Changing Etiological Spectrum of Premature Ovarian Insufficiency over the Past Decades: A Comparative Analysis of Two Cohorts from a Single Center.

: Premature ovarian insufficiency (POI) is a complex and heterogeneous condition affecting women of reproductive age. Historically, most POI cases have been classified as idiopathic due to limited diagnostic capabilities. However, due to the success of oncologic treatments and the increasing number of gynecologic surgeries enabled by improved diagnostics, the proportion of iatrogenic POI cases has risen substantially. : To investigate the current prevalence of POI etiologies, to compare the etiological distribution between two POI cohorts from a single tertiary center-one historical (1978-2003) and one contemporary (2017-2024)-and to explore how the spectrum of underlying causes has changed over the past four decades. : Data from 111 women diagnosed with POI between 2017 and 2024 were retrospectively reviewed and compared with those from a historical cohort of 172 patients. Etiologies were classified as genetic, autoimmune, iatrogenic, or idiopathic. Statistical comparisons were performed using chi-square and z-tests. Hormonal profiles and reproductive outcomes were also analyzed. : The current prevalence of POI etiologies is as follows: genetic 9.9%, autoimmune 18.9%, iatrogenic 34.2%, idiopathic 36.9%. In the historical POI cohort, etiologies were classified as genetic in 11.6%, autoimmune in 8.7%, iatrogenic in 7.6%, and idiopathic in 72.1%. The changes in the prevalence of autoimmune, iatrogenic, and idiopathic POI were statistically significant ( < 0.05). Reproductive outcomes remained limited: 10 pregnancies occurred in each cohort, with 7 live births in the contemporary group. : Our findings suggest a significant shift in the etiological landscape of POI, with a notable, more than fourfold rise in identifiable iatrogenic cases and a twofold increase in the autoimmune group, resulting in a halving of idiopathic POI. Prevalence of genetic etiology remained unchanged. While diagnostic capabilities have improved, reproductive outcomes remain largely unchanged and suboptimal.