Gender differences in long-term complications of chronic hypoparathyroidism: a systematic review

Background Chronic hypoparathyroidism (HypoPT) is a rare endocrine disorder associated with lifelong treatment and a wide spectrum of long-term complications. Potential gender differences in disease-related complications remain poorly defined. This systematic review aimed to evaluate sex-related differences in long-term complications of chronic HypoPT and to explore the impact of disease etiology on these outcomes. Methods A systematic search of PubMed, Scopus, EMBASE, and the Cochrane Library was conducted for English-language studies published from January 1980 to July 2025. Eligible studies included randomized controlled trials, cohort studies, case-control studies, and case series involving both women and men with chronic HypoPT and reporting long-term complications. Study selection and data extraction were performed independently by two reviewers according to PRISMA guidelines. Outcomes of interest included renal, skeletal, neurological, cardiovascular, neuropsychiatric complications, and quality of life. Results Forty-two studies were included. Renal complications showed sex-related patterns, with hypercalciuria more frequently reported in women and chronic kidney disease more commonly observed in men. Skeletal complications, particularly vertebral fractures, were more prevalent in postmenopausal women, while bone mineral density and turnover markers showed minimal sex differences. Neurological complications, including basal ganglia calcifications, did not consistently differ by sex, although women more frequently reported cognitive and neuropsychiatric symptoms. Cardiovascular risk appeared higher in women in some cohorts. Quality of life impairment and symptom burden were consistently greater in women, especially when assessed using disease-specific instruments. Conclusions Available evidence suggests gender-related trends in long-term complications of chronic HypoPT, but data are limited by heterogeneity and lack of sex-stratified analyses. Gender-informed research is needed to support personalized management strategies.