Do I Look Like a Horse?

In speaking to a lady friend about the subject of HRT and Premarin (horse estrogen) she commented: “Do I look like a horse!?!”  Dr. MacPherson later wrote down a reply and emailed it to her.

“Well, since you asked, I have been meaning to ask you…. why the long face?  Just because you may feel you are pasture prime and that you would like to be in a more stable place doesn’t mean you’re supposed to be taking horse hormones.  The mane thing to remember is that equine estrogen is not structurally, molecularly or functionally the same as human estrogen.  Taking Premarin (Pregnant Mares Urine) can in the short term improve menopausal symptoms but in the long run (or trot) the side effects may outweigh the benefits.  You don’t want to be saddled with the concerns of potential health risks, so just say neigh to non-bioidentical hormones.  It’s time to quit horsin’ around and only consider human bioidentical hormones if you choose to go on hormone replacement!”  Hay!!!… (thought that might get your attention) And then there’s Provera (progestin) or synthetic progesterone-like hormones which are not related to horses, but regardless, should have been put out to pasture long ago


Hormone Replacement Therapy
Clearing Up Some Confusion

Hormone replacement therapy or HRT is a complex and controversial subject.  A woman may hear of the beneficial effects of replacing hormones, especially around menopause yet hear as many fearful warnings of the increased health risks in doing so.  Let’s see if we can sort things out and clarify the facts surrounding this very important issue.  One confusing aspect is the terminology used, along with a lack of a balanced narrative surrounding this subject of hormone replacement.  HRT is a general term that is typically associated with the use of patented synthetic pharmaceutical compounds such as Premarin and Provera among other brand names.  These are not natural hormones as found in the human body.  This is mistake number one, but more on that later.  There are available what are termed bio-identical hormones, or hormones that are molecularly identical to the hormones we humans naturally produce.  When these hormones are used it is commonly referred to as BHRT (Bioidentical Hormone Replacement Therapy).  There is a huge difference between natural bioidentical hormones and synthetic hormones that are not structurally identical to the hormones that are so critical to healthy human physiology.  And, all the media coverage regarding HRT is based on studies relying only on the artificial female hormones and not on the type of hormones that women naturally have circulating in their bodies.  For those of us who believe that it isn’t smart to try to fool Mother Nature, it is no big surprise that many bad side effects were realized with the use of non-bioidentical hormones.  With the controversy surrounding one’s decision to begin HRT there must be a clear distinction between bioidentical hormones and the conventional synthetic ones.

The most commonly prescribed estrogen for decades has been Premarin.  What exactly is Premarin?  The name gives us a clue; Pregnant Mares Urine.  Yes, estrogens extracted from the urine of pregnant horses.  Estrogen is a general term relating to several varying types of estrogens.  In humans there are 3 main estrogens; estrone (E1), estradiol (E2) and estriol (E3).   In horses, there are some of the same hormones as in humans and there are other estrogens not found in humans.  So far, one could say… well ok, not ideal but at least they’re natural.  Well, the problem is that a company cannot patent anything already found in nature, so the pharmaceutical industry must then make further changes to the hormones in order to make them unique and not exactly as found in nature.  Therefore, not only is Premarin the wrong mix of estrogens for humans they are also further molecularly changed to make them patentable.  This laboratory alteration makes them into a form termed conjugated equine estrogens (CEE). This makes them even further from what would naturally be found in a woman’s body.

Provera is the prescription hormone used to replace progesterone.  It is not progesterone but rather medroxyprogesterone or generally referred to as a progestin.  Again, the natural hormone must be altered in order to patent it.  What can go wrong you might ask?  Enter the Women’s Health Initiative on HRT, a study beginning in the 1990s that followed thousands of women who were either on the combination of conjugated equine estrogens (CEE) and progestins, on CEE alone or on a placebo pill.

A summary of the study results can be found below but the most important point is that they noticed so many serious health effects that they had to stop the study early.  The conditions that have been broadly reported were increased rates of breast cancer, heart disease, and strokes depending on which hormone group they were in.  Essentially, the day after this news broke doctors immediately halted any prescriptions for HRT.  The problem is that both the medical profession and the media gave the impression that any hormone replacement was dangerous, never separating natural from these foreign substances they loosely called estrogen and progesterone.  To call a progestin a progesterone is technically illegal since only progesterone with its own unique molecular structure can be called progesterone.  Anything else, no matter how similar cannot be considered a progesterone.  There has never been any serious attempt by the mainstream media and the medical establishment to clarify the distinction between non-bioidentical and bioidentical hormones in relation to these studies or HRT in general.  This is what leaves millions of women in no-(wo)man’s land when trying to weigh the pros and the cons of hormone replacement.

