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The effect of underweight on female and male reproduction

      Highlights

      • Syndromes Related to underweight status are often accompanied by infertility.
      • The main pathophysiological mechanism for infertility in such women is a hypothalamic-pituitary-gonadal axis dysfunction.
      • Restoration of weight in underweight women results in the restoration of menses and resolution of infertility.
      • The management requires multidisciplinary treatment, such as lifestyle modification, pharmacotherapy psychological counseling.

      Abstract

      Chronic energy deficiency can impair the hypothalamic-pituitary-gonadal (HPG) axis and lead to hypothalamic anovulation in underweight women. This review presents the syndromes related to underweight status that are associated with infertility, summarizes the underlying mechanisms, and reviews the available treatment options. Eating disorders, such as anorexia nervosa (AN), constitute the most common cause of infertility in underweight women, who, in addition, experience miscarriages, and sexual dysfunction. The relative energy deficiency in sports (RED-S; former terminology: athlete's triad) involves menstrual dysfunction due to low energy availability, which results in anovulation. Moreover, lipodystrophies, malnutrition, starvation, systematic illnesses (malignancies, endocrinopathies, infectious diseases, advanced chronic diseases, neurologic illnesses), and the utilization of drugs can cause excessive weight loss. They may result in fertility problems due to the loss of adipose tissue and the subsequent hormonal disturbances. Each of these conditions requires multidisciplinary management. Nutritional counseling should target the restoration of energy balance by increasing intake and reducing output. Medical treatment, recommended only for patients who did not respond to standard treatment, may include antipsychotics, antidepressants, or leptin administration. Finally, psychiatric treatment is considered an integral part of the standard treatment.

      Abbreviations:

      ACOG (American College of Obstetricians and Gynecologists), ACTH (adrenocorticotropic hormone), AFI (activins-follistatins-inhibins), AgRP (Agouti-related protein), AMH (anti-Müllerian hormone), AN (anorexia nervosa), ART (assisted reproductive technology), AVP (arginine vasopressin), α-MSH (alpha-melanocyte-stimulating hormone), BED (binge eating disorder), BIA (bioimpedance analysis), BMI (body mass index), BN (bulimia nervosa), BSCL2 (Berardinelli-Seip congenital lipodystrophy type 2), CBT (cognitive behavioral therapy), CI (confidence interval), CRH (corticotropin-releasing hormone), fMRI (functional magnetic resonance imaging), FSH (follicle stimulating hormone), FST (follistatin), FSTL3 (follistatin-like 3), GCG (glucagon), GH (growth hormone), GLP1R (glucagon-like peptide-1 receptor), GnRH (gonadotropin-releasing hormone), GWAS (genome-wide association studies), HA (hypothalamic amenorrhea), HIV (human immunodeficiency virus), HPG (hypothalamic-pituitary-gonadal), HPO (hypothalamic-pituitary-ovarian), IGF-1 (insulin-like growth factor-1), IL (interleukin), IPT (interpersonal psychotherapy), LH (luteinizing hormone), LCA (lateral hypothalamic area), LIF (leukemia inhibitory factor), MCH (melanin-concentrating hormone), NICE (National Institute of Clinical Excellence), NPY (neuropeptide Y), NTS (neurotensin), OFC (orbitofrontal cortex), OR (odds ratio), ORFP (pyroglutamylated arginine–phenylalanineamide peptide), PCOS (polycystic ovary syndrome), POMC (proopiomelanocortin), PFC (ventromedial prefrontal cortex), QoL (quality of life), RCTs (randomized clinical trials), RED-S (relative energy deficient syndrome), RR (relative risk), rT3 (reverse triiodothyronine), TGF-β (transforming growth factor beta), Th1 (type-1 helper), TNF (tumor necrosis factor), TSH (thyrotropin), UCN (urocortin), VTA (ventral tegmental area), WAT (white adipose tissue), WHO (World Health Organization)

      Keywords

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