International Journal of Impotence Research (1997) 9, 27±37 ß 1997 Stockton Press All rights reserved 0955-9930/97 $12.00 Vasculogenic female sexual dysfunction: The hemodynamic basis for vaginal engorgement insuf®ciency and clitoral erectile insuf®ciency K Park, I Goldstein, C Andry, MB Siroky, RJ Krane and KM Azadzoi Department of Urology, Boston University School of Medicine and Boston Veteran's Administration Hospital, Boston, MA, USA Objective: Organic female sexual dysfunction may be related in part to vasculogenic impairment of the hypogastric-vaginal/clitoral arterial bed. The aim was to develop an animal model of vaginal engorgement insuf®ciency and clitoral erectile insuf®ciency. Methods: Pelvic nerve stimulated vaginal engorgement and clitoral erection were achieved in control (normal diet, n 8) and atherosclerotic (balloon injury of aorto-iliac arteries and 0.5% cholesterol diet, n 7) New Zealand White female rabbits. After 16 weeks, novel hemodynamic variables including vaginal wall and clitoral blood ¯ow, vaginal wall and clitoral intracavernosal pressure, vaginal length, vaginal luminal pressure, blood levels of cholesterol and triglycerides, aorto-iliac angiography and vaginal wall and clitoral erectile tissue histology were recorded in the two groups. Results: Concerning pelvic nerve stimulated vaginal hemodynamic changes, there was signi®cantly less increase in blood ¯ow (ml/min/100 gm tissue), wall pressure (mmHg) and length changes (mm) in atherosclerotic (9.3 Æ 3.7, 4.8 Æ 3.8, 67.3 Æ 8.3) compared to control (13.9 Æ 4.5, 5.5 Æ 2.6, 74.1 Æ 10.0) animals respectively. Histologic examination of clitoral erectile tissue demonstrated cavernosal artery atherosclerotic changes and diffuse vaginal and clitoral ®brosis. Aorto-iliac angiography in atherosclerotic animals revealed diffuse moderate to severe athero- sclerotic occlusion. Conclusions: Vaginal engorgement and clitoral erection depend on increased blood in¯ow. Atherosclerosis is associated with vaginal engorgement insuf®ciency and clitoral erectile insuf®ciency. Keywords: female sexual function; vasculogenic female sexual dysfunction; vaginal engorgement; vaginal engorgement insuf®ciency syndrome; clitoral erection: clitoral erectile insuf®ciency Introduction of the women had arousal or orgasmic dysfunc- tions.3 Similar to male sexual dysfunction, the prevalence of female sexual dysfunction has been Females have sexual dysfunction. Post-menopausal shown to increase with age and be associated with women often complain of discomfort with inter- the presence of vascular risk factors and the course, dryness of the vagina and diminished development of the menopause.4±6 Post-menopausal vaginal arousal.1,2 Studies comparing sexual dys- women and women with a history of vascular risk function in couples have revealed 40% of the men factors have been shown to have signi®cantly more had erectile or ejaculatory dysfunction whereas 63% complaints of self-reported female vaginal and clitoral dysfunctions than pre-menopausal women or women without vascular risk factors.5 Correspondence: Dr KM Azadzoi, Department of Urology, Despite the existence of widespread clinical B5-45, Boston VA Medical Center, 150 South Huntington pathology in both male and female sexual dysfunc- Avenue, Boston MA 02130. tions, there has been a virtual focus on the male in This manuscript was awarded the Jean-Paul Ginestie Prize at scienti®c investigations. Over the past decade, there the VII World Meeting of the International Society for has been widespread interest in the understanding Impotence Research in 1996. This work was supported by Grant DK 45087 from the of the physiology and neuroanatomy of male erectile Department of Health and Human Services and a grant from tissue, the pathophysiology of disease mechanisms Veterans Affairs Central Of®ce. inducing male erectile dysfunction and the diag- Received 1 June 1996; accepted 6 November 1996 nosis and treatment of male impotence syndromes. Vasculogenic female sexual dysfunction K Park et al 28 Over the same time period, however, there has been suf®ciency syndromes. In this model, supporting a dearth of research concerning the physiology of data from aortic and iliac artery arteriographic and female sexual dysfunction, the pathophysiologic vaginal spongy and clitoral erectile tissue histologic mechanisms of female sexual dysfunction and the studies were performed. It is the ultimate interest of development of diagnostic and therapeutic alterna- this research endeavor to hypothesize the existence tives for af¯icted female patients. of an underlying vascular pathology in female What is the basis for the apparent lack of interest sexual dysfunction (similar to the male) and to in the investigation and treatment of female sexual