Metabolic, Inflammatory, and Hemostatic Effects of a Low-Dose Continuous Combined HRT in Women With Type 2 Diabetes: Potentially Safer With Respect to Vascular Risk

Abstract

Conventional hormone replacement therapy (HRT), consisting of conjugated equine estrogen and medroxyprogesterone acetate, increases levels of triglycerides, C-reactive protein, and coagulation Factor VII. These changes could help explain the increased risk of coronary heart disease (CHD) and stroke associated with HRT. This is especially pertinent to women with type 2 diabetes, who have a much increased risk of CHD. This study examined the metabolic effects of a continuous combined HRT regimen containing 1 mg estradiol and 0.5 mg norethisterone. The study, using a double-blind, randomized, placebo-controlled design, enrolled 50 women with type 2 diabetes. The treatment and control groups were similar in age, blood pressure, body mass index, and time since menopause. Actively treated women had a significant reduction in gonadotropin levels and increased levels of estradiol and sex hormone-binding globulin compared with women in the placebo group. Although total testosterone did not change significantly, the free androgen index decreased. Both total and low-density lipoprotein (LDL) cholesterol fell significantly, the latter by 13%, in actively treated women compared with placebo recipients. There were no changes in high-density lipoprotein (HDL) cholesterol or triglycerides. Fasting C-peptide levels decreased 19% compared with values in placebo patients. Fasting blood glucose levels were reduced in the HRT group. Levels of Factor VII, tissue plasminogen activator, and interleukin-6 all decreased in the HRT group compared with control women. There were no significant changes in Factor IX, activated protein C resistance, fibrinogen, or C-reactive protein. Ten of 25 actively treated women and 4 of the 25 given placebo had a greater than 10% drop in LDL cholesterol. This degree of decline in Factor VII levels was found in 16 women receiving HRT and only 1 placebo patient. Low-dose HRT could be more suitable than the conventional regimen for women who require relief of menopausal symptoms or bone protection but who are at increased risk of CHD. Firm recommendations cannot, however, be made until a large randomized, controlled trial focusing on cardiovascular end points is completed.