Ovarian Insufficiency in Adolescent Females with Transfusion Dependent -thalassemia; Pituitary Versus Ovarian Iron Overload

Introduction: Females with transfusion-dependent -thalassemia (TDT) display menstrual irregularities and subfertility at certain points in their lives, even if well chelated, representing a significant physical and psychological burden. Little is known about the effects of pituitary and ovarian iron contents on ovarian reserve and function. Hence, this study aimed to assess ovarian reserve and pituitary-gonadal axis function in adolescent females with TDT and correlate them with pituitary and ovarian volume, pituitary iron load, and serum ferritin. Methods: Fifty adolescent females with TDTs were compared with 50 age-matched healthy females. Age at diagnosis of TDT, transfusion index, type of chelation therapy, age at menarche, and Tanner breast stage were assessed. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and ferritin levels were measured. Magnetic resonance imaging (MRI) was used to measure the pituitary iron content R2* and T2*, and 3-D transabdominal ovarian ultrasound was performed. Results: The mean age of the studied females with TDT was 14.54 ± 2.24 years. Ovarian insufficiency was found in 20 patients (40%). Compared with controls, adolescent females with TDT had a significantly delayed age of menarche, AMH, FSH, LH, antral follicle count (AFC), and ovarian volume. In a comparison of those with and without ovarian insufficiency, adolescents with TDT with ovarian insufficiency had significantly higher serum ferritin and pituitary MRI-R2* values than did those without insufficiency. Multivariate logistic regression revealed that pituitary MRI-R2* was the most significant independent variable associated with ovarian insufficiency among adolescent females with TDT. Conclusion: Adolescent females with TDT have decreased ovarian reserves, AFCs and gonadotropins, which are correlated with the serum ferritin level, pituitary iron load and ovarian volume. Hence, regular ovarian reserve assessment should be implemented as a part of the endocrinological follow-up of females with TDT-advising procedures to preserve fertility to those who are likely to have ovarian insufficiency.