• Vagina;
  • Clitoris;
  • Female Sexual Arousal;
  • Caveolin


Introduction.  Female sexual arousal disorder (FSAD) is a major component of female sexual dysfunctions, affecting 25–70% of women. The mechanisms of FSAD are poorly understood. Estrogen contributes to the control of genital blood flow during the sexual response. Vascular effects of estrogen are mostly attributed to its regulation of endothelial nitric oxide (NO) production. However, the role of endothelial NO synthase (eNOS) and the mechanisms that regulate eNOS in female genital tract structures are largely unknown.

Aim.  To review available evidence of the mechanisms of eNOS regulation in female genital tract structures.

Methods.  This article reviews the literature that relates to the role of NO and eNOS in female sexual arousal and its modulation by estrogen.

Main Outcome Measures.  Association between female sexual arousal, NO, and eNOS.

Results.  The NO/cyclic guanosine monophosphate pathway is believed to have a primary role in the regulation of clitoral and vaginal blood flow, and smooth muscle relaxation during sexual arousal. Estrogen is critical for maintaining vaginal and clitoral blood flow and vaginal transudate production. Estrogen regulates eNOS by genomic mechanisms, involving augmented mRNA transcription and protein synthesis, and by non-genomic mechanisms, which occur without alterations in gene expression. However, limited studies have evaluated the physiological role of endothelial NO and the molecular mechanisms of eNOS regulation in the female genital tract.

Conclusions.  The effects of estrogen on increasing genital blood flow and smooth muscle relaxation have been attributed mostly to regulation of eNOS. However, the exact mechanisms of eNOS regulation in female genital tract structures and the molecular basis for the eNOS defect with aging and vascular diseases warrant further investigation. Musicki B, Liu T, Lagoda GA, Bivalacqua TJ, Strong TD, and Burnett AL. Endothelial nitric oxide synthase regulation in female genital tract structures. J Sex Med **;**:**–**.