Postmenopausal cyclic estrogen-progestin therapy lowers lipoprotein[a].

In 21 postmenopausal women, ages 45 to 55 years, we assessed the effects of 3 months of cyclic estrogen-progestin therapy on lipoprotein[a] (Lp[a]), lipids, lipoproteins, apolipoproteins, blood pressure, and insulin/glucose relationships. After a pretherapy baseline study, conjugated estrogens (0.625 mg for 21 days) and medroxyprogesterone acetate (5 mg last 10 days) were given to the women cyclically for 3 months, and then the study was repeated. During hormone replacement therapy, mean plasma Lp[a] fell 25% (from 20 to 15 mg/dl) (p = 0.0001), apolipoprotein B fell 14% (p = 0.01), and triglyceride fell 15% (p = 0.01), while high-density lipoprotein cholesterol (HDLC) rose 26% (p = 0.0001) and apolipoprotein A1 rose 25% (p = 0.003). The area under the insulin curve after oral glucose tolerance fell 33% (p = 0.0001), while the ratio of insulin area to glucose area fell 22% (p = 0.006). Mean systolic and diastolic blood pressure fell, respectively, 6% and 10% (p = 0.0001 for both). We speculate that the potential cardioprotective effect of estrogen-progestin therapy in postmenopausal women may be mediated through lowering Lp(a) as well as raising HDLC and apolipoprotein A1, lowering apolipoprotein B and blood pressure, and decreasing insulin resistance.