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Lipids, Fibrinogen Favorably Altered by Hormone Replacement after Menopause

Observational studies suggest estrogen therapy in postmenopausal women can reduce by 50% the risk for ischemic heart disease. Unopposed estrogen therapy has been shown to increase high-density lipoproteins (HDL) and lower low-density lipoproteins (LDL), while progestin is suspected to blunt estrogen's cardioprotective effects.

In the three-year, multicenter, blinded Postmenopausal Estrogen/ Progestin Interventions (PEPI) Trial, 875 healthy postmenopausal women aged 45 to 64 years were randomized to one of four treatment groups: placebo; conjugated estrogen, 0.625 mg/day; conjugated estrogen plus cyclic medroxyprogesterone acetate, 10 mg/day for 12 days each month; or conjugated estrogen plus micronized progesterone, 200 mg/day for 12 days each month.

Mean HDL levels significantly increased in women in all three active treatment arms. Although the estrogen-only group had the greatest increase, women in this group had significantly more uterine hyperplasia and were more likely to require a hysterectomy. Estrogen plus micronized progesterone elevated HDL levels more than estrogen plus medroxyprogesterone, 4.1 mg/dl versus 1.6 mg/dl. LDL levels reached their nadir by 6 to 12 months, and were significantly lower for all three active treatments compared to placebo. Women taking the placebo had greater increases in plasma fibrinogen than did women assigned to active treatment. No differences were observed in systolic blood pressure among the groups.

Comment: The PEPI trial confirms that oral estrogen taken alone or with progestin is associated with favorable alterations in lipoprotein and fibrinogen levels. Despite the strong inverse association between HDL levels and heart disease risk, however, clinical trials have yet to show that increasing HDL reduces heart disease risk in women. Two large trials are under way to determine whether replacement therapy will reduce heart disease risk in healthy women (the Women's Health Initiative) or reduce the risk of new cardiovascular events in women with established coronary heart disease (the Hormone Estrogen/Progestin Replacement Study).

— GW Dec

Published in Journal Watch Cardiology April 1, 1995

Citation(s):

The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. JAMA 1995 Jan 18 273 199-208.

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