Effects of Progestins on the Metabolism of Cancellous Bone in Aged Oophorectomized Rats

The effects of progestins on bone loss in female oophorectomized (ovx) rats were evaluated. One-year-old Sprague-Dawley rats were divided into eight groups: (1) beginning controls (control); (2) sham-operated controls (sham); (3) ovx; (4) ovx treated with estrogen (ovx + E); (5) ovx treated with progesterone (ovx + P); (6) ovx treated with estrogen and progesterone (ovx + E + P); (7) sham group treated with estrogen (sham + E); and (8) sham group treated with progesterone (sham + P). Immediately after surgery, the rats in the hormone injected groups were subcutaneously (s.c.) injected daily for 15 weeks with estrogen (17-β-estradiol, 0.01 mg/kg in ethanol), or progesterone (4-pregnene-3,20-dione, 0.1 mg/kg in ethanol), or both. At the end of 15 weeks, the bone mineral density (BMD) and bone histomorphometry of the rats’ lumbar vertebrae and serological parameters were measured. In the sham, ovx, and ovx + P groups, treatment with progesterone alone did not maintain the BMD in the lumbar vertebrae, but in the ovx + E and ovx + E + P, sham + E, and sham + P groups, progesterone did not inhibit the action of estrogen in the aged ovx rat model. BMD in the sham + P group was significantly higher than in the sham group (270.8 ± 10.8 mg/cm2 versus 253.6 ± 10.2 mg/cm2; p< 0.01). Bone histomorphometry revealed that bone volume (BV/TV) increased more in the ovx + E + P group than in the ovx + E group and more in the sham + P group than in the sham group, but not significantly. The ovx + E, ovx + E + P, sham + E, and sham + P groups showed no significant differences in the bone formation and resorption parameters, but the bone formation variables tended to increase in the ovx + E + P and sham + P groups. We concluded that progesterone alone cannot prevent bone loss or the increase in turnover after ovx and that estrogen, not progesterone, accounted for all of the bone activity in this study. It seems doubtful that progesterone inhibits the action of estrogen, and in fact may have a beneficial effect on bone metabolism.