Ishida Yoichiro, Mine Takatomo, Taguchi Toshihiko
Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
Clin Endocrinol (Oxf). 2008 Mar;68(3):423-8. doi: 10.1111/j.1365-2265.2007.03059.x. Epub 2007 Oct 31.
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.
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).
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.
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).
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.
孕激素常用于激素替代疗法（HRT）和避孕。然而，孕激素对骨代谢的影响仍不明确，且常常存在争议。
本研究旨在验证以下假设：对于激素替代疗法而言，无显著糖皮质激素活性的孕激素可能比具有强糖皮质激素活性的孕激素更能有效改善骨代谢。104名年龄在50至75岁之间患有骨质疏松症的绝经后女性被随机分为三组：（1）结合雌激素加醋酸甲羟孕酮（HRT-MPA，具有显著糖皮质激素活性）；（2）结合雌激素加炔诺酮（HRT-NET，无显著糖皮质激素活性）；（3）对照组（不治疗）。
在为期2年的研究期间，于基线时及每6个月对腰椎X线及桡骨远端1/3处的骨密度（BMD）进行评估，并检测骨转换标志物。通过X线检查确定新发非椎体骨折的发生情况。
经过2年治疗后，HRT-MPA组、HRT-NET组和对照组相对于基线的平均骨密度变化分别为1.6%、2.3%和-1.9%。此外，HRT-NET组的骨密度增加率显著高于HRT-MPA组（P = 0.019）。对照组在2年治疗期间新发骨折的发生率为26%（9/34）。HRT-NET治疗显著抑制了新发骨折的发生（相对危险度0.14，95%可信区间0.02 - 0.93，P = 0.04），而HRT-MPA治疗未显示出统计学上的显著降低（相对危险度0.41，95%可信区间0.14 - 1.24，P = 0.11）。治疗6个月后，HRT-MPA组和HRT-NET组均使血清骨钙素水平显著下降，分别下降了29.4%和23.5%，HRT-MPA组的下降幅度显著大于HRT-NET组（P = 0.042）。
这些研究结果表明，对于激素替代疗法而言，无显著糖皮质激素活性的孕激素可能是更好的选择，与具有强糖皮质激素活性的孕激素相比，其对骨代谢具有更多有益作用。
