| Tweet |
Barry Schlafstein, M.D.
Over the past several years, the highly publicized Women's Health Initiative (WHI) Study has created quite a stir in the medical community, the media, and the lay public alike, and deserves some attention before we discuss the possible role of bio-identical hormones in the menopausal woman. What we know from the WHI trial is that conjugated equine estrogens (Premarin) taken alone seem to be safe. What appears to be a problem is that when one simultaneously takes medroxyprogesterone acetate (MPA), also known by the brand name Provera, the benefits of hormone therapy are diminished, and in fact the effects can be unsafe. This certainly requires a closer look.
Provera (MPA) is a synthetic molecule that is biomolecularly similar to naturally occurring progesterone. All substances that have progesterone-like activity but are not biologically identical to progesterone are called progestins. There are many progestins, of which Provera is the most commonly prescribed in the menopause. When Provera is ingested orally in pill form, or injected intramuscularly (Depo-Provera), the molecule eventually enters the body's blood stream. Because of its structural similarity to progesterone, these molecules seek and then bind to progesterone receptors throughout the body.
At the level of the uterine lining Provera molecules bind to these progesterone receptors, and activate (or stimulate) them. This activation provides a balance to the stimulatory effect of estrogen on the lining of the uterus, and prevents an overgrowth (hyperplasia) or cancer of the uterine lining from occurring. Thus a true physiologic, favorable progesterone-like effect is achieved in the uterus. In fact, Provera, because of its potency, is excellent in this capacity, which is in large part why it became the most popular and widely used menopausal progestin in this country.
If this were the entire story, then all would be well with this more traditional synthetic menopausal hormonal treatment. The problem with Provera (MPA) is that although the molecule has a favorable progesteronelike effect at the uterine level, in virtually every other organ system of the body this is not the case. In fact, Provera produces an unfavorable effect on other organ systems such as the breasts, cardiovascular system, and central nervous system. In these other organs Provera does indeed bind with the familiar progesterone receptors.
But instead of activating these receptors (to provide the natural balance for estrogen), the Provera molecule blocks, jams, or deactivates these receptors. This highly potent molecule thereby prevents any naturally occurring progesterone, or even estrogen from binding to the appropriate receptors at these secondary tissue sites, and eliminates any beneficial or favorable effect that these natural hormones would otherwise have. This deleterious effect of MPA is confirmed by the results of the WHI trial. Again in this trial, menopausal women were able to safely benefit from conjugated equine estrogens (Premarin) when taken alone.
But when the synthetic Provera was added (Prempro with MPA), the safety and benefits of therapy were virtually eliminated. The WHI findings demonstrate that the widely used synthetic progestin, Provera, is not an ideal choice for menopausal hormonal replacement. In fact Provera is a rather poor choice for hormonal replacement. But do these findings imply that all hormonal replacement regimens, including bio-identical hormones, are a poor choice? Because there are currently no adequate studies, to help answer this question we might look further at the natural production and function of female reproductive hormones in the body.
