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Background Although spironolactone is an effective treatment for androgen-mediated cutaneous disorders, the potential sexual side-effects are poorly documented in current literature. Aim The purpose of this study was to provide clinical evidence that spironolactone may be a cause of hormonally associated vestibulodynia and female sexual arousal disorder. Methods A database search of a vulvar disorders clinic revealed 7 cases in which spironolactone may have caused or contributed to dyspareunia and decreased arousal. In all cases, the patients stopped taking spironolactone and used a compounded estradiol 0.01%/testosterone 0.1% gel to the vestibule twice daily. 2 cases are discussed to further illustrate these previously unreported side effects. Outcomes Improvement in sexual function was determined after treatment. Results Examination of women taking spironolactone who presented with the complaints of introital dyspareunia revealed vulvar vestibular atrophy and tenderness, especially at the glandular ostia. After stopping spironolactone and applying a topical estrogen/testosterone gel to the vestibule, all women had significant improvement in their vulvar atrophy, resolution of their dyspareunia, and improved sexual arousal. Clinical Implications Use of spironolactone may be a cause of hormonally associated vestibulodynia and female sexual arousal disorder. Strengths and Limitations The influence of spironolactone on vulvar health and sexual function is poorly documented in the medical literature. The strength of this paper is that it examines the potential deleterious side effects of this medication on female sexual function. However, the most significant limitation of this case series is that it was not a prospective, controlled study. Conclusions Although treatment of androgen-mediated cutaneous disorders is warranted, medical providers should be aware of the potential sexual side effects of this anti-androgenic medication.