Importance of the balance of sex hormones for metabolic and reproductive health in men with Klinefelter syndrome

Descrizione riassuntiva dello studio

The current study aims to optimize the management of KFS by focusing on hypogonadism, metabolic defects, and infertility. The clinical trial is open to all individuals with Klinefelter syndrome who have a desire for fertility or wish to undergo fertility preservation (interventional group 1) or who are at high metabolic risk (interventional group 2). Patients will be randomly assigned to receive a certain study treatment. In men who wish to become parents or have an interest in fertility preservation (group 1), we will evaluate two hormonal stimulation strategies if there is no sperm retrieval during the first mTESE biopsy. Given the promising results from retrospective series, we will examine the efficacy of the aromatase inhibitor alone or in combination with human chorionic gonadotropin (hCG) to improve the chance of finding sperm. The underlying mechanisms, including a change in hormone ratios and modifications in the activity of different genes within the testis, will be explored. In men with high metabolic risk, we will study (i) whether normalizing the T/E ratio through an aromatase inhibitor (anastrozole) provides metabolic benefits compared to standard TRT treatment; and (ii) whether the use of a GLP1 receptor agonist can more effectively improve the metabolic profile while partially reversing testosterone deficiency. Furthermore, the clinical trial will also include an observational group of KFS patients who will not receive medication but will have blood samples taken to study the disease in depth and clarify the link between the genetic defect (genotype) and their clinical signs (phenotype).

(BASEC)

Intervento studiato

Interventional group 1:

Treatment A: Anastrozole® Teva (oral)

Treatment B: Anastrozole® Teva (oral) + Choriomon® (subcutaneous)

Interventional group 2:

Treatment A: control (standard care): Tostran® (gel)

Treatment B: Anastrozole® Teva (oral)

Treatment C: Ozempic® (subcutaneous)

(BASEC)

Malattie studiate

Klinefelter syndrome (KFS) is the most common chromosomal aberration in men, with an estimated prevalence of 1 in 500 births. KFS is suspected in the context of small testes, azoospermia, and elevated gonadotropins. The diagnosis is confirmed by a karyotype showing the presence of an extra X chromosome (47, XXY). The majority of affected men exhibit varying degrees of testosterone deficiency due to testicular insufficiency, as well as an altered testosterone/estradiol (T/E) ratio due to increased activity of an enzyme called aromatase. The function of this enzyme is to convert male hormones (testosterone) into female hormones (estrogens, especially estradiol). The main comorbidities of KFS include metabolic anomalies and infertility. Despite several advantages of testosterone replacement therapy (TRT), it is not effective in reversing the high metabolic risk in men with KFS and does not treat their infertility. The advent of microdissection biopsy for the extraction of testicular sperm (mTESE) has offered some men with KFS a potential for fertility, with successful sperm detection in about 30% of cases.

(BASEC)

Sponsor

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