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Effects on Human Males of In Utero Exposure to Exogenous Sex Hormones
Published in Takao Mori, Hiroshi Nagasawa, Toxicity of Hormones in Perinatal Life, 2020
Other cases of ambiguous genitalia following exposure to DES in utero have been reported. Cleveland and Chang28 reported a problem of intersex with an XX karyotype, but no uterus or Fallopian tubes, and with glands only being in scrotal folds and containing aplastic testicular tissue. Hoefnagel29 reported prenatal DES exposure and “typical clinical and laboratory findings of hypogonadotropic hypogonadism with anosmia’ ‘. (Histologic description of the gonads was not given.) Beral and Col well30 reported a case of hermaphroditism and a case of “underdeveloped external genitalia” following in utero exposure to DES and ethisterone.
Androgens
Published in Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer, Handbook of Systemic Drug Treatment in Dermatology, 2015
Danazol is a synthetic steroid derived from ethisterone. It is a weak androgen with additional antiprogestogenic and antioestrogenic actions and interferes with gonadal steroid synthesis. It also affects pituitary gonadotrophins, with inhibition of the mid-cycle surge of follicle stimulating hormone (FSH) and luteinizing hormone (LH), as well as altering the pulsatility of LH, and can reduce the mean plasma levels of these gonadotrophins after the menopause.
Mechanisms of Cholestasis
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
The cholestatic activity of the anabolic steroids has not been investigated to the same extent as that of the estrogens, even though the cholestatic jaundice induced by methyltestosterone (Figure 7) has been recognized since 1947 (Werner, 1947). Cholestasis has been observed primarily in patients treated with the anabolic steroids for Fanconi’s and aplastic anemias, however, their misuse/abuse by athletes has also led to a number of hepatic complications [see Ishak and Zimmerman (1987) for a recent review]. Intrahepatic cholestasis usually develops after short-term use of anabolic steroids, whereas their long-term use may result in peliosis hepatis or the induction of benign or malignant tumors. The functional impairment most often demonstrated in humans has been the plasma retention of BSP, whereas appearance of jaundice, i.e., retention of bilirubin, appears in only a minority of patients (Plaa and Priestly, 1976; Ishak and Zimmerman, 1987). Structure-activity relationship studies have demonstrated that an alkyl group in the C-17 position is a key requirement for induction of jaundice and hepatic dysfunction in humans since testosterone and 19-nortestosterone have only rarely caused hyperbilirubinemia and did not induce BSP retention (deLorimier et al., 1965; Lennon, 1966a,b). The incidence of BSP retention was highest for normethandrone and norethindrone (Figure 7), moderate with methyltestosterone, fluoxymestrone, and methandriol, and low with ethisterone (deLorimier, 1965). A keto group at the C-3 position increases toxicity relative to a hydroxy substituent whereas saturation of the A ring decreases toxicity. Potency for retention of BSP appears unrelated to the anabolic, androgenic, or progestational activity of these steroids (deLorimier et al., 1965).
Delivery of progestins via the subdermal versus the intrauterine route: comparison of the pharmacology and clinical outcomes
Published in Expert Opinion on Drug Delivery, 2018
Norman D. Goldstuck, Hung P. Le
The implants and IUSs differ from the third type of established LARC methods, namely the injectable progestins, depo-medroxy progesterone acetate (DMPA) and nor-ethisterone oenanthate (NET), in that they do not suppress FSH secretion and do not suppress ovarian estrogen synthesis, and are therefore not associated with the problem of osteoporosis, as is DMPA (NET is partially metabolized to estrogen and avoids this problem) .