el-Hajj Fuleihan G, Brown E M, Curtis K, Berger M J, Berger B M, Gleason R, LeBoff M S
Endocrine-Hypertension Division, Brigham and Women's Hospital, Boston, Mass. 02115.
Arch Intern Med. 1992 Sep;152(9):1904-9. doi: 10.1001/archinte.152.9.1904.
Continuous regimens of estrogen-progesterone have recently been favored over sequential regimens because of a lower incidence of withdrawal bleeding. To determine whether the beneficial effects of sequential hormonal therapy on bone metabolism are preserved with the newer continuous regimens, we studied indexes of skeletal metabolism and changes in bone mineral density during a 1-year prospective trial.
Our subjects were randomized to one of three treatment groups: those in group C-2.5 were treated with 0.625 mg of conjugated estrogen with 2.5 mg of micronized medroxyprogesterone acetate daily continuously; group C-5 received 0.625 mg of conjugated estrogen and 5.0 mg of micronized medroxyprogesterone acetate daily continuously; and group S-5 received 0.625 mg of conjugated estrogen on days 1 through 25 and 5 mg of micronized medroxyprogesterone acetate on days 14 through 25.
At 1 year, all groups demonstrated a significant decrease in indexes of bone formation turnover, including decrements in alkaline phosphatase levels of 11% to 30% and in osteocalcin levels of 45% to 60%. Intact parathyroid hormone levels rose 10% to 20%, with a concomitant near-significant decrement in ionized calcium levels at 12 months. In addition, there were significant decrements in the 24-hour urinary calcium-creatinine ratios and hydroxyproline-creatinine ratios of 13% to 28%, measures of bone resorption. Linear regression analyses showed that the subjects with the high bone resorption achieved the greatest increment in bone mineral density in response to hormone therapy.
The daily continuous estrogen-progesterone regimens are as efficacious as sequential hormonal therapy in decreasing indexes of bone turnover and stabilizing bone mineral density of the spine and proximal femur.
由于撤退性出血发生率较低，雌激素 - 孕激素连续治疗方案最近比序贯治疗方案更受青睐。为了确定在新的连续治疗方案中序贯激素治疗对骨代谢的有益作用是否得以保留，我们在一项为期1年的前瞻性试验中研究了骨骼代谢指标和骨矿物质密度的变化。
我们的研究对象被随机分为三个治疗组之一：C - 2.5组每天连续服用0.625 mg结合雌激素和2.5 mg微粉化醋酸甲羟孕酮；C - 5组每天连续服用0.625 mg结合雌激素和5.0 mg微粉化醋酸甲羟孕酮；S - 5组在第1至25天服用0.625 mg结合雌激素，在第14至25天服用5 mg微粉化醋酸甲羟孕酮。
1年后，所有组的骨形成转换指标均显著下降，包括碱性磷酸酶水平下降11%至30%，骨钙素水平下降45%至60%。完整甲状旁腺激素水平升高10%至20%，同时在12个月时离子钙水平近乎显著下降。此外，骨吸收指标24小时尿钙 - 肌酐比值和羟脯氨酸 - 肌酐比值显著下降13%至28%。线性回归分析表明，骨吸收高的受试者在接受激素治疗后骨矿物质密度增加最大。
每日连续雌激素 - 孕激素治疗方案在降低骨转换指标以及稳定脊柱和股骨近端骨矿物质密度方面与序贯激素治疗同样有效。
