AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025400426
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REVIEW ARTICLE

Rethinking obesity management through a sex-specific lens: A narrative review

Diogo Pinto da Costa Viana1,2,3†* ,  Thiago Bracks Oliveira3†
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1 Department of Gynecology, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil
2 Department of Gynecology, Brazilian Society for Research and Teaching in Medicine, Florianópolis, Santa Catarina, Brazil
3 Department of Gynecology, Brazilian Society of Obesity Medicine, Florianópolis, Santa Catarina, Brazil
†These authors contributed equally to this work.
EJMO, 025400426 https://doi.org/10.36922/EJMO025400426
Received: 2 October 2025 | Revised: 29 October 2025 | Accepted: 30 October 2025 | Published online: 16 December 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Obesity remains widely treated as a sex-neutral condition, despite decades of evidence revealing distinct sex-specific metabolic and behavioral trajectories between men and women. This neutrality perpetuates unequal outcomes: Men often achieve faster initial weight loss, whereas women face greater early resistance but display superior long-term resilience. The question persists: Why do men and women respond differently to the same intervention? The answer lies not in a single mechanism, but in the complex interplay among body composition, hormonal and neuroendocrine regulation, adaptive thermogenesis, and sociocultural determinants. To address this gap, this review proposes an integrative four-axis model encompassing: (i) Body composition and fat distribution, (ii) hormonal and neuroendocrine control, (iii) energy efficiency and adaptive thermogenesis, and (iv) sociocultural determinants. Drawing on literature from the past 25 years, it synthesizes physiological and behavioral evidence to explain how biological sex and menopausal status influence weight-loss responses. The narrative approach bridges clinical and experimental findings to offer a conceptual framework capable of guiding personalized strategies in obesity care. By integrating metabolic, hormonal, and psychosocial domains, the proposed model underscores that obesity cannot be reduced to a mere caloric equation. Recognizing sex-based dimorphism is essential for improving equity, sustainability, and precision in treatment outcomes. This framework invites a paradigm shift, from calorie-centered to complexity-informed medicine, where management is tailored to the distinct physiological and social realities of men and women.

Keywords
Obesity
Obesity management
Women
Men
Body composition
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
References
  1. Wahrenberg H, Lönnqvist F, Arner P. Mechanisms underlying regional differences in lipolysis in human adipose tissue. J Clin Invest. 1989;84:458-467. doi: 10.1172/JCI114187

 

  1. Lovejoy JC. The menopause and obesity. Prim Care. 2003;30:317-325. doi: 10.1016/s0095-4543(03)00012-5

 

  1. Jensen MD. Role of body fat distribution and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008;93:S57-S63. doi: 10.1210/jc.2008-1585

 

  1. Williams RL, Wood LG, Collins CE, Callister R. Effectiveness of weight loss interventions--is there a difference between men and women: A systematic review. Obesity Rev. 2015;16:171-186. doi: 10.1111/obr.12241

 

  1. Pearl RL, Wadden TA, Jakicic JM. Is weight stigma associated with physical activity? A systematic review. Obesity (Silver Spring). 2021;29:1994-2012. doi: 10.1002/oby.23274

 

  1. Ambikairajah A, Walsh E, Tabatabaei-Jafari H, Cherbuin N. Fat mass changes during menopause: A meta-analysis. Am J Obstet Gynecol. 2019;221:393-409.e50. doi: 10.1016/j.ajog.2019.04.023

 

  1. Hopkins M, Gibbons C, Blundell J. Fat-free mass and resting metabolic rate are determinants of energy intake: Implications for a theory of appetite control. Phil Trans R Soc B Biol Sci. 2023;378:20220213. doi: 10.1098/rstb.2022.0213

 

  1. Wallach JD, Sullivan PG, Trepanowski JF, Steyerberg EW, Ioannidis JPA. Sex based subgroup differences in randomized controlled trials: Empirical evidence from Cochrane meta-analyses. BMJ. 2016;355:i5826. doi: 10.1136/bmj.i5826

