Effects of Ovariectomy and Dehydroepiandrosterone (DHEA) on Vaginal Wall Thickness and Innervation

Abstract

Introduction One mechanism by which low sexual steroid activity observed after menopause could cause sexual dysfunction is by deficient vaginal innervation. Recently, it has been shown that intravaginal administration of dehydroepiandrosterone (DHEA) could produce beneficial effects on sexual dysfunction in postmenopausal women. Aim The goal of this study was to determine if DHEA could modify innervation in the rat vagina. Main Outcome Measures The area occupied by the nerve fibers immunoreactive for protein gene product 9.5 (PGP 9.5), a panneuronal marker or tyrosine hydroxylase (TH), a sympathetic nerve fiber marker, in the lamina propria and muscular layers, respectively, as well as the total area of each of these 2 layers were measured by stereological analysis. Methods The innervation of the rat vagina was examined 9 months after ovariectomy (OVX) compared to intact animals and treatment of OVX animals with DHEA (80 mg/kg). Four sections from each vagina (5 animals/groups) were immunostained. Results In OVX animals, the lamina propria area was decreased to 44%, an effect which was reversed by DHEA to 69% of the intact value. OVX also caused a 59% decrease in the area of PGP 9.5 fibers, an effect which was prevented by DHEA, thus showing a 68% stimulatory effect of DHEA on the density of PGP 9.5 fibers in the lamina propria compared to OVX animals. Following OVX, the muscular layer area was decreased by 61%. DHEA treatment induced 118% and 71% increases in TH fiber area compared to OVX and intact animals, respectively. The density of TH fibers was 182% increased over intact controls by DHEA treatment of OVX animals. Conclusions The relatively potent stimulatory effect of DHEA on intravaginal nerve fiber density provides a possible explanation for the beneficial effects of intravaginal DHEA on sexual dysfunction observed in postmenopausal women.

Estrogen Replacement Regulates Vaginal Innervations in Ovariectomized Adult Virgin Rats: A Histological Study

“…This is in agreement with data from Pelletier et al [11] and Ahmed et al [18] but differs from the results of Ting et al [7] and Griebling et al [6]. However, Pelletier et al [11] just showed a significant decrease (59%) in vaginal PGP 9.5-ir fibers 9 months after OVX without further estrogen replacement therapy. Ahmed et al [18] focused on estrogen recovering function on pudendal nerve crush, omitting vaginal innervation.…”

“…In this study, examination of plasma estrogen levels one month after OVX revealed that they were below the lower limit of the physiological range. Taken in combination with the results from Ting et al [7] and Pelletier et al [11], these data indicate that the dynamic changes in vaginal innervation after OVX may involve a short-term compensatory increase followed by a sustained decline. Furthermore, the discrepancy may partly be the narrow therapeutic range of estradiol, because the benefit of estrogen in vaginal innervation is diminished at larger doses.…”

“…Similar depletions in vaginal innervation were observed in rats following a sustained estrogen elevation at term pregnancy [8, 9]. In contrast, Pessina et al reported that estrogen treatment and OVX did not significantly affect vaginal innervation, while testosterone was found to increase the numbers of small adrenergic nerve fibers [10], while Pelletier et al showed a significant decrease in vaginal PGP 9.5-ir fibers following OVX [11]. Overall, the literature strongly indicates that the hormonal status can modulate vaginal innervation, but the role of estrogen in this process still remains unclear.…”

“…Ting et al [7] studied innervation one week after OVX (with continuous estrogen treatment for that week), while Pelletier et al [11] examined innervation in rats 9 months after OVX. In this study, examination of plasma estrogen levels one month after OVX revealed that they were below the lower limit of the physiological range.…”

New perspectives of the treatment of urogenital atrophy in women: intravaginal DHEA therapy

“…Podobnych wyników nie uzyskano podczas doustnego podawania preparatów z DHEA [4]. Wytłu-maczeniem tego zjawiska może być silny wpływ DHEA na zwiększenie gęstości włókien nerwowych w ścianie pochwy, który wykazano w doświadczeniu na zwierzę-tach [12]. W innych badaniach Labrie i wsp.…”