Do We Really Know What We Think We Know?

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If you have read any of my posts, you know that this is one of the questions that pervades my work. Do we really know what we think we know? More often than not, the answer is no. Upon examination, what we hold true falls short. In the field of pharmaceutical medicine, where money plays an enormous role in determining what is known about a particular drug, finding the real and honest truth about a medication is difficult and sometimes impossible. Hormonal contraception, because it has been on the market for decades and because as women we really want it to be safe and absent negative side effects, is one of those drugs where what we think we know and what we actually know are two entirely different things.

Over the last few years, we have been commissioned for a two studies on the safety of hormonal contraceptives. One study, the Real Risk project, ended early due to a loss of funding. As a result, Phase 2 data were never analyzed. (We decided to continue collecting data in the hopes of finding funding to complete the study at some point. We haven’t found the funding yet.) Nevertheless, we learned a lot and what we learned should be public. Slowly, some of that information is making its way into blog posts.

Below is a portion of the final report covering the history of the pill, a sort of ‘what they knew when’ of side effects. Looking back at the history of the development of the pill and other forms of hormonal contraception, it becomes clear that the health and safety of the female population was not a primary objective. Indeed, more often than not, the serious side effects were ignored, particularly in the US, setting the precedent for the almost total acceptance of the drug’s safety that we see today. As a woman who used hormonal birth control and developed many of the side effects noted by early researchers, side effects that were ignored by my physicians, reading this is eye-opening. If I had known then what I know now I would have never used this drug.

The History of Birth Control Induced Side Effects

The first case of birth control induced thrombosis, a pulmonary embolism, was reported in 1961, only one year after the drug’s release. This was soon followed by the first contraceptive induced myocardial infarction in 1963. In the years that followed, research groups, primarily in Great Britain, began delineating the risks and mechanisms by which hormonal contraceptives induced the state of hypercoagulability that led to thrombotic events. Much of this research, along with the publication of Barbara Seaman’s book, The Doctor’s Case Against the Pill, formed the impetus for the Nelson Pill Hearings (NPH) in 1970.

Early on, British researchers noted significant changes in blood clotting mechanisms in the women using oral contraceptives compared to those who did not, but also compared to pregnant women. Hormonal birth control, it appeared, increased several pro-clotting factors while simultaneously decreasing anti-clotting factors; changes in hemodynamics that were in many ways, though not entirely, akin to late pregnancy and early postpartum where blood clots are known risks. This was in addition to systemic vessel wall damage that simultaneously set the stage for both clotting and hemorrhage. They also found that clot risk increased over time and was compounded by other variables such as exercise and smoking. In 1967, based upon the results of three studies, the British Medical Research Council issued a preliminary communication that stated:

“The sum of the evidence, however, is so strong that there can be no reasonable doubt that some forms of thromboembolic disorder are associated with oral contraceptives. The association is particularly strong in the group of women with no known medical condition predisposing to thrombosis.”

Politics and Money Rewrite History

These findings, though clearly implicating hormonal contraceptives in thrombosis, became immediately controversial and were all-but-entirely dismissed by American medical societies who argued an inherent difference between British and American women (NPH pages 6222-6259); one that supposedly predisposed British women more strongly towards blood clots than their American counterparts.

Additionally, according to testimony made in the Nelson Pill Hearings, the American Medical Association allowed industry experts to write and publish the early safety statements while simultaneously refusing to publish research and case reports indicative of risk (NPH page 6113). G.D. Searle, one of the early manufacturers of oral contraceptives, went so far as to ‘vote away’ the risk of thrombosis at a medical conference (NPH pages 6108-6133). Sales and marketing materials were designed to dismiss the risk and obfuscate the research (NPH pages 6218-6296). This led American doctors, researchers, and the population as a whole, to presume falsely that the pill was safe and without risks. It bears noting that by failing to publish the evidence implicating the pill in thrombosis and by allowing industry experts to write and publish the safety reports, the American Medical Association set the precedent for what has now become a complete abrogation of scientific and medical ethics, not only regarding contraceptives, but also, for every other drug on the market.

