Non-surgical sterilization of male animals using sclerosing agents: A systematic review of intratesticular and intraepididymal injection protocols.

The overpopulation of free-roaming animals, particularly dogs and cats, poses a significant global public health concern, contributing to socioeconomic, ecological, political, and ethical issues. These animals reproduce freely, increasing the risk of zoonotic disease transmission, wildlife predation, and traffic accidents. Although surgical castration is the most widely used method for controlling the male animal population, it is costly, time-consuming, and requires specialized professionals and post-operative care. Therefore, there is an urgent need for practical, low-cost, large-scale, and welfare-friendly non-surgical sterilization methods. This systematic review aimed to evaluate the efficacy of intratesticular or intraepididymal injections of sclerosing agents for inducing permanent chemical sterilization. A total of 38 peer-reviewed articles were retrieved from Medline/PubMed, Web of Science, Embase, and Scopus. Among sixteen substances, calcium chloride was the most frequently studied, followed by zinc gluconate, hypertonic saline, chlorhexidine gluconate, mannitol, and glycerol. A single bilateral intratesticular and intraepididymal injection damaged testicular and epididymal tissues, thereby disrupting spermatogenesis, steroidogenesis, and sperm transport. Despite differences in the methodology and outcomes among studies, most tested agents showed promising results in disrupting reproductive function. None of the compounds fully met the two key criteria for their practical use, including the absence of side effects and consistent induction of irreversible azoospermia or infertility. Nevertheless, calcium chloride and hypertonic saline emerged as the most promising candidates, due to their robust mechanistic profiles, broad evidence base, and favorable cost-effectiveness. Therefore, researchers may prioritize these two agents in future studies to develop standardized, safe, and field-applicable protocols for large-scale population control.