Efficacy and safety in the treatment of hyperprolactinemia: A systematic review and network meta-analysis

J Clin Pharm Ther. 2021 Dec;46(6):1549-1556. doi: 10.1111/jcpt.13460. Epub 2021 Jun 16.


What is known and objective: Hyperprolactinemia is a neuroendocrine disease that is responsible for a quarter of cases of secondary amenorrhea, which can lead to infertility in women. Dopaminergic agonists (bromocriptine, cabergoline, quinagolide) can be used in the treatment. However, there is a lack of secondary studies that compare their efficacy and safety, especially through a network meta-analysis. Thus, to contribute to the decision-making, a systematic review and network meta-analyses (NMA) were performed to evaluate the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia.

Methods: Randomized clinical trials (RCT) were retrieved through PubMed, Web of Science and Scopus databases. The efficacy and safety of the drugs were compared, considering the following outcomes: prolactin (PRL) levels, number of patients with galactorrhoea, menstrual irregularities and adverse drug reactions. NMA was built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals. Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA) and Stochastic multicriteria acceptability analysis (SMAA).

Results and discussion: Seventeen RCTs were included in the systematic review and fifteen in the meta-analyses. The drugs had similar efficacy, considering the PRL levels. The SUCRA analysis showed that quinagolide (0.075 and 0.05 mg/day) was superior for reducing irregular menstruation, whereas bromocriptine was the best (97%) for galactorrhoea. Cabergoline proved to be the safest drug, except for abdominal pain at a dose of 1 mg/week. The SMAA demonstrated similar results to SUCRA.

What is new and conclusion: This is the first network meta-analysis that evaluated the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. The results of this review revealed that these drugs have similar efficacy, but cabergoline has a better safety profile.

Keywords: bromocriptine; cabergoline; hyperprolactinemia; meta-analysis; quinagolide; systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Dopamine Agonists / administration & dosage
  • Dopamine Agonists / adverse effects
  • Dopamine Agonists / therapeutic use*
  • Female
  • Galactorrhea / epidemiology
  • Humans
  • Hyperprolactinemia / drug therapy*
  • Hyperprolactinemia / epidemiology*
  • Menstruation Disturbances / epidemiology
  • Network Meta-Analysis
  • Prolactin / blood
  • Randomized Controlled Trials as Topic


  • Dopamine Agonists
  • Prolactin