Estrogen dominance: it's not just a theory

To bring my knowledge on Reproductive Aging up-to-date to deal with my menopause and to benefit the people I give advise on the matter, I've decided to check recent journal articles on the subject. To me, Progesterone in Orthomolecular Medicine by Dr. Raymond Peat (PhD)[1] is the bible in this field. The version I have is copyrighted at 1993, about 20 years after he wrote his doctoral dissertation. Dr. John Lee (M.D.), the author of What Your Doctor May Not Tell You About ... book series[2] [3] [4], started with what Dr. Peat introduced to him. Dr. Lee first published his data on osteoporosis in 1990[5], so he must have met Dr. Peat at least several years before that.
The basic phenomena observed and established by Dr. Peat and Dr. Lee are:
  1. Women's health issues are caused largely by "Estrogen dominance" where estrogen / progesterone balance is lost due to too much estrogen, too little progesterone or both.
  2. Correcting this imbalance using bio-identical (as opposed to fake) progesterone and nutritional supplements will correct or prevent most of the problems such as PMS and pre-, peri-, and post menopausal discomfort and health crisis.

Their reasoning is sound, their observations well informed, and millions of women, including me, have been following their advice and finding it helpful. Yet, there are so much medical myth yet to be dispelled. Most doctors are not informed. As recent as May of 2008, one of my readers contacted me to consult what went wrong with her doctor prescribed natural progesterone supplementation regimen, that made her bleed every week with pulsed schedule and feel awful with overdose. To end all that myth, misunderstandings, and disinformation once and for all, I decided to review up-to-date data and clarify some nagging questions that needed to be answered.

First I looked for a solid proof that "Estrogen dominance" is commonly seen in women as the reproductive aging advances. That was not hard at all. There it was published in 1996 Journal of Clinical Endocrinology and Metabolism by Nanette Santoro, et al[6]. (New Jersey Medical School). That's more than 10 years ago. So, anything written since then about hormonal status of aging women that does not take this study into consideration is probably not worth reading.
Now, if you have done some net search and visited the web sites backed by mainstream medical communities and the U.S. government, you already KNOW, as your reproductive system gets older, your estrogen gradually decreases, and you probably have no clue what happens to your progesterone level, but it did not seem to matter. For PMS, some site told you it may be caused by progesterone because PMS only happens during the time progesterone is secreted. And if you dig a little deeper, you will find plenty of clinical and experimental studies that seem to back up their recommendations, but at a closer look reveal serious flaws of overdose (see Hormone overdose: How can you tell?).

You also learned that the best treatment is birth control pills, be it PMS or peri- menopause symptoms, to boost estrogen, to regulate your periods with fake progesterone, and the contraception is the added bonus[7]. Of course, you have probably encountered plenty of Web sites like this one that warn you about those "mainstream" medical approaches.

An interesting article came out in 2007, written by Dr. Prior, an endocrinologist based on her own menopause transition experience and research that followed, as well as her fight to get a natural progesterone clinical trial approved (Walking the Talk: Doing Science with Perimenopausal Women and their Health Care Providers, Prior, et. al. 2007). Basically, she found out that the medical information she was taught as a physician was totally false and useless  to deal with her own preimenopause and her patients', and the "authority" did not want any clinical trial that can change the status quo of prescribing birth control pills for perimenopause problems.

Why the myth persists? And why are they perpetuating it ?(see The Hormone War is Heating Up). Progesterone does not cause PMS. It is estrogen dominance (often high estrogen and normal or low progesterone). For most women, the low estrogen level becomes an issue when her period becomes irregular and starts to skip months at a time. Even then estrogen can spike to an extreme level (Progesterone and ovulation across stages of the transition to menopause. Kathleen O'Connor, Rebecca Ferrell, Eleanor Brindle, Benjamin Trumble, Jane Shofer, Darryl Holman, Maxine Weinstein 2009). To level it out, progesterone along with ultra low dose of estradiol should be used (see Hormones: Dos and Don'ts). There is no need to use fake hormones including birth control pills (see Safe Use of Hormones: the Hard Evidence).

