Decreased circulating levels of estrogen alter vaginal and clitoral blood flow and structure in the rabbit

Aging and menopause related decline in circulating levels of estrogen has been shown to adversely affect female sexual arousal function. Our aim was to study the effects of circulating levels of estrogen on the hemodynamic mechanism of vaginal and clitoral engorgement and on the structure of the vaginal and clitoral cavernosal tissue in the rabbit. New Zealand White female rabbits (3.5 - 4 kg) were randomly divided into three groups with five rabbits in each group: control; bilateral oophorectomy; bilateral oophorectomy undergoing subcutaneous injection of estrogen (40 mug/kg/day). After 6 weeks, the serum levels of 17 beta -estradiol were measured and systemic blood pressure was monitored. Vaginal and clitoral cavernosal blood flows were measured with laser Doppler flowmeter before and after pelvic nerve stimulation. Cross sections of the clitoris and vagina were processed for histologic examination and histomorphometric image analysis. Serum level of 17 beta -estradiol (pg/ml; mean +/- s.d.) revealed a significant decrease in the oophorectomy group (25.4 +/- 5.1) compared with the control (38.5 +/- 7.6) and estrogen replacement (115.9 +/- 57.3) groups (P < 0.05). Nerve stimulation-induced peak vaginal and clitoral intracavernosal blood flows in the oophorectomy group (28.9 <plus/minus> 16.3 and 6.1 +/- 1.4, respectively) were significantly less than those recorded in the control (48.9 +/- 6.5 and 11.0 +/- 2.4, respectively) or estrogen replacement (48.7 +/- 12.2 and 10.1 +/- 12.8, respectively) group (P < 0.05). In histology, marked thinning of the vaginal epithelial layers, decreased vaginal submucosal microvasculature, and diffuse clitoral cavernosal fibrosis were evident in the oophorectomy group but not in the estrogen supplement and control groups. In histomorphometry, the percentage of clitoral cavernosal smooth muscle in the oophorectomy group (49.6 +/- 6.2) was significantly decreased compared with the control (56.8 +/- 2.6) and estrogen replacement (58 +/- 3.0) groups (P < 0.05). Our studies show that decline in circulating levels of estrogen impairs the hemodynamic mechanism of vaginal and clitoral engorgement and leads to histopathologic changes in the vagina and clitoral cavernosal tissue. These observations suggest that decreased circulating levels of estrogen, a physiologic change in the menopausal state, may play a role in the development of female sexual arousal dysfunction.