Recent product endorsements from celebrities on television have brought a new term into the vocabulary of many American women: bioidentical hormone therapy—treatment with hormone products that are identical in molecular structure to those in the human body.
Since 2002, when results of the Women’s Health Initiative1 raised questions about the safety of hormone replacement therapy, women have been inundated by commercials, talk shows, and self-help books that promote bioidentical hormone therapy as a safe and natural way to treat menopausal symptoms—and more.
Although this publicity has helped promote discussion about menopause, it has also perpetuated confusion and misinformation among the lay public and the general medical community concerning menopausal hormone therapy.
Many postmenopausal women suffering from vasomotor symptoms, vaginal dryness, and vaginal atrophy are apprehensive about seeking therapy, owing to concerns resulting from misinterpreted information derived from the Women’s Health Initiative trial.1 (See “What are the known risks of FDA-approved hormone therapy.”2–8) Many others are told to suffer through their symptoms, which may eventually pass. It is not surprising, then, that women turn to unconventional treatments that are claimed to be safer. This unfortunate situation has driven the business of many compounding pharmacies into the multibillion dollar level.
In this paper, we hope to clarify some of the misconceptions surrounding this issue. But first we need to define some terms in what has become a confusing area.
WHAT ARE BIOIDENTICAL HORMONES?
“Bioidentical” means identical in molecular structure to endogenous hormones. However, as we will see, a better distinction should be made between products that are approved and regulated by the US Food and Drug Administration (FDA) and those that are not.
Endogenous reproductive hormones
Women produce various reproductive hormones, including three estrogens—estradiol, estrone, and estriol—as well as progesterone and testosterone.9
17-beta estradiol (E2) is the most bioactive endogenous estrogen. It is primarily produced by the dominant ovarian follicle and the corpus luteum and is synthesized intracellularly through aromatase activity.10,11 The rest of the circulating estradiol is derived from peripheral conversion of estrone to estradiol, and this is the primary source in postmenopausal women not on hormone therapy.11
In postmenopausal women, serum estradiol levels are often below 15 pg/mL. Many physiologic effects of the cellular compartmentalized estradiol contribute to an over-riding force in certain tissues even after menopause.10 With the loss of estradiol, many tissues in postmenopausal women can be affected, particularly resulting in genitourinary atrophy and bone loss.
Estrone (E1), the second dominant human estrogen, is primarily derived from the metabolism of estradiol and from the aromatization of androstenedione in adipose tissue, with a small quantity being secreted directly by the ovary and the adrenal glands.9 In postmenopausal women, mean estrone levels are about 30 pg/mL.11
Estriol (E3), the least active of the endogenous estrogens, is very short-acting.
Progesterone is a 21-carbon steroid secreted by the human ovary.9 It is formed during the transformation of cholesterol to estrogens and androgens and is no longer produced after menopause.9
Testosterone. In premenopausal women, the androgen testosterone is synthesized by the ovary, the adrenal cortex, and the peripheral conversion of circulating androstenedione and dehydroepiandrosterone (DHEA).9 Over a woman’s life span, her androgen levels decline progressively.10 The rate of decline has not been shown to be appreciably affected by the onset of menopause.10
All these hormone therapy products are synthesized
Many nonmedical women’s health books erroneously classify the forms of estrogen used in hormone therapy as either bioidentical or synthetic. In fact, they are all man-made.
Bioidentical hormones are synthesized by chemically extracting diosgenin from plants such as yams and soy.12 Diosgenin is chemically modified to yield the precursor progesterone, which is then used to synthesize bioidentical estrogens and androgens.10
Nonbioidentical estrogen products include conjugated equine estrogens (CEE), which is extracted from the urine of pregnant mares. The two predominant estrogens found in CEE are equilin sulfate (native to horses) and estrone sulfate.10
Other nonbioidentical products include ethinyl estradiol, which is used in most combined oral contraceptives. It is formed after a minor chemical modification of estradiol that makes it one of the most potent estrogens. The ethinyl group at carbon 17 of ring D of the steroid nucleus greatly slows the hepatic and enzymatic degradation of the molecule and, thereby, makes oral ethinyl estradiol 15 to 20 times more active than oral estradiol.
Mestranol is an inactive prodrug that is converted in the body to ethinyl estradiol.
While many women may find the idea of natural bioidentical hormones derived from sweet potatoes or soybeans more acceptable than taking one made from horse’s urine, all the products undergo extensive chemical processing and modification.