Beyond Thrombosis: System Wide Side Effects

A persistent notion in contraceptive research is that progesterone and estradiol, the two hormones mimicked in contraceptives, are singularly involved with reproduction. What follows is a presumption that these hormones have no impact on other tissues and altering them affects nothing but the intended target. Contrary to this popular belief, these steroid hormones are not solely involved in reproduction. Hormone receptors are distributed throughout the brain and the body, on every organ, in every tissue, and in every fluid. Hormones, thus, regulate every physiological system. When synthetic hormones bind to endogenous or native hormone receptors, they effectively override the body’s natural regulatory functions in ways we have yet to comprehend fully. It is not unexpected then that the use of hormonal contraceptives would have broad based effects. Thus, in addition to the higher incidence of thrombotic events in otherwise healthy women, physicians and researchers testifying at the hearings noted clear associations between the use of hormonal contraceptives and a broad array of disease processes. Some of those effects are highlighted below.

Metabolic Disturbances

Perhaps some of the least well-recognized effects of these hormones include those to a woman’s general metabolism. Hormonal birth control induces wide ranging metabolic disturbances in insulin and glucose regulation, lipid control, and in heart rate, rhythm and pressure leading to weight gain, diabetes, high blood pressure, and cardiovascular disease. One researcher testified accordingly:

“There are more than 50 ways in which the metabolic functions of the body are modified, and to say therefore that normal physiological function has been demonstrated in the years of oral contraception is to overlook a very large amount of information (Dr. Victor Wynn, NPH page 6311).”

“When I say these changes occur, I mean they occur in everybody, more in some than in others, but no person entirely escapes from the metabolic influence of these compounds. It is merely that some manifest the changes more obviously than others (Dr. Victor Wynn, NPH page 6303).”

And yet another said:

“These alterations, which have been demonstrated, include changes in carbohydrate metabolism, fat metabolism, protein metabolism, and the endocrine, liver, nervous and vascular system, among others. The findings are straightforward and reproducible (Dr. Hilton Salhanick, NPH pages 6382).”

Impaired Reproductive Capacity

Impaired reproductive capacity, likely due to the pill’s effects on the pituitary gland and its ability to prevent ovulation was noted (Dr. James Whitelaw, NPH pages 6009-6019). Case studies presented by the physicians indicated use of hormonal birth control often delayed fertility while the body re-adjusted to its non-pill state. In at least 1-2% of the women who used the pill, however, it caused permanent infertility. Ovulation never resumed. Additionally, women who used the pill were more prone to miscarriage, stillbirth, and chromosomal abnormalities in the offspring; abnormalities that as one researcher indicated were:

“…completely incompatible with live birth…”

Sadly, much of this research was disregarded and there has been very little work since. In fact, the use of oral contraceptives to regulate cycles in advance of fertility treatment is now commonplace. Despite research suggesting it is contraindicated.

Beyond the immediate effects to fertility and reproduction, early researchers postulated potential transgenerational effects. That is, when women use hormonal contraceptives, ovulation is suppressed unnaturally and germ cell damage to the ovarian follicles is possible: damage that may not only express itself in the first generation, but also in subsequent generations, e.g. in her grandchildren and great grandchildren.

“An unequivocal abnormality produced by estrogen-progestogen is the suppression of ovulation itself. It is only reasonable to consider the ultimate fate of the ovum that would have been normally released from the ovary. We do not know whether the ovum dies or survives. If it survives, is it altered in any way?”


One of the most damning, but again disregarded and disputed, findings of the early researchers was the association between hormonal birth control and cancer. Researchers testifying at the Nelson Pill Hearings noted that cancer developed in all animal models tested when oral contraceptives were administered. In fact, the use of synthetic estrogens is banned in animal husbandry in Europe because it causes cancer in the animals and also in the workers. In the US, there is no such ban, owing partly to the decades delay in cancer onset but mostly to industry lobbying.

