Hormone replacement therapy and coronary heart disease in light of the PEPI trial

The Postmenopausal Estrogen/Progestins Interventions (PEPI) study evaluated the effects of hormone replacement therapy (HRT) on heart disease risk factors in 875 healthy women aged 45 to 64 followed for 3 years. Women were randomly assigned to receive: placebo; conjugated equine estrogens (CEE), 0.625 mg/day alone; CEE plus micronized progesterone (MP), 200 mg/day for 12 days/month; CEE plus medroxyprogesterone acetate (MPA), 10 mg/day for 12 days/month; and CEE plus daily MPA, 2.5 mg. Average increases in high-density lipoprotein cholesterol (HDL-C) were significantly higher in each treatment group than in the placebo group and highest among those receiving either CEE alone, or CEE and MP. HRT did not negatively affect blood pressure or serum insulin, while the age-related rise in fibrinogen was attenuated in active treatment groups. Treatments with MPA increased postchallenge glucose. Women with a uterus treated with CEE alone had a 33% excess risk of endometrial hyperplasia; there was no such excess risk among women receiving combination therapies. The PEPI study found metabolic differences between HRT regimens.