Hormone replacement therapy (HRT), used by many women to relieve the symptoms of menopause and for the prevention of osteoporosis, is available in an increasing number of formulations. Options include various combinations of estrogen and progestin as well as different routes of administration. For women with a uterus, who require a progestin, a convenient and commonly used option is combining the estrogen and progestin in a single pill. Such formulations have the lipid-modifying effects of estrogen, altered to specific type and dose of progestin used. The cardioprotective increases in levels of high-density lipoprotein cholesterol associated with exogenous estrogen may be blunted or even reversed with certain HRT regimens. In addition, some progestins minimize the increase in triglycerides that occurs with exogenous estrogen, whereas others do not. Because of the importance of lipid markers as risk factors for cardiovascular disease in postmenopausal women, these lipid effects should be carefully considered when selecting an HRT regimen.