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Updated: Jul 10, 2026
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Published on: September 27, 2024
Effect of progestins with different glucocorticoid activity on bone metabolism
Yoichiro Ishida1, Takatomo Mine, Toshihiko Taguchi
1Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan. myishida@yamaguchi-u.ac.jp
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.
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