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<p>Congenital adrenal hyperplasia (CAH) significantly impairs fertility due to hyperandrogenism and chronic dysregulation of the hypothalamic-pituitary-adrenal axis. Traditional glucocorticoid therapies improve hormonal control but often fail to prevent long-term, and sometimes irreversible, reproductive consequences, such as the development of testicular adrenal rest tumours (TARTs) in males and ovulatory dysfunction with menstrual irregularities in females. Recently, novel therapeutic strategies aim for a more physiological control of the circadian cortisol rhythm, reducing side effects. Among these, modified-release hydrocortisone (Efmody<sup>®</sup>/Chronocort<sup>®</sup>) has shown efficacy in improving 17-hydroxyprogesterone and androgen levels, thus promoting fertility restoration. Preliminary evidence suggests that this drug may enhance reproductive function in both sexes. CRH receptor antagonists (Crinecerfont<sup>®</sup>) allow for a reduction in daily glucocorticoid dose while maintaining disease control and normalising gonadotropin and sex hormone levels. However, their impact on reproductive outcomes has not yet been fully established. These innovative approaches offer a more favourable perspective for the reproductive management of patients with CAH, particularly when integrated into a personalised, multidisciplinary care pathway.</p>

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Fertilità e funzione gonadica nell’iperplasia surrenalica congenita: stato dell’arte e nuove prospettive farmacologiche

  • 期刊论文

  • 发表日期：

    2025年9月3日

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  • Davide Ferrari,
  • Lorenzo Arcolesse

摘要

Congenital adrenal hyperplasia (CAH) significantly impairs fertility due to hyperandrogenism and chronic dysregulation of the hypothalamic-pituitary-adrenal axis. Traditional glucocorticoid therapies improve hormonal control but often fail to prevent long-term, and sometimes irreversible, reproductive consequences, such as the development of testicular adrenal rest tumours (TARTs) in males and ovulatory dysfunction with menstrual irregularities in females. Recently, novel therapeutic strategies aim for a more physiological control of the circadian cortisol rhythm, reducing side effects. Among these, modified-release hydrocortisone (Efmody®/Chronocort®) has shown efficacy in improving 17-hydroxyprogesterone and androgen levels, thus promoting fertility restoration. Preliminary evidence suggests that this drug may enhance reproductive function in both sexes. CRH receptor antagonists (Crinecerfont®) allow for a reduction in daily glucocorticoid dose while maintaining disease control and normalising gonadotropin and sex hormone levels. However, their impact on reproductive outcomes has not yet been fully established. These innovative approaches offer a more favourable perspective for the reproductive management of patients with CAH, particularly when integrated into a personalised, multidisciplinary care pathway.