- In the calculation of risks and benefits, the fact that most women take estrogens post menopausally because of hot flashes, emotional stress, and other often very annoying menopausal symptoms was not considered. It is clear that estrogens are the best drugs for those complaints. In this study, risks outweighed benefits by a bit; on the other hand, relief of menopausal symptoms could tilt the equation to benefits outweighing risks for many women being treated for those menopausal complaints.

- This study adds to the evidence from other studies indicating that adding a progestin to estrogen increases the risk of breast cancer and probably neutralizes, at least in part, the beneficial effects of estrogen for the heart. The problem is that, if women take estrogens alone, the risk of uterine cancer is considerably increased; adding the progestin abolishes that risk, but appears to increase the risk of breast cancer to a small extent. Because of the risk of uterine cancer from estrogens alone, the only group of women for whom estrogen alone is recommended are those without a uterus (who have had a hysterectomy).

- The Women’s Health Initiative also had an estrogen alone component. That component has not been stopped because there is no indication harms outweigh benefits. It is quite likely that estrogens given alone will reduce the risk of coronary heart disease and heart attack. Even if that turns out to be the case, estrogens alone will not be recommended because of the risk of uterine cancer (unless the woman has had a hysterectomy). Estrogens alone probably increase the risk of breast cancer a bit for women taking the estrogens for more than five years.

- This study confirms the benefit of estrogens in preventing osteoporosis (bone thinning) and bone fractures. But, here again, estrogens alone will not be recommended because of the risk of uterine cancer. That is a problem for women found to have low bone strength (low bone density). This is called osteopenia. At least 30 percent of women over age 60 suffer from osteopenia. At present, there is no drug that has been proved to prevent bone fractures in osteopenic women; estrogens are probably the best. We do have drugs (such as Fosamax, Actonel, Evista) that can be used in osteoporotic women to reduce fracture risk, but none of these has yet been shown to be effective in fracture prevention in osteopenic women.

- Many experts are now saying that it is reasonably safe to take the estrogen-progestin combination for a few years for menopausal symptoms, but they say treatment for longer than four years is too dangerous. BUT, the increased risk of heart attack and stroke occurs in the first two years after starting estrogen plus progestin. Of course, as noted, the risk of these unpleasant events is small.

- Menopausal symptoms. If severe, this is still the most effective treatment. Women should try other available, but less effective, drugs. If that does not work, estrogens with progestins (estrogens alone if the uterus has been removed) should be strongly considered realizing there is a small risk of serious side effects, including heart attack, stroke, clots in the legs or elsewhere, and emboli to the lungs. All drugs entail some risk, including aspirin. For those who do decide to take estrogens, a side benefit is better bone strength and, perhaps (not yet proved), reduction in risk of bowel cancer.

- Treatment of low bone density (osteopenia) to prevent osteoporosis and fractures. The evidence here is good. BUT, the definitive study has not yet been completed. The Women’s Health Initiative is the best such study; unfortunately, the women were not studied for bone density prior to the start of the study. There could have been baseline differences in the groups. The dangers, though small, of estrogen or estrogen-progestin treatment are enough to recommend that estrogens or estrogen-progestin not be given to osteopenic women. Newer drugs are being tested. We will just have to be patient until we have effective drugs or until additional studies show drugs already available such as Fosamax, Actonel, or Evista actually do prevent fractures in osteopenic women. For now osteopenic women (indeed, all postmenopausal women) should: