Estrogens & Progesterone

While these hormones have far reaching effects on all bodily systems, they are principally associated with sexual function and menopausal symptoms. This is unfortunate as they are effective for preventative benefits such as preventing chronic illness and for long term wellness. The large WHI (Women’s Health Initiative) study using estrogen and progesterone for prevention of illnesses associated with menopause began in 1997 but ended early in 2002 for Prempro (Premarin and Provera combined) due to an increase in breast cancer rates. In 2004, the study was discontinued early for Premarin due to an increase in strokes.

Despite this, it was found that these forms of hormone therapy were safe for use by women in the 50 to 60 year old age group, since this particular age group did not exhibit increased risk for breast cancer/stroke and also displayed benefits such as less colon cancer, heart disease and bone loss (in both groups) when started early. For both groups, the overall death rate was no different than in the placebo group. The results of this study prompted the recommendation for all estrogen and progesterone formulations to ‘use the smallest dose, only if absolutely necessary, for the shortest possible time’. This is an unneeded precaution as the medical research has shown that the bioidentical forms of these hormones to be significantly safer.

Premarin is poor choice for replacement as it replaces amounts and types of hormones not produced in the ovaries as it is concentrated from horse urine. It is composed of over two hundred different hormones (estrogens, androgens and progestin’s). Fifty percent of the hormones in Premarin are estrone (E1), which has 5-10 times more estrone than the human ovaries produce. Estrone is also the estrogen most likely to be metabolized to cancer promoting breakdown products. Provera is also a poor choice as it is entirely non-bioidentical with resulting toxicity.

Bioidentical progesterone (both oral and transdermal), in contrast with Provera, is associated with a protective effect on breast cancer and enhances the heart and brain protective effects of transdermal bioidentical estrogens. Transdermal estrogen, in contrast to Premarin, does not raise the marker of inflammation called CRP and is not associated with increased ovarian cancer, blood clots and strokes. Bioidentical estrogens also are protective of osteoporosis and colon cancer. Estriol is a unique estrogen as higher levels are strongly associated with decreased risk of breast cancer and has even been used to treat breast cancer.

Taking progesterone and estrogen at the levels produced during the reproductive years requires their use in a cyclic pattern, with increasing and decreasing amounts that reproduce the ovarian release pattern and which results in continuation of menstrual periods. This treatment is called the Wiley Protocol. If these amounts of hormones were given at a fixed daily level (‘static dosing’), irregular uterine bleeding and other side effects would result. Lower doses of fixed daily hormones are necessary to prevent these unwanted side effects. While these lower does are not ‘bioidentical’ in terms of amount or pattern of use, they are still effective for most women for the The ovaries make estrone, estradiol, progesterone, and testosterone. In the perimenopausal period all of these hormones begin to decline. Progesterone has the earliest and largest decline and is often all that is needed to be replaced to delay the onset menopause or control symptoms.

Estrogen Metabolism

As the ovarian estrogens and testosterone decline, synthesis is shifted to the fat cells but at far lower levels than menstrual ovarian production. With this shift the percent of estrone increases, which then tends to be converted to a toxic cancer promoting metabolite. With estrogen metabolism there are two protective and two toxic metabolites.

Protective                                              Toxic

Estriol: E1                                                Hydroxyestradiol: 4OHE22 

methylestradiol: 2ME216                     Alpha-hydroxyestrone: 16(OH)E1

These metabolites can be checked in a 24 hour urine sample. Breast cancer risk is associated with a ratio of greater than 1.0 for either the 2ME2:16(OH)E1 ratio or the E3:E1 + E2 ratio. An elevated 4OHE2 level is also associated with an increased breast cancer risk. These ratios and levels can be improved by steering metabolism towards the protective metabolites with the use of dietary changes and nutritional supplements.