Systemic and topical hormone therapies reduce vaginal innervation density in postmenopausal women.
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.
Department of Urology and The Landon Center on Aging, Institute for Neurological Disorders, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Tomas L
TL
Griebling
Zhaohui
Z
Liao
Peter G
PG
Smith
D000284:Administration, Oral; D000287:Administration, Topical; D000368:Aged; D015415:Biomarkers; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008875:Middle Aged; D017933:Peripheral Nervous System / Q000737:chemistry / Q000187:drug effects; D017698:Postmenopause; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D014621:Vagina / Q000294:innervation*; D014660:Vasoactive Intestinal Peptide / Q000032:analysis
D015415:Biomarkers; D014660:Vasoactive Intestinal Peptide; D004958:Estradiol; D014446:Tyrosine 3-Monooxygenase; D015740:Calcitonin Gene-Related Peptide