In Endocrinology we learnt decades ago to use only human hormones in humans for endocrine ie hormone replacement, because of the problems of xenobiotics- animal (and plant) hormones eg:

1. risk of infection/ prion transmission;

2. risk of antibodies neutralizing their benefit;

3. they work on human hormone receptors- foreign hormones like equilins (and designer progestins) certainly bind to the respective sex hormone receptors, but they have some unwanted effects, and also block the intended human hormones from acting there.

4. the predominant hormone in premarin is estrone E1.  This hormone usually dominates by default post menopause- when women with low estradiol and often androgens suffer the multisystem degenerative aging diseases of hormone decline including breast cancers. Also, it is progestin and estrone dominance, not E2, which are most commonly associated with breast cancer.

5. For the above reasons, all hormone deficiencies that are treated by endocrinologists use only human hormones in physiological doses to produces blood levels in the healthy young range. Why are postmenopausal women denied the same right?

The Wiki Equilin entry says at present:

Equilin is one of the estrogens present in the mixture of estrogens isolated from horse urine and marketed as Premarin, the most commonly used form of estrogen for hormone replacement therapy in the United States of America. Estrone is the major estrogen in Premarin (about 50%) and equilin is present as about 25% of the total. “Estrone sulfate is usually the major form of estrogen in women.”. Equilin is not normally present in women” .

But under estrone wiki contradicts itself, it says “Estrone is the least abundant of the three hormones” in healthy young women ie less than estrone and estradiol. So it confirms the truth, that estrone is certainly not “the major form of estrogen in women”- at least not during the ~40years of menstruation. During the reproductive years, the blood estradiol averages about 20% higher than estrone.

XENOHORMONES: Why does wiki not even have an entry for xenohormone under xeno-, under premarin or under hormone replacement therapy? It states incorrectly under Estrogens that “nonsteroidal estrogens include synthetic estrogens known as xenoestrogens” – yet under Estinyl wiki states that estinyl was the first orally active synthetic steroidal estrogen. Wiki does say “ xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it”. Obviously equilins ie premarin are xenobiotic hormones in humans. But under Estrogens it does say “In a study by the NIH, esterified estrogens were not proven to pose the same risks to health as conjugated equine estrogens.” And “The “first orally effective estrogen”, Emmenin, derived from the late-pregnancy urine of Canadian women, was introduced in 1930 by Collip and Ayerst Laboratories.”   Actually  Chinese physicians introduced them 2600years ago.

But at least Emmenin is human hormones. Equilins are xenohormones ie potent foreign hormones not found in humans. It is unclear why women should be treated with premarin – ie horse excreta. In Western medicine, humans are generally advised NOT to drink urine or extracts of urine.   Where does the FDA keep it’s brains and ethics about women? – does it consider them mares?

So why (except for Wyeth’s and the FDA’s economic benefit, and women’s detriment) does the FDA allow premarin, when it is mostly equilins and estrone, with negligible estradiol? At least oral estradiol – even in micronised oral microdose- is the most physiological human hormone.

Conventional Premarin  by mouth to control menopause symptoms produces combined estrogen levels  and effects  >10 times higher than those of healthy young women, which is surely why it is associated with both early promotion of subclinical breast cancer so that there is a spike of cancer in the first 2 years (such cancers have surely been present, growing slowly for at least a decade); and gradual increase in new breast cancers presenting after  about 12 years on premarin – all of which are apparently triggered initially by progestin/ progesterone (Horwitz 2008). . By definition, horse waste premarin is NOT a hormone replacement in humans- it would indeed be HRT for mares.

English is an explicit language. In humans, “Hormone” refers to dozens of different messenger chemicals- Wiki lists at least 60- which include testosterone, progesterone and the estrogens estrone, estradiol and estriol- but progestins and the many equilins are not listed.

Common daily misuse should not change the meaning of words.

