Anogenital distance in Klinefelter syndrome: A case-control study

Background: Fall in total testosterone (tT) levels in Klinefelter syndrome (KS) may occur at different times of sexual development, although overt hypogonadism generally occurs after puberty. Nevertheless, it is still debated whether patients with KS are exposed to normal androgen levels during fetal life. Anogenital distance (AGD) is an anthropometric measure reflecting androgenization during the fetal period. A shorter AGD in men was associated with infertility, genital anomalies, and testicular cancer. Although other androgen-dependent anthropometric measures such as testicular volume and stretched penile length have been investigated in KS, this is to our knowledge the first study examining AGD in this population. Objectives: To investigate the role of AGD as an anthropometric marker of androgenization in adults with KS. Methods: We measured AGD, testicular volume, stretched penile length in 50 patients with KS and in 101 Caucasian men with normal total testosterone (tT) levels (> 12 nmol/L), using a digital caliper for AGD, an orchidometer for testicular volume and a common meter for stretched penile length. AGD was then correlated with anthropometric features and hormone levels (tT, LH, FSH). Results: AGD was similar between patients with KS and controls (p = 0.843), with mean values of 6.8 ± 1.6 cm (95% CI 6.4 to 7.3) and 6.9 ± 1.4 cm (95% CI 6.6 to 7.2), respectively. In both groups, AGD did not correlate with testicular volume, stretched penile length, arm span, or tT levels. Interestingly, AGD significantly correlated with waist circumference (p = 0.004), body mass index (p < 0.001) in patients with KS, while no relevant correlation was found among controls. Conclusions: AGD is not decreased in KS despite lower testosterone levels. This finding suggests that patients with KS are exposed to sufficient androgenization during fetal life.