Evidence inconclusive for immunosuppressing drugs’ influence on men’s sexual health
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A systematic review of 161 studies showed a lack of conclusive evidence on the influence and safety of immunosuppressive drugs on male sexual health, according to a study published in Human Reproduction Update.
“No major safety issues concerning paternal exposure to immunosuppressive drugs were found,” Luis Fernando Perez-Garcia, MD, PhD candidate and rheumatologist at the Erasmus University Medical Center in Rotterdam, the Netherlands, told Healio. “The advice not to prescribe certain medication to men with a wish to become a father is mainly due to lack of safety data, not to proven toxicity. Well-designed and fully powered observational cohort studies with longitudinal data should be conducted to properly label these drugs.”
Perez-Garcia and colleagues conducted a systematic review of studies evaluating the influence of immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy outcomes or offspring outcomes in men. Articles were identified through a search of bibliographic databases Embase, MEDLINE ALL, Cochrane Central Register of Trial and Web of Science Core Collection. Researchers also searched Google Scholar and clinical trial registries in Europe and the United States. All databases were searched through Aug. 31, 2019.
Mixed results on drugs, male fertility
The study included 130 articles on sexual function, reproductive hormones and fertility, with most of them focusing on male fertility. Of 14 drugs included in the review, three were found to negatively influence sperm quality in men. In 22 studies on men exposed to sulfasalazine, sperm abnormalities were reported in 40% to 100% of participants, with asthenozoospermia the most common abnormality. A negative effect on sperm quality and reproductive hormones was also found in 20 studies on patients exposed to cyclophosphamide to treat nephrotic syndromes associated with glomerulonephritis. In 11 studies involving sirolimus, all of them reported sperm abnormalities and reproductive hormonal alterations.
There was no negative effect on sperm quality found for acitretin, azathioprine, cyclosporine, isotretinoin, tumor necrosis factor-alpha inhibitors and vedolizumab (Entyvio, Takeda). Of nine tumor necrosis factor-alpha inhibitor studies in which a comparison was made before and after initiation of the drug, no differences were found in sperm quality in five studies, and three studies showed an improvement in sperm quality. For chloroquine, colchicine, methotrexate, NSAIDs and systemic glucocorticoids, results were inconclusive on male fertility.
“The potential negative effects of the disease on reproductive outcomes and potential flares need to be weighed against theoretical concerns of the drug effects,” Perez-Garcia said. “A shared decision-making process is thus highly recommended.”
Fifty articles in the review focused on pregnancy and offspring. No negative effect was found between any drug and pregnancy or offspring outcomes. Many of the studies included a small number of participants. Additionally, most of the larger, population-based studies were missing important details such as dose, indication and comedication.
A call to action
Perez-Garcia said the findings revealed an overall lack of conclusive evidence on many of the drugs. He suggested medical professionals from different fields come together to improve the quality of the research moving forward.
“Although this extensive systematic review did not lead to the conclusive evidence we were expecting, it gave us the opportunity to better understand this complex topic and inspired us to add a table with research recommendations,” Perez-Garcia said. “We also mentioned that a ‘call to action initiative’ is urgently needed moving forward. We have to see male sexual and reproduction health as much more than sperm quality and we have to work with our colleagues from many different fields to improve the quality of these studies in the near future.”
Recommendations for future research include conducting randomized controlled trials, case-control and prospective cohort studies over cross-sectional studies; using standardized screening and methods to measure sperm quality, hormones and other metrics; and considering comorbidities, disease activity and other possible confounders.
For more information:
Luis Fernando Perez-Garcia, MD, can be reached at l.perez@erasmusmc.nl; Twitter: @DrReumatologo.
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