 

  1. Daitch V, Turjeman A, Poran I, et al. Underrepresentation of women in randomized controlled trials: A systematic review and meta-analysis. Trials. 2022;23:1038. doi: 10.1186/s13063-022-07004-2

 

  1. Wang Z, Heshka S, Gallagher D, Boozer CN, Kotler DP, Heymsfield SB. Resting energy expenditure-fat-free mass relationship: New insights provided by body composition modeling. Am J Physiol Endocrinol Metab. 2000;279:E539-E545. doi: 10.1152/ajpendo.2000.279.3.E539

 

  1. Cano A, Ventura L, Martinez G, et al. Analysis of sex-based differences in energy substrate utilization during moderate-intensity aerobic exercise. Eur J Appl Physiol. 2022;122:29-70. doi: 10.1007/s00421-022-04961-z

 

  1. Tarnopolsky MA. Sex differences in exercise metabolism and the role of 17-beta estradiol. Med Sci Sports Exerc. 2008;40:648-654. doi: 10.1249/MSS.0b013e31816212ff

 

  1. Martínez De Morentin PB, González-García I, Martins L, et al. Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metab. 2014;20:41-53. doi: 10.1016/j.cmet.2014.03.031

 

  1. Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes (Lond). 2010;34:S47-S55. doi: 10.1038/ijo.2010.184

 

  1. Doucet E, St-Pierre S, Alméras N, Després JP, Bouchard C, Tremblay A. Evidence for the existence of adaptive thermogenesis during weight loss. Br J Nutr. 2001;85:715-723. doi: 10.1079/bjn2001348

 

  1. Carpentier AC, Blondin DP, Haman F, Richard D. Brown adipose tissue-a translational perspective. Endocr Rev. 2023;44:143-192. doi: 10.1210/endrev/bnac027

 

  1. Xu Y, Nedungadi TP, Zhu L, et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab. 2011;14:453-465. doi: 10.1016/j.cmet.2019.04.006. Erratum for: Cell Metab. 2011;14(4):453-465. doi: 10.1016/j.cmet.2011.08.009

 

  1. Papadakis GE, Hans D, Rodriguez EG, et al. Menopausal hormone therapy is associated with reduced total and visceral adiposity: The osteolaus cohort. J Clin Endocrinol Metab. 2018;103:1948-1957. doi: 10.1210/jc.2017-02449

 

  1. Allan CA, Strauss BJG, Burger HG, Forbes EA, McLachlan RI. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. J Clin Endocrinol Metab. 2008;93:139-146. doi: 10.1210/jc.2007-1291

 

  1. Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003;144:5081-5088. doi: 10.1210/en.2003-0741

 

  1. Frederiksen L, Højlund K, Hougaard DM, Brixen K, Andersen M. Testosterone therapy increased muscle mass and lipid oxidation in aging men. AGE (Dordr). 2012;34:145-156. doi: 10.1007/s11357-011-9213-9

 

  1. Bianchi VE. The anti-inflammatory effects of testosterone. J Endocr Soc. 2019;3:91-107. doi: 10.1210/js.2018-00186

 

  1. Liu X, Chan HC, Ding G, et al. FSH regulates fat accumulation and redistribution in aging through the Gαi/ Ca(2+)/CREB pathway. Aging Cell. 2015;14:409-420. doi: 10.1111/acel.12331

 

  1. Sponton CH, Kajimura S. Burning fat and building bone by FSH blockade. Cell Metab. 2017;26:285-287. doi: 10.1016/j.cmet.2017.07.018

 

  1. Mauvais-Jarvis F, Manson JE, Stevenson JC, Fonseca VA. Menopausal hormone therapy and type 2 diabetes prevention: Evidence, mechanisms, and clinical implications. Endocr Rev. 2017;38:173-188. doi: 10.1210/er.2016-1146

 

