{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:25:31Z","timestamp":1787037931691,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"\n Background<\/jats:title>\n Spexin is a recently identified neuropeptide that modulates the hypothalamic\u2013pituitary\u2013gonadal axis and has been shown to regulate granulosa cell function. Although circulating spexin levels decline with age and metabolic dysregulation, its relationship with ovarian reserve has not been investigated. This study aimed to evaluate serum spexin concentrations in infertile women with diminished ovarian reserve (DOR) compared with those with normal ovarian reserve (NOR).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This prospective case\u2013control study enrolled 90 infertile women (45 DOR, 45 NOR) presenting to the Infertility Outpatient Clinic at a tertiary care centre between May and October 2024. DOR was defined as serum anti-M\u00fcllerian hormone (AMH)\u202f&lt;\u202f1.1\u202fng\/mL. Serum spexin was measured by ELISA on days 2\u20134 of the menstrual cycle. Group comparisons were performed using the independent samples\n t<\/jats:italic>\n -test or Mann\u2013Whitney\n U<\/jats:italic>\n test, as appropriate. Diagnostic performance was assessed by ROC curve analysis. Correlations were evaluated using Spearman\u2019s rank correlation coefficient.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Serum spexin levels were significantly lower in the DOR group than in the NOR group (\n p<\/jats:italic>\n \u202f=\u202f0.001). However, the DOR group was significantly older (\n p<\/jats:italic>\n \u202f&lt;\u202f0.001), and after adjustment for age, the between-group difference was no longer significant (ANCOVA,\n p<\/jats:italic>\n \u202f=\u202f0.292). Age-stratified analysis showed no significant difference in spexin within any age band. Spexin did not independently predict DOR in multivariable logistic regression (OR\u202f=\u202f1.00,\n p<\/jats:italic>\n \u202f=\u202f0.406). Positive correlations between spexin and AMH (rho\u202f=\u202f0.375,\n p<\/jats:italic>\n \u202f&lt;\u202f0.001) and antral follicle count (AFC) (rho\u202f=\u202f0.351,\n p<\/jats:italic>\n \u202f=\u202f0.001) in the overall population were attenuated and lost significance after age adjustment.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Serum spexin has not previously been evaluated in relation to ovarian reserve in women. Although spexin levels were lower in the DOR group, this difference was largely explained by age, and spexin did not independently predict DOR after age adjustment. These findings suggest that circulating spexin reflects age-related reproductive decline rather than serving as an independent marker of ovarian reserve. Age-matched studies are needed to clarify whether spexin has any DOR-specific role.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmed.2026.1917389","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:41:55Z","timestamp":1787035315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum spexin levels in women with diminished ovarian reserve: a prospective case\u2013control study"],"prefix":"10.3389","volume":"13","author":[{"given":"Rumeysa Nur","family":"Ozkan","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Niksar State Hospital","place":["Tokat, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Dag","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Eyupsultan State Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysegul","family":"Bestel","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Health Sciences University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1101\/gr.5755407","article-title":"Identification of novel peptide hormones in the human proteome by hidden Markov model screening","volume":"17","author":"Mirabeau","year":"2007","journal-title":"Genome Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1210\/en.2013-2106","article-title":"Coevolution of the spexin\/galanin\/kisspeptin family: spexin activates galanin receptor type II and 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Ilhan","year":"2018","journal-title":"Fertil Steril"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"235","DOI":"10.37723\/jumdc.v12i3.577","article-title":"Kisspeptin and spexin: lipid profile and sperm parameters in infertile and fertile male subjects","volume":"12","author":"Mohummad","year":"2021","journal-title":"J Univ Med Dent Coll"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1210\/js.2018-00020","article-title":"Circulating Spexin levels negatively correlate with age, BMI, fasting glucose, and triglycerides in healthy adult women","volume":"2","author":"Lin","year":"2018","journal-title":"J Endocr Soc"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"5107","DOI":"10.3390\/jcm11175107","article-title":"Circulating spexin is associated with body mass index and fat mass but not with physical activity and psychological parameters in women across a broad body weight 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(Baltimore)"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"10635","DOI":"10.1038\/s41598-020-67624-z","article-title":"Spexin as an indicator of beneficial effects of exercise in human obesity and diabetes","volume":"10","author":"Khadir","year":"2020","journal-title":"Sci Rep"}],"container-title":["Frontiers in 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