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AROMATASE INHIBITORS AND ESTROGEN DOMINANCE 

by Peter D'Adamo, N.D.

Although we very often hear of health problems such as female menopause being linked with low estrogen, there are many clinical and subclinical conditions that can benefit from inhibiting the excess production of estrogen and enhancing the production of testosterone.

Though we think of declining estrogen as the hallmark of menopause, it's actually common for women to experience surges of abnormally high estrogen levels during the menopausal and premenopausal periods, as well as earlier in life.

Estrogen dominance can start early on in a women's menstrual cycle. Young women who suffer from this enter menarche with tremendously difficult periods, and doctors sometimes give these teenage girls birth control pills to help regulate the frequency and severity of their periods.

Some women will develop the estrogen dominance syndrome much later in life, sometimes as a result of diet, liver impairment, or environmental factors or also as a result of anovulatory cycles before menopause -- that is, menstrual cycles in which no ovulation has occurred. Ovulation is necessary in order to produce the corpus luteum, (which means "yellow body") that is found on the surface of the ovary after ovulation. Surrounding the ripening egg, the corpus luteum remains after ovulation to produce progesterone for the last half of the menstrual cycle. Without ovulation, less progesterone is produced, which can cause estrogen imbalance in some women.

Diseases or problems that are thought to be related to or affected by excess estrogen and deficient progesterone in women are:

We live in an estrogenic or feminizing environment. Certain chemicals in the environment and our foods, one of which is DDT, cause estrogenic effects. Although banned in 1972, DDT, like its breakdown product DDE, is an estrogen-like substance and is still present in the environment. Chlorine and hormone residues in meats and dairy products can also have estrogenic effects. In men, the estrogenic environment may result in declining quality of sperm or fertility rates. In women, it may lead to an epidemic of female diseases, all traceable to excess estrogen/deficient progesterone.

AROMATASE

Aromatase is an enzyme required for the conversion of androgens to estrogens. Aromatase inhibitors thus decrease the concentrations of estrogens in the body and are effective against tumors that depend on estrogen for growth. They are usually used as second-line therapy (after tamoxifen) for the treatment of breast cancer in postmenopausal women.

Clinically, there are a variety of reasons why doctors would prescribe an aromatase inhibitor for women. These include:

In men aromatase activity increases with age, converting what little testosterone is left into estrogen. It is perhaps this event that is most responsible for the many symptoms of “male menopause,” and possibly even enlarged prostates and prostate cancer. In women, most of the research on aromatase inhibitors addresses the treatment of clinical conditions known to be linked with excess estrogen production or sensitivity. In the general population, aromatase inhibitors are used by the bodybuilding community to increase lean muscle mass and decrease body fat.

Clinically, there are a variety of reasons why doctors would prescribe an aromatase inhibitor for men. These include:

The long-held theory of prostate cancer, that testosterone is bad stuff, and even worse when it's converted to dihydrotestosterone, is gradually falling into disfavor. A more prevalent current opinion is that prostate cancer has more to do with estrogen than with dihydrotestosterone. It appears that many men, as they get older, convert too much testosterone to estrogen and that this excessive estrogen is the cause of prostate enlargement or prostate cancer.  For men, we're just beginning to recognize that the overproduction of estrogen may be a large part of the problem. (We should remember, by the way, that in both sexes, testosterone metabolizes to estrogen by the action of aromatase. In women, of course, the great majority of the testosterone is converted, whereas in men, it's the opposite: most of the testosterone in a healthy man stays as testosterone, and only a little bit becomes estrogen.) The reasons for an excess of estrogen in some men may be genetic or are perhaps environmental - we've all heard about those environmental "estrogen-mimicking molecules." 

ESTROGEN BLOCKERS AND AROMATASE INHIBITORS

Indole-3-Carbinols: These compounds, found in cruciferous vegetables like cabbage, brussels sprouts, cauliflower, collards and broccoli, help to transform dangerous estrogen into more benign forms, as recognized by the National Cancer Institute. They have also been shown to stop the growth of breast-cancer cells by inhibiting the action of a specific enzyme.  

Chrysin: Found in the herb Passiflora incarnata, the flavone chrysin is a potent natural aromatase inhibitor. In a study published 1993 chrysin and 10 other flavonoids were compared to an aromatase-inhibiting drug (aminoglutethimide). Chrysin was the most potent aromatase-inhibitor, and was shown to be similar in potency and effectiveness to the aromatase-inhibiting drug. The scientists conducting the study concluded by stating that the aromatase-inhibiting effects of certain flavonoids may contribute to the cancer preventive effects of plant-based diets. (1)

Apigenin: Found in most species of Chamomile, the flavone apigenin is also a safe and effective aromatase inhibitor, with an inhibitory effectiveness about equal to chrysin. (2)

Isoflavones: The isoflavones in soy, most notably genistein and diadzein were shown in studies to be potent aromatase inhibitors (4)

An advantage to using plant extracts to boost testosterone in lieu of drugs is that the plant extracts have ancillary health benefits. Chrysin, for example, is a potent antioxidant that possesses vitamin-like effects in the body. It has been shown to induce an anti-inflammatory effect, possibly through inhibition of the enzymes 5-lipoxygenase and cyclooxygenase inflammation pathways. 

AROMASTAT is an all natural blend of herbs shown in clinical studies to inhibit the enzyme aromatase.* Aromatase is an enzyme found in the liver that converts testosterone into estradiol and androstenedione into estrone. Thus, its primary action is to convert steroid hormones into estrogen class hormones.

1. Pelissero C, Lenczowski MJ, Chinzi D, Davail-Cuisset B, Sumpter JP, Fostier Effects of flavonoids on aromatase activity, an in vitro study. J Steroid Biochem Mol Biol. 1996 Feb;57(3-4):215-23.

2. Jeong HJ, Shin YG, Kim IH, Pezzuto JM. Inhibition of aromatase activity by flavonoids. Arch Pharm Res. 1999 Jun;22(3):309-12.

3. Kellis JT Jr, Vickery LE. Inhibition of human estrogen synthetase (aromatase) by flavones. Science. 1984 Sep 7;225(4666):1032-4.

4. Kao YC, Zhou C, Sherman M, Laughton CA, Chen S. Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: A site-directed mutagenesis study. Environ Health Perspect. 1998 Feb;106(2):85-92.