Ask The Doctor: Hormone Replacement Therapy

There is no single molecule called ‘estrogen’; rather it is a general term that is used when talking about a group of molecules that can lock into estrogen receptors and cause them to alter the behavior of estrogen-sensitive cells.

ASK THE DOCTOR: Hormone Replacement Th erapy

BY STEVE LASATER, M.D.

Dr. Lasater, may I ask your advice? My new doctor has recommended that I start bio-identical hormone replacement because I’m having fairly severe symptoms of menopause, with my last period having been one year ago, just as I turned 50. He also points out that the hormones may reduce my risk of heart disease, which runs in my family, including my mother. His advice seems quite worthwhile. But then I talked to several of my friends, and they’re strongly advising me NOT to start the hormones because “As you should know, Kathy, they’ll cause cancer!” I’m now totally uncertain of what to do. Please advise! — Kathy

DEAR KATHY, Th is is a fairly complex issue, and to fully address it would take nearly an entire book. As it is, I will address the issue in this column and next months. However, in a nutshell, I think that you probably should follow your doctor’s advice and start the bio-identical hormones. Th ere are several reasons why I believe this would be the best approach:

1. Di erent hormones are di erent. Th ere are two main classes of hormones a woman produces during the normal menstrual cycle and are replaced in HRT—they go by the names ‘estrogens’ and ‘progestins.’ Th ere is no single molecule called ‘estrogen’; rather it is a general term that is used when talking about a group of molecules that can lock into estrogen receptors and cause them to alter the behavior of estrogen-sensitive cells. ‘Estradiol’ is the name of the principal estrogen produced by the human ovary; estrone and estriol are metabolites of estradiol. Premarin® is a mixture of some 12 diff erent equine (i.e., horse) estrogens and only one human estrogen, estrone.

‘Progesterone’ is the name of the principal progestin of the ovary. ‘Medroxyprogesterone acetate’ is the generic name for the progestin Provera® which has been the most commonly used progestin in the United States for hormone replacement therapy (HRT), and although it contains the term ‘progesterone’ within its name, it is a very diff erent molecule than bio-identical progesterone. Progestins then are a class of molecules that have similar eff ects in progestin-sensitive tissues; estrogens are molecules that have similar eff ects in estrogen-sensitive tissues. Note that there is a dramatic diff erence between diff erent forms of hormones, even those from the same class. Conjugated equine estrogens (from horses) are diff erent from the types of estrogen (primarily estradiol) that a woman’s ovaries have made during her reproductive years. Estradiol appears to be a more eff ective choice for reducing cardiovascular risk than oral conjugated estrogens.

Th ere is an even more signifi cant diff erence between types of progestins than between types of estrogens. Th e synthetic hormone medroxyprogesterone acetate, or MPA (Provera®), to be honest, is a rather nasty character. MPA increases a woman’s risk of breast cancer, whereas progesterone decreases the risk. (See discussion below.) Th is diff erence is lost whenever one asks, Are hormones good or bad? Th e answer depends on the particular hormones being discussed. Why, then, haven’t the headlines been, “Provera® increases a woman’s risk of breast cancer?”

I believe that this is how the headlines should have been written and therefore instead of stopping hormone replacement therapy (HRT) altogether, women should have gotten off of Provera®. Alas, that is not how it went. Instead, the headlines were, “HRT is Dead” or some sensationalistic version of this. While it’s easy to blame only the media for this, the problem lies deeper and comes from a concept that many physicians and researchers have been slow to abandon—class eff ect.

Physicians and researchers who generalize experimental fi ndings based on a particular type of hormone to all forms of hormone replacement therapy are clinging to the concept that all molecules of a particular class have exactly the same eff ects in all tissues and it really doesn’t matter which one you use. So they contend that if MPA (Provera®) causes an increased risk of breast cancer, then progesterone does as well. Or, if conjugated equine estrogen (Premarin®) causes an increase in blood clots in post-menopausal women, then so does estradiol. Th e problem is that there is ample data to suggest that this is just not true.