Recently advanced computerized technology was applied to the investigation of morphometric, immunohistological and three-dimensional changes of the endometrial mucosa in order to evaluate quantitatively the effects of three doses of a new slow-release vaginal progesterone on the endometrium in post-menopausal women. A total of 20 menopausal women, deprived of ovarian function, were given oestrogen for 12 days and a combined therapy of oestrogen (administered orally) and progesterone for another 12 day period. Progesterone was administered vaginally through a new gel (Crinone) utilizing a bioadhesive, biocompatible polymer as a base to achieve a sustained release effect. An endometrial biopsy was taken before treatment, after oestrogen-only treatment and after the oestro-progestogen therapy. Before treatment, all the patients exhibited an atrophic endometrium. After oestrogen-only treatment, typical proliferative changes occurred: an increase in the endometrium thickness, an increase in the mitotic index, numerous cylinder-like glands and no coiled glands, and high concentrations of oestrogen receptors (ER) and progesterone receptors (PR). After the oestro-progestogen therapy, whatever the dose of progesterone given, a secretory transformation of the endometrial mucosa occurred, mitotic activity decreased significantly, more ramified and coiled glands were observed, and a decrease in PR content was noted in epithelial and stromal nuclei, and a decrease in PR content was also observed in epithelial nuclei but not in stromal nuclei. Accurate new techniques of image analysis have shown that crinone therapy could eliminate the proliferative effects of oestrogen treatment in post-menopausal women, despite doses as low as 45 mg of progesterone administered vaginally every other day. The results suggest that the sustained release effects of Crinone are clinically relevant.

A computerized morphometrical investigation was performed on endometriotic tissue from the peritoneum (n = 225) and rectovaginal nodules (n = 65) to compare histologically and stereologically the rectovaginal septum endometriotic nodule to peritoneal endometriosis. Mitotic activity, stromal vascularization and the epithelium/stroma ratio were found to be significantly different in peritoneal and rectovaginal endometriosis. The evaluation revealed a major role of glandular epithelium in rectovaginal nodules where the stroma sometimes appeared absent around glandular epithelium. The study demonstrated opposite effects of gonadotrophin-releasing hormone agonists (GnRHa) and lynestrenol on the two lesions. Indeed, in peritoneal endometriosis, after GnRHa therapy, our study demonstrated a lower rate of mitosis and poor stromal vascularization. The same drug was unable to induce the same effects in the nodule although, in contrast, lynestrenol has a strong effect on nodule vascularization. In conclusion, it is suggested that the rectovaginal adenomyotic nodule is a specific disease, different from peritoneal endometriosis. It is not the consequence of 'deep infiltrating' endometriosis but can probably develop from Mullerian rests present in the rectovaginal septum.