Pharmacological Hyperprolactinemia: a Retrospective Analysis of 501 Hyperprolactinemia Cases in Primary Care Setting

Purpose: To describe a series of cases with pharmacological hyperprolactinemia in primary care setting and the prolactin levels, clinical implications of different causes of pharmacological hyperprolactinemia.

Methods: A retrospective study of all patients with detected hyperprolactinemia in hormonal studies was performed between 2019 and 2020 in 20 Spanish primary care centers. Hyperprolactinemia is defined as a serum prolactin >19.4ng/ml in men and >26.5ng/ml in women. Four pharmacological causes of hyperprolactinemia were established: (i) oral contraceptives (OCPs) and other hormonal treatments; (ii) antipsychotics and antidepressants; (iii) other drugs (calcium antagonists, antiemetics, H2 antihistamines, opioids, and anabolic agents); and (iv) hyperprolactinemia due to several drugs.

Results: From a sample of 501 patients with elevated serum prolactin, 39.4% (n=162) had pharmacological hyperprolactinemia. The most common cause of pharmacological hyperprolactinemia in women was OCPs (n=61) while in men antipsychotics/antidepressants (n=21). In the cases of hyperprolactinemia due to antipsychotics/antidepressants, the prolactin levels were significantly higher in patients taking classical antipsychotics than in those taking second-generation antipsychotics (80.0±43.17 vs. 50.7±28.66 ng/dL, P=0.035). The antidepressant/antipsychotic group showed hyperprolactinemia-related symptoms more frequently than the group of other treatments (58.9% vs. 32%, P=0.001). The concomitant use of several drugs caused hyperprolactinemia-related symptoms more frequently than one drug alone (73% vs. 44%, P=0.031).

Conclusion: In this series of cases, drugs represented the 39.4% of the causes of hyperprolactinemia. The most common drugs were OCPs in women and antipsychotics/antidepressants in men. Antidepressants/antipsychotics were drugs that caused the greatest elevation of the prolactin levels and showed hyperprolactinemia-related symptoms more frequently.