Does improving erectile function increase fertility?

December 15, 2023

Research published this week in the British Medical Journal investigated links between penis stiffness and health outcomes, including number of children fathered, number of sexual partners, and subjective measurements of happiness. Results suggest that policies to improve erectile function may increase fertility levels.

The study, led by researchers at the MRC Biostatistics Unit (BSU), University of Bristol, and Imperial College London, explored naturally occurring variability in the mechanism of action for drugs used to treat erectile dysfunction, such as sildenafil (better known by the trade name Viagra).

Sildenafil acts by dampening the effect of an enzyme called phosphodiesterase 5, which affects smooth muscle cells that are present in the penis and in the lungs. The drug relaxes blood vessels, which enables the penis to be filled with blood more easily, facilitating robust erections. Sildenafil is also used clinically as a treatment for pulmonary hypertension, a disease characterised by high blood pressure in the blood vessels of the lungs.

Not everyone produces the same amount of phosphodiesterase 5. Some individuals carry genetic variants that predispose them to having higher levels of phosphodiesterase 5, meaning that they naturally have more robust erections. As individuals cannot choose which genetic variants they are born with, genetic associations are a more reliable indicator of causality compared with other approaches, such as comparisons between erectile medication users and non-users. Genetic regulators of phosphodiesterase 5 were associated with lower blood pressure and lower risk of pulmonary hypertension, justifying the claim that these genetic variants mimic the action of drugs like sildenafil, and enabling insights into the potential effects of taking these drugs. Analyses were performed in the UK Biobank dataset, a large ongoing survey of 500,000 British residents.

The team found that genetic mimics of the sildenafil drug class were associated with fertility in men: having a genetic predisposition to a stiff penis increased the average number of children a man fathered. However, there were no clear associations with number of sexual partners a man had or his subjective well-being. This suggests that interventions in the male population to improve erectile function via this drug class could increase fertility. Similar associations were not observed in women. Together, this provides supportive evidence that the observed genetic link with fertility is likely due to erectile health.

This is a somewhat satirical study – the article isn’t trying to encourage governments and healthcare systems to increase prescription of erectile dysfunction drugs to raise fertility rates. However, it is a serious statistical analysis that illustrates the possibility of using genetic variation to mimic treatments in large studies of generally healthy people, such as UK Biobank. These analyses can provide clinical insights in a time- and cost-efficient way. For example, such analyses can predict any long-term negative effects of certain drugs, or potential benefits, such as reduction in cardiovascular disease risk.

"Viagra was originally developed as a blood pressure lowering drug, and was then repurposed to treat erectile dysfunction based on anecdotal reports from early trial participants. Analyses like ours can guide the development of drugs to identify new disease targets in a more systematic way.”

Stephen Burgess, Programme Leader at the MRC Biostatistics Unit

"Drug manufacturers do not know the long-term consequences of treatments until after they have been tested in humans. This approach can provide reliable evidence on long-term effects using existing healthcare data.”

Benjamin Woolf, an epidemiologist who led the study, based at University of Cambridge and University of Bristol

"This study aimed to serve as an entertaining example of the type of insights that human genetic data can offer to inform the drug development cycle. This paradigm has the potential to tremendously improve the efficiency of drug development and should be embraced whenever it can be meaningfully implemented.”

Dipender Gill, a clinical pharmacologist who supervised the study at Imperial College London

Read full paper: “A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study” is published in the Christmas edition of the British Medical Journal and available at https://www.bmj.com/content/383/bmj-2023-076197