So  HORMONE REPLACEMENT HRT in humans refers to physiological replacement of any available  missing hormone  by the same human hormone to the usual healthy functional level eg insulin by insulin to normal insulin and glucose levels, thyroid by thyroid, or cortisone by cortisone etc . Using a different hormone would be substitution. One cannot in practice replace a human heart  or kidney by anything but a human heart or kidney, nor human red blood cells by anything but compatible human red blood cells . One cannot effectively and safely replace insulin, growth hormone or most other hormones (including testosterone, estradiol and progesterone) by mouth- which is why percutaneous insulin has been available for >80years, and percutaneous sex hormones for >60years  (see eg Sex Endocrinology Handbook for the Profession: Schering Corporation, New Jersey  first edition 1944). And a human kidney transplant – not dialysis- is replacement of physiological kidney function.

We do not  use or need  the longterm risks of costly  synthetics eg bisphosphonates  to prevent and treat osteoporosis when the natural supplements- appropriate HRT, fish oil, minerals and vitamins safely abolish osteoporotic bone fractures – which bisphosphonates cannot do since they address only one of many  fracture risk factors . There is no evidence whatsoever to justify the wiki marketing hype that “bisphosphonates are the main pharmacological measures for treatment”, nor that  “newer drugs such as teriparatide and strontium ranelate” are anywhere as effective and safe in osteoporosis. In addition, none of these marketed drugs give the ~50% reduction in all premature aging disease and mortality that the full collation of natural supplements do.

HORMONE THERAPY HT refers to use of (usually megadoses ie) supraphysiological doses for treatment of some pathology eg highdose cortisone for allergy, asthma; premarin or estinyl for treatment of a bleeding problem or prostate cancer; or estinyl for contraception- suppression of normal physiology; or high-dose testosterone HT for the androgen resistance syndrome or female breast cancer, highdose thyroid for thyroid resistance syndrome.  Thus kidney dialysis uses synthetics, artificial therapy to purify the blood until a working transplant replaces the dead kidneys.

Thus metformin and the dozens of similar insulin sensitizers are prohormones for hormone therapy of metabolic syndrome and type 2 diabetes because they reduce insulin resistance, allowing insulin to work effectively at  normal insulin levels rather than the futile raised insulin levels found in insulin resistance or after sulphonylureas.

It is at least  thirty years since it was first observed that xenoestrogens and xenoprogesterones – especially by mouth- are not compatible with older women in that they cause common and serious adverse effects both short term and long term, whereas physiological doses  and blood levels of  appropriate balanced human hormones adjusted to tolerance do nothing but good.

While oral premarin alone in historical American doses  (and oral estradiol in Europe),  in appropriate use in young postmenopausal women (eg in the WHI), reduced all deaths and all major degenerative diseases by a third, these still increase the risk of thrombosis, gallstones and hypertension. And oral progestins block many of the benefits of estrogen and human progesterone, and promote breast cancer.

At present, apart from foodstuffs and plant extracts,  it seems that only one solitary animal ie non-human extract is indispensable for human therapy: chondroitin. Trials show that it is best combined with glucosamine (from cornstarch). Recent RCT for long enough shows that this combination not just reverses cartilage loss but (in not too advanced cases with bone grating on bone) actually restores cartilage so that normal function returns to previously crippled knees needing replacement. But unlike the xenoestrogens in premarin and EE, chondroitin is a natural  essential glycoprotein in all species including humans. We simply do not any longer harvest chondroitin or growth hormone from human corpses- only blood and organs for transplantation from highly selected donors, with exhaustive permission. (we also need extra free fatty acids- fish EPA and DHA- but technically these are not made by fish, they are made by marine algae).

Thus premarin and EE are unique in being the only xenohormones, xenobiotics from other species, that humans- women (rarely men)- are advised by doctors to take for “replacement”- when there has never been any evidence that they are as  effective and safe longterm as pure human estrogen  whether orally or parenterally.

It is difficult to find on Google a definition of esterified estrogen EE versus conjugated equine estrogen CEE. But the landmark 2004 article from Washington State and Leiden Universities gives the game away. It shows that Conjugated equine estrogen CEE (ie premarin) contain estrone sulfate approximately 53% and equilin sulfate about 25% (and dozens of other steroids in the remaining 22%). Esterified estrogen EE contains approximately 80% estrone sulfate and approximately 11% equilin sulfate; and in that trial, at equivalent medium to high doses, the CEE gave over double the risk of deep vein thrombosis VT; whereas (compared to controls), EE use did not increase VT.. .And under Estrogen, wiki states (without a reference) “In a study by the NIH, esterified estrogens were not proven to pose the same risks to health as conjugated equine estrogens.”

