Not all hormones are created equally.

MUCH OF THE CONFUSION regarding hormone safety is due to inaccurate terminology. Bio-identical hormones are identical on a molecular basis to the hormones produced by a human body. Though these are still derived synthetically in a lab - and not naturally occurring as they are often misunderstood to be - the end result is a product that is indistinguishable from human hormones. These are all too often confused with the synthetically derived non-bioidentical hormones that are marketed by large pharmaceutical companies. Think Premarin - a Canadian invention dating to the 1940s - which is a mix of estrogens extracted from pregnant mare urine. Or Provera - a compound designed to mimic progesterone in the body (though should be referred to as a progestin to distinguish it from real progesterone). This distinction is crucial to understanding the mechanism and safety of BHRT.

What was the Women's Health Initiative (WHI)?

In 1991, Wyeth Pharmaceuticals, in liaison with the National Institute of Health (NIH) and National Heart, Lung, and Blood Institute (NHLBI), launched an unprecedented study of 68,132 women between the ages of 50 and 79 which lasted for 15 years, the largest and most costly health initiative ever undertaken in the United States.  The objective of the “Women’s Health Initiative,” or the WHI as it would become more commonly known, was to research the effects of hormone replacement therapy on the prevention of cardiovascular disease, cancer and osteoporosis in post-menopausal women.  The WHI employed conventional synthetic hormone replacement therapy (HRT) in two separate legs of the study.  The first leg of the WHI concerned women who had not had a hysterectomy.  They received either continuous combined Premarin (CEE) and Provera (MPA) or a placebo.  The second leg of the study was comprised of women who had already had a hysterectomy and who were prescribed Premarin alone.  This became known as the estrogen-only leg of the WHI.

What were the risks associated with the WHI?

In the first combined leg of the study coronary heart disease rose by 29% while the risk of stroke rose by 41%.  These figures were alarming, but much less than the risk of thromboembolism (clot formation within a blood vessel) which more than doubled.  Taken together, the rise in these risk factors were enough for the oversight safety committee to stop this section of the study.  Breast cancer too, in this first leg of the study, rose by 26% and only confirmed the suspension of the WHI.  In the second estrogen-only leg of the study the risk of heart disease actually dropped by 9% compared with those on the placebo while the risk of stroke saw only a marginal decline. Compared to the heightened risk of blood clots in the first leg of the study, the second estrogen-only leg saw only a 34% increase, which was still unacceptable.  Eventually, even this leg of the WHI was suspended. Although interpreters of the WHI data went to great lengths in qualifying the differences between those who received conventional Hormone Replacement Therapy (HRT) and those who received only the placebo, as well as differences registered in the two different legs of the study, what was more than curious was their inability to notice the dramatic drop in breast cancer in the estrogen-only leg of the study.  Compare to the placebo, participants registered a 23% drop in instances of breast cancer, but still more markedly, registered a 49% reduction in risk of breast cancer when compared to the first Premarin/Provera combined leg of the study.  What this tells us is that even though the WHI used a strong form of estrogen in the estrogen-only leg of the study, it still resulted in a drop in breast cancer.

I heard that estrogen might increase my risk for a heart attack or breast cancer.  Is this true?  What are the different kinds of estrogen and what estrogen was used in the WHI?

Although there seems to be some special property native to the estrogen-only leg of the WHI that reduces the risk of breast cancer there are some theories that oral estrogen increases the production of sex hormone binding globulin (SHBG).  Increased levels of SHBG are associated with a greater incidence of breast cancer.  It is important to note at this juncture that not all estrogens are created equally.  Estrone (E1) is a weak form of estrogen, with cancer promoting effects.  Estradiol (E2) is a strong form of estrogen which has all of the good effects of estrogen but which still has some of the cancer promoting effects of Estrone, especially with respect to breast tissue.  Estriol (E3) is the weakest form of estrogen produced in elevated levels during pregnancy and has native cancer protective qualities.  This is why women who have more children and have them at an earlier age experience a reduced risk of breast cancer.  Premarin, the synthetic conjugated estrogen tablet used in the estrogen-only leg of the WHI, is comprised of seven different types of estrogen derived from pregnant mares’ (horse) urine from which the name premarin is derived.  What most do not know is that the estrogens derived from horse urine were different enough from human estrogens that they needed to be topped up with 50% Estrone, the weak form of cancer-promoting estrogen.  In fact, synthetic oral estrogens, such as Premarin, when metabolized in the first pass through the liver, increase Sex Hormone Binding Globulin (SHBG) which absorbs a good part of Estradiol reducing the risk of breast cancer.  Again, oral Estrogens like Premarin also increase C-reactive protein (CRP), a blood-clotting protein which is an established factor in heart disease leading ultimately to an elevated risk of coronary atherosclerosis and heart attacks.

How is Bio-Identical Hormone Replacement Therapy different from the HRT used in the WHI?

Unlike either synthetic oral estrogen tablets, bio-identical estrogens are applied in the form of transdermal creams (creams applied across the exterior of the skin) which are absorbed directly into the body’s tissues and bloodstream thereby avoiding the problem of a first-pass metabolizing by the liver.  By avoiding the problem of metabolism associated with a first pass through the liver, bio-identical transdermal creams avoid spiking SHBG and C-reactive protein levels thereby avoiding the elevated risks of blood-clotting and cardiac arrest associated with the WHI.  It should also be noted here that the WHI prescribed dosages which were four times the body’s natural level whereas at True Balance BHRT transdermal creams are prescribed within normal physiological ranges.  More importantly, BHRT does not use Estrone (E1) in any of its treatments but uses instead a preparation cream, known as “Biest”, which is comprised of an 80/20 ratio of Estriol (E3) and Estradiol (E2).  Estriol is the weaker form of estrogen and reduces the risk of breast cancer.

It is also important to note here that women involved in the WHI were all postmenopausal with an average age of sixty-three. This is significant inasmuch as most of these women had 15 years of declining hormone levels to develop diseases that estrogen, progesterone, and testosterone supplementation might have prevented.  The primary advantage of bio-identical hormone replacement, if diagnosed and begun at the menopause, or when symptoms develop, is that it avoids this long duration of hormone deficiency in which the diseases of inflammation arise.



How do bio-identical hormones differ from synthetic hormones?

Because pharmaceutical companies cannot patent a naturally-occurring hormone, they modify natural hormones with synthetic additions in the hope that they will retain some of their original native properties and functions.  A hormone needs to fit with its hormone receptor in a very specific fashion much like a key fits into its lock. Synthetic hormones are shaped differently enough to allow for some receptor confusion given their slight structural modification allowing for “crosstalk” with other hormone receptors, which results in either unwanted side effects or the failure to produce the desired physiological effects sought from the hormone therapy in question.  In fact, synthetic hormones are more different from their natural counterparts than are totally different natural hormones are from each other.  For instance, Medroxyprogesterone, commercially known as Provera, is more different from natural progesterone than natural progesterone is from natural testosterone!  If only a subtle molecular shift marks the difference between natural progesterone and testosterone, then it is not hard to imagine how a more radical molecular departure from natural hormone structures may result in unwanted side effects.  The reality is that hormones are not all created equal and that there is no substitute for the real thing.