{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:08:34Z","timestamp":1788847714013,"version":"build-2803163510"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Canadian Menopause Society"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"Abstract<\/jats:title>\n \n STUDY QUESTION<\/jats:title>\n What is the incidence of premature ovarian insufficiency (POI) and its associated factors in Ontario, Canada, between 1995 and 2019?<\/jats:p>\n <\/jats:sec>\n \n SUMMARY ANSWER<\/jats:title>\n The incidence of POI increased after 2011, driven primarily by non-iatrogenic POI, and was highest among women with a history of endometriosis.<\/jats:p>\n <\/jats:sec>\n \n WHAT IS KNOWN ALREADY<\/jats:title>\n Recent estimates suggest a global POI prevalence of \u223c3.7%, with increasing rates over time. POI has heterogeneous etiologies, including genetic, autoimmune, infectious, and iatrogenic causes; however, the cause remains unknown in \u223c70% of non-iatrogenic cases. Existing incidence estimates are limited by recall bias, cross-sectional designs, small sample sizes, and limited assessment of associated factors.<\/jats:p>\n <\/jats:sec>\n \n STUDY DESIGN, SIZE, DURATION<\/jats:title>\n This population-based cohort study included all women aged \u2264 39\u2009years residing in Ontario between 1995 and 2019. Follow-up continued until POI diagnosis, age 40\u2009years, death, loss of provincial health insurance, or end of the study period.<\/jats:p>\n <\/jats:sec>\n \n PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n POI was defined using administrative health data as a diagnosis occurring before age 40\u00a0years identified by either (i) surgical menopause or (ii) \u22651 physician consultation coded as menopause (ICD-9 627). Annual incidence rates (IRs) were calculated using census data, with the Ontario female population aged \u2264 39\u2009years as the denominator. POI was classified as non-iatrogenic, surgical, post-chemotherapy and\/or radiotherapy, or combined surgical with chemotherapy and\/or radiotherapy. Associations between clinical factors and POI were estimated using age-adjusted modified Poisson regression to derive incidence rate ratios (IRRs).<\/jats:p>\n <\/jats:sec>\n \n MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n Among 3\u00a0635\u00a0702 eligible women, 168\u00a0173 developed POI from any etiology (IR 389.4 per 100\u00a0000 person-years). Median follow-up was 11\u2009years (IQR 6\u201318), and median age at POI diagnosis was 31\u2009years (IQR 25\u201336). IRs were 351.4 per 100\u00a0000 person-years for non-iatrogenic POI, 30.2 for surgical POI, 5.5 for post-chemotherapy and\/or radiotherapy POI, and 2.3 for combined surgical with chemotherapy and\/or radiotherapy POI. Overall POI incidence declined between 2002 and 2008, followed by a sustained increase through 2019, largely attributable to non-iatrogenic POI. The incidence of surgically induced POI decreased from 60 per 100\u00a0000 person-years in 1995 to 20 in 2019, while combined surgical with chemotherapy and\/or radiotherapy POI increased steadily over the study period. Factors associated with higher POI incidence included endometriosis (IRR 3.45, 95% CI 3.39, 3.52), cancer treated with chemotherapy or radiotherapy (IRR 2.01, 95% CI 1.89, 2.14), drug or tobacco use (IRR 1.59, 95% CI 1.51, 1.67), chromosomal disorders (IRR 1.50, 95% CI 1.42, 1.59), and autoimmune diseases (IRR 1.19, 95% CI 1.17, 1.22).<\/jats:p>\n <\/jats:sec>\n \n LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n Use of administrative health data may result in outcome misclassification and limited availability of detailed clinical and demographic information.<\/jats:p>\n <\/jats:sec>\n \n WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n These findings provide contemporary population-based estimates of POI incidence and identify endometriosis as a major associated factor. The marked decline in surgically induced POI over time suggests increased adoption of ovarian-preserving surgical approaches, while rising non-iatrogenic POI incidence underscores the need for improved risk stratification, counselling, and further studies to elucidate underlying mechanisms and modifiable risk factors.<\/jats:p>\n <\/jats:sec>\n \n FUNDING<\/jats:title>\n Canadian Menopause Society.<\/jats:p>\n <\/jats:sec>\n \n DISCLOSURES<\/jats:title>\n Nothing to disclose.<\/jats:p>\n <\/jats:sec>\n \n TRIAL REGISTRATION NUMBER<\/jats:title>\n N\/A.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/humrep\/deag111","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:42:31Z","timestamp":1784090551000},"page":"1612-1621","source":"Crossref","is-referenced-by-count":0,"title":["Incidence and factors associated with premature ovarian insufficiency: a population-based cohort study"],"prefix":"10.1093","volume":"41","author":[{"given":"J N","family":"Macintyre","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Queen\u2019s University , Kingston, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7000-2605","authenticated-orcid":false,"given":"J","family":"Pudwell","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Queen\u2019s University , Kingston, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Shellenberger","sequence":"additional","affiliation":[{"name":"ICES , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4834-8279","authenticated-orcid":false,"given":"M P","family":"Velez","sequence":"additional","affiliation":[{"name":"ICES , Toronto, ON,","place":["Canada"]},{"name":"Department of Obstetrics and Gynecology, McGill University , Montreal, 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