TY - JOUR

T1 - A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing

T2 - mendelian randomisation study

AU - Woolf, Benjamin

AU - Rajasundaram, Skanda

AU - Cronjé, Héléne T.

AU - Yarmolinsky, James

AU - Burgess, Stephen

AU - Gill, Dipender

N1 - Publisher Copyright: © 2019 Author(s) (or their employer(s)).

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1136/bmj-2023-076197

DO - 10.1136/bmj-2023-076197

M3 - Journal article

C2 - 38086555

AN - SCOPUS:85179649154

VL - 383

JO - The BMJ

JF - The BMJ

SN - 0959-8146

M1 - e076197

ER -