A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e076197 |
| Tidsskrift | BMJ |
| Vol/bind | 383 |
| Antal sider | 8 |
| ISSN | 0959-8146 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
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.
Funding Information:
Funding: BW is funded by an Economic and Social Research Council (ESRC) South West Doctoral Training Partnership 1+3 PhD studentship award (ES/P000630/1) and UK Research and Innovation Medical Research Council (UKRI MRC) (MC_UU_00002/7 and MC_UU_000011/7). HTC is supported by the Novo Nordisk Foundation challenge programme: Harnessing the Power of Big Data to Address the Societal Challenge of Ageing (NNF17OC0027812). SB is supported by the Wellcome Trust (225790/Z/22/Z) and the UKRI MRC (MC_UU_00002/7). This research was supported by the National Institute for Health and Care Research Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. DG is supported by the British Heart Foundation Centre of Research Excellence at Imperial College London (RE/18/4/34215). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.
Funding Information:
This project was conducted using UK Biobank application No 15825. UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish government, and the Northwest Regional Development Agency. It has also had funding from the Welsh government, British Heart Foundation, Cancer Research UK, and Diabetes UK. UK Biobank is supported by the NHS. UK Biobank is open to bona fide researchers anywhere in the world.
Publisher Copyright:
© 2019 Author(s) (or their employer(s)).
ID: 383874451