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Phosphodiesterase 5 (PDE5) inhibitors, like sildenafil, are widely recognized for treating erectile dysfunction and pulmonary hypertension. Recent research provides fascinating insights into the possible effects of PDE5 inhibitors on male fertility. This study used mendelian randomisation to explore the genetic links between PDE5 inhibition and various outcomes, including fertility, sexual behavior, and subjective wellbeing.
The study gathered data from the International Consortium for Blood Pressure and UK Biobank, focusing on individuals of European ancestry. Researchers found that genetically proxied PDE5 inhibition could result in men fathering 0.28 more children on average, but this association was not seen in women. Interestingly, no significant links were found between PDE5 inhibition and the number of sexual partners, the likelihood of never having had sexual intercourse, or self-reported wellbeing in either male or female participants.
When asked about the study’s significance, lead researcher Benjamin Woolf explained, “Our findings suggest that PDE5 inhibitors may have beneficial effects on male fertility, likely through their ability to sustain robust penile erections. However, further studies are needed to confirm these results, and we caution against the indiscriminate use of PDE5 inhibitors due to potential adverse effects.”
This genetic evidence supports the hypothesis that PDE5 inhibition might increase the number of children fathered by male participants. “While our study provides valuable insights, it does not suggest that PDE5 inhibitors should be used freely to boost fertility. Medical consultation is necessary before any such decision is made,” Woolf added.
In terms of safety and long-term outcomes, the study did not show any impact on subjective wellbeing or sexual behavior. This is crucial because PDE5 inhibitors are readily available over the counter in some countries, such as the UK, and their potential misuse could have unintended consequences. “The study highlights that PDE5 inhibitors don’t influence the number of sexual partners or sexual activity levels,” said co-author Stephen Burgess. “Their primary effect seems focused on improving penile function, which could indirectly support conception.”
However, the study also revealed the importance of cautious use. “Our results shouldn’t promote indiscriminate use of PDE5 inhibitors, as they can have harmful side effects,” Burgess warned. The absence of fertility-related effects in women reinforces the idea that PDE5 inhibition primarily enhances male sexual function, specifically related to erections.
Ultimately, the study contributes to the growing body of genetic research on drug effects beyond their primary indications. The use of mendelian randomisation has proven particularly effective in identifying potential causal relationships between genetic markers and health outcomes. Yet, while the study offers valuable insights, further research is needed to fully understand the broader implications of long-term PDE5 inhibition.
Citation:
Woolf B, Rajasundaram S, Cronjé HT, Yarmolinsky J, Burgess S, Gill D. A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study. BMJ. 2023;383. doi:10.1136/bmj-2023-076197.
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