Epigenetics of functional hypothalamic amenorrhea

Abstract

Functional hypothalamic amenorrhea (FHA) is a temporary infertility characterized by the suppression of the hypothalamic–pituitary–gonadal (HPG) axis, induced by the inhibition of the hypothalamic pulsatile secretion of the gonadotropin-releasing hormone (GnRH), in the presence of stressors, including eating disorders, excessive exercise, and psychological distress. Although the stressful factors that may lead to FHA are well-established, little is known about the inter-individual variability in response to stress and the consequent inhibition of the HPG axis. Not all women, indeed, manifest FHA in presence of stressful conditions. Recent studies highlighted a genetic contribution to FHA. Rare or polymorphic variants in genes that control the development and/or function of GnRH neurons may contribute, indeed, to the adaptability of the reproductive axis to stress factors. Also epigenetic changes have been associated with different pathways involved in the HPG axis and therefore, take part in FHA and confer a personal predisposition to anovulation consequent to a stressful event, or represent biological markers of response to stress. This review summarizes recent advances in the identification of the contribution of (epi)genetics to FHA and to long-term complications of functional amenorrhea, and reports insights into the involvement of additional genetic loci in FHA development on the bases of the clinical and molecular overlap with other gynecological and/or psychological conditions. Finally, we describe the promising application of induced pluripotent stem cells (iPSCs) as a new approach to investigate the molecular pathways involved in FHA.

Endocrine and psychosomatic disorders in patients with amenorrhea

“…И хотя стрессовые факторы, которые могут привести к ФГА, изучаются давно, на данный момент не представляется возможным прогнозировать индивидуальную реакцию на них, или не всегда одинаковые тяжелые события вызывают сходные патологические реакции, что свидетельствует о генетической предрасположенности к менструальным дисфункциям, а стресс играет возможную роль триггера [ 17 ].…”

Mapping the complexities of Relative Energy Deficiency in Sport (REDs): development of a physiological model by a subgroup of the International Olympic Committee (IOC) Consensus on REDs

“…Genetics/epigenetics Genetic factors that are unrelated to LEA may cause exacerbate several health outcomes identified as possible REDs outcomes, such as FHA 113 (reproductive system), low BMD 114 115 (bone health) and hyperlipidemia 116 (glucose and lipid metabolism).…”

Оксидативний Стрес – Обов'язковий Учасник Патогенезу Стрес-Індукованих Розладів Репродукції

“…Manifestations of reproductive disorders induced in women by prolonged and severe stress are extremely diverse: insufficiency of the luteal phase of the ovarian cycle, hypothalamic oligo-or amenorrhea, premenstrual dysphoric disorders, impaired ovum quality [14], impaired embryo implantation, early pregnancy loss, premature birth, endometriosis, early menopause [15][16][17].…”