Menopausal Hormone Therapy . . . Current Concepts
Medical Author: Carolyn J. Crandall, MD,
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
First of all, it's interesting to notice what we ALREADY knew before the
recent, highly publicized Women's Health Initiative:
therapy (HT) probably does not protect against heart disease or
stroke, contrary to what many researchers used to think several years ago.
- Hormone therapy (HT) probably does protect
against colon cancer and hip fractures, but scientists were not really
positive prior to WHI.
- 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
- Hormone therapy (HT) increases the risk of vein clots in the legs and
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
(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
noticeably increased stroke risk.
- Blood clots in the lungs (pulmonary emboli) and leg
veins (deep vein thrombosis or
): 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.