encourage young investigators to pursue needed dysfunction? While the answer remains complex new scienti®c knowledge in this developing ®eld. and multi-factorial, there have been at least three postulated explanations. There has existed a strong taboo and even a hostility against the laboratory Materials and methods study of female sexual function.7,8 There has existed a lack of support from the major research funding Experimental model agencies.7,8 There has existed a lack of a relatively inexpensive, reliable and appropriate animal model of female sexual dysfunction.7,8 In particular, the The New Zealand White female rabbit (3±3.5 kg) was historic dif®culty with the availability of a female selected as the animal model to examine prelimin- animal model was based on the hypothesis that the ary female vaginal and clitoral sexual physiology prime expression of female sexual dysfunction was and pathophysiology. The animals were divided orgasmic-related and thus the only appropriate into control (n 8) and atherosclerotic (n 7) model for laboratory investigation was the human.7 groups. Control animals received a regular diet There have been few previous studies with while atherosclerotic animals underwent balloon animals concerning female sexual responses.9±12 At injury of the common and external iliac arteries and the level of the pelvic organs, female sexual were placed on 0.5% cholesterol diet. response has been evidenced by the appearance of After 16 weeks, control and atherosclerotic vaginal lubrication along with tumescence of the animals were anesthetized with titrated intravenous clitoris.13 Both are physiologic phenomena asso- phenobarbital and hydrated with intravenous 0.9% ciated with localized autonomic nerve stimulated NaCl. An angiocatheter was placed into the carotid increases in blood ¯ow. Previous investigations of artery for measurement of systemic arterial pressure. such hemodynamic evens have thus far been Through a midline abdominal incision, the abdom- plagued by methodological problems. Measure- inal aorta and both iliac arteries were exposed. ments have been based largely on indirect maneu- Arterial blood ¯ow (ml/min) through the right and vers such as photoplethysmography, thermal left common iliac arteries was monitored by placing clearance and other temperature-based methods.7 an appropriately sized perivascular ¯ow sensor Direct measurement of both vaginal and clitoral around the respective artery. The ¯ow sensor was blood ¯ow using laser Doppler ¯ow probe technol- connected to an ultrasonic ¯owmeter (Transonic ogy following local pelvic nerve stimulation has not, Systems., Ithaca NY). to the best of our knowledge, previously been The pelvic nerve branch to the vagina and clitoris reported. was identi®ed and carefully dissected under the The overall goal of our study was to apply perivesical fat on the postero-lateral aspect of the recognized techniques for the scienti®c study of vagina as the nerve emerged from its associations male erectile dysfunction14,15 to initiate novel in- with the rectum, bladder and uterus. The clitoris vestigation into the physiology of female sexual and corresponding corporal bodies were exposed via function and the pathophysiology of female sexual a midline incision. dysfunction. One speci®c aim was to establish, for the ®rst time, preliminary data concerning a reliable and relatively inexpensive animal model for the Pelvic nerve stimulation physiologic investigation of pelvic-nerve stimulated vaginal engorgement and clitoral erection. In this A Harvard subminiature electrode was placed model, direct measurements of physiologic variables around the pelvic nerve (Figure 1). Unilateral pelvic such as vaginal and clitoral blood ¯ow, vaginal nerve stimulation was performed by square wave spongy and clitoral erectile tissue pressure, vaginal unidirectional stimulation (10 V, 16 Hz, 8 ms) deliv- length changes and vaginal luminal pressure were ered for 20 s with a Grass SD-9 stimulator (Grass able to be performed. A second speci®c aim was to Instruments, Quincy, Massachusetts). These stimu- develop, for the ®rst time, preliminary data con- lation parameters produced reliable and reproduci- cerning a reliable animal model of the pathophy- ble hemodynamic responses. Preliminary frequency siology of atherosclerosis-induced vaginal response studies revealed that maximal blood ¯ow engorgement insuf®ciency and clitoral erectile in- responses were observed at 16 Hz. This frequency of Vasculogenic female sexual dysfunction K Park et al 29 Measurement of vaginal luminal pressure A dual lumen 9F rectal pressure catheter (Life-Tech) was ®lled with saline, and inserted into the distal 1/ 3 of the vaginal lumen. One port was connected to a pressure transducer to an ampli®er.