A Retrospective Long-Term Study on Age at Menarche and Menstrual Characteristics in 85 Young Women with Transfusion-Dependent β-Thalassemia (TDT)

Background: Menarche is an important milestone in a feminine reproductive life, and regular menstrual cycles reflect normal functioning of the hypothalamic-pituitary-ovarian axis, a vital sign of women's general health.

Aim Of The Study: We explored the age at menarche and the following menstrual cycles characteristics among 85 unmarried Transfusion-Dependent β-Thalassemia (TDT) women, born between 1965 and 1995, concerning iron chelation therapy (ICT) with desferrioxamine (DFO) and nutritional status, assessed by body mass index (BMI).

Results: 53 adolescents who had begun ICT before the age of 10 years experienced menarche at 13,7 ± 1,6 years (mean ± DS), whereas 32 who began treatment after ten years experienced menarche significantly later (15.5 ± 1.9 yrs; p: 0.001). At the age of menarche: BMI-Z score (n= 67, -0,09 ±1) was inversely correlated with both age at starting ICT (r = -0,39; p = 0001) and age at menarche (-0,45, p = 0,0001). Serum ferritin levels (SF) were significantly correlated with the age at starting chelation therapy (n = 79; r = 0,34; p = 0,022). In 56 TDT adolescents who developed secondary amenorrhea (SA), the SF levels were significantly higher (4,098 ± 1,907 ng/mL) compared to 23 TDT adolescents with regular menstrual cycles (2,913±782 ng/mL; p = 0,005). Nutritional status of "thinness" at menarche was associated with a lower prevalence of subsequent regular menstrual cycles and a higher prevalence of early SA.

Conclusion: An early ICT in TDT patients was associated with a normal "tempo" of pubertal onset and a higher frequency of subsequent regular menstrual cycles. In TDT patients, who developed SA, a diagnosis of acquired central hypogonadism was made, mainly due to the chronic exposure to iron overload, however other potential causes linked to nutritional status, deficient levels of circulating nutrients, and the chronic disease itself cannot be fully excluded.