Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens
Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens
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DOI：
10.1016/j.jsbmb.2013.08.002
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发表时间：
2013-11-01
影响因子：
4.1
通讯作者：
Gomez, Jose-Luis
中科院分区：
文献类型：
--
作者：
Labrie, Fernand;Martel, Celine;Gomez, Jose-Luis
为了避免非生理性全身暴露的风险，正常绝经后妇女中雌二醇 (E-2) 和睾酮（通过基于质谱的测定法测量）的血清浓度应保持在 95 百分位数以下，测量值分别为 9.3 pg/ml 和 0.26 ng/ml。为了记录实现这一治疗目标的可能性，我们测量了患有外阴阴道萎缩 (VVA) 的女性的个体 24 小时血清 E-2 和睾酮浓度，这些女性接受每日阴道内施用临床有效剂量的 6.5 mg 普拉酮（脱氢表雄酮，DHEA）。在超过 10 个时间间隔的情况下，对血清 E-2 和睾酮以及 DHEA 及其九种其他代谢物进行了测定。每天阴道给药6.5 mg prasterone的第一天和第七天的24小时。没有观察到平均24小时血清E-2或睾酮浓度与基线相比的显着变化。此外，平均24小时血清DHEA保持在正常绝经后范围内。雌酮硫酸盐和雄激素代谢物雄甾酮葡萄糖苷酸和雄甾烷-3α，17β-二醇葡萄糖苷酸没有变化，从而证实分别不存在任何生物学相关的雌激素和雄激素全身暴露。每日阴道内给予6.5mg普拉甾酮后，雌激素和雄激素代谢物的血清浓度保持在正常绝经后范围内。正如其他研究表明的那样，通过阴道内注射普拉睾酮，可以在外周组织中局部形成性类固醇，而不会在循环中显着释放 E-2 或睾酮。因此，普拉甾酮是治疗 VVA 症状的一种有前途的生理学且有吸引力的解决方案。 (C) 2013 年，爱思唯尔有限公司出版。
In order to avoid the risks of non-physiological systemic exposure, serum concentrations of estradiol (E-2) and testosterone (as measured by mass spectrometry-based assays) should remain below the 95th centiles measured at 9.3 pg/ml and 0.26 ng/ml for these respective sex steroids in normal postmenopausal women. To document the possibility of achieving this therapeutic objective, we have measured individual 24 h serum E-2 and testosterone concentrations in women with vulvovaginal atrophy (VVA) receiving daily intravaginal administration of a clinically effective dose of 6.5 mg prasterone (dehydroepiandrosterone, DHEA).Serum E-2 and testosterone, as well as DHEA and nine of its other metabolites, were assayed at ten time intervals over 24h on the first and seventh days of daily vaginal administration of 6.5 mg prasterone.No significant change from baseline of average 24h serum E-2 or testosterone concentrations was observed. Moreover, average 24h serum DHEA remained within the normal postmenopausal range. Estrone sulfate and the androgen metabolites androsterone glucuronide and androstane-3 alpha, 17 beta-diol glucuronide did not change, thus confirming the absence of any biologically relevant systemic exposure to estrogens and androgens, respectively.Serum concentrations of metabolites of both estrogens and androgens remain within the normal postmenopausal range following daily intravaginal administration of 6.5 mg prasterone. As other studies have shown, local formation of sex steroids in peripheral tissues without significant release of E-2 or testosterone in the circulation can be achieved with intravaginal prasterone. Thus, prasterone is a promising physiological and attractive solution to treating VVA symptoms. (C) 2013 Published by Elsevier Ltd.