Institutional members access full text with Ovid®

Share this article on:

Systemic and topical hormone therapies reduce vaginal innervation density in postmenopausal women

Griebling, Tomas L. MD, MPH1,2; Liao, Zhaohui MD2,3,4; Smith, Peter G. PhD2,3,4

doi: 10.1097/gme.0b013e31823b8983
Original Articles

Objective Menopause is often accompanied by vaginal discomfort including burning, itching, dryness, and spontaneous or provoked pain. Although the direct effects of estrogen withdrawal on vaginal cells are implicated, surgical menopause in rodents causes autonomic and sensory nerves to proliferate, suggesting that indirect effects mediated by changes in vaginal innervation may contribute. We assessed whether postmenopausal women display hormone-dependent changes in vaginal innervation.

Methods Vaginal biopsies from 20 postmenopausal women undergoing surgery for stress urinary incontinence and pelvic organ prolapse were fixed and immunostained for the pan-neuronal marker protein gene product 9.5, sympathetic marker tyrosine hydroxylase, parasympathetic marker vasoactive intestinal polypeptide, and sensory nociceptor marker calcitonin gene-related peptide. Innervation density was measured as an apparent percentage of the section area occupied by immunofluorescent axons. Specimens were grouped according to whether participants received systemic hormone therapy (HT), topical (vaginal) HT, or no HT.

Results Women not receiving HT showed relatively high levels of total innervation, with most axons expressing tyrosine hydroxylase or vasoactive intestinal polypeptide immunoreactivity. In women receiving systemic HT, overall innervation was reduced, as were presumptive parasympathetic, sympathetic, and sensory axon populations. Topical HT elicited more dramatic reductions in innervation than in systemic HT.

Conclusions Hormone therapy reduces autonomic and sensory vaginal innervation density, which may, in part, contribute to relief from vaginal discomfort. Moreover, topical therapy is more effective than systemic therapy, which may help explain the greater improvement reported with topical compared with systemic HT.

This study showed that systemic or topical estrogen reduces numbers of vaginal sensory and autonomic axons in postmenopausal women, raising the possibility that changes in innervation may contribute to some menopausal symptoms.

From the 1Department of Urology and The Landon Center on Aging, 2Institute for Neurological Disorders, 3Department of Molecular and Integrative Physiology, and 4Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS.

Received August 14, 2011; revised and accepted October 4, 2011.

Funding/support: This work was funded by NIH NICHD R01HD049615 with core support from NICHD P30HD002528.

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Peter G. Smith, PhD, University of Kansas Medical Center, Kansas Life Sciences Innovation Center, 3901 Rainbow Blvd., Kansas City, KS 66160. E-mail:

©2012The North American Menopause Society