Prolactin-raising antipsychotics may increase gynecological cancer risk
Study: Absolute rise was small, 'entailing little clinical significance'
Women prescribed antipsychotics that raise the levels of prolactin, a hormone that stimulates milk production and regulates reproductive hormones, had double the rate of gynecological cancer compared with those on prolactin-sparing drugs, according to a large-scale study in Hong Kong. The increase was seen mainly in ovarian and endometrial cancers.
Rates were higher in women older than 51 and in those with psychotic disorders. Still, the absolute increase — about one additional case of gynecological cancer for every 2,300 women treated each year — was small, “entailing little clinical significance,” researchers wrote.
“To the best of our knowledge, this is the first [group] study, and the largest real-world study, to compare prolactin-increasing with prolactin-sparing antipsychotic use in terms of [frequency] of gynecological cancers,” the team added. Researchers also acknowledged limitations, such as the study being restricted to women in Hong Kong.
The study, “Incidence of gynecological cancers following prolactin-increasing antipsychotic use: a population cohort study,” was published as a letter to the editor in World Psychiatry.
Some antipsychotic medications can raise prolactin levels
Prolactin, a hormone produced by the brain’s pituitary gland, is best known for stimulating the growth of breast glands and triggering milk production after childbirth. It also has broader effects, influencing reproductive tissues and promoting cell growth.
Some antipsychotic medications can raise prolactin levels. These prolactin-increasing antipsychotics and their use have been linked to a higher risk of certain cancers, particularly breast cancer. Among the most widely used prolactin-increasing agents are haloperidol (sold as Haldol and generics) and risperidone (sold as Risperdal, among others).
Haloperidol is approved for the treatment of schizophrenia and acute psychotic episodes, and is often used off-label for acute agitation, delirium, and severe behavioral disturbances. Risperidone is approved for schizophrenia, bipolar disorder, and irritability associated with autism, and is also prescribed off-label for behavioral symptoms in dementia, post-traumatic stress disorder, and severe anxiety.
A recent analysis combining results from several studies suggested that the use of antipsychotic medications may be associated with a 70% higher risk of developing gynecological cancers compared with non-users, according to the researchers. These studies, however, were often limited by small sample sizes, inconsistent methods, or designs that could not easily establish cause and effect.
“There was also no direct comparison between users of prolactin-increasing and prolactin-sparing antipsychotics on a comparable [time frame],” the researchers wrote.
126 women developed gynecological cancer during follow-up period
To fill this gap, researchers in Hong Kong carried out the first large study of its kind, analyzing anonymized health records from 84,061 women, ages 18 to 85, who began antipsychotic treatment between January 2006 and December 2018.
Women with a prior history of cancer, previous antipsychotic use, or who had undergone surgical removal of the uterus (hysterectomy) or one or both breasts (mastectomy) were excluded.
Each woman was then followed from the start of treatment until a diagnosis of gynecological cancer, a change or discontinuation of therapy, death, or the end of the study in December 2023, whichever came first. The median follow-up period was just over one year, though some women were followed for as long as 15 years.
Of the total group, 61,771 women (73.5%) were prescribed prolactin-increasing antipsychotics, most commonly haloperidol and risperidone. Quetiapine (sold as Seroquel and generics)was the most frequently prescribed prolactin-sparing antipsychotic.
Among health conditions noted in their records, schizophrenia, bipolar disorder, depression, and anxiety were observed, along with other health problems such as high blood pressure or diabetes.
During the follow-up period, 126 women developed gynecological cancer. Of these cases, 96 occurred in women taking prolactin-increasing antipsychotics, compared with 30 in those using prolactin-sparing drugs. This equates to about 88 cases per 100,000 women each year in the prolactin-increasing group versus 57 in the prolactin-sparing one.
Our study showed that prolactin-increasing antipsychotics are associated with an increased rate of gynecological cancers compared with prolactin-sparing antipsychotics, although the [absolute increase in cases] is small, entailing little clinical significance.
After adjusting for other factors, women on prolactin-increasing drugs were almost twice as likely to develop a gynecological cancer compared with those on prolactin-sparing drugs. This translates to an absolute increase of about 43 cases per 100,000 women each year, or roughly one extra case for every 2,300 women treated.
When broken down by cancer type, endometrial cancer occurred at about twice the rate in women taking prolactin-increasing antipsychotics compared with prolactin-sparing users. Ovarian cancer also showed a marked difference, with more than a threefold higher rate among women on prolactin-increasing drugs.
Women over 51 had about double the gynecological cancer rate compared with those on prolactin-sparing drugs, and women with psychotic disorders showed nearly a tenfold higher rate compared with those without such a diagnosis.
In head-to-head drug comparisons, haloperidol and risperidone were each associated with more than twice the rate of gynecological cancer compared with quetiapine.
The researchers suggested that prolactin itself may play a role in cancer development by promoting cell growth and survival in reproductive tissues, including the ovaries and endometrium.
“Our study showed that prolactin-increasing antipsychotics are associated with an increased rate of gynecological cancers compared with prolactin-sparing antipsychotics, although the [absolute increase in cases] is small, entailing little clinical significance,” the researchers wrote.
About the Author
