Out of step societal and Darwinian adaptation during evolution is the cause of multiple women’s health issues

Abstract

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’s 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.

Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

“…The author first discusses why and how repeated menstruation causes impaired decidualization. More frequent reports of menstruation-related disorders, such as dysmenorrhea, hypermenorrhea, anemia, or migraine headaches, are observed in patients with incessant menstruation than in controls [ 16 , 116 , 117 ]. Furthermore, regular, cyclical menstruation ovulation and excess estrogen exposure increase endometriosis risks, possibly through inflammation, hypoxia, and oxidative stress [ 116 , 117 ].…”

Pathophysiological Effects of Contemporary Lifestyle on Evolutionary-Conserved Survival Mechanisms that Disturb the Hallmarks of Health in Polycystic Ovary Syndrome

“…These recommendations are based on evidence that lifestyle therapies, such as diet and exercise, can control and reverse many of the biochemical and endocrine features of PCOS (2,3). It has been hypothesized that contemporary lifestyle and environmental exposures are instrumental in the pathogenesis of PCOS due to a mismatch between our ancient and modern lifestyle and environment (1,(4)(5)(6).…”

“…Contemporary lifestyle exposures are significantly different to the environmental conditions that existed throughout most of human evolution. Namely, starvation, predation, fear, increased maternal mortality and exposure to different climatic conditions (4,27,49). The reduction of chronic disease following lifestyle interventions such as diet, exercise and smoking cessation, has provided strong evidence for contemporary lifestyle as the primary "cause" of many diseases, including PCOS (50).…”

“…Optimal health and well-being is achieved when metabolic, cellular and wholebody homeostasis is synchronized with the prevailing environmental conditions (42). Multiple adaptive survival mechanisms (immune, metabolic, neurological, hormonal) have evolved to ensure re-establishment of homeostasis during periods of environmental and personal stress, and work synergistically to maintain health (4,5,27,53,54). Epigenetic modifications provide a mechanism for organisms to rapidly respond to changing environmental conditions to ensure survival and restore homeostasis (52).…”

“…Epigenetic modifications provide a mechanism for organisms to rapidly respond to changing environmental conditions to ensure survival and restore homeostasis (52). Rapid social evolution has created a contemporary lifestyle and environment that is out of step with our evolutionary past (1,4). Chronic disturbance to adaptive cellular signaling systems disrupts the epigenetic machinery and other regulatory processes, resulting in maladaptive metabolic, immune and physiological responses, that manifest as complex chronic diseases such as obesity, T2DM and PCOS (figure 1) (55,56).…”