4A-03 - Incidence of gynecologic cancers following prolactin-increasing antipsychotic use: a territory-wide retrospective cohort study

Background: Preclinical research has suggested a relationship between elevated prolactin levels and gynecological cancers (GCs). Whether prolactin-increasing antipsychotics are associated with GCs risks, however, remains inconclusive.


Objectives: This study aims to examine the potentially increased risk of GCs between prolactin-increasing and prolactin-sparing antipsychotic users.


Methods: A retrospective cohort study was conducted based on a territory-wide longitudinal health record database in Hong Kong. All women aged 18–85 who first used antipsychotics between Jan 2006 and Dec 2018 were included, ensuring at least five years of follow-up (data until 31 Dec 2023). All patients were categorized into a prolactin-increasing antipsychotic user group and a prolactin-sparing antipsychotic user group. They were followed from the index date (first use of antipsychotics) until the diagnosis of GCs, 365 days after change of antipsychotics or drug discontinuation, death, and the end of the study period (31st December 2023), whichever occurred the earliest. To avoid reversed causality, patients developing cancer within 30 days of the index date were censored upon cancer diagnosis. Poisson regression with robust variance estimation, weighted by the inverse probability of treatment, was used to estimate the incidence rate ratio (IRR) of GCs as a composite outcome as well as separate subtypes (endometrial, ovarian, cervical and vaginal cancer). Rate difference (RD) was also estimated.


Results: In total, 84,061 women were included, 61,771 (73.5%) were prolactin-increasing antipsychotic users. The average follow-up period was approximately 2 years (up to 15 years at maximum). Compared to prolactin-sparing antipsychotic users, prolactin-increasing antipsychotic users had a significant IRR of 1.99 (95%CI 1.13, 3.50) for GCs with an absolute RD 42.58 (11.77, 69.32) per 100,000 person-years. Findings were consistent across subgroup analyses, and significant results were seen in patients aged over 51 years (IRR 2.09 [1.02, 4.26], RD 59.10 [11.29, 102.61] per 100,000) and patients diagnosed with psychotic disorders (IRR 9.69[1.32, 71.10], RD 78.62 [43.86, 113.03] per 100,000).


Conclusions: We identified a twofold elevated rate of GCs among prolactin-increasing antipsychotics users compared to prolactin-sparing antipsychotics, but the absolute rate difference is small with limited clinical significance.