“I think here is the proper place to point out that when we talk about the pill being used by 18 million people in the prime of life throughout the world, we are in fact considering an internal pollution, the extent of which is not yet known, but the nature of which is indeed known. And we are threatening the destruction of a large segment of one of our most precious natural resources, the young women of our society (Dr. J. Harold Williams, NPH pages 6219).”


Liver function, because of its role in drug metabolism and detoxification, is inevitably altered by the use of any medication. To what extent the liver is impacted, is a key safety issue reviewed during drug approval considerations. As one might expect, hormonal contraceptives degrade liver function. At the hearings, researchers testified to four key changes in liver function.

  • A 40% reduction in the ability to clear sulfobromophatalein (a compound used to test liver function)
  • An increase in liver enzyme activity (a marker of liver damage) in 20% of the women who use hormonal contraceptives
  • Jaundice in 1 in 10,000 women that subsided after discontinuation of OC (Dr. Philip Corfman, NPH Pages 6391-6426)
  • Reduction in total plasma protein level (Dr. William Spellacy, NPH Pages 6426-6445)

Overall, the changes in liver function were summed up as follows:

“The immediate effects include the alteration of several of the laboratory tests used in medical diagnoses. Aggravation of existing liver disease, if present, to the point where jaundice may be seen has also been shown. There is no answer to the query of will permanent liver damage result from the use of the oral contraceptives.”

We have yet to answer the question of permanent damage, although a large study in 1997 suggests that liver damage abates upon cessation.

Disturbed Immune Function

One of the most commonly recognized but simultaneously disregarded effects of hormonal contraception include disturbances in immune function. Autoimmune diseases such as lupus and rheumatoid arthritis are significantly more common in women than men, especially in women who use hormonal contraceptives. Once again, the onset and increased incidence post-pill use was noted as soon as these medications hit the market, but because of the complexity of these diseases, all but disregarded. Early researchers noted that with new onset cases once contraceptive use ceased, symptoms resolved and most patients remained symptom free for at least the 2.5 years of the study period (Dr. Giles Boles, NPH pages 6086-6108). In recent years, awareness of this connection has increased somewhat.

“Over the past three years we have seen 22 young women who… after beginning oral contraceptives developed [arthritic symptoms]. The joint swelling was usually limited to the hands. On cessation of the oral contraceptive, the symptoms disappeared… We specifically inquire as to the use of oral contraceptives in all young women we see with rheumatic complaints…”

In addition to the increased incidence of autoimmune diseases associated with hormonal contraception, other immune system changes were noted, and again, dismissed.

“The Pill, by interfering with the natural secretions of the vagina, leaves women susceptible to a variety of infections, including syphilis and gonorrhea. Those who use the Pill develop VD, other sexually transmitted infections, and vaginitis twice as often as the female population as a whole.”

Namely, the use of hormonal contraception increases the incidence of bacterial and fungal infections and the risk for developing sexually transmitted diseases. More recently, researchers have identified the mechanisms by which contraceptives initiate these disease processes – via changes in cervical immune composition that increase a woman’s vulnerability to infection.  Hormonal contraceptives also predispose women to persistent MRSA infections.

Psychiatric Illness

Perhaps one of the more disturbing findings regarding hormonal contraceptives is their role in new onset psychiatric illness and their capacity to induce suicide. In the original trials, at least one women committed suicide while taking the pill. Her case, along with at least 18 other deaths (Dr. Edmond Kassouf, NPH pages 6108-6133), was omitted in the reports filed to the FDA.

“There is considerable incidence of mild to moderate psychiatric morbidity [disease] associated with the use of combination oral contraceptive agents… In three of the four studies, there seems to be agreement that those who have required psychiatric care in the past will be more at risk for the development of morbidity, including psychosis. One study also suggests that there may be some increase in the depth of illness the longer the medication is taken (Dr. Francis Kane, NPH page 6457).”

“The emotional or psychiatric problems are the complications which seem to me to have the most serious potential danger. Three patients have stated that they were desperately afraid that they were going to kill themselves… After the pills were omitted, the depression and suicidal fears of the three patients disappeared, as did the depression of the other patients (Dr. John McCain, NPH page 6473).”

“It is disturbing to consider the patients on the pills whose depression may have ended in suicide and/or homicide with no recognition of any association with the contraceptive pills… Personality changes could be a factor in other conditions such as automobile accidents and divorces (Dr. John McCain, NPH page 6473).”

Despite the early research, connections between hormonal contraceptives and mental health have been largely ignored. In fact, since the nineties, hormonal contraceptives have been marketed specifically for depression and anxiety in direct opposition to the data suggesting these medications cause and/or exacerbated psychiatric illness. As recently as three years ago, an epidemiological study suggested,

“…a protective association between hormonal contraceptive use and depressive symptoms, as well as suicide attempts, in a population-based sample of young, sexually active US women.”

Fortunately, the tide appears to be changing. Fifty years after the release of these medications and after generations of women have complained of serious mental health issues while using hormonal contraceptives, a large study published definitive data indicating that hormonal contraceptives did indeed induce depression, especially in adolescents. No doubt, industry sponsored studies will surface shortly and contradict these findings.

Hormonal Contraceptives Today

Today, 80% of American women will use hormonal contraception at some point in their lives, mostly oblivious to their risks for thrombosis or any other of the side effects. Indeed, most women and physicians consider the side effects extremely rare, if they consider them at all. This is largely due to the fact that the American College of Obstetrics and Gynecology and other medical associations routinely claim they are safe. At any given time, 62% of women of reproductive age are using at least one contraceptive method. In contrast to the perceived lack of side effects, the numbers tell a different story. Fully 60% of women will cease using hormonal birth control within six months of initiation because of side effects and 30% will try up to five different types of hormonal contraceptives, switching between brands to temper side effects.  Given that most brands may vary in name only, switching between brands is often a fruitless endeavor, something prescribing physicians seem not to appreciate.

That there are over 200 brands currently available on the market worldwide, suggests an abundance of options, but from a pharmacological standpoint, not much has changed in hormonal contraceptive technology over the last half century. The predominant estrogen used in contraceptives remains the same as was developed decades ago, a compound called ethinyl estradiol (EE2). With the exception of the fourth generation progestins, the progestins used in modern contraceptives involve only slight modifications to the original compounds. Even the ‘newer’ delivery methods, like the intrauterine device and the cervical ring, were developed decades ago, in the 1950s and 1960s. For all practical purposes, contraceptive technology remains as it was over half a century ago. Therefore, today’s contraceptives carry as many or more of the side effects and risks as their predecessors did.

Only now, our increased familiarity with these drugs has fostered a deeply ingrained but false sense of safety. Phrases suggesting that after 50 years on the market these are among ‘the most studied medications’ pepper the literature. When in fact, these medications were never studied properly before their release:

“Evidently, for whatever reasons, there is no sound body of scientific studies concerning these possible effects available today, a situation which I regard as scandalous. If we proceed in the future as we have in the past, we will continue to stumble from one tentative and inadequately supported conclusion to another, always relying on data which come to hand, and which were not designed for the purpose (Dr. Paul Meier, NPH pages 6548-6560).”

And they have not been studied conclusively since. For all intents and purposes, safety issues associated with hormonal birth control remain largely under-investigated and unrecognized. What research exists generally favors commercial interests, and if we’re honest, our interests as women. We want easy, safe and effective birth control. We need it and so we ignore the side effects and ignore any research that confirms our suspicions. We allow ourselves to accept the risks. Maybe it’s time we didn’t. Maybe it’s time we dig in and find out what is really going on and then fix the problems.

