{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:01:44Z","timestamp":1785301304737,"version":"3.55.0"},"reference-count":222,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Obesity is a multifactorial condition that profoundly affects female reproductive health through endocrine, metabolic, and inflammatory mechanisms that disrupt the hypothalamic\u2013pituitary\u2013gonadal (HPG) axis. Women with obesity frequently develop menstrual irregularities, anovulation, amenorrhea, infertility, polycystic ovary syndrome (PCOS), impaired endometrial receptivity, and adverse pregnancy outcomes. Central obesity and insulin resistance contribute to hyperinsulinemia, reduced sex hormone-binding globulin (SHBG) levels, hyperandrogenism, altered gonadotropin secretion, and impaired folliculogenesis, while adipokines such as leptin and chronic inflammation further impair ovarian steroidogenesis and ovulatory function. Obesity-related oxidative stress and lipotoxicity also negatively affect oocyte quality, embryo development, implantation, and assisted reproductive technology outcomes, increasing the risk of gestational diabetes, preeclampsia, miscarriage, and preterm birth. This review evaluates the therapeutic potential of pharmacological weight-loss therapies in obesity-associated female reproductive dysfunction. A comprehensive literature review was conducted using various databases, focusing on anti-obesity pharmacotherapy on obesity, infertility and fertility in reproductive-aged women. Evidence suggests that several FDA-approved and off-label anti-obesity agents, including orlistat, liraglutide, semaglutide, phentermine\/topiramate, bupropion\/naltrexone, metformin, exenatide, and tirzepatide, may improve reproductive outcomes primarily indirectly through weight reduction and metabolic improvement. GLP-1 receptor agonists, particularly liraglutide, semaglutide, and exenatide, appear especially promising, demonstrating beneficial effects on insulin sensitivity, menstrual regularity, ovulation, androgen levels, and pregnancy rates in women with PCOS. Tirzepatide, a dual GLP-1\/GIP receptor agonist, has shown potent weight-loss and metabolic effects with potential indirect fertility benefits. Metformin improves insulin sensitivity and is widely used in PCOS to regulate androgen levels and restore ovulation, although its effects on pregnancy and live birth rates remain controversial. However, evidence for several agents remains limited, and concerns persist regarding reproductive safety during pregnancy. Overall, anti-obesity pharmacotherapy may represent an important adjunctive strategy for improving reproductive and metabolic health in women with obesity, although larger randomized clinical trials are still required.<\/jats:p>","DOI":"10.3390\/medicina62081445","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:26:23Z","timestamp":1785115583000},"page":"1445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Potential of Anti-Obesity Drugs in Obesity-Associated Female Reproductive Dysfunction: Translating Mechanistic Evidence into Personalized Clinical Strategies"],"prefix":"10.3390","volume":"62","author":[{"given":"Fani-Niki","family":"Varra","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, Cyprus"},{"name":"Medical School, Democritus University of Thrace, 6810 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Theodosis-Nobelos","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria-Konstantina","family":"Varra","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, 26504 Patra, Greece"},{"name":"Division of Aesthetics and Cosmetic Science, Department of Biomedical Sciences, School of Health and Welfare Sciences, University of West Attica, Aigaleo, 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Varras","sequence":"additional","affiliation":[{"name":"Fourth Department of Obstetrics and Gynecology, \u2018Elena Venizelou\u2019 General and Maternity Hospital, Plateia Elenas Venizelou 2, Ampelokipoi, 11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3892\/mmr.2024.13219","article-title":"Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation-mediating treatment options (Review)","volume":"29","author":"Varra","year":"2024","journal-title":"Mol. 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