Half a century ago, the National Institutes of Health sponsored a study on the metabolic effects of hormonal contraceptives. In the committee’s final report, Dr. Salhanick wrote:
“These accumulated data and others suggest that no tissue or organ system is free from a biological, functional, and/or morphological effect of contraceptive steroids.” [ NPH, Page 6567 ]
Fifty years later, the words of Dr. Noel Rose, the Father of Autoimmune Disease, rang with an eerie familiarity as he (almost proudly) proclaimed, “There is an autoimmune disease for every organ in the body.”
There’s no such thing as a typical autoimmune disease (AI). Even in their commonalities they like to express their individuality. Like cousins determined to be different, each autoimmune disease has a unique relationship with estrogen. Researchers examining the differences in Multiple Sclerosis (MS) and Systemic Lupus Erythematosus (SLE) found that rising estrodiol levels create a protective effect in an MS patient, while it provokes and enhances flares in a lupus patient. They explained the complex distinctions this way:
“The effects of sex hormones (such as estrogens) on autoimmune diseases cannot be generalized and is context/disease-dependent. It is not surprising that the outcome of estrogen-mediated autoimmune responses is different among autoimmune diseases since estrogens affect all cells of the immune system, and the triggering and pathogenic mechanisms are varied among different diseases.”
Teams of scientists are just beginning to identify the complex stew of variables that contribute to AI diseases. Identification of the specific Tregs (a type of T-cell that modulates the immune system), cytokines (proteins that play an important role in cell signaling), and receptor cells (the soldier cells of the immune system) will help unlock the greatest mysteries of each AI disease. For now, researchers all seem to agree on one thing – estrogen affects EVERY cell in the immune system. One unfortunate stumbling block in this process is the generic use of the term ‘estrogen.’ The word is frequently used interchangeably to describe estradiol (estrogen produce naturally within the body) and the synthetic estrogens used in birth control or hormone replacement therapy. These synthetic molecules differ greatly from natural estradiol, and consequently, have very different affects on our immune systems. We can see the potential impact of synthetic estrogens by examining the evolution of lupus.
The Mysterious Evolution of Lupus
Imagine you are a rheumatologist. You developed a foundational understanding of lupus in medical school, but you really define lupus by what you have seen first-hand in your practice. Everything you know about the onset of disease, the typical patient, when it flares, and when it doesn’t is based on (and somewhat limited by) your time in practice.
Now, forget everything you know about lupus, and look at it through the eyes of a physician practicing in the late 60s.
Everything Dr. Giles Bole Jr. knew about lupus from his time in practice was being challenged. Events he had first classified as anomalies grew more frequent. Through conversations with concerned colleagues, he realized other doctors felt uneasy about birth control pills. Even some medical journals started doubting the ‘miracle pills’ that had been on the market for less than a decade. An editorial in the October 1969 edition of The Lancet said,
“The wisdom of administering such compounds to healthy women for many years must be seriously questioned.” [ NPH p. 6109]
Dr. Bole took up research that landed him before congress at the Nelson Pill Hearings in 1970. He described the phenomenon of young women contracting rheumatoid arthritis and “a much rarer disorder, Systemic Lupus Erythematosus.” He presented several examples of young women who developed symptoms within months of starting The Pill. In many cases, the symptoms reversed when the women stopped taking the synthetic hormones. Scientists at that time were already aware of certain medications causing Drug-Induced Lupus Erythematosus (DILE), but this was different because it was happening in young woman, and in many cases, the symptoms were irreversible.
These weren’t just isolated cases in Dr. Bole’s lab. Later in the hearings, Dr. Herbert Ratner estimated that one of every 2,000 birth control users developed lupus [NPH p. 6737]. Dr. Bole speculated that the synthetic compounds in birth control were to blame, saying that the ability to crossover between synthetic and natural hormones had limitations. He added, “I believe that it is clear to all of us that additional long-term studies relating to the biological effects of these compounds are extremely important.”
A report published in Arthritis and Rheumatism in 1999 concluded that the incidence of lupus had tripled in the past forty years. An estimated 1.5 million people in the United States currently suffer from lupus (compared to 1.3 million with rheumatoid arthritis), and 90% of them are women. Clearly, something sparked this once rare disease.
In 2009, scientists from McGill University in Montreal released the results of a massive population study. They collected data on 1.7 million women, and found that women on oral contraceptives were 50% more likely to develop lupus. The greatest risk was in the first three months, when there was a 2.5-fold increased risk.
Overwhelming preliminary evidence points to a causal relationship with lupus. Unfortunately, we aren’t much closer to confirming the suspicions today than we were when Dr. Bole testified.