The next question is what the Estrogen Dominance (high level of estrogen before ovulation and the high level of estrogen along with the low level of progesterone in the latter half of the cycle) does to a woman. By 1993, Dr. Peat already had pretty good idea about what, how, and why of Estrogen Dominance symptoms. Actually, by 1977 Katharina Dalton, a British doctor, has written The Premenstrual Syndrome and Progesterone Therapy[8] based on her success with natural progesterone. Dr. Peat lists about 30 manifestations of Estrogen Dominance in his Progesterone in Orthomolecular Medicine and explained the underling mechanism at molecular level. Has there been any follow up studies to confirm their finding and insights?

Since PMS is the most common hormone related cyclic complaints, it is an obvious place to look into. Did anyone analyzed the correlation between PMS and Estrogen Dominanc? I searched BioInfoBank Library with key words "PMS progesterone estradiol". Of course, it is such an obvious and doable study, it has been studied by measuring PMS severity, estradiol and progesterone levels throughout the cycle. It has also been studied by adding or blocking estradiol and/or progesterone. They consistently show high estrogen level in premenstrual days relates to worse PMS symptoms even with normal level of progesterone. They also show early drop in progesterone  level correlates with worse PMS symptoms. I also found studies that demonstrated a high dose of progesterone supplementation makes everyone feel really bad (100mg/day and up, some even used 400mg 3 times a day!! see also Hormone overdose: How can you tell?) and those studies have been used to argue that progesterone is the cause of PMS! Since it's been sometime since Progesterone and its metabolites Allopregnanolone have been know to work as GABAa mediated sedative and make you feel calm at a right dosage, but an overdose makes you feel tired, sleepy, and sluggish, slowing down psychomotor, and digestive functions, and it even causes swelling in some people, you must ask the motives of those researchers. For more on PMS, see PMS: The Underlying mechanism

Estrogen only and estrogen + fake progesterone menopausal hormone therapies  are another area of studies that has consistently demonstrated ill effects of estrogen dominance as I have reviewed in Safe Use of Hormones: the Hard Evidence and Hormone overdose: How can you tell?

Another fields that seem to have a good accumulation of research is the assisted reproductive treatments that uses hormones to stimulate ovulation, which induces the exact hormonal imbalance as estrogen dominance[9]. It even has a name, Ovarian Hyper Stimulation Syndrome, OHSS for short. It is potentially a life threatening condition (didn't we know it!) with massive fluid shift similar to bloating only exponentially amplified. The established guideline for the prevention of OHSS is to give the women real progesterone after ovulation as luteal phase hormonal support. In fact, the effect of progesterone in reducing bloating/swelling is so strong that it has been demonstrated to save brain injured patients[10] [11].

Now, never mind about the fact that if she is given progesterone and some nutritional advice to restore the hormone balance, she probably can get pregnant on her own. That will be another topic.

Real progesterone (often called natural progesterone or bio-identical progesterone) should not be confused with all those fake progesterone doctors and drug companies and even your government have been heavily promoting as cure-all contraceptive/HRT to the detriment of women's health. The only substance qualified to be called "progesterone" is the real, natural, bio-identical progesterone. The use of fake progesterone for fertility treatment is totally unwarranted. They come with a long list of side effects both to the baby and to the mother, while real progesterone is safe and readily available (after all, it is identical to what your body makes). You need to make sure what you are getting is real progesterone, because an average doctor doesn't seem to know the difference.


