Masculinization of a female foetus with oestrogenic effect.

Masculinization of a female foetus by androgenic hormones produced by an arrhenoblastoma in the mother during pregnancy was described by Brentnall (1945). Masculinization and pseudohermaphroditism caused by the administration of 17-methyltestosterone to the mother during pregnancy was reported by Hayles and Nolan (1957), Grunwaldt and Bates (1957) and others. Since Wilkins, Jones, Holman and Stempfel (1958) described masculinization of the female foetus attributed to the administration of progestins with androgenic activity, an increasing number of cases of non-adrenal pseudohermaphroditism are being recognized. Their paper reports 21 cases of nonadrenal masculinization of the external genitalia. In 15 cases the oral progestin 17-ethinyl-testosterone (ethisterone or anhydrohydroxyprogesterone) had been given, in two cases the mother had received intramuscular injections of progesterone, in one case the progesterone had been given together with oral methyltestosterone and in three cases no steroid had been administered. Since the publication of their paper the number of cases observed by them or collected from colleagues' reports has risen to 60. The mothers of 25 had received 17-ethinyltestosterone; the mothers of 28 had been given 17-ethinyl-19-nortestosterone (norethindrone, norlutin) (Wilkins, 1959). The clinical picture resembles the more familiar pseudohermaphroditism of the adrenogenital syndrome. Phallic enlargement varies according to the degree of labio-scrotal fusion. Complete fusion and a penile urethra may occur, though the formation of a urogenital sinus or phallic enlargement alone is more usual. The baby is chromatin positive. The mother has been given a progestin early in the pregnancy, usually with the intention of preventing a miscarriage. There is no increase in the urinary 17-ketosteroids and no abnormality of the internal genitalia. The condition is not progressive once the baby has been removed from the influence of the administered progestin and, apart from surgical correction of the external abnormality, if necessary, for psychological, cosmetic or reproductive purposes, no treatment is required. The outlook for childbearing is good. Our case is believed to be unique in that, although there was masculinization, there is also strong evidence of a potent oestrogenic effect.