Low-Dose Estrogen Therapy Brings Benefits Without Increasing Risk

Endometrial hyperplasia is the overgrowth of tissue in the inner lining of the uterus. It is non cancerous but can lead to excessive uncontrollable bleeding and can be a precursor to endometrial cancer. It normally effects women over the age of 35 and is thought to be brought on by raised levels of estrogen.

But a recent study indicates that women are able to reap the benefits of estrogen therapy, such as increased bone density without increasing the risk of endometrial hyperplasia, as long as the doses of estrogen given are low. The study, reported in the Archives of Internal Medicine (157:2609-2615) involving 406 postmenopausal women found that a 0.3-mg does of estrified estrogens resulted in positive bone and lipid changes without inducing endometrial hyperplasia.

Each woman in the study was given 100 mg/d calcium and was randomly assigned to receive continuous estrifed estrogens (0.3, 0.625, or 1.25 mg/d) or placebo for 24 months. All doses of estrified estrogens produced significant increases in bone mineral density of the lumbar spine compared with baseline and placebo. Clinically relevant rates of endometrial hyperplasia were noted only in groups receiving 0.625 and 1.25 mg of estrified estrogens daily.

The study has identified what seems to be a point of balance between risk and benefit. Normally the increased risk of endometrial hyperplasia with hormone replacement therapy has been managed by prescribing a combination of estrogen and progesterone. The logic behind this course of treatment is that this combination stimulates menstruation, which decreases the risk of endometrial cancer by stimulating the body to regularly shed the endometrium. If the endometrium is not shed, any division of cells (cancer) will remain in the uterus rather than getting flushed out. What this study tells us is that there might be another option, where the levels of estrogen used are low enough that cell division is not stimulated and so there is no need for induced menstruation, but the levels are high enough to increase bone density.

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