Sex differences in the clinical presentation and complications of primary hyperparathyroidism: insights from a single-center cohort study.

PURPOSE: Primary hyperparathyroidism (PHPT) predominantly affects women, particularly after menopause. Whether sex-related differences extend beyond epidemiology to influence the clinical expression of the disease remains incompletely understood. We investigated sex-related differences in the clinical phenotype of PHPT. METHODS: We retrospectively analyzed clinical, biochemical, imaging, and histopathological data from patients with PHPT referred to our Endocrinology Unit over a 5-year period. RESULTS: A total of 315 patients were included (64 men and 251 women; female-to-male ratio 3.9:1). Mean age at diagnosis was similar between sexes (60 ± 16 vs. 59 ± 13 years, p = 0.499), and 77% of women were postmenopausal. Despite comparable mean serum calcium levels, men more frequently presented with serum calcium concentrations > 1 mg/dL above the upper limit of normal (42% vs. 29%, p = 0.042), higher urinary calcium excretion, and lower serum phosphate levels. Women showed significantly greater skeletal involvement, with a higher prevalence of osteopenia/osteoporosis (71.7% vs. 53.1%, p = 0.004), vertebral fractures (44% vs. 12%, p < 0.001), non-vertebral fragility fractures (34% vs. 12%, p = 0.003), and bone and muscle pain (60.7% vs. 10.3%, p < 0.001). Conversely, nephrolithiasis (p = 0.013) and cardiovascular comorbidities (p = 0.046) were more frequent in men. Women also displayed a less favorable metabolic profile, characterized by higher HbA1c and HOMA index values, a greater prevalence of dyslipidemia (p = 0.001), and more frequent depressive symptoms (p = 0.001) and fatigue (p = 0.040). CONCLUSIONS: PHPT exhibits distinct sex-specific clinical phenotypes. Men present a more severe biochemical and cardiovascular profile, whereas women show greater skeletal involvement, a less favorable metabolic profile, and a higher burden of non-classical symptoms. These findings support a sex-specific approach to the evaluation and management of PHPT.