Menopausal Hormone Therapy . . . Current Concepts

Doctor's Archive

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.

There are 2 ways to think about decision-making regarding hormone therapy (HT). In general terms, we can group the "good things" together and the "bad things" together and compare them. The way scientists do this is to multiply the numbers of women by the number of years that they are taking the hormone therapy. This measure is called "person-years". In the WHI, the numbers of expected good things (protection against colorectal cancer and hip fracture, were less than the number of expected bad things (heart disease, stroke, blood clots in the lungs, and breast cancer) - specifically, 11 extra "good things" as compared to 31 extra "bad things" per 10,000 person-years for the women taking estrogen/progesterone therapy compared to taking placebo. For the women taking estrogen therapy, the corresponding numbers are 18 extra "good things" and 15 extra "bad things". Each individual woman will have a different opinion about whether the 31 extra "bad things" per 10,000 women taking estrogen/progesterone therapy for a year is enough to make her avoid hormone therapy. Because of this, the decision whether to initiate hormone therapy is a highly personal decision.

If this is too confusing, consider the following seven possible scenarios:

  1. A woman just recently becomes menopausal. She had her last menstrual period a year ago and is began taking CEE/MPA due to bothersome hot flashes. What should she do with the CEE/MPA she is taking?

If she is at otherwise low risk for stroke, heart disease, or blood clots (which she will determine with her physician), she can consider continuing her CEE/MPA to control her hot flashes. Although this is a highly personal decision, the otherwise healthy woman who takes the hormone therapy for a short-term period (fewer than 4 or 5 years) to relieve hot flashes is in fact currently the best candidate for hormone therapy. The "risk and benefit" is likely to be in her favor because she is otherwise healthy, she will only use the hormone therapy for a short period, and hormone therapy is an the most effective therapy (the only FDA-approved therapy) for reducing hot flashes.

  1. A woman has been taking hormone therapy for 2 years due to hot flashes, but a different hormone preparation, not CEE/MPA. She wants to know how to apply the results of the WHI in her own case.

The WHI did not include any preparation other than CEE/MPA. Therefore, we cannot make firm conclusions. It is probably reasonable to say that similar overall risks and benefits apply as in the woman in example 1 above. Again, each women has to carefully consider her individual health profile and balance of risk versus benefit, optimally with her physician. If her overall health is good (no particular risk of heart disease, stroke, blood clots, or breast cancer prior to starting therapy); if she is going to use the therapy for only a few years; and if her hot flashes are bothersome enough that she wants to take therapy; she can reasonably opt to continue the therapy with an generally low risk of complication. Again, as mentioned above, each individual woman has to decide what level is increased risk is "acceptable."

  1. A woman has been taking hormone therapy for 8 years. She feels great and is afraid of stopping because her mother has terrible osteoporosis. She needs to know what to do about her family history of osteoporosis. Her mother had a hip fracture.


If menopause occurs in a woman younger than ___ years, it is considered to be premature. See Answer

This answer is relatively clear and established even before the WHI results: A logical plan is to check bone density results. If the woman has low bone density, or has already experienced an osteoporosis-related fracture, there are other non-hormone options for her bones that she can try. If she does not have low bone density, she can just continue bone monitoring at appropriate intervals.

  1. A woman has been taking hormone therapy for 8 years because she was already found to have osteoporosis when she was 58 years old.

In this case, she wouldn't need to have a bone density test because we already know she has osteoporosis. She needs to consider and discuss with her physician the possibility of switching to a non-hormone osteoporosis medication. The irony is that the WHI actually did show us for the first time ever, conclusive proof that hormone therapy prevents osteoporosis fractures; however, the problem is the balance of risk and benefit would lead us to avoid long-term hormone therapy because of the possible risks of breast cancer, heart disease and vein clots, and because there are safer non-hormonal options available.

  1. A woman has been taking hormone therapy for 8 years. Several 1st degree relatives had heart attacks at an early age. She has never had any heart trouble herself, and she does not have hot flashes.

Although we used to think hormone therapy reduced heart disease risk, we recently began to realize (even before WHI) that hormone therapy (either estrogen therapy or estrogen/progesterone therapy) does not prevent heart disease, and indeed may actually increase coronary heart disease risk in otherwise healthy women, i.e., women who are not taking hormone therapy to reduce hot flashes. Neither estrogen/progesterone therapy nor estrogen therapy should be used primarily for protection from, or therapy of, coronary heart disease. The WHI results provided additional sound proof for this recommendation. The woman with a strong family history of coronary heart disease should generally be recommended to avoid hormone therapy for any purpose.

  1. A woman was diagnosed with a heart attack about 9 years ago. Two years after her heart attack her doctor recommended CEE/MPA due to her osteoporosis, and because at the time her physician felt it might prevent recurrence of heart events in the future. What should she do?

The WHI did not specifically address the effects of hormone therapy on heart disease in women who already had heart disease. However, pre-WHI studies specifically carried out in women with known heart disease had already provided unequivocal proof that hormone therapy does not protect against, and may actually increase risk of, heart disease recurrence in women who already have coronary heart disease. Neither CEE/MPA nor CEE alone should be continued long-term for the purpose of treating heart disease. In this case, The hormones may actually be increasing her cardiac risk, and possibly increasing breast cancer risk. Most experts would recommend that she stop the hormone therapy. Again, the irony is that the hormone therapy was probably doing a good job at preventing her from osteoporosis-related fractures, as proven by the WHI. A different osteoporosis medication would have to be substituted in place of the hormone therapy.


How should a woman stop hormone therapy? There is not a strict guideline, nor is there any reliable clinical study, telling physicians how to discontinue hormone therapy, however, it is clear that many woman have temporary unpleasant symptoms with stopping the hormones suddenly. Most menopause experts currently recommend that women "taper" or "wean" hormone therapy.

Each woman will have to continue speaking with her physician face-to-face in a calm and thoughtful way, so she can make the decision that is right for her. Different women will continue to come to different conclusions depending on their individual circumstances.

It is comforting to have a well-done large and comprehensive research study available for reference. The WHI was long overdue and necessary. Although the WHI confirmed many things we had already suspected, its new findings and the findings of prior studies can help guide womens' decisions about hormone therapy. The decisions are difficult and will likely remain difficult for the next several years.

One more word of caution: It is critical to remember that people who do not conduct research may report study results accurately, but they are usually not able to accurately report the quality of a study, or how a study should fit into the actual day-to-day health of women. Fortunately, in the case of the WHI, the study was very well performed, but in general, women would do well to discuss any worries they have regarding media reports with a caring physician who feels qualified to discuss the quality of the research. Often a woman will be relieved to know the research may not even apply to her particular health concerns.

For information about "HT" and "ET," please read Dr. Crandall's Doctor's View, "HT/ET, Making Sense of It!"


What Is Osteoporosis? Treatment, Symptoms, Medication See Slideshow

Health Solutions From Our Sponsors