[1] Progesterone in Orthomolecular Medicine by Raymond Peat, PhD, available at Dr. Ray Peat's Web site.
Every time I read it, it impresses me how much was know in biology by mid 1970s, and infuriates me to see that even today, more than 30 years later most doctors are still clueless. And it is sickening to realize we still have to fight against FDA who is stepping up their campaign to scare off the consumers by questioning the efficacy and the safety of bio-identical hormones from compounding pharmacies and supplement companies, all the while the same substances that is packaged by big drug companies at ridiculously high doses are left unquestioned.
[2] What Your Doctor May Not Tell You About Breast Cancer, by John R. Lee, M.D. David Zava, Ph.D, and Virginia Hopkins, 2001 Cahners Business Information.
The co-author David Zava is a big name in breast cancer research and saliva hormone test field. If you want to know why estrogen and the chemicals that mimic estrogen cause cancers, and how progesterone protect you against it, all at molecular level, this is the book to read. You will find the effective prevention strategies self evident, calling early detection a prevention is a spin, and why the mammography is actually bad for your breast.
[3] What Your Doctor May Not Tell You About PreMenopause, by John R. Lee, M.D. Jesse Hanley, M.D., and Virginia Hopkins, 1999, Warner Books.
[4] What Your Doctor May Not Tell You About Menopause, by John R. Lee, M.D. with Virginia Hopkins, 1996, Warner Books.
This is the first of the series. The courage to go beyond what other doctors are doing and the intellectual integrity behind it, you will know when you read it. The unfortunate aspect of this book is that it gives you an impression that no one need to take estrogen for menopause, which is not quite true and he repeatedly corrected later.
[5] Lee, John R., M.D., "Osteoporosis Reversal: The Role of Progesterone," International Clinical Nutrition Review (1990), 10:384-391.
The first study to show Osteoporosis can be reversed. It is heard to believe that most of the well established journals did not take it serious enough to publish it. Today no one questions about the fact that you can increase your bone mass at any age, and that all three factors (nutrition, use of muscle, and hormone balance) can contribute to the reversal. You knew, didn't you?
[6] Santoro N, Brown JR, Adel T, Skurnick JH. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996;81(4):1495-1501.
They collected urine every morning for 6 month from women at various reproductive stages (5 to 6 women in each group) and measured the metabolites of estradiol and progesterone, as well as LH and FSH. Their clever method of analysis made the data clean and easy to understand. A land mark study that was expanded into much larger studies, the Study of Women?'s Health Across the Nation (SWAN) and the Daily Hormone Study (DHS). Any hormone study that does not take this study into consideration is not worth reading.
[7] Ismail Hassan, Khaled Mk Ismail, Shaughn O'brien PMS in the perimenopause. J Br Menopause Soc. 2004 Dec;10 (4):151-6 15667751
"The simplest approach may be to give oestradiol transdermally and to administer the progestogen by the intrauterine route using the levonorgestrel intrauterine system." is their conclusion. It is clear to them that estrogen alone can take care of the symptoms. But in case she wants to keep her uterus, levonorgestrel intrauterine system can prevent the uterine cancer and avoid PMS like symptoms Provera causes. It even works as contraceptive. Natural progesterone? not quite sure, but why bother? seems to be their attitude. The case is closed as far as they are concerned. That was exactly what was prescribed to me after my hysterectomy in 1985 and in a few years I found my health slowly deteriorating. They flush their knowledge of latest this or that, but no fundamental changes in their approach, which I assume reflecting the current state of the mainstream medicine. Anyhow, I cannot give a serious consideration to any perimenopause study that does not mention Santoro et al. 1996. Also to suggest progesterone/allopregnanolone causes depression is such a spin and disinformation.
[8] Katharina Dallton, The Premenstrual Syndrome and Progesterone Therapy., Year Book Medical Publishers, Inc., Chicago, 1977.
I have not read this book yet.
[9] Abbas Aflatoonian, M.D., Tahereh K. Bidgoli, M.D. Prevention is the ideal treatment of OHSS!!! Iranian Journal of Reproductive Medicine Vol.3. No.2 pp:51-61, 2005
A good review with good focus and good balance.
[10] Wright et al., ProTECT: A Randomized Clinical Trial of Progesterone for Acute Traumatic Brain Injury, Ann Emerg Med. 2007;49:391-402.
After 20 years of animal experiments, they finally had the opportunity to take it to the clinical trial. The astonishing success of this landmark study is changing the landscape of hormone research.
[11] Ann Emerg Med. 2007 Jun 21; : Does Progesterone Have Neuroprotective Properties? Donald G Stein, David W Wright, Arthur L Kellermann Brain Research Laboratory, Department of Emergency Medicine, School of Medicine (Stein, Wright).
According to Dr. Peat, progesterone protect a lot more than your brain. As the name suggests, it protects pregnancy, the fetus and the mother from ill effects of stress and toxic substances. But you don't have be pregnant or even woman to have the protective effects of progesterone. The brain injury patients they saved in ProTECT were all men.