Reversible male hypogonadotropic hypogonadism due to energy deficit

CONTEXT: Calorie restriction and overtraining are increasingly seen in young men who suffer from increasing societal pressure to attain a perceived ideal male body image. The resulting energy deficit can lead to multiple endocrine consequences, including suppression of the male gonadal axis. DESIGN: We reviewed the literature, including two unpublished cases. RESULTS: We identified 23 cases, aged median (range) 20 years (16-33), with a body mass index of 15.9 kg/m2 (12.5-20.5). Total testosterone was 3.0 nmol/L (0.6-21.3), and luteinizing hormone (LH) 1.2 mIU/L (<0.2-7.5), with 91% of cases demonstrating hypogonadotropic hypogonadism. Associated findings included evidence of growth hormone resistance (increased growth hormone in 57% and low insulin-like growth factor-1 in 71%), hypercortisolaemia (50%) and a nonthyroidal illness picture (67%). In cases with longitudinal measurements following weight regain, serum testosterone (n = 14) increased from median [interquartile range] 3.2 nmol/L [1.9-5.1] to 14.3 nmol/L [9.3-21.2] (P < 0.001), and LH (n = 8) from 1.2 IU/L [0.8-1.8] to 3.5 IU/L [3.3-4.3] (P = 0.008). CONCLUSIONS: Hypogonadotropic hypogonadism can occur in the context of energy deprivation in young otherwise healthy men and may be underrecognized. The evidence suggests that gonadal axis suppression and associated hormonal abnormalities represent an adaptive response to increased physiological stress and total body energy deficit. The pathophysiology likely involves hypothalamic suppression due to dysregulation of leptin, ghrelin and pro-inflammatory cytokines. The gonadal axis suppression is functional, because it can be reversible with weight gain. Treatment should focus on reversing the existing energy deficit to achieve a healthy body weight, including psychiatric input where required