The effect of three hormone replacement regimens on bone density in the aged ovariectomized rat

To investigate the effects of estrogen (E) alone or with cyclic, continuous, or interrupted P regimens on bone density in an aged rat model.

Randomized controlled trial.

Twenty 12-month-old female Sprague-Dawley rats were sham operated (intact control) and 100 were ovariectomized (OVX).

Four groups of 20 OVX rats were implanted with silastic capsules containing 5% E2 (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 micrograms norethindrone/rat per day for 2 of every 4 weeks (cyclic; group 4); 3 micrograms norethindrone/rat per day every day (continuous; group 5); or 3 micrograms norethindrone/rat per day for 3 of every 6 days (interrupted; group 6).

Bone mineral content (BMC) and bone mineral density (BMD) in the femur and vertebrae were measured by dual-energy roentgenogram absorptiometry.

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 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.

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.