THE EFFECT OF 3 HORMONE REPLACEMENT REGIMENS ON BONE-DENSITY IN THE AGED OVARIECTOMIZED RAT

Objective: To investigate the effects of estrogen (E) alone or with cyclic, continuous, or interrupted P regimens on bone density in an aged rat model. Design: Randomized controlled trial. Animals: Twenty 12-month-old female Sprague-Dawley rats were sham operated (intact control) and 100 were ovariectomized (OVX). Intervention: Four groups of 20 OVX rats were implanted with silastic capsules containing 5 E(2) (wt/wt) in cholesterol. All rats in the intact control (group 1), OVX (group 2), and the first of the OVX plus E groups (group 3) were injected subcutaneously daily for 6 months with corn oil (vehicle). Three other groups of rats with E capsules received daily injections of norethindrone in corn oil, according to the following dosage schedules: 6 mu g norethindrone/rat per day for 2 of every 4 weeks (cyclic; group 4); 3 mu g norethindrone/rat per day every day (continuous; group 5); or 3 mu g norethindrone/rat per day for 3 of every 6 days (interrupted; group 6). Main Outcome Measures: Bone mineral content (BMC) and bone mineral density (BMD) in the femur and vertebrae were measured by dual-energy roentgenogram absorptiometry. Results: The OVX rats (group 2) receiving corn oil alone had the lowest BMD. Intact controls (group 1), E plus cyclic P (group 4), and E and interrupted P (group 6) were all similar and had significantly greater bone density in the vertebrae than the OVX controls. In contrast, vertebral BMD with E alone (group 3) and continuous E and P (group 5) was not significantly different from b the OVX group. Femur BMD was significantly lower in the OVX group compared with the other five groups, which did not differ significantly from each other. Conclusion: In this experimental model, compared with OVX controls, combined hormone replacement therapy with E and cyclic or interrupted P resulted in the best vertebral BMD whereas continuous E and P resulted in the worst BMD. In the femurs, E alone and E plus P had equal effects on BMD.