Saturday, 27 October 2007 Presented October 25th - 28th, 2007 at the 2007 Urological Research Society (URS) Meeting - Napa, California
Introduction: Diabetes has profound effects on sexual function in men and women. However, the effects of diabetes on sexual function in women have received limited attention in basic and clinical research. A recent literature survey over the last 10 years demonstrated that there was considerable disparity in investigating the effects of diabetes on male erectile dysfunction and female sexual dysfunction. The effects of diabetes on female genital tissue structure, innervation and function as well as the sexual arousal response, remains poorly characterized.
Aim and Methods: To investigate the effects of diabetes-induced hyperglycemia on vaginal tissue structural integrity and the estrogen and androgen signaling in mediating vagina and the physiological arousal response. We have employed two animal models to investigate type 1 and type 2 diabetes on vaginal structural and functional integrity. In control and streptozotocin-treated female rats, we investigated the effects of diabetes on vaginal blood flow,tissue morphology,and expression of arginase I, endothelial nitric oxide synthase (eNOS) and cGMP-dependent protein kinase (PKG), key enzymes that regulate smooth muscle relaxation. We further related these changes with estrogen receptor alpha (ER?)and androgen receptor (AR) expression. In a mouse model of type 2 diabetes, we investigated the impact of diabetes on vaginal structural and functional integrity and the potential effect of estrogen supplementation to ameliorate diabetes induced metabolicalterations. The framework is illustrated in the figure below.
Results: In addition to significantly elevated blood glucose levels, diabetic rats had decreased mean body weight, lower levels of plasma estradiol, and higher plasma testosterone concentration, compared to age-matched controls. Eight weeks after administration of buffer (control) or 65 mg/ kg of streptozotocin (diabetic), the vaginal blood flow response to pelvic nerve stimulation was significantly reduced in diabetic rats. Histological examination of vaginal tissue from diabetic animals showed reduced epithelial thickness and atrophy of the muscularis layer. Diabetic animals also had reduced vaginal levels of eNOS and arginase I, but elevated levels of PKG, as assessed by Western blot analyses. These alterations were accompanied by a reduction in both ERα and AR in nuclear extracts of vaginal tissue from diabetic animals. Marked vaginal atrophy was also noted in type 2 diabetic animals with loss of the muscularis layer and reduction in the expression of sex steroid receptors.
Conclusions: We noted a marked decrease in vaginal blood flow, alterations in tissue structure, ERα, arginase I and eNOS in diabetic animals. We hypothesize that diabetes lead to multiple disruptions in sex steroid hormone signaling and action. These pathological events may cause dramatic changes in tissue structure and key enzymes that regulate cell growth and smooth muscle contractility, ultimately affecting the genital response during sexual arousal. The significance of these observations is that new approaches to management of sexual dysfunction in diabetic women are needed.
Authors: Traish A, Cushman T, Kim N
UroToday.com is grateful to be offered exclusive coverage of the Urological Research Society.