No auto mechanic in his right mind would replace worn parts in a Mercedes with new parts made for a Chevy. Unfortunately, many physicians (and pharmaceutical companies) seem to have less common sense than the average auto mechanic when it comes to treating menopausal women.
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The "estrogen" replacement most doctors prescribe today for menopausal and premenopausal women is a pill known generically as conjugated equine estrogens (CEE). The best known brand of CEE is Premarin®. Many studies suggest that in many women, Premarin does help reduce symptoms of menopause, including hot flashes, vaginal thinning, memory loss, and urinary incontinence. It also appears to reduce the risk of developing postmenopausal cardiovascular disease (the leading killer of women) and osteoporosis (the crippling progressive bone weakness).
It also may help to prevent a significant proportion of Alzheimer's disease and senile dementia.
Premarin is Horse Estrogen Derived From Horse Urine
So what's wrong with CEE? Take a close look at the names. Notice the word "equine?" Yes, that equine! Premarin is horse estrogen! It is derived from the urine of pregnant mares, hence, its brand name. Premarin works great in female horses, just as Chevy parts work great in Chevys. But replacing human estrogens with horse estrogens may be asking for trouble, and here's why.
For the last several million years, the human female reproductive system has been running quite well on three separate estrogens: estriol, estrone, and estradiol, which occur in an approximate ratio of 90%:3%:7%1 (Fig. 1). Compare that with Premarin, which consists of estrone (75-80%), equilin (6-15%), estradiol + two other equine estrogens (5-19%).2 Notice that, in addition to having larger proportions of estrone and estradiol, Premarin also contains equilin and two other forms of estrogen found exclusively in horses.
The female human body contains all the enzymes and cofactors it needs to process estriol, estrone, and estradiol — when they occur in their natural human proportions. On the other hand, it has none of the enzymes and cofactors required to metabolize equilin and the other horse estrogens, nor does it have enough of these important substances to deal with the excessively large amounts of estrone and estradiol found in Premarin (or in the 100% estradiol "patch"). Horses, of course, are well equipped to handle CEE. The difference in reproductive hormones is just one of many differences between horses and humans. You may have noticed that horses also have four hooves and a mane, whereas human females don't.
It should come as no surprise, then, that the presence of Premarin in the human body induces a hormonal imbalance that can have important adverse consequences. To physicians who prescribe Premarin, this hormonal imbalance doesn't seem to carry much weight. After all, the drug works, doesn't it? But, as two leading reproductive physiologists point out, when women take Premarin, "Levels [of equilin] can remain elevated for 13 weeks or more post-treatment due to storage and slow release from adipose [fat] tissue. In addition, metabolism of equilin to equilenin and 17-hydroxyequilenin may contribute greatly to the estrogen stimulatory effect of [conjugated estrogen] therapy." Another metabolite of equilin, 17- -dihydroequilin has been found to be eight times more potent than equilin for inducing endometrial growth, a possible precursor to cancer.3
As a result, Premarin produces "estrogenic effects" that are much more potent and longer lasting than those produced by natural human estrogens.
This explains why so many women feel "unnatural" on Premarin, why Premarin causes so many side effects and discomforts (see box). It even explains why Premarin has been associated with a significant risk of breast and endometrial cancer, because one of the primary effects of equilin, estradiol and estrone is to promote the growth of tissue in the endometrial (uterine) lining and also in the breast. This growth is important for preparing the premenopausal body for pregnancy and lactation, but if some of that tissue becomes cancerous or precancerous, look out. According to Premarin's official labeling, taking it for a year (without also taking progesterone; see box), increases a woman's risk of endometrial cancer by as much as 14%.2
Most conventional physicians, not to mention the self-serving pharmaceutical industry, are quick to rationalize the cancer and other risks of horse estrogens. Every treatment has its risks, they point out, but the risk of a postmenopausal woman dying of a heart attack or stroke if she doesn't take Premarin are far greater than her risk of dying from cancer or an osteoporosis-related fracture if she does.
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Schliesman B, Robinson L. Serum estrogens: quantitative analysis of the concentration of estriol compared to estradiol and estrone. Meridian Valley Laboratory. 1997;Kent, WA:Data on file.
Premarin® (conjugated estrogen tablets). Wyeth-Ayerst Company. Physicians' Desk Reference, 52nd Edition. Montvale, NJ: Medical Economics Company; 1998:3111-3113.
Barnes R, Lobo R. Pharmacology of Estrogens. In: Mishell D, Jr, ed. Menopause: Physiology and Pharmacology. Chicago: Year Book Medical Publishers, Inc.; 1987.
Heimer G. Estriol in the postmenopause. Acta Obstet Gynecol Scand. 1987;Suppl 139:1- 23.
Lauritzen C. Results of a 5 years prospective study of estriol succinate treatment in patients with climacteric complaints. Horm Metabol res. 1987;19:579-584.
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Utian W. The place of oestriol therapy after menopause. Acta Endocrinol. 1980;233 (suppl):51-56.
Lemon H. Oestriol and prevention of breast cancer. Lancet. 1973;1:546-547.
Lemon H, Kumar P, Peterson C, Rodriguez-Sierra J, Abbo K. Inhibition of radiogenic mammary carcinoma in rats by estriol or tamoxifen. Cancer. 1989;63:1685-1692.
Lemon H, Wotiz H, Parsons L, Mozden P. Reduced estriol secretion in patients with breast cancer prior to endocrine therapy.JAMA. 1966;196:112-120.
Follingstad A. Estriol, the forgotten estrogen? JAMA. 1978;239:29-30.
The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1995;273:199-208.
Lee J. What Your Doctor May Not Tell You About Menopause. New York: Warner Books; 1996.
Lee J. Is natural progesterone the missing link in osteoporosis prevention and treatment? Medical Hypotheses. 1991;35:316-318.