While a significant body of evidence exists on peripheral effects of estrogen on female urogenital tissue, there is limited data on the effects of testosterone on vaginal structure and function. The goal of this study was to evaluate presence of androgen receptors in human vaginal tissue and characterize differences in receptor density based on age, menopausal status, and vaginal location.
Methods:
Demographic information including age, menopausal status, and hormone replacement therapy were recorded from 27 women undergoing surgery for prolapse. Vaginal specimens were obtained and characterized as proximal vagina (proximal 2/3rds) or distal (distal 1/3rd). Specimens were fixed in 4% formaldehyde, paraffin-embedded, and immunostained with a polyclonal antibody against androgen receptor. Slides were examined for nuclear receptor staining, and graded by percentage of positive cells per high-power field and by staining intensity.
Results:
Specimens were obtained from 27 women, mean age 62. Seven were premenopausal and 20 were postmenopausal. 14 of the postmenopausal women were receiving hormone replacement therapy in the form of oral estradiol. Testosterone receptors were predominantly localized in the nucleus of vascular endothelial, smooth muscle, and stromal cells in vaginal submucosa. Proximal vaginal specimens had significantly higher submucosal androgen receptor density scores than distal vaginal specimens. Factors that were significantly associated with diminished mean androgen density score were increasing age, distal vaginal location, and estrogen replacement therapy. Vaginal specimens from older women and women receiving estrogen replacement therapy had significantly lower vaginal mucosal and submucosal androgen receptor density scores than premenopausal women or post menopausal women not receiving estrogen replacement therapy.
Conclusions:
These findings suggest that androgens may play a role in regulating vaginal smooth muscle and blood flow. Diminished androgen receptor expression in vaginal sub-epithelium of women on estrogen replacement therapy may result from estrogenic stimulation of SHBG, leading to less free testosterone and less production of androgen receptors. Persistent symptoms of vaginal atrophy and dryness in menopausal women receiving estrogen replacement therapy may in part be related to impaired androgen responsiveness derived from decreased vaginal androgen receptors, and/or reduced levels of circulating or vaginal testosterone.
