Diagnostic Evaluation of Primary Ovarian Insufficiency in a Cohort of 290 Pakistani Women: Clinical, Hormonal, and Genetic Perspectives

Background: Primary ovarian insufficiency (POI) is a heterogeneous disorder with multifactorial etiologies. Accurate diagnosis requires an integrated clinical, hormonal, and genetic evaluation, yet data from Pakistan are limited, and the burden of idiopathic and genetically predisposed cases remains largely unknown. Methods: A total of 345 women under 40 years presenting with amenorrhea or menstrual irregularities were screened. After excluding pregnancy, cases not meeting the European Society of Human Reproduction and Embryology (ESHRE) diagnostic criteria, and incomplete records, 290 women were included. Comprehensive clinical, hormonal, and genetic investigations were performed according to ESHRE guidelines to determine underlying etiologies. Results: The mean age at presentation was 33 ± 4.5 years, with a median symptom duration of 6 months. The mean age at menarche was 13 ± 1 years, and the mean body mass index (BMI) was 24.5 ± 3.4 kg/m2. Most women presented with amenorrhea (80%) or oligomenorrhea (20%). Secondary infertility was reported in 72.8% and primary infertility in 2.4%. A history of miscarriage was documented in 5.9% of participants. Common clinical features included hot flushes (75.9%), depression (72.4%), high stress (65.5%), mood changes (62.1%), vaginal dryness or dyspareunia (55.2%), and night sweats (54.5%). Coexisting comorbidities were observed in 12.4%, most frequently migraines (4.1%). Hormonal evaluation confirmed elevated follicle-stimulating hormone (FSH) levels (>25 IU/L) and low estradiol (<50 pg/mL) in all participants. Etiological classification identified iatrogenic causes in 7.2%, genetic causes in 3.8% (confirmed in women with suggestive genetic features or isolated POI), autoimmune causes in 6.6%, and idiopathic POI in 82.4%. Statistically significant differences in confirmed diagnoses were observed among most etiological groups (p < 0.0001), except for women with features suggestive of a genetic cause (p ≈ 0.8500). Conclusions: POI presents with diverse clinical features. Evaluation based on ESHRE guidelines enables identification of iatrogenic, autoimmune, and genetic contributors, and highlights the high prevalence of idiopathic cases, which may have an underlying genetic predisposition.