Abstract

Abstract Introduction The link between the attainment of healthy sexual function and a high quality of life in women is well established. However, while the management of male sexual dysfunction has been afforded huge research and development, far less time and effort has been lent in the achievement of successful remedies for females experiencing sexual dysfunction. The use of oral phosphodiesterase type 5 (PDE5) inhibitors, such as Sildenafil, has been the mainstay of treatment for male sexual dysfunction for the last two decades. PDE5 inhibitors have been shown to initiate penile erection, through smooth muscle relaxation and the subsequent increase in intracellular cGMP levels. PDE5-containing cells, similar to those found in the penis, have also been confirmed within the clitoris. No previous pooled analysis has been performed, looking at the possible effect of PDE5 inhibitors on female sexual function, in a population comprising of heterosexual cisgender population. Objectives We aimed to perform a systematic review and meta-analysis of the best possible available studies, to evaluate the efficacy and safety of PDE5 inhibitors versus placebo when used in an exclusively female population. Methods We conducted a comprehensive search of electronic databases (MEDLINE, PubMed, EMBASE, CINAHL, CENTRAL, SCOPUS, Google Scholar, Web of Science, EBSCO Host, TRIP and Epistemonikos), identifying studies comparing the PDE5 inhibitors versus placebo, and the resultant effect on female sexual function. The Cochrane risk-of-bias tool for RCTs and the Newcastle-Ottawa scale for observational studies were used to assess the included studies. Random effects modelling was used to calculate pooled outcome data. Results Searches of electronic databases resulted in 67 articles, from which 13 randomised control trials (RCTs) met the eligibility criteria, enrolling a total of 1605 patients. The use of PDE5 inhibitor was associated with a significantly improved orgasm satisfaction (P=0.01), increased sexual arousal (P=0.02), increase in sexual satisfaction (P=0.007) when compared to placebo. The use of PDE5i was also found to have a significant association with the incidence of headaches (P<0.0001) and flushing (P<0.00001). Conclusions Our meta-analysis demonstrated that the use PDE5 inhibitor was associated with a significantly higher attainment of orgasm satisfaction, sexual arousal, and sexual satisfaction when administered to a solely female population, when compared with placebo. However, the use of PDE5 inhibitors was also associated with a significantly increased risk of headache and flushing. Further large-scale high-quality RCTs are required in order to further evaluate the potential role of PDE5i’s in women, particularly in those suffering from significant sexual dysfunction. These future studies should focus on a more homogenous patient group, with stricter definitions of inclusion criteria. Disclosure

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