So it is unarguably clear from both 50 years of observation and trials that postmenopausal women are put in jeopardy whether they are denied appropriate  sex hormone replacement SHRT for almost the second half of their lives , or given the false comfort of “convenience” oral therapy especially with xenohormones such as premarin and progestin, or bisphosphonates. Men are not exposed to such bias at the behest of a giant USA manufacturer like Wyeth, and the USA government – the FDA – or the scientifically unverified change of mind of a leading gynaecologist like William Masters between 1953 and 1957). .

Men (and women) with biochemically and clinically proven (relative) hypoandrogenism are given the best endocrine  replacement ie testosterone through the skin. As with oral HT in women, androgens by mouth have been shown for decades to be either hazardous or ineffective, whereas testosterone through the skin to physiological  balanced youthful sex hormone  blood levels does nothing but good in men and women.

Wiki does not even have articles on androgen deficiency in men and women, merely mentioning the deficiency among many causes of sexual dysfunction. . But it is crucial to note that, irrespective of sexual complaints (which many patients are too inhibited to raise), relative androgen deficiency (in relation to available estrogenics) is common in most older people with chronic diseases, and worth trial of replacement.

Physiological correction of testosterone deficiency (from levels below the average of healthy robust sexually active young adults) into the upper range of healthy young adults often gives major improvement not just in sexual function, but also in reversing overweight- metabolic syndrome- obesity; depression; mood and mental problems; chronic fatigue and pain; osteoporosis and frailty; hypertension and cardiovascular disease; cancer, autoimmune diseases and infectivity; and anaemia.

The benefits of parenteral human  SHRT (as opposed to oral xenoHT) – including reduction in the mortality from cancer, cardiovascular, osteoporotic, autoimmune, mental and  mood diseases, and total mortality even on HRT after breast cancer- are set out in detail in a major 2008 review “Could transdermal estradiol + progesterone be a safer postmenopausal HRT” by a leading International Menopause Society team under Professor Andreas Genazzani.

By contrast, a 13year review of 67700 postmenopausal US women by the American cancer Society released 2 days ago showed an incidence of breast cancer of only 0.26% per year. The adjusted rate on estrogen+progestin (largely premarin + provera there) was increased by about 80% compared to non-users, mostly in the first 2 years as in the Womens’ Health Initiative. On premarin alone, in  average ie overweight to obese women , premarin alone associated with 50% more cancer only after >10years – as in Henderson’s study of 1982.

As discussed above after 60years of use of appropriate balanced non-oral human hormone replacement (estradiol, prodesterone, testosterone), the evidence is that if anything breast cancer and deaths from all causes are reduced.

So why use oral HT especially premarin and progestin for shortterm convenience,  when non-oral appropriate  (triple) HRT  gives minimal risk but major lifetime benefits?

And two centers (Harvard, and North Carolina) review fresh data that restoring low testosterone level to average level  with depot tesosterone injection in symptomatic men with androgen deficiency provides mulltisystemic benefits without increasing any risks including that of prostate cancer.

In conclusion, it is obvious that for researching health matters, the public is advised to use first the websites of international expert associations eg ISSAM- the International Society for Aging Males; IMS- the International Menopause Society; and Medline- Pubmed;

rather than those which are prone to commercial or academic local bias (by drug/ equipment companies and other local vested/ financial interests) like universities, patient support associations, the FDA/NIH, other National Health Services, private practice and craft groups, wikipedi or lay associations/ reports and advice.

Wikipedia health articles should be depended on only if they are certified by international consensus bodies like ISSAM and IMS, or if material facts are referenced to a verifiable expert source. Neither trials, reviews nor metanalyses are necessarily reliable evidence.

This review is not criticism of Wikipedia for providing an excellent open forum, it just highlights the potential biases in a forum which is not subject to oversight by an international panel of specialists in that field who do not individually  have vested interests or limited experience. And who doesn’t? The two criteria are in a sense mutually exclusive, since  the greater one’s  age and experience, the more biased, closed-minded, entrenched one may become.

Detailed referenced reviews the past year on each of these topics are published below.

ndburman mrcp(uk) gonadopause physician.


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