Mullerian inhibiting substance, sex hormone binding globulin and sex hormone levels in stimulant-naive, first-diagnosed prepubertal boys with attention-deficit/hyperactivity disorder: comparison with matched healthy controls as well as before and after oros-methylpenidate treatment

Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder with strong male predominance. Since Mullerian Inhibiting Substance (MIS) produces sex-linked bias in animal studies, we aimed to investigate the role of MIS, Sex Hormone Binding Globulin (SHBG) and sex hormone levels in boys with ADHD. Methods: We compared prepubertal, psychostimulant-naive boys with ADHD with age-matched healthy control boys (HCs). Patients were re-evaluated after 30 days of methylphenidate treatment assessing ADHD severity, and serum MIS, testosterone, estradiol, and albumin concentrations. Results: Compared to 30 HCs, with ADHD (n = 49, age = 6.9 +/- 0.2 years) had lower SHBG (p = .014), and higher free testosterone (p = 0.006) and bioavailable testosterone (p = .002) percentages. Methylphenidate improved ADHD measures (all p < .0001) and abnormal baseline hormonal levels, increasing SHBG levels (p = .024), and lowering free (p = .001) and bioavailable testosterone (p = .016) percentages so that only free testosterone percentages remained higher versus HCs post-treatment (p = .02). Conclusions: Compared to age- and sex-matched HCs, prepubertal, stimulant-naive boys with ADHD had significantly lower SHBG and higher free and bioavailable testosterone percentages, suggesting a possible contribution of sex hormones to ADHD. Osmotic-release oral system methylphenidate treatment for 30 days significantly improved ADHD symptoms and abnormal sex hormone levels, normalizing SHBG and bioavailable testosterone percentages that were similar to HCs while free testosterone remained elevated versus HCs.