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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 Genetic

United kingdomCity ofDipender gillBenjamin woolfJames yarmolinskySkanda rajasundaramStephen burgessCare research cambridge biomedical centreCentre research ethics committeeNational institute for healthResearch council south west doctoral training partnershipResearch councilRegional development agencyNovo nordisk foundationComputing research centreBritish heart foundation