Mortality in patients with dopamine agonist-treated hyperprolactinemia: a large matched-cohort study

Purpose: Data on mortality risk in patients with hyperprolactinemia is limited. This study aimed to evaluate all-cause mortality in a cohort of dopamine agonist (DA)-treated patients with hyperprolactinemia. Methods: A nationwide retrospective study (2000–2023) using the Clalit Health Services database evaluated all-cause mortality in patients with DA-treated hyperprolactinemia, matched 1:5 with controls by age, sex, socioeconomic status, and BMI. The primary outcome was all-cause mortality. Secondary outcomes included the impact of hyperprolactinemia severity, prolactin (PRL) normalization, and other mortality risk factors. Results: The study included 2,492 patients with hyperprolactinemia (mean age ± SD:38.7 ± 14.8 years, 59.6% women) and 12,456 controls (38.7 ± 14.8 years, 59.6% women). Over > 17 years of follow-up, 182 patients (7.3%) and 936 controls (7.5%) died (HR = 0.972, 95% CI 0.829–1.139), with similar mean age at death. Causes of death in both groups were mainly infectious, cardiovascular, and malignancies. Compared to controls, patients achieving PRL normalization within 1 year had lower mortality (HR = 0.730), while those without normalization had similar risk. Patients with baseline PRL < 5×ULN had lower mortality (6.9% vs. 7.9%, HR = 0.725) than those with ≥ 5×ULN. Mortality was higher in men than in women with hyperprolactinemia but not versus controls. Independent predictors for all-cause mortality included older age, higher BMI, male sex, heart failure, malignancy, hypertension, diabetes, and ischemic heart disease. Conclusion: All-cause mortality in patients with DA-treated hyperprolactinemia is not increased compared to matched controls, however is higher in men vs. women. Mortality is primarily influenced by age, sex, BMI, and comorbidities. Achieving PRL normalization within a year decreases mortality compared with controls.