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  • SB 290157 trifluoroacetate salt Matsuzaki et al attempted fe

    2024-04-16

    Matsuzaki et al. attempted fertility therapy in a 26-year-old female with secondary amenorrhea and 17OHD who was a SB 290157 trifluoroacetate salt heterozygote for delF53/54 and the missense mutation H373L, which has <23% 17-hydroxylase activity and <5% 17,20-lyase activity compared with wild type (22). Endometrial preparation with sequential transdermal E2 and IM P yielded a 6-mm endometrial stripe on ultrasound with biopsy revealing absence of stroma. A COH cycle with recombinant FSH produced a 19-mm ovarian follicle and a 6.1-mm endometrial stripe on cycle day 7, with a low serum E2 concentration of 36.5 pg/mL; no pregnancy resulted. In addition to searching PubMed for reports on fertility in individuals with 17OHD, electronic communications were sent to over 50 authors who had published any articles regarding 17OHD. These communications yielded no additional unpublished reports of fertility therapy or pregnancy. Table 3 summarizes the published experience of fertility treatments and outcomes in patients with 17OHD. Although a literature review by Araki et al. reported normal T production in 3/22 males with 17OHD, we found no reports of fertility in males with 17OHD (36). All patients thus far described with isolated 17,20-lyase deficiency were infertile. Nevertheless, the literature might be clouded with an ascertainment bias, which might prevent the diagnosis of patients with partial defects. The diagnosis of 17OHD is typically only considered in 46,XY DSD patients when hypertension and hypokalemia are present. Milder cases of 17OHD might be assumed to be “idiopathic hypospadius” if not evaluated thoroughly. Consequently, the capacity of men with partial 17OHD to reproduce might be higher than assumed from more severe cases. In summary, 17OHD is a rare form of CAH that is associated with infertility. The mechanism of infertility in females is likely primarily anovulation due to arrested folliculogenesis. A lack of aromatizable substrates might account for anovulation-related infertility in females with 17OHD, and chronically elevated adrenal-derived P might also contribute to infertility. The adrenal-derived P can be normalized with glucocorticoid therapy; however, the blockade in sex steroid synthesis has been difficult to overcome with conventional infertility therapies. Furthermore, gonadal-derived P will rise prematurely during gonadotropin stimulation, owing to the block of CYP17A1 in the ovaries as well. Administration of T with assisted reproductive technology did not result in pregnancy, suggesting further defects distal to the CYP17A1-catalyzed reactions. Uterine dysfunction might also contribute to impaired fertility, as hypoplastic uteri are common in females with 17OHD 36, 43, 44, 46. Although assisted reproductive technologies bypass some of these defects, uterine underdevelopment has been associated with impaired cervical mucus production, which impedes sperm transport. Although 17OHD case reports did not routinely report endometrial thickness, hypoplasia might also involve the endometrium, preventing implantation. The aberrant hormonal profile seen in females with 17OHD contributes to both ovarian and uterine abnormalities, with high P and low estrogen levels inhibiting follicular and endometrial growth. Successful live birth after exogenous sex steroid hormone administration with a cryopreserved ET cycle supports this theory. Oocyte dysfunction with decreased granulosa cell activity might also contribute in females with 17OHD, as circulating E2 levels were low in cycles despite administration of exogenous gonadotropins. In males, poor gonadal androgen production contributes to arrested spermatogenesis and infertility.
    Introduction Prostate cancer is one of the most prevalent cancers among men in the USA and Europe. In most cases, growth, maintenance and progression of prostate cancer is androgen-dependent.2, 3 Therefore, the current first-line treatment for prostate cancer is hormone therapy, such as surgical castration or medical castration via administration of a luteinizing hormone-releasing hormone (LH-RH) agonist, which reduces the production of testosterone secreted by the testes. However, resistance to this therapy eventually occurs and this clinical condition is referred to as castration-resistant prostate cancer (CRPC). Despite very many studies in this field, the mechanism of progression to CRPC has not been fully understood. However, recent studies have suggested that residual adrenal androgen dehydroepiandrosterone (DHEA) after surgical castration could be responsible for the development of CRPC.5, 6