The State of Lupus Research
Instead of developing more extensive trials to investigate The Pill’s role in triggering lupus, researchers gave us the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) trial, which resulted in the study director writing, “Should oral contraceptives be prescribed in SLE? In the last five years, we have come a long way. The answer today is frequently ‘yes’, whereas before, the answer was almost always ‘never.’”
The trial seemed to be designed for the sole purpose of reversing the answer to that question – to identify a new market of hormonal contraceptive users, a subset of SLE patients who could ‘safely’ take The Pill.
The trial’s summary claimed, “The results of the study will show whether it is safe for women with SLE to use the pill.” This is a very broad statement given the selective group of 183 SLE patients who participated in the trial. To be included, investigators required a patient to have inactive or stable disease requiring less than 0.5 mg prednisone per kg of body weight per day over a 2-year period. They excluded patients with blood pressure higher than 145/95, any history of thrombosis, APL antibodies, hepatic dysfunction, diabetes, or complicated migraines. We’re talking about a very select group of healthy SLE patients being tested. Therefore, it is not surprising their trial concluded ‘that oral contraceptives do not increase the risk of flare among women with SLE whose disease is stable.’ Of course, for those so inclined, it is easy enough to drop the mitigating phrase from the end of that sentence and proclaim The Pill to be safe for SLE patients, period.
The Art of Deception
Studies like these muddy the waters. They give the impression that birth control won’t affect lupus, but read any lupus forum and you will find entries like this one:
“…At this point I decided to stop my birth control because I felt my body needed a break from medications. Within 6 months my hair was growing back, my fatigue went away, as well as the severe swelling. I was able to workout again and live my life! This was 4 years ago and I feel great. I still have flare ups, but it is not constant like it used to be. Recently I tried going on a different type of birth control (lowest hormone levels offered called Loestrin Fe) and had the same side effects within 8 months. I try to find info on birth control and lupus symptoms and how they correlate but have had no luck. Does anyone else have this problem or heard of birth control doing this? My doctor isn’t convinced that it is the birth control, but I think it is. Instead of taking me off the birth control, he is giving me anti-depressants to help me sleep so I’m not tired all the time.”
Let me take a moment to punctuate the absurdity of her situation. She went off The Pill, and her symptoms improved dramatically. Years later, she tried a new formulation of birth control, and the symptoms returned. BUT, her medical professional doesn’t think it’s The Pill. So, he’s prescribing anti-depressants instead!! I really wish I could say I’ve never heard anything like this before, but I have. And, I’ve heard variations of the scenario so frequently that I’m beginning to wonder if this is the new norm.
It doesn’t help when the website for the advocacy group, Lupus Foundation of America, contains information like this:
Many women have more lupus symptoms before menstrual periods and/or during pregnancy when estrogen production is high. This may indicate that estrogen somehow regulates the severity of lupus. However, no causal effect has been proven between estrogen, or any other hormone, and lupus. And, studies of women with lupus taking estrogen in either birth control pills or as postmenopausal therapy have shown no increase in significant disease activity.
No mention of the SLE needing to be stable – no mention of dangerous secondary symptoms to take into consideration – just straight up, “If you have lupus, The Pill is no cause for concern.” Doctors five years ago surely had some reason to tell lupus patients they should ‘never’ take The Pill.
It is true ‘no causal effect has been proven,’ but only because the drug manufacturers don’t want it to be proven. Look up virtually any illness that has been linked to birth control, and you will find someone friendly to the drug companies (and The Lupus Foundation certainly receives enough funding from drug companies to fall into this category) who throws out the ‘not proven’ argument. In his 1969 book, Pregnant or Dead, Dr. Harold Williams described how drug companies already employed this strategy to deny the link to serious thromboembolic issues:
“So long as the data presented could be claimed as “the best available” there was a ready-made defense for any hiatus in the data. As long as The Pill proponents expressed a desire for more complete data – all the while taking steps to thwart its compilation – they were safe…Then came the British. They reported preliminarily that a well-planned study was showing a distinctly higher incidence of thromboembolic disasters among Pill takers…This required some new strategy. Now it became necessary to try to discredit the British work, and at the same time to continue stalling studies in the United States that might yield similar results.” [Pregnant or Dead, pages 59-61]
What’s the Point?
By now, you may think the point of this article is that you can’t trust advocacy groups, the drug industry, or even your doctor, and, to an extent, I guess that’s true. But the most important point is this – trust your questions more than the answers. If an answer doesn’t ring true, you don’t have to accept it just because it came from your doctor, or some online expert.
