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. 2023 Dec 12:383:e076197.
doi: 10.1136/bmj-2023-076197.

A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study

Benjamin Woolf  1   2   3 , Skanda Rajasundaram  4   5 , Héléne T Cronjé  6 , James Yarmolinsky  2   7 , Stephen Burgess  3 , Dipender Gill  8
Affiliations

A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study

Benjamin Woolf et al. BMJ. .

Abstract

Objective: To investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile dysfunction, with fertility, sexual behaviour, and subjective wellbeing.

Design: Two sample cis-mendelian randomisation study.

Setting: Summary data on genetic associations obtained from the International Consortium for Blood Pressure and UK Biobank.

Participants: Individuals of European ancestry from the International Consortium for Blood Pressure (n=757 601) for estimating PDE5 inhibition (using the surrogate biomarker of diastolic blood pressure reduction), and UK Biobank (n=211 840) for estimating the fertility, sexual behaviour, and subjective wellbeing outcomes in male participants.

Intervention: Genetically proxied PDE5 inhibition.

Main outcome measures: Number of children fathered, number of sexual partners, probability of never having had sexual intercourse, and subjective wellbeing.

Results: Genetically proxied PDE5 inhibition was associated with male participants having 0.28 (95% confidence interval 0.16 to 0.39) more children (false discovery rate corrected P<0.001). This association was not identified in female participants. No evidence was found of an association between genetically proxied PDE5 inhibition and number of sexual partners, probability of never having had sexual intercourse, or self-reported wellbeing in male participants.

Conclusions: The findings of this study provide genetic support for PDE5 inhibition potentially increasing the number of children fathered by male individuals. Absence of this association in female participants supports increased propensity for sustained and robust penile erections as a potential underlying mechanism. Further studies are required to confirm this, however, and these findings should not promote indiscriminate use of PDE5 inhibitors, which can also have harmful adverse effects.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: BW is funded by an Economic and Social Research Council South West Doctoral Training Partnership 1+3 PhD studentship award and UK Research and Innovation Medical Research Council (UKRI MRC), HTC is supported by a Novo Nordisk Foundation challenge programme, SB is supported by the Wellcome Trust, UKRI MRC, and National Institute for Health and Care Research Cambridge Biomedical Research Centre, DG is supported by the British Heart Foundation Centre of Research Excellence at Imperial College London; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Schematic depiction of study design. PDE5=phosphodiesterase 5
Fig 2
Fig 2
Mendelian randomisation results for genetically proxied phosphodiesterase 5 (PDE5) inhibition, scaled per 5.5 mm Hg lower diastolic blood pressure (which is the approximate effect of 100 mg sildenafil). Subjective wellbeing is measured in standard deviation units. CI=confidence interval
See this image and copyright information in PMC

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