Abstract
Patients with congenital adrenal hyperplasia (CAH) both with severe (classical CAH) and mild (nonclassical NCAH) forms exhibit a wide spectrum of reproductive dysfunction. In this review, only CAH cases with 21-hydroxylase deficiency (21-OHd) will be discussed, as they represent almost all of the patients in reproductive clinical settings.
Altered reproductive function is common in adult women with classical CAH and NCAH due to 21-OHd. However, there are important differences between these two groups, the former presenting with a higher rate of infertility because of chronic anovulation and increased progesterone levels during the follicular phase impacting on endometrial function. Most adult 21-OHd NCAH women present with menstrual irregularities and secondary polycystic ovary syndrome (PCOS), but fertility is reduced only in 30% of them, suggesting that, in most patients, ovulatory cycles may occur. In both classical CAH and NCAH women, pregnancy loss is common but may be reduced by using glucocorticoids.
In adult males with classical CAH due to 21-OHd, primary gonadal failure due to testicular adrenal rest tumors (TARTs) may be observed, and they reduce fertility; however, in adult males with 21-OHd NCAH, no reduction in spontaneous fertility is observed.
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References
Kim JH, Choi JH, Kang E, Kim YM, Lee BH, Yoo HW. Long-term consequences of congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency in adolescents and adults. Exp Clin Endocrinol Diabetes. 2017;125:196–201. https://doi.org/10.1055/s-0042-123037.
Claahsen-van der Grinten HL, Stikkelbroeck N, Falhammar H, Reisch N. Management of endocrine disease: gonadal dysfunction in congenital adrenal hyperplasia. Eur J Endocrinol. 2021;184:R85–97. https://doi.org/10.1530/EJE-20-1093.
Smita Jha S, Turcu AF, Sinaii N, Brookner B, Auchus RJ, Merke DP. 11-oxygenated androgens useful in the setting of discrepant conventional biomarkers in 21-hydroxylase deficiency. J Endocr Soc. 2020;5:192. https://doi.org/10.1210/jendso/bvaa192.
Reichman DE, White PC, New MI, Rosenwaks Z. Fertility in patients with congenital adrenal hyperplasia. Fertil Steril. 2014;101:301–9. https://doi.org/10.1016/j.fertnstert.2013.11.002.
Cabrera MS, Vogiatzi MG, New MI. Long term outcome in adult males with classic congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2001;86:3070–8. https://doi.org/10.1210/jcem.86.7.7668.
Chatziaggelou A, Sakkas EG, Votino R, Papagianni M, Mastorakos G. Assisted reproduction in congenital adrenal hyperplasia. Front Endocrinol (Lausanne). 2019;10:723. https://doi.org/10.3389/fendo.2019.00723.
Moran C, Azziz R, Carmina E, Dewailly D, Fruzzetti F, Ibanez L, et al. 21-Hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study. Am J Obstet Gynecol. 2000;183:1468–74. https://doi.org/10.1067/mob.2000.108020.
Carmina E. Pathogenesis and treatment of hirsutism in late-onset congenital adrenal hyperplasia. Reprod Med Rev. 1995;4:179–87. https://doi.org/10.1017/S0962279900001162.
Livadas S, Dracopoulou M, Dastamani A, Sertedaki A, Maniati-Christidi M, Magiakou AM, et al. The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene. Clin Endocrinol. 2015;82:543–9. https://doi.org/10.1111/cen.12543.
Levin JH, Carmina E, Lobo RA. Is the inappropriate gonadotropin secretion of patients with polycystic ovary syndrome similar to that of patients with adult-onset congenital adrenal hyperplasia? Fertil Steril. 1991;56:635–40. https://doi.org/10.1016/s0015-0282(16)54592-0.
Carmina E, Lobo RA. Ovarian suppression reduces clinical and endocrine expression of late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Fertil Steril. 1994;62:738–43. https://doi.org/10.1016/s0015-0282(16)56998-2.
Carmina E, Dewailly D, Escobar-Morreale HF, Kelestimur F, Moran C, Oberfield S, et al. Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency revisited: an update with a special focus on adolescent and adult women. Hum Reprod Update. 2017;23:580–99. https://doi.org/10.1093/humupd/dmx014.
Feldman S, Billaud L, Thalabard JC, Raux-Demay MC, Mowszowicz I, Kuttenn F, et al. Fertility in women with late-onset adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab. 1992;74:635–9. https://doi.org/10.1210/jcem.74.3.1310999.
Moran C, Azziz R, Weintrob N, Witchel SF, Rohmer V, Dewailly D, et al. Reproductive outcome of women with 21-hydroxylase-deficient nonclassic adrenal hyperplasia. J Clin Endocrinol Metab. 2006;91:3451–6. https://doi.org/10.1210/jc.2006-0062.
Lekarev O, Lin-Su K, Vogiatzi MG. Infertility and reproductive function in patients with congenital adrenal hyperplasia: pathophysiology, advances in management, and recent outcomes. Endocrinol Metab Clin N Am. 2015;44:705–22. https://doi.org/10.1016/j.ecl.2015.07.009.
Bidet M, Bellanne-Chantelot C, Galand-Portier MB, Golmard JL, Tardy V, Morel Y, et al. Fertility in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2010;95:1182–90. https://doi.org/10.1210/jc.2009-1383.
Witchel SF. Non-classic congenital adrenal hyperplasia. Steroids. 2013;78:747–50. https://doi.org/10.1016/j.steroids.2013.04.010.
Wasniewska M, Raiola G, Galati MC, Salzano G, Rulli I, Zirilli G, et al. Non-classical 21-hydroxylase deficiency in boys with prepubertal or pubertal gynecomastia. Eur J Pediatr. 2008;167:1083–4. https://doi.org/10.1007/s00431-007-0625-6.
Pinkas H, Fuchs S, Klipper-Aurbach Y, Zvulunov A, Raanani H, Mimouni G, et al. Non-classical 21-hydroxylase deficiency: prevalence in males with unexplained abnormal sperm analysis. Fertil Steril. 2010;93:1887–91. https://doi.org/10.1016/j.fertnstert.2008.12.037.
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Carmina, E. (2021). Reproductive Dysfunction in Classical and Nonclassical Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. In: Ertorer, M.E. (eds) Fertility and Reproductive Outcomes in Different Forms of Congenital Adrenal Hyperplasia. Springer, Cham. https://doi.org/10.1007/978-3-030-82591-1_6
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