Login to Access Video or Poster Abstract: MP81-13
Sources of Funding: Support provided by a WVCTSI pilot grant.

Introduction

Vaginal estrogen delivery is the recommended treatment for_x000D_ vulvovaginal atrophy with menopause to minimize systemic estrogen_x000D_ exposure. Both human and animal studies have indicated a_x000D_ restorative effect of local estrogen therapy on the vaginal_x000D_ epithelium however little is known of its effect on other aspects of_x000D_ vaginal physiology. The objective of this study was to determine the_x000D_ effect of vaginal estrogen delivery on vaginal non vascular smooth_x000D_ muscle (vaginal muscularis) structure and function in a rodent model_x000D_ of menopause.

Methods

Three month old ovariectomized (OVX) and sham ovariectomized (SH)_x000D_ Sprague Dawley rats were ordered from a commercial supplier. Two_x000D_ weeks following surgery, animals were treated vaginally with either_x000D_ a vehicle cream (SHVV,OVXVV) or an 0.002% 17 β estradiol cream_x000D_ (OVXVE). Animals were euthanized after 4 weeks of daily vaginal_x000D_ cream delivery and uterine and vaginal weight were recorded._x000D_ Immmunohistochemical analysis of α actin expression was_x000D_ performed with vaginal tissue(n=3/group). In vitro contractility_x000D_ studies of proximal and distal vaginal strips were conducted (n=3)._x000D_ Dose response curves to carbachol (a muscarinic agonist) were_x000D_ constructed to calculate the EC50 and maximal amplitude of_x000D_ contraction (force normalized to KCl). Data are presented as means ±SEM. Data were statistically analyzed using a one way ANOVA_x000D_ followed by Tukeys test(GraphPad Prism software).

Results

Vaginal wet weight was decreased (P<0.05) in OVXVV animals compared_x000D_ to SHVV, an effect reversed by local estrogen delivery. Qualitative_x000D_ analysis of vaginal cross sections indicated reversal of ovariectomy_x000D_ induced atrophy of the vaginal muscularis with estrogen treatment._x000D_ In vitro contractility studies with carbachol demonstrated a trend_x000D_ of a lower EC50 (increased sensitivity) of vaginal strips obtained_x000D_ from OVXVV animals compared to SHVV and OVXVE. The amplitude of_x000D_ contraction to 10 uM carbachol was greater of proximal strips from_x000D_ OVXVV animals compared to SHVV and OVXVE (P<0.05).

Conclusions

Our results indicate that vaginal estrogen is effective at reversing_x000D_ not only OVX induced atrophy of the epithelium but also the_x000D_ vaginal muscularis. We report an increased contractile response to_x000D_ carbachol in OVXVV animals, an effect also reversed by vaginal_x000D_ estrogen. Interestingly, previous studies have shown an increase in_x000D_ vaginal sensory innervation in ovariectomized rodents. More studies_x000D_ are needed to evaluate changes in autonomic innervation with this_x000D_ animal model to identify new therapeutic uses of vaginal estrogen_x000D_ treatment.

Funding

Support provided by a WVCTSI pilot grant.