{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T06:45:40Z","timestamp":1782456340544,"version":"3.54.5"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Psychological distress is common among women with unexplained infertility and may interact with neuroendocrine stress pathways. However, the relevance of single-time endocrine stress markers such as cortisol and dehydroepiandrosterone sulfate (DHEAS) in reflecting chronic emotional burden remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the association between psychological distress and single-time endocrine stress markers in women with unexplained infertility and to compare psychometric assessment with synchronized hormonal measurements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective case\u2013control study, consecutive women with primary unexplained infertility (n = 50) and age-matched fertile controls (n = 52) were enrolled from the same tertiary gynecology outpatient clinic. Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS). Clinically relevant psychological distress was defined as HADS-Anxiety \u22658 and\/or HADS-Depression \u22658. Serum cortisol and DHEAS concentrations were measured under standardized morning fasting conditions during the early follicular phase. Multivariable logistic regression analysis was performed using a parsimonious adjusted model including age, body mass index, smoking status, residential environment, cortisol level, and HADS-defined psychological distress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Women with unexplained infertility demonstrated significantly higher HADS-Anxiety and HADS-Depression scores compared with fertile controls (p &amp;lt; 0.05 for both comparisons). Based on predefined HADS subscale cut-off values (HADS-A \u22658 and\/or HADS-D \u22658), HADS-defined psychological distress was significantly more prevalent in the unexplained infertility group (76.0% vs. 42.3%, p = 0.001). Although follicle-stimulating hormone and estradiol levels differed significantly between groups, all measured values remained within physiological reference ranges. No statistically significant between-group differences were observed for cortisol, dehydroepiandrosterone sulfate (DHEAS), or anti-M\u00fcllerian hormone levels. In the final parsimonious multivariable logistic regression model adjusted for age, body mass index, smoking status, residential environment, cortisol level, and HADS-defined psychological distress, psychological distress remained independently associated with unexplained infertility (adjusted OR 3.907, 95% CI 1.610\u20139.478, p = 0.003). Exploratory ROC analyses demonstrated limited discriminatory performance of isolated single-time cortisol and DHEAS measurements for identifying HADS-defined psychological distress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Psychological distress was more prevalent among women with unexplained infertility, whereas single-time serum endocrine stress markers were not significantly different between groups. These findings support the relevance of psychological assessment in women with unexplained infertility; however, the cross-sectional case\u2013control design does not allow causal inference regarding the direction of this association.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1859428","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:45:49Z","timestamp":1782452749000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Psychological distress, but not single-time endocrine stress markers, is associated with unexplained infertility: a prospective case\u2013control study"],"prefix":"10.3389","volume":"17","author":[{"given":"Serta\u00e7","family":"Ay\u00e7i\u00e7ek","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Gazi Ya\u015fargil Training and Research Hospital","place":["Diyarbak\u0131r, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ber\u00e7em","family":"Ay\u00e7i\u00e7ek","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Istinye University Faculty of Medicine","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.socscimed.2010.08.006","article-title":"The experience of infertility: a review of recent literature","volume":"71","author":"Greil","year":"2010","journal-title":"Soc Sci Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/gco.0000000000000261","article-title":"The impact of stress on fertility","volume":"20","author":"Rooney","year":"2018","journal-title":"Dialogues Clin Neurosci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2015.03.019","article-title":"Diagnostic evaluation of the infertile female: a committee opinion","volume":"103","year":"2015","journal-title":"Fertil Steril"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/15.3.723","article-title":"Optimal use of infertility diagnostic tests and treatments. 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