Summary of the Women’s Health Initiative HRT Study *

The Women’s Health Initiative (WHI) was planned and launched in the 1990s when there was substantial evidence that estrogen with or without a progestin might prevent disease in postmenopausal women. The WHI Hormone Therapy Trials included 27,347 women ages 50-79 who were followed during active treatment (5.6 years in the estrogen-plus-progestin trial, 7.2 years in the estrogen-alone trial) and for an extended period with no treatment, for a total follow-up of 13 years.

This study summarizes comprehensively and for the first time over 117 different publications and a wealth of WHI data on overall health risks and benefits of hormone therapy for postmenopausal women. The study shows a side-by-side comparison of the findings in the two Hormone Therapy Trials during treatment, after stopping, and by age group. We compare rates of coronary heart disease, stroke, breast cancer, blood clots in the lungs, hip fracture, colorectal cancer, endometrial cancer, and death among women assigned to the hormones and women assigned to placebo study pills. These illnesses and death were also combined in a global index to measure the balance of harm and benefit. Other important outcomes were also studied. The study showed differences and similarities in the effects of estrogen-plus-progestin and estrogen-alone:

Heart Disease: Estrogen-plus-progestin increased coronary heart disease risk by 80% during the first year but only by 18% over the entire treatment period; this risk did not differ by age. Estrogen-alone did not increase coronary heart disease risk during this time, but there was a decreased risk among women in their 50s which became significant over the total 13-year follow up period.

Breast Cancer: Estrogen-plus-progestin progressively increased breast cancer risk to 24% over the entire treatment period, with cancers diagnosed at a more advanced stage. This risk remained elevated over the total follow-up time of 13 years. Estrogen-alone decreased breast cancer risk, an effect that became statistically significant over the total follow-up time of 13 years.

Stroke and Blood Clots: Both estrogen-plus-progestin and estrogen-alone increased stroke risk by about one-third during the treatment period. These regimens also increased the risk of blood clots in the legs or lungs, although this effect was greater for estrogen-plus-progestin than for estrogen-alone. The increased risks of stroke and blood clots were not seen after women stopped treatment and did not differ by age group.

Hip Fracture: Both estrogen-plus-progestin and estrogen-alone decreased hip fracture risk by 33% during the treatment period. After stopping, this risk slowly increased but was still lower in women who had taken estrogen-plus-progestin and similar in women who had taken estrogen-alone.

Colorectal Cancer: Estrogen-plus-progestin decreased colorectal cancer risk, with cancers diagnosed at a more advanced stage; differences by age were not seen. Estrogen-alone had no overall effect on colorectal cancer risk, but the risk was increased in older than younger women. After stopping, there were no hormone effects in either trial.

Overall Illness and Death (Global Index): Estrogen-plus-progestin increased the global index of combined illness and death by 12% during the treatment period. Estrogen-alone had no effect on overall illness and death, although the risk was reduced for women in their 50s and increased for women in their 70s. After stopping, there were no hormone effects in either trial.

Other Results: Probable dementia in women 65 years and over was increased by hormone use. Memory was not affected in women aged 50-54. Gallbladder disease and urinary incontinence increased by 50-60% during both trials, and diabetes decreased by 14-19%. Hot flashes and night sweats were decreased in women ages 50-54 years in both trials.

These findings provide the strongest evidence base available to guide individualized counseling and personal decisions about hormone therapy. Estrogen-alone in women who have had a hysterectomy, particularly younger women, has a very different and more favorable risk-benefit profile than estrogen-plus-progestin in women with an intact uterus.

Taking all the study effects into account, hormone therapy is not recommended for prevention of chronic disease, but it remains a reasonable option for managing menopausal symptoms short-term in younger women.

