Background: The impact of nipple sensation and its relationship to sexual function have often been neglected in medical literature. However, several recent studies report the importance of the nipple/areola complex (NAC) in sexual arousal and overall function. The nipple is composed of smooth muscle that can be erected via adrenergic nerves. In two complementary studies, we demonstrate that stimulation of the alpha-1 adrenergic receptor in the NAC with topical adrenergic agents can initiate erection of the nipple, increase NAC sensitivity, and improve sexual function. Materials and Methods: Thirteen breast surgery patients with nipple sensitivity loss were recruited to an unblinded study of topical phenylephrine hydrochloride. Sensitivity to pressure was measured before and after the application of the intervention to the NAC. In a second pilot study, 35 women completed a double-blinded placebo-controlled trial of a novel formulation, RJ101, containing a norepinephrine releasing agent. The intervention or placebo was applied to the NAC 30 minutes before sexual activity over the 4-week trial period. The arousal, lubrication, and orgasm domains of the female sexual function index (FSFI) were used to measure sexual function. Results: The application of phenylephrine hydrochloride was shown to increase nipple sensitivity to pressure by an average of 20% in our cohort of 13 breast augmentation patients. In addition, it was shown that intermittent application of the alpha-1 agonist for 8 weeks increased basal NAC sensitivity. In the follow-up pilot study, we demonstrate that stimulation of the NAC with RJ101 produced statistically significant increases versus placebo in the lubrication and orgasm domains of the FSFI, p = 0.0226 and p = 0.0269, respectively. Conclusion: For the first time, we demonstrate that the application of a topical alpha-1 adrenergic receptor agonist or a norepinephrine-releasing agent increases the sensitivity of the NAC and subsequently significantly improves sexual function.
