Absence of systemic hormonal effects in an oestradiol diether topically active on the vaginal mucosa.

The women in this study were either post-menopausal or ovariectomised for at least 1 yr prior to the study. They had also been treated for cancer of the cervix (27 women), endometrium (5), ovaries (5) or breast (1). All women presented with sexual troubles, mainly genital discomfort (dyspareunia or vaginism). In a double-blind fashion, gynaecological capsules containing either an oestradiol diether (ICD: promestriene) or only the excipient were administered for 40 consecutive days. At the end of the treatment, the FSH, LH, oestrone (E1) and oestradiol (E2) plasma levels were not found to be significantly different from the pre-therapeutic values. These results suggest that promestriene acts on the vaginal mucosa, therefore not being converted back into the hormone from which it was derived. Also, in its dietheroxide form, promestriene is incapable of crossing the malpighian (vaginal or epidermal) epithelium and of reaching the general blood circulation. This discrepancy between the local anti-atrophic effects and the inability to exert systemic oestrogen activities singles out promestriene and justifies its therapeutic use when hormonally active oestrogens are contra-indicated, as in patients who have an oestrogen-sensitive cancer in their medical history.

Hyperplasia of the parathyroids and the pituitary in rats with experimental leydigiomas and inhibitory effect of several steroids.

Bilateral orchidectomy performed on 10- to 15-day-old Wistar rats, immediately followed by the homograft of one testis into the splenopancreatic epiploon, resulted 6 months later in leydigiomas at the site of the graft in 100% of the animals. After this latency period, the tumors continued to grow proportionately to time elapsed and were associated with both pituitary microadenomas of the aldehyde-fuchsin-, aldehyde-thionin-periodic acid-Schiff-, and periodic acid-Schiff-positive cells and diffuse hyperplasia of the parathyroids, affecting in particular the chief cells of the latter. After a 6- or 12-month leydigioma latency period, the rats were given a daily treatment by gavage for 45 days of one or two of the following steroids: Compound A, 17alpha-ethynyl, (5alpha)-androst-2-en, 17beta-ol (17 beta-acetate) (5 mg/kg when alone; 2.5 mg/kg when combined); Compound B, 17 alpha-ethynyl, (5 alpha)-androst-2-en, 17 beta-ol (17 beta-nicotinate) (always given in combined form at 2 mg/kg); Compound C, 16-oximinoestrone, 3-allyl ether (2 mg/kg when combined). The treatments caused, in various degrees, (a) involution of the leydigiomas until complete disappearance in up to 50% of the cases; (b) recovery of the characteristic morphological pattern of the pituitaries; and (c) cytolysis and interstitial fibrosis in the previously hyperplastic parathyroids.