Polycystic ovary syndrome (PCOS) is an endocrine condition associated with reproductive and psychiatric disorders, and with obesity. Eating disorders, such as bulimia and recurrent dieting, are also linked to PCOS. They can lead to the epigenetic dysregulation of the hypothalamic–pituitary–gonadal (HPG) axis, thereby impacting on ovarian folliculogenesis. We postulate that PCOS is induced by psychological distress and episodes of overeating and/or dieting during puberty and adolescence, when body dissatisfaction and emotional distress are often present. We propose that upregulated activation of the central HPG axis during this period can be epigenetically altered by psychological stressors and by bulimia/recurrent dieting, which are common during adolescence and which can lead to PCOS. This hypothesis is based on events that occur during a largely neglected stage of female reproductive development. To date, most research into the origins of PCOS has focused on the prenatal induction of this disorder, particularly in utero androgenization and the role of anti-Müllerian hormone. Establishing causality in our peripubertal model requires prospective cohort studies from infancy. Mechanistic studies should consider the role of the gut microbiota in addition to the epigenetic regulation of (neuro) hormones. Finally, clinicians should consider the importance of underlying chronic psychological distress and eating disorders in PCOS.
Bibliographical noteFunding Information:
Funding: This work was funded by the Department of Obstetrics and Gynaecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands, and no external funding was either sought or obtained for this study. P.W.J. received support from ZonMW (Mental Health Care Research Program, Fellowship 636320005). K.D.S. was in receipt of funding from the Biotechnology and Biological Sciences Research Council, UK (BB/R007985/1) and the National Institute of Environmental Health Sciences, USA (1R01ES030374-01A1).
Conflicts of Interest: J.S.E.L. has received fees or grant support in the most recent 5-year period from the following organizations (in alphabetical order): AnshLabs, Webster, TX, USA, the Dutch Heart Foundation, Utrecht NL, Dutch Medical Research Council (ZonMW), Amsterdam, NL, Astellas, Tokyo, Japan, Ferring, Hoofddorp, NL, Roche Diagnostics, Hochkreutz, Switzerland, and Titus Healthcare, Hoofddorp, NL. He also has received personal fees from AnshLabs, Webster, TX, USA, Ferring, Hoofddorp, NL and Titus Health Care, Hoofddorp, NL. The other authors declare no conflicts of interest.
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