Agnusdei D, Gennari C, Bufalino L
Institute of Internal Medicine and Medical Pathology, University of Siena, Italy.
Osteoporos Int. 1995;5(6):462-6. doi: 10.1007/BF01626609.
Hormone replacement therapy is the optimal therapeutic choice for postmenopausal syndrome. While low doses of estrogens (0.3 mg/day of conjugated estrogens) can counteract neurovegetative menopausal symptoms, higher doses (0.625 mg/day of conjugated estrogens) are required to prevent bone loss in postmenopausal women. Experimental and clinical studies have shown that ipriflavone, a non-hormonal isoflavone derivative, is effective in the prevention and treatment of postmenopausal osteoporosis. The aim of the present investigation was to evaluate the efficacy and tolerability of ipriflavone and very low doses of equine conjugated estrogens on bone loss in early postmenopausal women. Eighty-three healthy postmenopausal women (50.3 +/- 0.7 years) were enrolled for this 1-year multicenter study. All subjects were randomly allocated to receive: double placebo (n = 24; group A), placebo plus conjugated equine estrogens 0.30 mg/day (n = 31; group B) or conjugated equine estrogens 0.30 mg/day plus oral ipriflavone 200 mg tris in die at meals (n = 28; group C), according to a double-masked design. Among women who completed the treatment period (valid completers), those of group A showed a progressive decrease in forearm bone density (FBD; measured by dual photon absorptiometry) that reached 1.7% after 12 months. The women in group B maintained their FBD in the first 6 months of treatment but, at the end of the study, showed a bone loss of 1.4% compared with basal values. By contrast, women in group C showed a significant increase in FBD after 1 year of treatment (+5.6%; p < 0.01). Both valid completers and intention to treat analyses revealed a significant difference (p < 0.05) between group A and group C over the study period. None of the treatments produced significant changes of biochemical markers of bone turnover, while hot flushes and other climacteric symptoms were significantly reduced after the sixth month of treatment in women receiving estrogens. Adverse events were generally mild, and did not differ among the groups. The results of this study suggest that low doses of estrogens combined with ipriflavone could represent a new therapeutic approach to the treatment of the postmenopausal syndrome.
激素替代疗法是绝经后综合征的最佳治疗选择。低剂量雌激素（0.3毫克/天结合雌激素）可对抗绝经后的植物神经症状，而预防绝经后女性骨质流失则需要更高剂量（0.625毫克/天结合雌激素）。实验和临床研究表明，异黄酮衍生物依普黄酮在预防和治疗绝经后骨质疏松症方面有效。本研究的目的是评估依普黄酮和极低剂量马结合雌激素对绝经后早期女性骨质流失的疗效和耐受性。83名健康绝经后女性（50.3±0.7岁）参与了这项为期1年的多中心研究。根据双盲设计，所有受试者被随机分配接受：双安慰剂（n = 24；A组）、安慰剂加0.30毫克/天马结合雌激素（n = 31；B组）或0.30毫克/天马结合雌激素加口服依普黄酮200毫克每日三次（n = 28；C组）。在完成治疗期的女性（有效完成者）中，A组女性的前臂骨密度（通过双能X线吸收法测量）逐渐下降，12个月后达到1.7%。B组女性在治疗的前6个月保持了骨密度，但在研究结束时，与基础值相比骨量流失了1.4%。相比之下，C组女性在治疗1年后骨密度显著增加（+5.6%；p < 0.01）。有效完成者分析和意向性分析均显示，在研究期间A组和C组之间存在显著差异（p < 0.05）。所有治疗均未使骨转换生化标志物发生显著变化，而接受雌激素治疗的女性在治疗第6个月后潮热和其他更年期症状显著减轻。不良事件一般较轻，各组之间无差异。本研究结果表明，低剂量雌激素联合依普黄酮可能代表绝经后综合征治疗的一种新方法。
