微粉化孕酮对接受雌激素替代疗法的绝经后妇女骨转换的影响。

Azizi G, Hansen A, Prestwood K M

Hanover Medical Specialists, PA, Wilmington, North Carolina, USA.

Endocr Res. 2003 May;29(2):133-40. doi: 10.1081/erc-120022294.

PURPOSE

To determine whether daily oral micronized progesterone affects bone turnover, as estimated by serum and urine biochemical markers, in postmenopausal women on long-term estrogen replacement therapy (ERT).

METHODS

We recruited 14 women aged 65 or older to participate in a 9-week trial with micronized progesterone. Each woman had undergone a hysterectomy and was on unopposed ERT at time of study entry. Women received micronized progesterone 100 mg twice daily in the first week and then received 200 mg twice daily in weeks 2-9. We measured markers of bone turnover in serum and urine collected at baseline and at 3 weeks, 6 weeks, and 9 weeks on treatment. Markers of bone formation were serum bone alkaline phosphatase (BAP), N-terminal procollagen peptides (PINP), and osteocalcin (OC). Markers of bone resorption were urinary cross-linked N-terminal and C-terminal telopeptides of type I collagen. In addition, we measured serum progesterone, estradiol and sex hormone binding globulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL)-cholesterol levels at baseline and at 9 weeks on treatment.

RESULTS

Mean serum progesterone levels increased from 1.6 +/- 1.1 to 15.2 +/- 3.9 ng/mL, which was within the luteal phase range (3-25 ng/mL). Crosslinked C-telopeptides of type I collagen and osteocalcin increased significantly (p < 0.05) with progesterone treatment, however, other bone markers did not change. Estradiol, estrone, and SHBG levels did not change with treatment. High-density lipoprotein-cholesterol levels decreased 19% (p < 0.001) at 9 weeks on treatment compared to baseline but total and low-density lipoprotein (LDL) cholesterol and triglycerides did not change with treatment.

CONCLUSION

In postmenopausal women on long-term estrogen replacement therapy, micronized progesterone (400 mg/d) increased one marker each of bone resorption and bone formation. Other sensitive markers of bone turnover did not change with treatment. Further, micronized progesterone decreased HDL-cholesterol in these women. Our data do not support a beneficial effect of micronized progesterone on bone or cardiovascular risk factors in postmenopausal women.

目的

通过血清和尿液生化标志物评估，确定长期接受雌激素替代疗法（ERT）的绝经后女性每日口服微粉化孕酮是否会影响骨转换。

方法

我们招募了14名65岁及以上的女性参与一项为期9周的微粉化孕酮试验。每位女性均已接受子宫切除术，且在研究入组时正在接受单纯雌激素替代疗法。女性在第一周每天两次接受100毫克微粉化孕酮治疗，然后在第2至9周每天两次接受200毫克治疗。我们在治疗基线时以及治疗第3周、6周和9周时收集的血清和尿液中测量骨转换标志物。骨形成标志物包括血清骨碱性磷酸酶（BAP）、N端前胶原肽（PINP）和骨钙素（OC）。骨吸收标志物为尿I型胶原交联N端和C端肽。此外，我们在基线时以及治疗第9周时测量血清孕酮、雌二醇、性激素结合球蛋白、甘油三酯、总胆固醇和高密度脂蛋白（HDL）胆固醇水平。

结果

血清孕酮平均水平从1.6±1.1 ng/mL升至15.2±3.9 ng/mL，处于黄体期范围（3 - 25 ng/mL）内。孕酮治疗后，I型胶原交联C端肽和骨钙素显著升高（p < 0.05），然而，其他骨标志物未发生变化。雌二醇、雌酮和SHBG水平在治疗后未改变。与基线相比，治疗第9周时高密度脂蛋白胆固醇水平下降了19%（p < 0.001），但总胆固醇、低密度脂蛋白（LDL）胆固醇和甘油三酯水平在治疗后未改变。