*Taken from: “Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized Trials (Manson et al., 2013)

I cannot disagree with their findings or overall assessment based on the fact that all the women in the study who were on HRT were on the patented non-human hormones. If one were to decide to use Premarin and Provera or their generics, then the warnings in this study are very much warranted.  The problem is that there is no discussion let alone hint that these hormones being used are simply not compatible with women’s natural biochemistry and physiology.  Put simply; expect poor outcomes when you’re using the wrong ingredients!  But without bothering to distinguish between natural and artificial the takeaway for the lay public (not to mention many doctors) is that any hormone therapy may be dangerous.

Bioidentical hormones have been in use for decades now.  There has been no sign of increased incidence of the conditions as found with the use of Premarin or Provera.  Logically, since natural endogenous (produced by the body) hormones have been with us for millions upon millions of years their safety record can be well confirmed.  If these natural hormones were doing as much harm as the pharmaceutically altered forms, then we might have gone extinct long ago.  Though not as well-publicized as the WHI study there have been several well-designed peer-reviewed studies showing the safety of bioidentical hormones.  Also, there have been few if any complaints to the FDA and few if any signs of adverse events when used properly at the correct dosages.  When you weigh the many health benefits of restoring hormones to their optimal and balanced levels to any potential health risks you find the benefits greatly outweigh any risks.  And though the conclusion of the WHI study claimed that HRT was not recommended for prevention of chronic disease, the use of bioidentical hormones appears to be one of the best approaches at warding off many of the common conditions of aging.

Beyond the WHI studies, there are several studies confirming the fact that using non-bioidentical progestins will significantly increase the risk of breast cancer and that using oral Premarin will increase blood clots and strokes.   On the positive side, even horse estrogens greatly improved bone density and it was already a known fact that endogenous estrogen was critical to bone health.  Therefore, using bioidentical estrogen will provide all the benefits of bone-building/prevention of osteoporosis without the side effects.

There obviously is no lack of evidence for the dangers of using Premarin and progestins but what about the studies showing the safety of bioidentical hormone replacement.  I have included several references below should you like to review some of these studies yourself.  In summary and in sharp contrast to the findings of the WHI, these studies on bioidentical hormones find none of the adverse effects associated with non-bioidentical hormones and for certain health conditions a reduced risk.  Let’s look at just one study as published in the journal:

Breast Cancer Research and Treatment. 2008 Jan; 107:103-11.

In this study, 80,000 postmenopausal women using various forms of HRT were followed for over 8 years.  It found that compared to women who had never used HRT, those using estrogen plus synthetic progestins had a 40% increased risk of breast cancer, while those using estradiol plus progesterone (bioidenticals) had a 10% decreased risk of breast cancer.

Other Scientific Studies backing the Safety of Bioidentical HRT

The following studies have determined that bioidentical progesterone does NOT induce estrogen-stimulated breast cell proliferation.


Jpn J Cancer Res. 1985 Aug;76(8):699-704.

Breast Cancer Res Treat. 1986;8(3):179-88.

J Gynecol Obstet Biol Reprod (Paris). 1990;19(3):269-74.

Fertil Steril. 1995 Apr;63(4):785-91.

Fertil Steril. 1998 May;69(5):963-9.

J Steroid Biochem Mol Biol. 2000 Jun;73(3-4):171-81.

Climacteric. 2003 Sep;6(3):221-7.

The following study found that women who used estrogen combined with bioidentical progesterone had a slight tendency toward a reduced risk of breast cancer, compared to women who had never used HRT.

Reference: Int J Cancer. 2005;114:448-54.

Another earlier study found similar results indicating a trend toward reduced risk of breast cancer in 1,150 women using bioidentical progesterone, compared to non-users of progesterone.

Reference: Cancer Detect Prev. 1999;23(4):290-6

In a study of 31,451 postmenopausal women on HRT, it was determined that women who used estrogen (without progestins) did not have an increased risk of breast cancer compared to women who never used HRT.

Reference: Int J Cancer. 2004 Oct 20;112(1):130-4.

Given the above information, there should be little question regarding the choice between using Premarin and Provera (progestin) or using bioidentical estrogen and progesterone hormone replacement.  The only question is whether to go on hormone therapy, but the big pharma non-bioidentical hormones should never be a consideration.

It is certainly fair for one to question whether to begin hormone restoration therapy, but one should never consider anything other than bioidentical hormones!