Objective: Progestins are commonly prescribed for hormone replacement therapy (HRT) and contraception. However, the effects of progestins on bone metabolism remain unclear and are often controversial.
Design and patients: This study was conducted to test the hypothesis that progestins with no significant glucocorticoid activity may be a better choice for HRT to achieve increased beneficial effects on bone metabolism than progestins with strong glucocorticoid activity. A total of 104 postmenopausal women aged 50-75 years with osteoporosis were allocated randomly to three groups: (1) conjugated oestrogen plus medroxyprogesterone acetate (HRT-MPA, with significant glucocorticoid activity); (2) conjugated oestrogen plus norethisterone (HRT-NET, with no significant glucocorticoid activity); and (3) control (no treatment).
Measurements: Vertebral X-rays and bone mineral density (BMD) at distal 1/3 radius were assessed at baseline and every 6 months during the 2-year study period, along with markers of bone turnover. The occurrence of new nonvertebral fractures was identified by X-ray.
Results: After the 2-year treatment, mean BMD changes relative to baseline in the HRT-MPA, HRT-NET and control groups were 1.6%, 2.3% and -1.9%, respectively. In addition, the rate of increase in HRT-NET was significantly greater than that in HRT-MPA (P = 0.019). The incidence of new fractures during the 2-year treatment in the control group was 26% (9/34). HRT-NET treatment significantly inhibited the occurrence of new fractures (RR 0.14, 95% CI 0.02-0.93, P = 0.04), while HRT-MPA treatment failed to show a statistically significant reduction (RR 0.41, 95% CI 0.14-1.24, P = 0.11). Both HRT-MPA and HRT-NET treatments significantly decreased serum osteocalcin levels by 29.4% and 23.5%, respectively, after 6 months of treatment, with the decrease in HRT-MPA being significantly greater than that in HRT-NET (P = 0.042).
Conclusions: These findings suggest that progestins with no significant glucocorticoid activity may be a better choice for HRT, resulting in increased beneficial effects on bone metabolism compared with progestins with strong glucocorticoid activity.