FDA-approved medications that impair human spermatogenesis

Abstract

We herein provide an overview of the single-ingredient U.S. Food and Drug Administration (FDA)-approved drugs that affect human spermatogenesis, potentially resulting in a negative impact on male fertility. To provide this information, we performed an in-depth search of DailyMed, the official website for FDA-approved drug labels. Not surprisingly, hormone-based agents were found to be the drugs most likely to affect human spermatogenesis. The next category of drugs most likely to have effects on spermatogenesis was the antineoplastic agents. Interestingly, the DailyMed labels indicated that several anti-inflammatory drugs affect spermatogenesis, which is not supported by the peer-reviewed literature. Overall, there were a total of 65 labels for drugs of various classes that showed that they have the potential to affect human sperm production and maturation. We identified several drugs indicated to be spermatotoxic in the drug labels that were not reported in the peer-reviewed literature. However, the details about the effects of these drugs on human spermatogenesis are largely lacking, the mechanisms are often unknown, and the clinical impact of many of the findings is currently unclear. Therefore, additional work is needed at both the basic research level and during clinical trials and post-marketing surveillance to fill the gaps in the current knowledge. The present findings will be of interest to physicians and pharmacists, researchers, and those involved in drug development and health care policy.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction

“…The current reproductive toxicity testing should be able to provide useful results for clinical extrapolation. However, as noted above, our current study and previous studies about spermatotoxicity [3,105,106] have shown that studies in animals have relatively low predictive value for human toxicity. In some cases, the lack of useful findings is due to the high doses of the compounds used in the toxicity studies.…”

“…The most important findings of the present study include the following: only 27% (63/235) of the drugs that had a negative effect in animals reported in the drug label were found to have a documented negative impact on human sperm (in the drug labels or literature). Further, a previous study [3] showed that fewer than half of the drugs with labels indicating that they adversely affected human sperm had similar findings in animals. In addition, for more than half of the drugs found to negatively affect animal spermatogenesis or spermatozoa, Based on studies of combination treatment the impact in humans is unclear either because no testing or surveillance has been performed, or because the results have not been reported.…”

“…Despite the various considerations made to improve the testing process and provide the best predictions of toxicity, there have been numerous studies that reported a lack of efficacy for toxicity testing, including reproductive toxicity testing [104][105][106][107]. In a previous study, a total of 65 labels for single-ingredient FDA-approved drugs were found in DailyMed that indicated that the drugs had a negative impact on human spermatogenesis [3]. In agreement with our present findings suggesting that animal studies have limited predictive power for human spermatotoxicity, fewer than half of the drug labels (26 of 65) indicated that they had effects on animal spermatogenesis.…”

“…The present review focuses on the spermatotoxic effects (from the generation of spermatogonia to fertilization) of prescription drugs in various experimental animals. This review was prompted by a previous publication that examined the impact of FDA-approved drugs on human spermatogenesis [3]. In that study, frequent discrepancies were noted in the drug warning labels between the adverse effects of drugs on human and animal spermatogenesis, as well as some inconsistencies between the published peer-reviewed literature and the DailyMed database (a federal repository of drug warning Elizabeth R. Rayburn and Liang Gao should be considered joint first authors.…”

Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males

“…It has been shown that exposure to CD causes decrease in epididymal sperm in rats without any changes in morphology of reproductive organs 60 . It was suggested that any drug that affect spermatogonia could lead to defects in sperm maturation and spermatogenesis 61 . We did not perform fertility tests, as studies have shown that even a 50–60% decline in sperm count will have no appreciable effect on fertility in mice (Schurmann et al ., 2002; Zhang et al ., 2006).…”