Determinants of attained estradiol levels in response to oral estradiol plus progesterone therapy

Abstract

Objectives

Among postmenopausal women taking hormone therapy (HT), the estradiol (E2) dose and E2 levels were differentially associated with change in metabolic measures. We evaluated determinants of attained E2 levels in response to HT.

Methods

Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models assessed characteristics associated with E2 levels among women with ≥80% HT compliance, adjusted for E2 dose and baseline E2 level.

Results

Among 1173 postmenopausal women with mean (standard deviation) age 55 (4.3) years and 5.2 (4.8) years since menopause, higher treated E2 levels were significantly related to younger age, more recent menopause, and current alcohol use, while lower E2 levels were related to current smoking. Both age and time since menopause were significantly inversely associated with E2 levels; time since menopause had a stronger association with E2 levels. In the final multivariable model, E2 levels were positively associated with current alcohol use, and inversely associated with time since menopause and current smoking.

Conclusion

Adjusting for E2 dose and baseline E2 level, on-trial E2 levels were significantly associated with time since menopause, current smoking, and current alcohol use. Practitioners should consider these factors in individual women to achieve a desirable E2 level during HT.

摘要

目的：在接受激素治疗（HT）的绝经后妇女中, 雌二醇（E2）剂量和E2水平与代谢指标变化的关系存在差异。我们评估了在HT作用下达到E2水平的决定因素。

方法：纳入“补充试验”的绝经后妇女测试了四种口服雌二醇孕酮联合制剂, 并与安慰剂进行了比较。混合效应线性模型评估了HT依从性≥80%的妇女中与E2水平相关的特征, 从而调整E2剂量和基线E2水平。

结果：在1173名绝经后妇女中, 平均年龄为55岁（4.3岁）和绝经后5.2年（4.8岁）, 治疗后E2水平较高与年龄较小、距离绝经时间最近和当前饮酒显著有关, 而E2水平较低与目前吸烟有关。年龄和绝经后时间与E2水平呈显著负相关, 绝经后时间与E2水平的相关性更强。在最终多变量模型中, E2水平与当前酒精摄入呈正相关, 与绝经后时间和当前吸烟呈负相关。

结论：调整E2剂量和基线E2水平后, 试验中E2水平与绝经后时间、当前吸烟和当前饮酒显著相关。从业人员应个体化考虑这些因素使接受HT治疗的妇女达到理想的E2水平。

Keywords:

• Estradiol level
• estradiol and progesterone therapy
• smoking
• alcohol
• time since menopause

Potential conflict of interest

I. Sriprasert, H. N. Hodis, and W. J. Mack received an unrestricted research grant from TherapeuticsMD. B. Bernick and S. Mirkin are employees of TherapeuticsMD and own stock/stock options of the company.

Additional information

Funding

This work was supported by TherapeuticsMD [unrestricted research grant].