Sexual dimorphism or sex bias in diseases and mental disorders have two biological causes: sexual selection and sex hormones. We review the role of sexual selection theory and bring together decades of molecular studies on the variation and evolution of sex-biased genes and provide a theoretical basis for the causes of sex bias in disease and health. We present a Sexual Selection-Sex Hormone theory and show that male-driven evolution, including sexual selection, leads to: (1) increased male vulnerability due to negative pleiotropic effects associated with male-driven sexual selection and evolution; (2) increased rates of male-driven mutations and epimutations in response to early fitness gains and at the cost of late fitness; and (3) enhanced female immunity due to antagonistic responses to mutations that are beneficial to males but harmful to females, reducing female vulnerability to diseases and increasing the thresholds for disorders such as autism. Female-driven evolution, such as reproduction-related fluctuation in female sex hormones in association with stress and social condition, has been shown to be associated with increased risk of certain mental disorders such as major depression disorder in women. Bodies have history, cells have memories. An evolutionary framework, such as the Sexual Selection–Sex Hormone theory, provides a historical perspective for understanding how the differences in the sex-biased diseases and mental disorders have evolved over time. It has the potential to direct the development of novel preventive and treatment strategies.

疾病和精神障碍中的性二态性或性别偏见有两个生物学原因：性选择和性激素。我们回顾了性选择理论的作用，并汇集了数十年关于性别偏见基因变异和进化的分子研究，为疾病和健康中性别偏见的成因提供了理论基础。我们提出了一种性选择——性激素理论并表明，男性驱动的进化，包括性选择，导致：（1）由于与男性驱动的性选择和进化相关的负面多效效应，增加了男性的脆弱性；(2) 男性驱动的突变和表观突变的发生率增加，以响应早期适应度的提高和晚期适应度的代价；(3) 由于对有益于男性但对女性有害的突变的拮抗反应，增强了女性的免疫力，降低了女性对疾病的脆弱性，并增加了自闭症等疾病的阈值。女性驱动的进化，例如与压力和社会状况相关的与生殖相关的女性性激素波动，已被证明与某些精神障碍（如女性重度抑郁症）的风险增加有关。身体有历史，细胞有记忆。一个进化框架，例如性选择——性激素理论，为理解性别偏见疾病和精神障碍的差异如何随着时间的推移而演变提供了一个历史视角。它具有指导开发新型预防和治疗策略的潜力。