Fertility And Sexual Function In CAH: CALLIOPE

Condition(s) studied

Study summary

This is a multicenter study designed to assess the effects of groundbreaking CAH therapies on a spectrum of clinical and biochemical outcomes, with a special emphasis on reproductive and sexual health. Fertility is a profound concern for individuals with CAH, given the high prevalence of gonadal dysfunction that arises from the hormonal derangements that characterize this complex disease. At our endo-ERN accredited center for rare diseases at Policlinico Umberto I, addressing these fertility issues in CAH patients represents a daily commitment. The revolution of the pharmacological management of CAH is one of the most debated topics to date. Data on the effects of novel management options for CAH on fertility are scarce, but the anecdotal improvements in sperm count and menstrual regularity reported in the latest clinical trials have significantly motivated us to design the CALLIOPE study. Thus, we aim to delve deeper into the fertility and sexual function of CAH patients, employing advanced seminal parameter evaluations, multiparametric gonadal ultrasound, and sophisticated hormonal analyses in both females and males performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Beyond fertility, the CALLIOPE trial aspires to provide further understanding of therapy's effects on body composition, metabolism, immune function, coagulation, and quality of life, among other factors. We will explore the immunological impact of novel CAH therapies by quantifying Peripheral Blood Mononuclear Cells (PBMCs) and analyzing transcriptomic profiles to unveil gene expression patterns and identify biomarkers that could signal therapeutic targets or disease management strategies in CAH. Moreover, seminal plasma will be used to assess the expression of adrenal miRNAs regulating steroidogenesis and metabolism.

The research will be conducted at our rare disease referral center (Policlinico Umberto I, Sapienza University of Rome) in collaboration with leading centers across Italy: Modena (Università degli Studi di Modena e Reggio Emilia), Naples (Università Federico II), Rome (Ospedale Sant'Andrea) and Bologna (Alma Mater Studiorum - Università di Bologna).

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Eligibility

Primary outcome measure(s)

• Change in sperm concentration (total count per ejaculate) at semen analysis (male subjects) — At baseline and during follow-up (up to 5 years)
  Sperm concentration will be evaluated through standard semen analysis in male participants, according to WHO guidelines. Measurements will be used to assess changes over time in relation to disease control and treatment modifications. Semen analyses will be repeated at follow-up visits if clinically indicated or in case of significant therapeutic changes. Unit of Measure: millions per ejaculate (10⁶/ejaculate)
• Change in sperm concentration (concentration per mL) at semen analysis (male subjects) — At baseline and during follow-up (up to 5 years)
  Sperm concentration will be evaluated through standard semen analysis in male participants, according to WHO guidelines. Measurements will be used to assess changes over time in relation to disease control and treatment modifications. Semen analyses will be repeated at follow-up visits if clinically indicated or in case of significant therapeutic changes. Unit of Measure: millions per mL (10⁶/mL)
• Change in Serum Testosterone:LH ratio (female subjects) — At baseline and during follow-up (up to 5 years)
  Assessment of changes in the ratio between serum total testosterone and luteinizing hormone (LH) concentrations in female participants. Blood samples will be collected in the early follicular phase or as appropriate based on menstrual status. The ratio will be calculated at each time point, and changes will be expressed as percent change from baseline or through paired comparison. The aim is to evaluate this ratio as a potential biomarker of hyperandrogenism severity and treatment response. Unit of Measure: Ratio (ng/dL per IU/L)
• Change in serum Estradiol:FSH ratio (female subjects) — At baseline and during follow-up (up to 5 years)
  Evaluation of changes in the ratio between serum estradiol (E2) and follicle-stimulating hormone (FSH) concentrations in female participants. Blood samples will be collected in the early follicular phase when possible or based on clinical context. The E2:FSH ratio will be calculated at each visit and used to assess hypothalamic-pituitary-ovarian axis function and treatment effects over time. Changes will be analyzed using paired comparisons or percentage variation from baseline. This outcome is part of a broader hormonal assessment that includes additional ratios such as Testosterone:LH. Unit of Measure: Ratio (pg/mL per mIU/mL)

Trial sites (1)

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