Antihistamine use may be linked with impaired fertility in men

The overuse of over-the-counter antihistamine medications may be associated with impaired fertility in men, according to a review of animal and human studies published in Reproduction.

“In recent years, a wide variety of antihistamine compounds have been introduced in the clinics, and most of these antihistamines are available without prescription,” Carolina Mondillo, PhD, a researcher with the Institute of Biology and Experimental Medicine in Buenos Aries, told Endocrine Today. “The present study describes the existence of multiple functions, local sources and targets of histamine within the male reproductive system of several species, including human. While clinical studies in humans are still limited, clinicians and patients should be aware that the overuse of antihistamine drugs could have long-term side effects on male fertility.”

In a research review, Mondillo and colleagues assessed the effects of histamines on various testis cell types, with a special focus on Leydig cells, as well as the adverse effects of antihistamines on normal testis function, in both animal and human models. The researchers cited several studies indicating that antihistamine drugs may affect testicular homeostasis by enhancing or decreasing androgen production, including several studies suggesting that daily use of the antihistamine cimetidine (1,200 mg per day) was associated with a decrease in testosterone levels and lower sperm count in humans, while also exerting moderate effects on sperm morphology and motility.

“The potential negative impact of antihistamines on male reproduction becomes even more significant if we consider that [histamines have] been implicated in penile erection and sexual behavior, as well as steroidogenesis and spermatogenesis,” the researchers wrote, adding that histaminergic effects could be provided by extracellular vesicles secreted by other testicular cells expressing histamine receptors.

“The data compiled in this review collectively indicate the crucial involvement of histamine in the orchestration of testicular functions during development and adulthood,” Mondillo said. “Even so, there is still much to learn regarding the complex interplay between histamine-synthesizing cells and targets for histamine within the male reproductive system.”

Mondillo said more research is needed on the potential role of histamine transport via extracellular vesicles between testicular cells, either over short distances or between cells that are not close neighbors.

“As extracellular vesicles can also carry membrane proteins to the recipient cells, histamine receptors could also be transferred to any testicular cell,” Mondillo said. “Thus, the question arises whether extracellular vesicles can influence the development of male gonads (Leydig cells) during embryogenesis or later in adulthood. In order to develop novel drugs aimed at treating histamine-related pathologies that are effective, safe and have minimum or null negative impact on fertility, an evaluation of the possible negative effects of such drugs on reproductive and sexual health should definitely be made part of clinical studies.” – by Regina Schaffer