Although conventional hormone replacement therapy (HRT) definitely prevents postmenopausal osteoporosis, its side effects are dose related and have limited the number of women who can benefit from its bone-sparing effects. This study was designed to evaluate a combination of 0.3 mg of conjugated equine estrogen and 2.5 mg of medroxyprogesterone daily in 128 generally healthy white women older than 65 years whose spinal bone mineral density (BMD) at baseline (measured by dual-energy x-ray absorptiometry) was 0.9 gm/cc or less. A randomized, double-blind, placebo-controlled design was used, and a 3.5-year treatment time was planned. Patients whose dietary calcium intake was less than 1 gm daily received a calcium supplement sufficient to bring dietary calcium to 1 gm per day. Patients also received 25-hydroxyvitamin D if needed to increase the serum level to at least 75 nmol/liter.
Compliance with treatment exceeded 90 percent for participants who completed the study period. BMD in the spine increased significantly in patients receiving HRT compared with placebo recipients, especially in the first 6 months (Fig. 1). The peak gain was 4 percent over baseline after 3 years of treatment (Fig. 2). Total-body bone mineral content increased steadily for 18 months to a gain of 3.1 percent over baseline in the HRT group; placebo patients gained 1.5 percent during the same time period. The overall gain in BMD in the femoral neck was not significant, but the trend for radial BMD significantly favored HRT. Side effects considered to be related to the HRT were mild and short-lasting and were easily tolerated by the majority of patients. Most of these effects no longer were present after 6 months of treatment, and no patients had vaginal bleeding or spotting after 12 months. FIGURE
Continuous low-dose HRT, when combined with calcium and vitamin D supplements, is an effective and relatively inexpensive way of preventing osteoporosis in elderly postmenopausal women. It has a potent bone-sparing effect, and side effects are tolerated by most patients.
Ann Intern Med 1999;130:897-904