On-demand testosterone for the treatment of female sexual dysfunction: a systematic review

Female sexual dysfunction is common, distressing, and notoriously difficult to treat. In the last two decades, short-course ("on-demand") testosterone (T) regimens-delivered sublingually, intranasally, inhaled, topically, or intramuscularly-have been explored as rapid-acting prn enhancers of female libido. The objective of this study is to quantify efficacy, safety, and pharmacokinetics (PK) of short-term T therapy (prn) in women with sexual dysfunction.

PRISMA 2020 guidelines for systematic reviews were followed. Twelve RCTs and five PK studies (n = 940) were identified via Embase/MEDLINE/Web of Science (inception-March 2025). Outcomes included desire/arousal scores, satisfying sexual events (SSE), pharmacokinetics, and adverse events. Risk of bias was assessed using the Cochrane risk-of-bias tool.

Although absolute serum T excursions differ widely across formulations, most achieve supra-physiological free-T peaks within 15 min and return to baseline within 2-6 h. There is mixed evidence that this window coincides with maximal central arousal effects. However, when combined with phosphodiesterase-5 or 5-HT1A agonists, there tends to be improved genital vasocongestion and sexual satisfaction. Adverse events were mild but tended to be common.

Short-term T therapy combined with phosphodiesterase-5 inhibitors or 5-HT1A agonists may be benefit select subgroups of women with sexual dysfunction with a favorable short-term safety, however, sample sizes remain small and further research is required.Registration: This study was registered in PROSPERO: CRD42024615106.