{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:09:32Z","timestamp":1790492972405,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"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. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To investigate the efficacy and underlying mechanisms of a combined therapy of estradiol\/dydrogesterone and escitalopram in treating perimenopausal anxiety and depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 195 patients were randomized to receive escitalopram, estradiol\/dydrogesterone, or combination therapy for 12 weeks. The primary efficacy endpoints were the changes in scores of the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) at week 12 compared with the baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the baseline, all groups reported a gradual decrease in Patient Health Questionnaire Somatic Symptom Scale (PHQ-15), the Patient Health Questionnaire Depression Scale (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), HAMD, and HAMA scores (P&amp;lt;0.001 for all), and a gradual increase in serum estradiol (E2) and 5-Hydroxytryptamine (5-HT) (P&amp;lt;0.001 for both), with the most pronounced changes in the Combined group (Comb group). In intergroup comparison, at weeks 4, 8, 12, the scores of PHQ-15, GAD-7, PHQ-9, HAMA, and HAMD were most reduced in the Comb group; At weeks 2, 4, 8, 12, E2 level was significantly higher in the Comb group and estradiol\/dydrogesterone group (E\/D group) than in the escitalopram group (ESC group); at weeks 4, 8, and 12, 5-HT level was significantly higher in the Comb group than in the E\/D group; and at week 4 and 12, 5-HT level was significantly higher in the Comb group than in the ESC group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Estradiol\/dydrogesterone plus escitalopram significantly improves anxiety, depression, and somatic symptoms in perimenopausal women. These findings provide clinical evidence of estradiol\/dydrogesterone plus escitalopram regimen for the treatment of patients with perimenopausal anxiety and depression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1728736","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T04:21:09Z","timestamp":1775103669000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of estradiol\/dydrogesterone combined with escitalopram in the treatment of anxiety and depression in perimenopausal women: a randomized controlled trial"],"prefix":"10.3389","volume":"17","author":[{"given":"Shufang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neurology, Fujian Medical University Union Hospital","place":["Fuzhou, China"]},{"name":"Fujian Key Laboratory of Molecular Neurology, Fujian Medical University","place":["Fuzhou, 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