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As many as 10 million American women 50 to 74 years of age describe reduced vaginal lubrication, uncomfortable or frankly painful intercourse, decreased arousal, and difficulty reaching orgasm. These symptoms have been associated with the postmenopausal drop in estrogen levels. The P2Y 2 receptor agonists are purinergic receptor ligands currently under study for their prosecretory effects in numerous clinical settings. Stimulation of P2Y 2 receptors activates phospholipase C, prompting intracellular release of calcium that increases surface liquid and hydrates secretions. This study examined the potential role for P2Y 2 receptor agonists in treating vaginal dryness. Two weeks after ovariectomy, rabbits received daily instillations of one of two agonists, 0.9% INS45973 or 8.1% INS365, for 16 days, while control animals received vehicle only. Swabs were used as moisture probes. In situ hybridization studies were carried out to estimate receptor mRNA in vaginal and cervical tissues from female cynomolgus monkeys. Vaginal moisture was significantly reduced after ovariectomy in vehicle-exposed rabbits. Both P2Y 2 receptor agonists increased moisture in ovariectomized animals. Moisture levels were comparable to those in control animals when INS365 was administered and significantly higher than in controls with INS45973. Ovariectomy resulted in minimal inflammation, which was not observed when animals were given either agonist. The cytoplasm of cells in both cervical gland and endocervical epithelium, but not the stroma, exhibited positive staining for receptor mRNA. Examination of vaginal tissue samples showed positive staining in the cytoplasm of stratified squamous epithelial cells, but not in the submucosa or muscularis. Synthetic P2Y 2 receptor agonists are able to increase vaginal moisture in estrogen-deprived animals, and they could relieve postmenopausal vaginal dryness by increasing mucin production as well as augmenting pelvic blood flow. This approach might be safer than systemic or topical estrogen replacement in high-risk women.

Objective To report gray scale, volumetric, and duplex ultrasound data before and after sexual stimulation in a large population of women with sexual dysfunction. Design Retrospective review of women with sexual dysfunction. Setting An academic center. Patient(s) Pre- and postmenopausal women with sexual dysfunction. Intervention(s) None. Main outcome measure(s) This is an Institutional Review Board-approved retrospective study of 142 women who underwent duplex Doppler ultrasound (DDU) arousal testing for sexual dysfunction. Result(s) This study revealed that DDU was able to record morphologic, volumetric (clitoral and corpora spongiosa diameters), and hemodynamic (peak systolic and end-diastolic) changes in women with sexual dysfunction before and after sexual stimulation. Resistive index measurements, which are indicative of veno-occlusive function, did not significantly change before and after arousal in both the clitoris and corpora spongiosa. We also found a correlation between genital diameter and genital end-diastolic velocity value. Gray scale scanning revealed tunical thickening or plaque in several patients who sustained blunt perineal trauma. Conclusion(s) The role of DDU in the management of women with sexual dysfunction remains to be determined; however, end-diastolic velocity values suggest that this parameter has an important physiologic implication as a direct determinant of genital engorgement.

Objective: In women, androgens modulate the physiological function of many reproductive and sexual organs, including the ovaries, uterus, vagina, oviducts, clitoris, and mammary gland. In this article, we review the mechanisms of androgen action and discuss new data on the effects of androgens in vaginal and clitoral tissues. Main Outcome Measure(s): In this study, we characterized the androgen receptor expression in rabbit vaginal tissues from control and ovariectomized animals treated with or without androgen replacement therapy. We investigated the effects of androgen deprivation and replacement on the expression and activity of nitric oxide synthase and arginase and on vaginal smooth muscle contractility. Result(s): Androgens enhanced nitric oxide synthase activity and down-regulated arginase activity in proximal vagina. Estrogens down-regulated nitric oxide synthase activity and increased arginase activity in distal vagina. Androgens facilitated vaginal smooth muscle relaxation to electric field stimulation and vasoactive intestinal polypeptide, whereas estrogens attenuated vaginal tissue relaxation to electric field stimulation and to vasoactive intestinal polypeptide. Conclusion(s): These observations suggest that androgens may play an important role in modulating the physiology of vaginal tissue and contribute to female genital sexual arousal.