{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T23:01:26Z","timestamp":1781478086463,"version":"3.54.1"},"reference-count":102,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Shanghai science and Technology innovation action Plan Program","award":["18411953800"],"award-info":[{"award-number":["18411953800"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During human evolution, major changes in our societal conditions and environment took place without sufficient time for concomitant genetic alterations, leading to out of step adaptation and diseases in women. We first discuss recent societal adaptation mismatch (menstrual bleeding; increases in cancers of reproductive organs, endometriosis; mother\u2019s nursing; polycystic ovarian syndrome; transgenerational epigenetic modifications), followed by Darwinian out of step adaptation (labor difficulties; sex chromosomes, human diseases and sex disparity in genomic DNA). We discuss the evolutionary basis of menstrual bleeding, followed by recent increases in cancers of reproductive organs and endometriosis. The importance of breastfeeding by mothers is also emphasized. Earlier onset of menarche, decreased rates of childbirths and breastfeeding resulted in increased number of menstrual cycles in a lifetime, coupled with excess estrogen exposure and incessant ovulation, conditions that increased the susceptibility to mammary and uterine cancers as well as ovarian epithelial cancer and endometriosis. Shorter lactation duration in mothers also contributed to more menstrual cycles. We further discuss the evolutionary basis of the prevalent polycystic ovary syndrome. During the long-term Darwinian evolution, difficulties in childbirth evolved due to a narrowed pelvis, our upright walking and enlarged fetal brain sizes. Because there are 1.5% genomic DNA differences between woman and man, it is of significance to investigate sex-specific human physiology and diseases. In conclusion, understanding out of step adaptation during evolution could allow the prevention and better management of female reproductive dysfunction and diseases.<\/jats:p>","DOI":"10.1093\/humrep\/deac156","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T17:00:47Z","timestamp":1658854847000},"page":"1959-1969","source":"Crossref","is-referenced-by-count":14,"title":["Out of step societal and Darwinian adaptation during evolution is the cause of multiple women\u2019s health issues"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3500-2124","authenticated-orcid":false,"given":"Zhenle","family":"Pei","sequence":"first","affiliation":[{"name":"Department of Genetics, Shanghai Ji Ai Genetics & IVF Institute, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital of Fudan University , Shanghai, China"},{"name":"Department of Integrative Medicine and Neurobiology, Institute of Integrative Medicine of Fudan University, Institute of Brain Science, School of Basic Medical Sciences, Fudan University , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, Institute of Integrative Medicine of Fudan University, Institute of Brain Science, School of Basic Medical Sciences, Fudan University , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, Institute of Integrative Medicine of Fudan University, Institute of Brain Science, School of Basic Medical Sciences, Fudan University , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-281X","authenticated-orcid":false,"given":"Congjian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Genetics, Shanghai Ji Ai Genetics & IVF Institute, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital of Fudan University , Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6971-1383","authenticated-orcid":false,"given":"Aaron J W","family":"Hsueh","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, Institute of Integrative Medicine of Fudan University, Institute of Brain Science, School of Basic Medical Sciences, Fudan University , Shanghai, China"},{"name":"Division of Reproductive and Stem Cell Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine , 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