Sunday, July 20, 2008

Hormones are Critical to Health

Below are some thoughts to help clarify the confusion we hear in the media. If you are really interested there are extensive footnotes at the end for more research.

Hormones Are Critical for Health

Without hormones, we cannot live. Why then do we speak as though hormones are dangerous substances? And why do we assume that the harmful effects of non-hormones will be like those of our endogenous hormones?

The answer is suggested by the fact that medical students and doctors in training have minimal exposure to physiology and massive exposure to pharmacology. Exogenous chemicals, different from the actual hormone they are meant to replace, are used interchangeably in clinical practice, the popular press, and in prestigious medical journals, producing much of the controversy that surrounds hormone replacement

With the increase in life expectancy we enjoy in the 21st century, we can expect to live a substantial part of our lives in a state of hormonal deficiency. The age-related decline in hormones produces many of the diseases associated with midlife. We have several options:

1) Do nothing and experience the adverse effects of hormonal deficiency
2) Take exogenous chemicals (drugs) to ameliorate the effects resulting from this decline; or
3) Treat the root causes of disease by replacing exactly what is missing.

Hormonal decline is associated with a loss of function as well as an increase in diseases such as heart disease. Effects include bone loss, cognitive decline, loss of muscle mass, and thinning of skin.

There are many specific benefits of hormonal supplementation. Testosterone reduces neuronal secretion of Alzheimer's β-amyloid peptides and improves cognitive function. Progesterone increases bone mass. Mood is improved with testosterone and progesterone. Hormones also improve sleep; decrease inflammation; ameliorate chronic fatigue; improve sexual function, mood, muscle strength, and body composition; normalization blood clotting; improved spatial recognition; and induced apoptosis of breast cancer cells.

The Importance of the Identical Structure

Molecular structure determines activity. The smallest of changes can completely change the physiologic effect. Consider how similar testosterone is to one of the estrogens – Estrone. While chemically they are very close to one another – we all know the effects of these two hormones differ radically.

Why the Confusion?
Much of the confusion about bioidentical hormone replacement flows from the failure to distinguish hormones from non-hormones. Obtaining FDA approval for a hormone-mimicking compound, such as medroxyprogesterone (Provera) or conjugated equine estrogens (Premarin), does not turn it into a hormone. Unfortunately, many scholarly articles have even referred to Provera as “progesterone,” and to and conjugated equine estrogens as “estrogen.”

Before the release of the results of the Woman’s Health Initiative (WHI), the medical community expected PremPro to help mitigate the postmenopausal increase in cardiovascular disease. While the extract of pregnant mares urine known as Premarin does contain one human estrogen, Estrone, it also contains numerous equine estrogens foreign to human physiology. The WHI study demonstrated that the combination of Premarin with Provera produces the following adverse effects: a 26% increase in risk of invasive breast cancer; a 29% increase in risk of myocardial infarction or death from CHD; a 41% increase in risk of stroke; and a 200% increase in risk of 200 % increased risk thromboembolism.

The Importance and Safety of Progesterone Supplementation

Many of the adverse effects in the WHI apparently result from the failure to use the human hormone progesterone. We should not expect the exogenous chemical medroxyprogesterone to necessarily have the same physiologic effect. Physicians who prescribe bioidentical hormones emphasize the importance of balancing estrogens with progesterone, rather than progestins. There are critically important differences between the two.

Progesterone is a pregnancy class B drug. It is used in assisted reproductive technology as Crinone and may be useful for pre-term labor. Medroxyprogesterone is a pregnancy class X drug—a compound known to cause birth defects, and never to be used in pregnancy.

Progesterone and physiologic levels of estrogens down-regulate inflammation. Medroxyprogesterone prevents the cardioprotective and anti-inflammatory effects of estradiol.

In contrast to medroxyprogesterone, several lines of evidence suggest that progesterone reduces breast cancer risk. It is known to have an anti-proliferative effect.

Higher Progesterone levels correlate with dramatically lower rates of Breast Cancer

1. A low progesterone level has been correlated with a 500% increase in premenopausal breast cancer risk in women experiencing infertility when compared with infertile women with normal hormone levels.

2. Contrariwise, a higher progesterone level in premenopausal women correlates with lower risk of breast cancer. Comparing the highest with the lowest tertile for progesterone in women with regular menses, the adjusted risk for breast cancer was 0.12 or about 1/8 the risk.

Combined these two studies suggest progesterone may have a dramatic protective effect against breast cancer. A potential mechanism for the protective effect is suggested by an in vitro study that evaluated the effect of progesterone on the growth of T47-D breast cancer cells. It demonstrated increased breast cancer cell death (apoptosis) as mediated by regulation of the controlling genes.

The Essential Balance between Progesterone and Estrogen

Physiologically, progesterone levels fall faster than estrogens; therefore, progesterone supplementation is typically needed years before estrogen declines. The physiologic role of progesterone goes far beyond the need to prevent unopposed estrogen stimulation of the endometrium of the uterus. The French E3N-EPIC study showed that while estrogen alone slightly increased the risk of breast cancer (up 10%) the risk was actually reduced 10% when estrogen was combined with progesterone. Independent of the presence or absence of the uterus, progesterone (not progestins) should always be used to balance estrogen.

Why Estriol?

Although estriol has been used in western Europe since the mid-1900s, most U.S. physicians are not familiar with it. It offers most of the benefits of estradiol, such as relief of vasomotor symptoms and vaginal atrophy, but appears safer.

One argument for the safety of estriol (as well as progesterone) is that human zygotes have been demonstrated to experience healthy embryogenesis and development in a milieu of high estriol and progesterone concentrations—levels present physiologically during pregnancy.

If carcinogenesis does not occur with high levels of estriol during the most fragile phase of life, why should it be expected at much lower levels in mature adults? Estriol has even been shown to protect against carcinogen-induced breast cancer. Clinical studies have demonstrated that daily dosing results in minimal proliferation of breast and endometrial tissue.

Studies on the ability of estriol to prevent bone loss have produced inconsistent results. For this reason many physicians use Bi-Est with 20% estradiol and 80% estriol.
Currently the FDA is banning the use of estriol on the basis that it has not gone through new-drug FDA approval—even though the FDA has said that there is no safety issue with estriol and despite its inverse correlation with breast cancer (i.e. the more estriol, the lower the rate of cancer). This blatant play to big pharma should enrage all who love freedom. Let freedom ring! Please go to and let your congressmen hear from you.