Thalassemia-Associated mixed hypogonadism (TAMH): unraveling a unique endocrine pattern and its impact on cardiovascular risk

Background: Transfusion Dependent Thalassemia (TDT) is a hereditary hematologic disorder requiring chronic transfusions, leading to iron overload and frequent endocrinological complications, notably hypogonadism, defined as secondary or hypogonatropic, potentially impacting quality of life and cardiovascular (CV) risk. This study aimed to evaluate the pattern of hypogonadism in TDT and its impact on CV risk compared to non-hypogonadal subjects with TDT and hypogonadal subjects without TDT. Methods: A cross-sectional observational study assessed 22 TDT patients with hypogonadism (H-TDT) and 31 TDT without a diagnosis of hypogonadism (NH-TDT) aged 18 years or older. A control group of adult non-thalassemic hypogonadotropic hypogonadism patients (HH-C) was included for comparison. Data on medical history, clinical signs/symptoms of hypogonadism, lifestyle factors, blood pressure, and hormone levels were collected. CV risk was assessed using Framingham and Progetto Cuore scores, as well as echocardiographic parameters. Results: H-TDT patients had significantly higher FSH and LH levels than HH-C (p < 0.001). Significant differences in CV and total cholesterol levels were found between TDT patients with and without hypogonadism (p = 0.046, p = 0.004, respectively). CV risk was similar between H-TDT patients and the HH-C. Conclusions: The nature of hypogonadism in TDT is essentially mixed, definitively transcending a purely hypogonadotropic profile. Furthermore, while the CV risk is higher in subjects with H-TDT compared to NH-TDT, it remains extraordinarily low and not pathological according to two validated scores in the general population. This suggests a need to identify more suitable tools for the CV risk in TDT patients.