More about estrogen

The effects of estrogen on the cardiovascular system are complicated. There is good evidence that estrogens increase HDL and decrease LDL cholesterol. In primate models, estrogen has been shown to have beneficial effects on the development of arteriosclerotic plaques in the coronary arteries, which were independent of the effects on the lipids. Estrogen also modulates vasoreactivity in human studies.

There is a discrepancy between long-term observations of women who decided to take estrogens, and relatively short-term randomized trials. The observations have strongly suggested a benefit of estrogen on cardiovascular disease. The Women's Health Initiative results were described above, showing negative effects of estrogen-progestin and neutral effects of estrogen alone and beneficial effects of estrogen alone in the younger women. There are several theories to explain these differences, and so far none have been proven, although some are more popular than others.

  1. Hormone therapy could increase arteriosclerotic disease in women who have baseline subclinical disease, but help to prevent the development of arteriosclerosis in women with no disease (Phillips). In this case, women who start hormones at a younger age would not experience the adverse effects of the hormones. Observational studies may include more women who started hormones before the development of any arteriosclerosis. The WHI results in women within ten years of menopause were different from older women; these women probably had less chance of subclinical disease.
  2. Women who decide to take estrogen could already be healthier women. There is some data to support this contention (higher educational level, greater income, more frequent visits to doctors, more exercise) - but statistical adjustment for these factors does not completely remove the positive benefit of estrogen in large observational studies.
  3. Progestin, particularly medoxyprogesterone, could have a negative effect. The results from the estrogen-only study lend support to this theory.
  4. It could take at least ten years of estrogen before any cardiovascular benefits are seen. In this respect, it is interesting that in the Women's Health Initiative, there were more CHD events in the placebo group than the estrogen group during the final year, results similar to those in the HERS study in which the rates crossed during the 4th year.
Unopposed estrogen increases the risk of endometrial cancer from 1/1000/year to about 6/1000/year. This type of cancer has a high cure rate with hysterectomy. The rate of endometrial hyperplasia is 34% over 3 years. In women taking postmenopausal hormones, there is a trade-off between breast cancer and endometrial cancer.
Estrogens increase some of the proteins in the clotting cascade. This causes measurable changes in laboratory tests of coagulation but only minor clinical adverse events. Several studies ( Perez Gutthann, Varas-Lorenzo, Miller) have suggested that the incidence of thrombophlebitis increased with estrogen, especially during the first year of therapy. The annual risk was 1.3 cases per 10,000 women who didn't use estrogen and 2.6 cases per 10,000 women using estrogen. The Women's Health Initiative also found an increased relative risk of venous thromboembolism (16 per 10,000/yr without and 34 per 10,000/yr with hormones). Estrogens should not be used in women with a history of coagulopathy, although a remote history of a single episode of thrombophlebitis associated with surgery, trauma or pregnancy is not a contraindication. The recent HERS study showed a higher incidence of thrombophlebitis in women who already had coronary artery disease. Again, women in the estrogen group had about twice as many side effects related to this than women in the placebo group.
  • The risk of gallstones doubles with estrogen.
  • Estrogens help to delay the loss of skin collagen and are therefore beneficial to the skin.
  • Estrogen is the only effective treatment for vasomotor instability (hot flashes) associated with menopause. It also is used to treat vaginal atrophy.
  • Preliminary epidemiological studies had suggested that there is a lower incidence of Alzheimer's disease in women who take estrogen, but the Women's Health Initiative found no support for this in the five year study, and more details of the study of dementia will be published soon.
  • Contrary to popular opinion, estrogens do not cause weight gain. In fact, the PEPI study showed that women who used estrogen averaged 1.0 kg less weight gain and 1.2 cm less increase in waist girth.

Updated 5/21/08
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