I have spoken with women who were convinced their autoimmune disease must have been caused by The Pill… until they spoke with a doctor. Afterwards, they were convinced it was genetic. Of course, it’s genetic – estimates say that one in every four people carries a genetic variant that makes them more likely to develop an autoimmune disease [The Autoimmune Epidemic by Donna Jackson Nakazawa, page 71]. A patient must be genetically susceptible to acquire any AI disease, and perhaps some doctors are comfortable letting patients think it ends with genetics. However, environmental triggers that enter our body and mimic estradiol play a huge role in the actual activation of AI diseases like lupus.
Listen to your body. If it tells you that something doesn’t ‘feel right’ about your hormonal contraceptive, pay attention even if your doctor acts like it’s nothing (especially if he/she suggests anti-depressants as the solution).
Trust your questions more than the answers.
Real Risk Study: Birth Control and Blood Clots
Lucine Health Sciences and Hormones Matter are conducting research to investigate the relationship between hormonal birth control and blood clots. If you or a loved one have suffered from a blood clot while using hormonal birth control, please consider participating. We are also looking for participants who have been using hormonal birth control for at least one year and have NOT had a blood clot, as well as women who have NEVER used hormonal birth control. For more information or to participate, click here.
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About 3-4 months after starting Sprintec, I developed migraines with vomiting. After the migraines started, approximately a week later I broke out with a lupus skin rash confirmed through a skin biopsy. Prior to taking Sprintec, I had no history of migraines or skin rashes. Three months after stopping Sprintec, I have not had any more migraines, but my rash remains. Treatment is in progress…
In fact, I first heard about lupus since I started watching my favorite TV series, Dr. House. I think everyone who looked understood that this is one of House’s favorite diseases. But I never would have thought that due to the fact that a woman is taking birth control pills, it could have such dire consequences. This proves once again that many should reconsider their contraception. It may even be worth negotiating with a partner about his contraception. Otherwise, women’s health will be even more threatened.
Given estrogen can stimulate mast cells, this makes so much sense! Although testing for mast cell activation disorder is not as common as an immune panel, there is commonly a mast cell component to most autoimmune disorders.
This is an alarming article. Recently, my partner was diagnosed with IgG4-SRD, an autoimmune disease. Although I realize the fallacy of correlating birth control with her disease, I can’t ignore the possibility that her life threatening symptoms began not long after she started depo. I hope more research is done on this topic, and more women are informed of the potential risks and possible links between autoimmune disease and birth control.
Ann Coulter is in a new television show that will air in a few months, please reach out to her. I was the first girl to get the Depo shot when it first became available, I was 16. I told Dr. after Dr. and specialist after specialist that the shot completely ended my cycles, none of would even consider the possibility. I was nearly 40 before there was any research to support what I already knew. I finally got a name for my disease autoimmune disorder of the pituitary gland. I also have RA, Vascusitis, DDD, migraines, ADD, and fibromyalgia just to list the big ones. I would love to know if a decision I made when I was 16 set my fate?
I believe with the genetic tests now available to us that Dr.’s should be required to determine if an implant, IUD, or birth control pill could trigger an autoimmune disease or at least her odds. Without all the information it’s impossible to make an informed decision.
Thank you for your work, your article made me feel like I’m not as crazy as I have been told. I’ve had Dr.’s say it’s all in your head, well yes it is, just not the derogatory way they intended. What an important part of a woman’s health the pituitary glad is and how very sad that we don’t know enough about it.
In the meantime, do you have any suggestions on how I can get my RA doctor to research the impact of imbalanced pituitary gland hormones impact my flairs and disease progression?
Thanks again for helping me hold on to my sanity.
First, thank you for your kind words. It gives me the motivation to continue my work.
It’s one of those things that would be impossible to prove, but it certainly sounds like the Depo could have been responsible for a lot of your issues. I wish there was a way to accurately predict the risks individual women are submitting themselves to when they go on a BC prescription, but the variations in each person’s body chemistry are just too complex. In theory, I like the idea of genetic tests that could warn a woman, but in practice, I would have the same issue I have with the tests related to clotting disorders. They can give women a false sense of security. I’ve heard several stories of women who tested negative for clotting factors but still suffered clotting issues when they went on hormonal BC.
As for your last question, I wish I knew how to get a doctor to take the risks of birth control seriously, but for whatever reason, it’s difficult to get most doctors to recognize the risks of these potent hormones. That said, there are a lot of great doctors out there. I recently collaborated with some of them to develop a petition asking the FDA to remove Depo from the market and place new black box warnings on remaining BC. Please consider adding your comments to the petition at this link: https://www.regulations.gov/document?D=FDA-2019-P-2289-0001
Also, you could share your story here on Hormones Matter. The silence of the doctors is too great. Those of us who have seen the damage caused by these drugs need to be all the more vocal!