The Invisible Epidemic: A Population-Based Cohort Study on the Rising Burden of Premature Ovarian Insufficiency in Pakistani Women and the Unmet Need for a Multidimensional Care Framework

Abstract

Premature Ovarian Insufficiency (POI) is a profound clinical syndrome with significant implications for fertility, metabolic, cardiovascular, and psychosocial health. While global data exists, population-specific epidemiology, etiological patterns, and comprehensive care models in low-resource, high-consanguinity settings like Pakistan remain critically underexplored. To determine the population-based prevalence, characterize the etiological and clinical profile, and evaluate the systemic gaps in the management of POI among women of reproductive age in Lahore, Pakistan. A prospective, cross-sectional cohort study was conducted from 1st January 2024 to 30th November 2025. Women aged 18-40 years presenting with ≥4 months of amenorrhea and two elevated serum Follicle-Stimulating Hormone (FSH) levels (>25 IU/L) measured ≥4 weeks apart were recruited from the outpatient clinics of Fatima Memorial Hospital and two affiliated community health centers. Participants underwent a standardized protocol including detailed history, physical examination, pelvic ultrasonography, karyotyping, FMRI premutation analysis, and screening for associated autoimmunity. Validated questionnaires (HADS, MENQOL) assessed psychological and quality-of-life impact. Among 15,342 screened women, 247 met the diagnostic criteria for POI, yielding a prevalence of 1.61% in our study population, significantly higher than the oft-cited global average of 1%. Consanguinity was reported in 38% of cases. A definitive etiological classification was possible in 52%: genetic causes (22%, predominantly FMRI premutation and Turner syndrome mosaicism), iatrogenic (18%, mainly post-oncological care), and autoimmune (12%). A striking 48% were classified as idiopathic. Over 85% of women presented with profound distress (HADS score ≥11) and significantly impaired quality of life. Less than 10% had previously been counseled on bone or cardiovascular health. This study reveals a potentially higher burden of POI in our population, with a substantial idiopathic fraction and a strong association with consanguinity, pointing to a likely polygenic and oligogenic inheritance pattern. The near-universal deficiency in holistic care underscores an urgent need for the development and implementation of a standardized, multidisciplinary national guideline for POI management in Pakistan, integrating reproductive health with long-term metabolic, skeletal, and psychological support.