Clinical Presentations of Drug-Induced Hyperprolactinaemia: A Literature Review

Abstract

Screening for drug-induced hyperprolactinaemia, a condition characterised by higher-than-normal levels of serum prolactin induced by drug treatments, requires a comprehensive understanding of the clinical presentations and long-term complications of the condition. Using two databases, Embase and MEDLINE, we summarised the available evidence on the clinical presentations and long-term complications of drug-induced hyperprolactinaemia. Clinical and observational studies reporting on drug treatments known or suspected to induce hyperprolactinaemia were included. Database searches were limited to the English language; no date or geographic restrictions were applied. Fifty studies were identified for inclusion, comprising a variety of study designs and patient populations. Most data were reported in patients treated with antipsychotics, but symptoms were also described among patients receiving other drugs, such as prokinetic drugs and antidepressants. Notably, the diagnosis of drug-induced hyperprolactinaemia varied across studies since a standard definition of elevated prolactin levels was not consistently applied. Frequent clinical presentations of hyperprolactinaemia were menstrual cycle bleeding, breast or lactation disorders, and sexual dysfunctions, described in 80% (40/50), 74% (37/50), and 42% (21/50) of the included studies, respectively. In the few studies reporting such symptoms, the prevalence of vaginal dryness impacted up to 53% of females, and infertility in both sexes ranged from 15 to 31%. Clinicians should be aware of these symptoms related to drug-induced hyperprolactinaemia when treating patients with drugs that can alter prolactin levels. Future research should explore the long-term complications of drug-induced hyperprolactinaemia and apply accepted thresholds of elevated prolactin levels (i.e., 20 ng/mL for males and 25 ng/mL for females) to diagnose hyperprolactinaemia as a drug-induced adverse event.Trial Registration PROSPERO International Prospective Register Of Systematic Reviews (CRD42021245259).

Fig. 1

PRISMA diagram. PRISMA Preferred Reporting Items for Systematic Reviews and Meta-analyses, RCT randomised controlled trial

Fig. 2

Study design of the included studies. RCT randomised controlled trial

Fig. 3

Underlying diagnosis for which the drug known or suspected to have induced HPL was administered (a), and treatment known or suspected to have induced HPL (b). HPL hyperprolactinaemia, NR not reported. Note: Underlying diagnosis refers to the diagnosis for which the drug known or suspected to have induced HPL was administered. Some studies described patients with HPL, but the specific diagnoses and drugs related to the development of HPL were not reported. Importantly, only diagnoses that were clearly documented were extracted; no interpretations were made to avoid biasing the results

Fig. 4

Clinical presentations according to symptom categories