  1. Owen BM, Ding X, Morgan DA, et al. FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab. 2014;20:670-677. doi: 10.1016/j.cmet.2014.07.012

 

  1. Kelesidis T, Kelesidis I, Chou S, Mantzoros CS. Narrative review: The role of leptin in human physiology: Emerging clinical applications. Ann Intern Med. 2010;152:93-100. doi: 10.7326/0003-4819-152-2-201001190-00008

 

  1. González-García I, García-Clavé E, Cebrian-Serrano A, et al. Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1. Cell Metab. 2023;35:438-455.e7. doi: 10.1016/j.cmet.2023.02.004

 

  1. Hirschberg AL. Sex hormones, appetite and eating behaviour in women. Maturitas. 2012;71:248-256. doi: 10.1016/j.maturitas.2011.12.016

 

  1. Salem AM. Variation of leptin during menstrual cycle and its relation to the hypothalamic-pituitary-gonadal (HPG) axis: A systematic review. Int J Womens Health. 2021;13:445-458. doi: 10.2147/IJWH.S309299

 

  1. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346:1623-1630. doi: 10.1056/NEJMoa012908

 

  1. Smith A, Woodside B, Abizaid A. Ghrelin and the control of energy balance in females. Front Endocrinol (Lausanne). 2022;13:904754. doi: 10.3389/fendo.2022.904754

 

  1. Levine JA. Nonexercise activity thermogenesis (NEAT): Environment and biology. Am J Physiol Endocrinol Metab. 2004;286:E675-E685. doi: 10.1152/ajpendo.00562.2003

 

  1. Rosenbaum M, Goldsmith R, Bloomfield D, et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest. 2005;115:3579-3586. doi: 10.1172/JCI25977

 

  1. De Andrade PBM, Neff LA, Strosova MK, et al. Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding. Front Physiol. 2015;6:254. doi: 10.3389/fphys.2015.00254

 

  1. Hall KD. Metabolic adaptations to weight loss. Obesity (Silver Spring). 2018;26:790-791. doi: 10.1002/oby.22189

 

  1. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365:1597-1604. doi: 10.1056/NEJMoa1105816

 

  1. Short KR, Bigelow ML, Kahl J, et al. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci USA. 2005;102:5618-5623. doi: 10.1073/pnas.0501559102

 

  1. Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: A new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14:576-590. doi: 10.1038/s41574-018-0059-4

 

  1. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR, Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86:724-731. doi: 10.1210/jcem.86.2.7219

 

  1. Greendale GA, Sternfeld B, Huang M, et al. Changes in body composition and weight during the menopause transition. JCI Insight. 2019;4:e124865. doi: 10.1172/jci.insight.124865

 

  1. Lovejoy JC, Champagne CM, De Jonge L, Xie H, Smith SR. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond). 2008;32:949-958. doi: 10.1038/ijo.2008.25

 

  1. Abildgaard J, Pedersen AT, Green CJ, et al. Menopause is associated with decreased whole body fat oxidation during exercise. Am J Physiol Endocrinol Metab. 2013;304:E1227-E1236. doi: 10.1152/ajpendo.00492.2012

 

  1. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16-31. doi: 10.1093/ageing/afy169

 

  1. De Paoli M, Zakharia A, Werstuck GH. The role of estrogen in insulin resistance: A review of clinical and preclinical data. Am J Pathol. 2021;191:1490-1498. doi: 10.1016/j.ajpath.2021.05.011

 

  1. Heid IM, Jackson AU, Randall JC, et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet. 2010;42:949-960. doi: 10.1038/ng.685

 

  1. Acosta A, Camilleri M, Shin A, et al. Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults. Genes Nutr. 2014;9:384. doi: 10.1007/s12263-014-0384-8

 

  1. Álvarez-Martín C, Caballero FF, De La Iglesia R, Alonso-Aperte E. Association of MC4R rs17782313 genotype with energy intake and appetite: A systematic review and meta-analysis. Nutr Rev. 2025;83:e931-e946. doi: 10.1093/nutrit/nuae075

