Progestagens and progesterone receptor modulation: Effects on the brain, mood, stress, and cognition in females

IF 6.5 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology Pub Date : 2024-11-06 DOI:10.1016/j.yfrne.2024.101160

Celine Bencker , Laura Gschwandtner , Sibel Nayman , Ramunė Grikšienė , Billie Nguyen , Urs M. Nater , Rachida Guennoun , Inger Sundström-Poromaa , Belinda Pletzer , Marie Bixo , Erika Comasco

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Abstract

Progesterone is a highly lipophilic gonadal hormone that can influence behavior and mental health through its receptors in the brain. Fluctuations in progesterone levels across critical periods of a females life are associated with increased susceptibility to mental conditions.

This review highlights the effects of progestagens, including progesterone and synthetic progestins, on the brain, mood, stress, and cognition in females. The primary focus is on experimental pharmacological research that teases out the distinct effects of progestagens from those of estrogens. Additionally, the key literature on puberty, the menstrual cycle, pregnancy, perimenopause, hormonal contraceptives, and menopausal hormone therapy is reviewed, although conclusions are limited by the nested effects of progestagens and estrogens.

Single study-findings suggest an influence of progesterone on amygdala reactivity related to processing of emotional stimuli and memory. In patients with premenstrual dysphoric disorder, progesterone receptor modulation improves premenstrual mood symptoms and potentially enhances fronto-cingulate control over emotion processing. The interaction between progestagens and the systems involved in the regulation of stress seems to influence subjective experiences of mood and stress. Sparse studies investigating the effects of progestin-only contraceptives suggest effects of progestagens on the brain, mood, and stress. Progesterone and progestins used for contraception can influence neural processes as myelination and neuroprotection, exerting protective effects against stroke. Concerning menopausal hormonal therapy, the effects of progestins are largely unknown.

Levels of progesterone as well as type, administration route, timing, dose regimen, metabolism, and intracellular activity of progestins in hormonal contraceptives and menopausal hormonal therapy are factors whose effects remain to be elucidated. Altogether, current knowledge highlights the potential role of progestagens in females health but also calls for well-designed pharmaco-behavioral studies disentangling the effects of progestagens from those of estrogens.

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孕激素和孕酮受体调节：对女性大脑、情绪、压力和认知的影响。

孕酮是一种亲脂性很强的性腺激素，可通过其在大脑中的受体影响行为和心理健康。在女性生命的关键时期，孕酮水平的波动与精神疾病的易感性增加有关。本综述强调了孕激素（包括黄体酮和合成孕激素）对女性大脑、情绪、压力和认知的影响。主要侧重于实验药理学研究，以揭示孕激素与雌激素的不同作用。此外，还回顾了有关青春期、月经周期、怀孕、围绝经期、激素避孕药和绝经期激素疗法的主要文献，但结论受到孕激素和雌激素嵌套效应的限制。单项研究结果表明，黄体酮会影响杏仁核对情绪刺激和记忆处理的反应。在经前期情绪障碍患者中，黄体酮受体调节可改善经前期情绪症状，并有可能增强前扣带回对情绪处理的控制。孕激素与压力调节系统之间的相互作用似乎会影响情绪和压力的主观体验。对纯孕激素避孕药影响的调查研究很少，这表明孕激素对大脑、情绪和压力有影响。用于避孕的孕酮和孕激素可影响神经过程，如髓鞘化和神经保护，对中风有保护作用。关于更年期荷尔蒙疗法，孕激素的作用在很大程度上是未知的。激素避孕药和更年期激素疗法中孕激素的水平、类型、给药途径、时间、剂量方案、代谢和细胞内活性等因素的影响仍有待阐明。总之，目前的知识强调了孕激素在女性健康中的潜在作用，但同时也要求进行精心设计的药物行为研究，将孕激素的作用与雌激素的作用区分开来。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Neuroendocrinology 医学-内分泌学与代谢

CiteScore

13.30

自引率

6.80%

发文量

审稿时长

68 days

期刊介绍： Frontiers in Neuroendocrinology (FIN) publishes a wide range of informative articles including comprehensive reviews, systematic reviews, opinion pieces, and meta-analyses. While the majority of reviews are invited, we also embrace unsolicited reviews and meta-analyses, as well as proposals for thematic special issues, provided they meet our rigorous quality standards. In addition, we encourage authors to submit commentaries that concisely present fresh ideas or offer further analysis to delve deeper into the implications of an article published in our journal.