Effect of dehydroepiandrosterone on vaginal and uterine histomorphology in the rat

Dehydroepiandrosterone (DHEA) applied on the dorsal skin of ovariectomized animals, at the twice daily dose of 30 mg, resulted in a complete reversal of the vaginal atrophy seen 1, 3 and 6 months after ovariectomy, and induced proliferation and mucification of the vaginal epithelium. A similar mucification of the vaginal epithelium related to androgenic action was observed in intact rats treated with DHEA. While treatment of intact rats with DHEA resulted in a significant increase in uterine weight at 1 month, the value of the same parameter decreased by approximately 30% after 3 and 6 months of DHEA administration. In ovariectomized DHEA-treated animals, uterine weight was increased at all time intervals. At histopathological examination, following DHEA administration to intact animals, stimulation was seen in the myometrial layers of the uterus whereas atrophy, involving especially the endometrium, became apparent after 3 and 6 months of treatment. In ovariectomized animals, the endometrium remained atrophic at all time intervals during DHEA treatment and the uterine epithelium thus remained atrophic under DHEA treatment. Examination of the effect of DHEA on the vaginal epithelium indicates that local application of DHEA on the vaginal mucosa is approximately 10-fold more efficient than application at a distant site on the skin. Reversal of the ovariectomy-induced increase in serum LH levels was also observed after DHEA treatment. The present data suggest that DHEA possesses a tissue-specific action, through its local transformation into active estrogens in the vaginal epithelium while the uterine epithelium remains atrophic. In addition, the site of administration of DHEA appears to be a significant factor, at least for its stimulatory effect on the vaginal mucosa.