|CARDIOVASCULAR AND LIPID|
|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.
|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.|