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This article was published originally in June 2017. 

Chandler Marrs MS, MA, PhD spent the last dozen years in women’s health research with a focus on steroid neuroendocrinology and mental health. She has published and presented several articles on her findings. As a graduate student, she founded and directed the UNLV Maternal Health Lab, mentoring dozens of students while directing clinical and Internet-based research. Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). Dr. Marrs received her BA in philosophy from the University of Redlands; MS in Clinical Psychology from California Lutheran University; and, MA and PhD in Experimental Psychology/ Neuroendocrinology from the University of Nevada, Las Vegas.


  1. Dr Marrs, what are your views on the copper iud? I’m a college student trying to figure out birth control and I was not willing to take synthetic hormones but just tracking my cycle is not realistic with my lifestyle right now. So about 3 weeks ago I got the copper placed but am worried about potential long term effects…do you think it’s safe? So far I’ve only noticed increased bloating. Are there specific precautions I can take while on this to stay healthy? I’m extra conscious of my health compared to others my age because I had a traumatizing experience with a medication when I was younger and it took me a year to recover…Thanks for all the work on this site by the way, it was key to my healing.

  2. I agree about contraception, but how about the use of hormone replacement therapy for women with reproductive issues, such as primary ovarian insufficiency? I was diagnosed with this condition in December of last year and the standard treatment is HRT until natural menopausal age. I’m only 22. I’ve had mixed reactions to hormonal medication, as both birth control and Provera have given me very severe insomnia (notably, after trying BC for four days I did not sleep for a whole week; it took one month for my sleep to normalize afterwards). Perhaps because they are synthetic? I’ve been on a low-dose, bio-identical estradiol patch with no side-effects. It’s a strange condition. I am now avoiding synthetic hormones.

    I hope the thiamine will help with my hormones. I’ve also had POTS and I’m noticing huge improvement with the thiamine on that front. Finding this website was a relief to me because many of my symptoms seemed to match thiamine deficiency. I now supplement 100 mg Lipothiamine a day.

  3. Wow, what an impressive blog. I just found this and this is a mountain of amazing information. What do you propose for young adult women to use for contraception? I thought the IUD was safer but I ran across one of the articles here suggesting it is not. How does the IUD impact the gut microbiome? Similarly to the OC?

  4. I hate being on the pill. But it’s the only thing that’s ever helped me with PMS/PMDD, and it’s helped with PCOS symptoms as well.

    In addition to endocrinologists, gynecologists, and dermatologists, I’ve seen a reputable DC, an OD, and functional medicine internists. I eat a restricted diet to avoid common food sensitivities. I monitor my blood sugar and adjust my diet accordingly. I take a cabinet’s worth of vitamins. At different times, I’ve been prescribed topical progesterone creams, compounded bioidenticals, and herbal concoctions, as well as exercise regimens and meditation.

    But after a decade of avoiding the pill, I learned that (a) I wasn’t ovulating at all anymore, (b) there’s a good chance I have endometriosis in addition to PCOS. So, feeling like a failure, I went on the pill, and my PMS/PMDD vanished–along with the kind of cramps that keep you home from work; painful, disfiguring cystic acne; and occasional cystitis flare-ups.

    I hate the side effects (dry eye, anxiety, low sex drive, weight gain, even more trouble with blood sugar and vitamin deficiencies, recurring VB that I had never experienced before, etc.). I learned the hard way that even minor jet lag will cause a week of spotting. I dread the trimonthly placebo week when attenuated symptoms briefly return. I’m concerned about increasing risks as I get older.

    Was I doing something wrong? Were my doctors doing something wrong? (I have to wonder, if Yaz helps this much, why didn’t the bioidenticals?) Is there a guide to quitting the pill for someone with my issues? I can’t bring myself to “opt in” to interstitial cystitis, cystic acne, menstrual cramps, and severe monthly mood disruptions, when taking the pill lets me opt out of these things. If there’s a better way, I want to know.

    • You’re still not ovulating while on the pill, its just a withdrawal bleed that seems like a period. Were you doing something wrong? Who knows. Sadly, even the experts don’t know much about the female menstrual cycle particularly things go awry. There are a so many combinations of causes and it is difficult to ferret out for each woman, often, only through years of trial and error. Nutrients are critical, which ones and at what dosages is entirely dependent upon the woman. There is no one size fits all or even a one size fits some. Reduced sugars are critical, seriously critical, something we all struggle with. My guess, there are some mitochondrial issues that prevent/limit the needed nutrient absorption and limit their ability to detox so even though you were taking vitamins, you may not have been absorbing them. Since mitochondria are responsible for all sorts of things, including the synthesis of steroid hormones and the management of inflammation, when they are starving (mitochondria absolutely need nutrients to function), they stop working as they should, shutting down pathways that are not needed for survival, like hormone production and so your hormones go haywire. Simultaneously, they cannot shut down the inflammatory pathways because 1) inflammation is needed response to toxicant exposures, so you need the inflammation, but also because 2)they just don’t have the cellular energy (ATP) to unwind those responses. So everything cascades, wreaking havoc. The pill, substitutes the hormones your body would produce with synthetic versions. They are almost the same, but not really, so they breakdown differently and ultimately cause more damage to the mitochondria (they are effectively toxicants, that have to be dealt with, further taxing the already taxed mitochondria). Why they seem to help initially and maybe even for a while, is because your body doesn’t have to produce the hormones, that saves a little energy. Your body needs those hormones, even hormone substitutes to function. Some of those basic function are now controlled by the synthetics. The problem, since the synthetics flood your body. the body doesn’t need to produce the hormones at all any more. So those systems too begin shutting down. Just like if you were taking any other drug, to the extent the drug supplies the substrate, the body doesn’t have to and those systems shut down. The problem, when you try to withdraw, your body cannot suddenly kick into gear and produce the needed hormones, and if it was having problems before, they will be worse now. Effectively, everything has been shut down. Just like an heroin addict suffers from withdrawal, so to do women who take hormonal contraceptives. Only we don’t recognize it in women (we don’t recognize most of the health issues in women). Long story short, your chemistry is a mess, and it will take a lot of effort, time, and luck to correct it. Probably not what you wanted to hear.

      • Thank you. I actually appreciate hearing that my chemistry is a mess; it’s what my body has been telling me in all these different ways.

        I think your comment helps me see a potential path. To avoid the problems of taking synthetics, I could give bioidenticals another try… while addressing nutrient deficiencies to improve mitochondrial health… with the goal of eventually not needing the bioidenticals. Something like that, depending on what my doctor advises.

        (I am grateful that my doctors help me with a lot of what I ask for and are open-minded about CAM, though I know they aren’t very familiar with vitamin therapies or the relevance of mitochondria. It’s my hope that the new thiamine book will reach doctors like mine.)

        • I’m glad my response was helpful. I think that is solid plan. Keep us posted.

          I take it you bought the book? Although, we didn’t get to spend much time on women’s health, (I have to write a second book on that topic), I think you and your doctor will find it useful as a framework for understanding the chemistry. Unwinding these issues is a complicated process, but I believe it is doable if one works from the chemistry up.

          • I have a young adult daughter who truly needs that 2nd book now! Can you tell me if it is in the works, and if not (yet) who might be able to advise us? Thanks so much, Jacalyn

            • I am afraid that it won’t be finished for another year or so. In the meantime, consider our first book. Thiamine Deficiency Disease, Dysautonomia and High Calorie Malnutrition. There’s a link in the sidebar of the blog. It is the foundation for health and despite the somewhat ominous title, it is very readable and useful for a huge number of medical conditions.

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