Lin Hsin-Yi, Chen Jie-Hong, Chen Kuo-Hu
Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan.
Department of Medicine, MacKay Medical University, New Taipei City 25245, Taiwan.
Int J Mol Sci. 2025 Sep 3;26(17):8568. doi: 10.3390/ijms26178568.
Dehydroepiandrosterone (DHEA) and its sulfate ester form DHEAS, are multifunctional steroid hormones primarily produced in the adrenal cortex, with additional synthesis in peripheral tissues. DHEA/DHEAS serve as precursors to sex steroids and exhibit neuroprotective, anti-inflammatory, and immune-modulating effects. DHEA levels decline significantly with age, a phenomenon termed "adrenopause", prompting interest in supplementation to mitigate age-related symptoms. Particularly in postmenopausal women, DHEA has shown potential benefits in treating genitourinary syndrome of menopause (GSM), including improved vaginal health, lubrication, and sexual function. While intravaginal DHEA appears effective and safer than systemic estrogen therapy, especially for women with estrogen sensitivity, results remain mixed for oral administration. DHEA and DHEAS exhibit diverse neuroactive properties through modulation of GABA-A, NMDA, and sigma-1 receptors. These neurosteroids contribute to neuroprotection, synaptic plasticity, and mood regulation. Altered DHEA/DHEAS levels have been implicated in neurodegenerative disorders and depression, with emerging evidence supporting their potential therapeutic value. In addition, DHEA plays a multifaceted role in aging-related physiological changes. It supports muscle anabolism, bone density maintenance, cardiovascular protection, and immune regulation. Though supplementation shows potential benefits, especially in conjunction with resistance training, results remain discrepant. Current evidence has revealed that the therapeutic effects of DHEA supplementation are inconsistent in different human systems among different studies. The diversity of results is mainly due to heterogeneous receptor distribution, various action pathways, and distinct tissue responses in different systems. Further research is needed to define its efficacy and dosage across various systems.
脱氢表雄酮（DHEA）及其硫酸酯形式硫酸脱氢表雄酮（DHEAS）是主要在肾上腺皮质产生的多功能甾体激素，在外周组织中也有额外合成。DHEA/DHEAS作为性甾体激素的前体，具有神经保护、抗炎和免疫调节作用。DHEA水平会随着年龄显著下降，这种现象被称为“肾上腺功能衰退”，这引发了人们对补充DHEA以减轻与年龄相关症状的兴趣。特别是在绝经后女性中，DHEA在治疗绝经后泌尿生殖综合征（GSM）方面已显示出潜在益处，包括改善阴道健康、润滑和性功能。虽然阴道内使用DHEA似乎比全身雌激素治疗更有效且更安全，尤其是对雌激素敏感的女性，但口服给药的结果仍不一致。DHEA和DHEAS通过调节GABA-A、NMDA和sigma-1受体表现出多种神经活性特性。这些神经甾体有助于神经保护、突触可塑性和情绪调节。DHEA/DHEAS水平的改变与神经退行性疾病和抑郁症有关，新出现的证据支持它们的潜在治疗价值。此外，DHEA在与衰老相关的生理变化中发挥多方面作用。它支持肌肉合成代谢、维持骨密度、保护心血管和调节免疫。尽管补充DHEA显示出潜在益处，特别是与抗阻训练相结合时，但结果仍存在差异。目前的证据表明，在不同研究中，DHEA补充剂在不同人体系统中的治疗效果并不一致。结果的多样性主要是由于不同系统中受体分布不均、作用途径各异以及组织反应不同。需要进一步研究来确定其在各种系统中的疗效和剂量。
