Objective:

Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD.

Methods:

In this sex-separated multicenter longitudinal study, the authors analyzed 12-month data on real-life alcohol use (from 21,460 smartphone entries), menstrual cycle, and serum progesterone-to-estradiol ratios (from 667 blood samples at four individual study visits) in 74 naturally cycling females and 278 males with AUD between 2020 and 2022, using generalized and general linear mixed modeling.

Results:

Menstrual cycle phases were significantly associated with binge drinking and progesterone-to-estradiol ratio. During the late luteal phase, females showed a lower predicted binge drinking probability of 13% and a higher predicted marginal mean of progesterone-to-estradiol ratio of 95 compared with during the menstrual, follicular, and ovulatory phases (binge drinking probability and odds ratios vs. late luteal phase, respectively: 17%, odds ratio=1.340, 95% CI=1.031, 1.742; 19%, odds ratio=1.523, 95% CI=1.190, 1.949; and 20%, odds ratio=1.683, 95% CI=1.285, 2.206; difference in progesterone-to-estradiol ratios, respectively: −61, 95% CI=−105.492, −16.095; −78, 95% CI=−119.322, −37.039; and −71, 95% CI=−114.568, −27.534). In males, a higher progesterone-to-estradiol ratio was related to lower probabilities of binge drinking and of any alcohol use, with a 10-unit increase in the hormone ratio resulting in odds ratios of 0.918 (95% CI=0.843, 0.999) and 0.914 (95% CI=0.845, 0.988), respectively.

Conclusions:

These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females and males with AUD, highlighting the progesterone-to-estradiol ratio as a promising treatment target. Moreover, the results indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments.

中文翻译：

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酒精使用障碍中月经周期和孕酮/雌二醇比率与饮酒量的关联：一项按性别划分的多中心纵向研究

 客观的：

酒精使用障碍（AUD）构成了一个重要的公共卫生问题，并且具有特定性别的特征。初步证据表明，黄体酮和雌二醇可能分别减少或增加酒精摄入量。然而，需要更好地了解女性的月经周期以及女性和男性的黄体酮与雌二醇的比例如何影响 AUD 患者的饮酒模式。

 方法：

在这项按性别划分的多中心纵向研究中，作者分析了 12 个月的现实生活中饮酒数据（来自 21,460 个智能手机条目）、月经周期和血清孕酮与雌二醇比率（来自四次单独研究访问的 667 个血液样本） ）在 2020 年至 2022 年间，使用广义和一般线性混合模型对 74 名自然循环女性和 278 名患有 AUD 的男性进行了研究。

 结果：

月经周期阶段与暴饮暴食和黄体酮与雌二醇的比率显着相关。与月经期、卵泡期和排卵期相比，在黄体期晚期，女性的预测暴饮概率较低，为 13%，黄体酮与雌二醇比值的预测边际平均值较高，为 95（暴饮概率和比值比）与黄体后期分别：17%，优势比=1.340，95% CI=1.031，1.742；19%，优势比=1.523，95% CI=1.190，1.949；和 20%，优势比=1.683，95 % CI=1.285、2.206；孕酮与雌二醇比率的差异分别为：-61、95% CI=-105.492、-16.095；-78、95% CI=-119.322、-37.039； CI=−114.568,−27.534)。在男性中，较高的孕酮与雌二醇比率与较低的酗酒和饮酒概率相关，激素比率增加 10 个单位，优势比为 0.918 (95% CI=0.843, 0.999)和 0.914 (95% CI=0.845, 0.988)。

 结论：

这些生态学上有效的研究结果表明，高孕酮与雌二醇比率可以对患有 AUD 的女性和男性有问题的饮酒具有保护作用，强调孕酮与雌二醇比率是一个有前途的治疗目标。此外，结果表明患有 AUD 的女性可能会受益于针对月经周期阶段的治疗。