Morbidity and mortality in patients with hyperprolactinaemia: the PROLEARS study

Abstract

Purpose: High serum prolactin concentrations have been associated with adverse health outcomes in some but not all studies. This study aimed to examine the morbidity and all-cause mortality associated with hyperprolactinaemia.

Methods: A population-based matched cohort study in Tayside (Scotland, UK) from 1988 to 2014 was performed. Record-linkage technology was used to identify patients with hyperprolactinaemia that were compared to an age-sex-matched cohort of patients free of hyperprolactinaemia. The number of deaths and incident admissions with diabetes mellitus, cardiovascular disease, cancer, breast cancer, bone fractures and infectious conditions were compared by the survival analysis.

Results: Patients with hyperprolactinaemia related to pituitary tumours had no increased risk of diabetes, cardiovascular disease, bone fractures, all-cause cancer or breast cancer. Whilst no increased mortality was observed in patients with pituitary microadenomas (HR = 1.65, 95% CI: 0.79-3.44), other subgroups including those with pituitary macroadenomas and drug-induced and idiopathic hyperprolactinaemia demonstrated an increased risk of death. Individuals with drug-induced hyperprolactinaemia also demonstrated increased risks of diabetes, cardiovascular disease, infectious disease and bone fracture. However, these increased risks were not associated with the degree of serum prolactin elevation (P_trend > 0.3). No increased risk of cancer was observed in any subgroup.

Conclusions: No excess morbidity was observed in patients with raised prolactin due to pituitary tumours. Although the increased morbidity and mortality associated with defined patient subgroups are unlikely to be directly related to the elevation in serum prolactin, hyperprolactinaemia might act as a biomarker for the presence of some increased disease risk in these patients.

Keywords: breast cancer; hyperprolactinaemia; mortality; pituitary gland; prolactin.

Figure 1

Estimated HRs (± 95% CI) for several clinical outcomes in patients with hyperprolactinaemia according to serum prolactin levels. Footnote: Quintiles of maximum serum prolactin levels (<1130, 1131–1360, 1361–1762, 1763–2637, >2637 U/L). Hazard ratios calculated using Cox proportional hazards’ models. (A) Diabetes mellitus model adjusted for age and gender. Wald linear test of parameter estimates Chi² (3) = 3.59, P = 0.30. (B) Non-fatal cardiovascular disease model adjusted for age, gender, history of diabetes mellitus and renal impairment; Wald linear test Chi² (3) = 0.93, P = 0.81. (C) Bone fractures model adjusted for history of bisphosphonates use, prednisolone use and renal impairment; Wald linear test Chi² (3) = 0.73, P = 0.86. (D) Mortality model adjusted for age, gender, history of non-fatal cardiovascular disease, renal impairment and a Scottish index of multiple deprivation; Wald linear test Chi² (3) = 3.26, P = 0.35.