 

  1. Bjune JI, Strømland PP, Jersin RÅ, Mellgren G, Dankel SN. Metabolic and epigenetic regulation by estrogen in adipocytes. Front Endocrinol (Lausanne). 2022;13:828780. doi: 10.3389/fendo.2022.828780

 

  1. Lumish HS, O’Reilly M, Reilly MP. Sex differences in genomic drivers of adipose distribution and related cardiometabolic disorders: Opportunities for precision medicine. Arterioscler Thromb Vasc Biol. 2020;40:45-60. doi: 10.1161/ATVBAHA.119.313154

 

  1. El Hajj N, Schneider E, Lehnen H, Haaf T. Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment. Reproduction. 2014;148:R111-R120. doi: 10.1530/REP-14-0334

 

  1. Deodati A, Inzaghi E, Cianfarani S. Epigenetics and in utero acquired predisposition to metabolic disease. Front Genet. 2020;10:1270. doi: 10.3389/fgene.2019.01270

 

  1. OECD. Caregiving in crisis: Gender inequality in paid and unpaid work during COVID-19. In: OECD Policy Responses to Coronavirus (COVID-19). Paris: OECD Publishing; 2021. doi: 10.1787/3555d164-en

 

  1. Moroshko I, Brennan L, O’Brien P. Predictors of dropout in weight loss interventions: A systematic review of the literature. Obes Rev. 2011;12:912-934. doi: 10.1111/j.1467-789X.2011.00915.x

 

  1. Keski-Rahkonen A, Mustelin L. Epidemiology of eating disorders in Europe: Prevalence, incidence, comorbidity, course, consequences, and risk factors. Curr Opin Psychiatry. 2016;29:340-345. doi: 10.1097/YCO.0000000000000278

 

  1. Karastergiou K, Smith SR, Greenberg AS, Fried SK. Sex differences in human adipose tissues - the biology of pear shape. Biol Sex Differ. 2012;3:13. doi: 10.1186/2042-6410-3-13

 

  1. Lopez P, Taaffe DR, Galvão DA, et al. Resistance training effectiveness on body composition and body weight outcomes in individuals with overweight and obesity across the lifespan: A systematic review and meta‐analysis. Obes Rev. 2022;23:e13428. doi: 10.1111/obr.13428

 

  1. Morton RW, Murphy KT, McKellar SR, et al. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018;52:376-384. doi: 10.1136/bjsports-2017-097608corr1

 

  1. Chew HSJ, Chng S, Rajasegaran NN, Choy KH, Chong YY. Effectiveness of acceptance and commitment therapy on weight, eating behaviours and psychological outcomes: A systematic review and meta-analysis. Eat Weight Disord. 2023;28:6. doi: 10.1007/s40519-023-01535-6

 

  1. Abbott S, Smith E, Tighe B, Lycett D. Group versus one‐to‐one multi‐component lifestyle interventions for weight management: A systematic review and meta‐analysis of randomised controlled trials. J Hum Nutr Diet. 2021;34:485-493. doi: 10.1111/jhn.12853

 

  1. Tate DF, Lutes LD, Bryant M, et al. Efficacy of a commercial weight management program compared with a do-it-yourself approach: A randomized clinical trial. JAMA Netw Open. 2022;5:e2226561. doi: 10.1001/jamanetworkopen.2022.26561

 

  1. Pujia C, Ferro Y, Mazza E, Maurotti S, Montalcini T, Pujia A. The role of mobile apps in obesity management: Systematic review and meta-analysis. J Med Internet Res. 2025;27:e66887. doi: 10.2196/66887

 

  1. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989-1002. doi: 10.1056/NEJMoa2032183

 

  1. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-216. doi: 10.1056/NEJMoa2206038

 

  1. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221-2232. doi: 10.1056/NEJMoa2307563
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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