Intrauterine release of oestriol in castrated rhesus monkeys induces local but not peripheral oestrogenic effects: a possible approach for the treatment and prevention of Asherman's syndrome

Abstract

Two types of oestrogen-medicated intrauterine devices (IUD) were studied in ovariectomized rhesus monkeys. An oestradiol (E2) fibre-wrapped IUD that released E2 at a rate of 3.57 micrograms/cm/day, or an oestriol (E3) fibre-wrapped IUD that releases E3 at a rate of 6.4 micrograms/cm/day, was inserted in eight animals and left in place for 4 weeks. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), E2 and E3 were determined by radioimmunoassay for 1 week before the IUD insertion, during the time the IUD was in place, and for 3 weeks after its removal. Uterine histology was performed at the time of IUD insertion and removal by light and transmission electron microscopy. Both E2 and E3 IUDs induced similar histological changes in the uterus, i.e. four- to five-fold increase in endometrial thickness, a shift of the gland/stroma ratio from 1:4 to 1:1, transformation to a marked pseudostratified epithelium with pronounced coiling of the glands, appearance of subnuclear and luminal secretion and, finally, change from spindle-dense stromal cells to plump eosinophilic cells. Oestradiol fibre-wrapped IUDs produced circulating E2 levels of 150-200 pg/ml during the entire 4 weeks. FSH and LH levels were decreased to an average of 55% and 65% from a castration baseline (P less than 0.001 and P less than 0.05, respectively). Oestriol fibre-wrapped IUDs produced circulating E3 levels of 100-250 pg/ml. However, FSH and LH levels were not altered in this group. The specific local oestrogenic effect of E3-IUDs without affecting the pituitary secretion of gonadotrophins, suggests their possible application in cases in which an exclusively oestrogenic effect at the uterine level, such as in Asherman's syndrome, is desired.

Management of Asherman’s syndrome

“…Investigation Asch et al (1991) inserted oestrogen fibre-wrapped IUD into the uteri of castrated rhesus monkeys. The devices induced marked endometrial proliferation and the authors suggested that such a device might provide the same efficacy as oral oestrogen treatment but without the systemic side effects.…”

Asherman's Syndrome

“…Asch et al placed estrogen fiber-wrapped IUDs into the uteri of castrated rhesus monkeys to induce marked endometrial proliferation and suggested that such a device might provide the same efficacy as oral estrogen treatment but without the systemic side effects. 55 Some studies using sildenafil (Viagra) 100 mg vaginally or 6 mg of L-arginine (which may strengthen blood vessels) daily have shown increased endometrial thickness and an improvement in radial artery-resistance indexes. 56 There are encouraging, but scanty data demonstrated thickened endometrium after a 6-month use of pentoxifylline (800 mg/day) and vitamin E (1000 IU/ day).…”

Prévention des synéchies après hystéroscopie opératoire

“…En 1991, Asch et al [12] rapportaient dans une étude l'utilisation de deux types de dispositifs intra-utérins (DIU) aux estrogènes (oestradiol et oestriol) laissés pendant trois semaines chez des singes rhésus ovariectomisés. Les auteurs analysaient alors les taux circulants d'oestradiol, de FSH, de LH et les effets sur la muqueuse utérine.…”