{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T22:28:33Z","timestamp":1780093713425,"version":"3.54.0"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The perception that hormonal contraception causes weight gain is a general belief that frequently hinders the initiation and continuation of effective family planning. This narrative review analyses data from Cochrane systematic reviews and recent pharmacogenomic studies to separate patient perception from metabolic reality. Analysis of high-quality data, including Cochrane systematic reviews, indicates that the association between Combined Hormonal Contraceptives (CHCs)\u2014including oral pills, the transdermal patch, and the vaginal ring\u2014and weight gain is not supported by consistent high-quality evidence. Placebo-controlled trials demonstrate that these methods are weight-neutral on average. Perceived weight increases in CHC users are likely mediated in part by fluid retention linked to the estrogenic stimulation of the Renin\u2013Angiotensin\u2013Aldosterone System (RAAS), rather than adipose tissue accumulation. Conversely, Depot Medroxyprogesterone Acetate (DMPA) represents a verified clinical risk for weight gain, showing a demonstrated clinical association with significant fat mass accumulation. Hypothesized biological mechanisms for this increase include hypothalamic appetite stimulation and glucocorticoid-like activity. The etonogestrel implant occupies a complex middle ground. While population-level data suggests weight neutrality, recent exploratory pharmacogenomic research has identified a specific variant in the Estrogen Receptor 1 (ESR1) gene. For the minority of women carrying this variant, the implant may trigger clinically significant weight gain, suggesting a biological basis for their subjective experience despite statistical evidence. Ultimately, the persistence of the weight gain concern is fueled by the nocebo effect and the misattribution of natural age-related weight trajectories to contraceptive use.<\/jats:p>","DOI":"10.3390\/life16040553","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:33:33Z","timestamp":1774622013000},"page":"553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Contraceptive-Induced Weight Gain\u2014Myth and Reality Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6524-145X","authenticated-orcid":false,"given":"Tudor","family":"Butureanu","sequence":"first","affiliation":[{"name":"Grigore T Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Mother and Child, \u201cElena Doamna\u201d University Hospital of Obstetrics and Gynecology, 700398 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Apetrei","sequence":"additional","affiliation":[{"name":"Grigore T Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Mother and Child, \u201cElena Doamna\u201d University Hospital of Obstetrics and Gynecology, 700398 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-8991","authenticated-orcid":false,"given":"Raluca Anca","family":"Balan","sequence":"additional","affiliation":[{"name":"Grigore T Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Pathology Department, \u201cElena Doamna\u201d University Hospital of Obstetrics and Gynecology, 700398 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Haliciu","sequence":"additional","affiliation":[{"name":"Grigore T Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Mother and Child, \u201cElena Doamna\u201d University Hospital of Obstetrics and Gynecology, 700398 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2769-9483","authenticated-orcid":false,"given":"Ioana","family":"Pavaleanu","sequence":"additional","affiliation":[{"name":"Grigore T Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Mother and Child, \u201cElena Doamna\u201d University Hospital of Obstetrics and Gynecology, 700398 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0979-0200","authenticated-orcid":false,"given":"Demetra","family":"Socolov","sequence":"additional","affiliation":[{"name":"Grigore T Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Mother and Child, \u201cCuza Vod\u0103\u201d University Hospital of Obstetrics and Gynecology, 700036 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8969-8016","authenticated-orcid":false,"given":"Razvan","family":"Socolov","sequence":"additional","affiliation":[{"name":"Grigore T Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Mother and Child, \u201cElena Doamna\u201d University Hospital of Obstetrics and Gynecology, 700398 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","first-page":"CD003987","article-title":"Combination contraceptives: Effects on weight","volume":"2014","author":"Gallo","year":"2014","journal-title":"Cochrane Database Syst. 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Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.contraception.2010.06.010","article-title":"Nonspecific side effects of oral contraceptives: Nocebo or noise?","volume":"83","author":"Grimes","year":"2011","journal-title":"Contraception"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7652408","DOI":"10.1155\/2022\/7652408","article-title":"10-Year Weight Gain in 13,802 US Adults: The Role of Age, Sex, and Race","volume":"2022","author":"Tucker","year":"2022","journal-title":"J. Obes."},{"key":"ref_6","unstructured":"(2026, January 12). Renin-Angiotensin-Aldosterone System (RAAS)\u2014Cleveland Clinic. 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