Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations: analysis of studies published from 1974–2000

Objective: To establish reference estimates of the effects of different hormone replacement therapy (HRT) regimens on lipid and lipoprotein levels. Design: Review and pooled analysis of prospective studies published up until the year 2000. Setting: Clinical trials centers, hospitals, menopause clinics. Patient(s): Healthy postmenopausal women. Intervention(s): Estrogen alone, estrogen plus progestogen, tibolone, or raloxifene in the treatment of menopausal symptoms. Main Outcome Measure(s): Serum high- and low-density lipoprotein (HDL and LDL) cholesterol, total cholesterol, triglycerides, and lipoprotein (a). Result(s): Two-hundred forty-eight studies provided information on the effects of 42 different HRT regimens. All estrogen alone regimens raised HDL cholesterol and lowered LDL and total cholesterol. Oral estrogens raised triglycerides. Transdermal estradiol 17-beta lowered triglycerides. Progestogens had little effect on estrogen-induced reductions in LDL and total cholesterol. Estrogen-induced increases in HDL and triglycerides were opposed according to type of progestogen, in the order from least to greatest effect: dydrogesterone and medrogestone, progesterone, cyproterone acetate, medroxyprogesterone acetate, transdermal norethindrone acetate, norgestrel, and oral norethindrone acetate. Tibolone decreased HDL cholesterol and triglyceride levels. Raloxifene reduced LDL cholesterol levels. In 41 studies of 20 different formulations, HRT generally lowered lipoprotein (a). Conclusion(s): Route of estrogen administration and type of progestogen determined differential effects of HRT on lipid and lipoprotein levels. Future work will focus on the interpretation of the clinical significance of these changes.