Doctor's Archive

Menopausal Hormone Therapy . . . Current Concepts

Medical Author: Carolyn J. Crandall, MD, MS, FACP
Medical Editor: William C. Shiel, Jr., MD, FACP, FACR

Well women, here we go again...Estrogen Therapy (ET) Confusion!

July 2002 brought a confusing mass of media reports for the public and the physicians, owing to publication of the results of the "Women's Health Initiative" (WHI).

First of all, it's interesting to notice what we ALREADY knew before the recent, highly publicized Women's Health Initiative:

  1. Hormone therapy (HT) probably does not protect against heart disease or stroke, contrary to what many researchers used to think several years ago.
  2. Hormone therapy (HT) probably does protect against colon cancer and hip fractures, but scientists were not really positive prior to WHI.
  3. Hormone therapy (HT), particular Estrogen/Progesterone Therapy (EPT), over the longer term probably increased the risk of breast cancer (but only after 5 years of continuous treatment), and the progesterone that is used with estrogen is probably bad for the breast also.
  4. Hormone therapy (HT) increases the risk of vein clots in the legs and lungs.

If we already suspected these facts, then why did we need the Women's Health Initiative? Because the Women's Health Initiative (WHI) was the first study ever strictly designed to empirically (factually) show the effects of hormone therapy (HT) on the heart, colon, breast, and bone. To date, no single study had ever been done on these topics in a reliable fashion. In addition, the hormones in the study were conjugated equine estrogens (CEE, otherwise known as Premarin, 0.625mg daily) and medroxyprogesterone acetate (MPA, otherwise known as Provera, 2.5mg daily), thus the results would apply to many women in the U.S. who use this common combination of hormones.

Furthermore, the study compared the hormones to an identical looking placebo (sugar pill), so that neither the participants nor the researchers knew which women were taking the estrogen therapy (ET) pills, or the placebo pills (double blind study). This type of study lends strength to the reliability and results of the study. Finally, the study involved a very large number of women (16,608), which also lends credibility to the results. The study included 16,608 menopausal women aged 50-79 years and was meant to continue for 8.5 years, but instead it was halted after only 5.2 years because the overall health risks of CEE/MPA (Premarin, 0.625mg/Provera, 2.5 mg daily) of breast cancer appeared to exceed the possible health benefits.

Here is what we now know, from the results of the WHI:

  • Colon cancer: The WHI showed that colon cancer is probably prevented by estrogen/progesterone therapy (EPT), but maybe not by estrogen therapy , in otherwise healthy women.
  • Hip fracture: The WHI was the first study that conclusively showed that estrogen therapy  (CEE alone) and estrogen/progesterone therapy  (combined CEE/MPA) each protect against osteoporotic fractures in generally healthy women. Both estrogen therapy  and estrogen/progesterone therapy  appear to decrease the risk of hip fracture and vertebral (spine) fracture. In WHI, CEE/MPA therapy decreased the risk of hip fracture by about 30% and decreased total risk of fracture (all types combined) by about 25%. Hip and vertebral fracture risks were each reduced about 40% in the women taking CEE alone in WHI. For more, see the review of osteoporosis.
  • Breast cancer: The WHI also confirmed what we already suspected, that use of estrogen/progesterone therapy  (combined CEE/MPA), but not estrogen therapy  (CEE alone) increases the risk of breast cancer. As was already suspected, the increased risk of breast cancer with estrogen/progesterone therapy  was only noted after about 4-5 years of use.
  • Heart disease: In WHI, estrogen/progesterone therapy  raised the risk of coronary heart disease, whereas estrogen therapy  probably did not noticeably affect coronary heart disease risk compared to a placebo pill.
  • Stroke: In WHI, estrogen/progesterone therapy  (CEE/MPA) appeared to be associated with increased risk of stroke, whereas estrogen therapy  (CEE alone) may not have noticeably increased stroke risk.
  • Blood clots in the lungs (pulmonary emboli) and leg veins (deep vein thrombosis or DVT ): Blood clots in the lungs and blood clots in the leg veins were each noted more frequently in both the estrogen therapy  (CEE alone) and estrogen/progesterone therapy  (CEE/MPA) groups, although estrogen/progesterone therapy  use seemed to be more strongly linked with increased risk than estrogen therapy  use.
  • Uterine cancer: CEE/MPA combination therapy did not increase the risk of uterine cancer (which is proof that the progesterone MPA was doing it's job of protecting the uterus from the potential harm of estrogen). It did not alter the general overall risk for cancer as a whole. It did not alter the risk of death due to other causes.