Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome.

Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9-20.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of treatment status. In patients evaluated before and during TRT, a tendency toward a more beneficial body composition with a significant reduction in the ratio between android fat percentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly lower when compared to the reference. This study confirms that patients with KS have an unfavorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters.

Serum Testosterone Levels in 3-Month-Old Boys Predict Their Semen Quality as Young Adults.

CONTEXT: It remains unknown how the postnatal activation of the hypothalamic-pituitary-gonadal axis in infancy, also known as "minipuberty", relates to adult testis function. OBJECTIVE: To investigate how markers of reproductive function in 3-month-old boys correlate with adult reproductive health parameters. METHODS: This population-based birth cohort study (the Copenhagen Mother-Child cohort), conducted at Copenhagen University Hospital, Denmark, included 259 boys examined once around 3 months of age and again at 18 to 20 years. Reproductive hormones, penile length, testis volume, and semen quality were analyzed. Minipubertal markers of testis function (by tertiles, T1-T3) were explored as predictors of adult semen quality using linear regression models. Associations between reproductive outcomes in infancy and young adulthood were estimated by intraclass correlation coefficients (ICCs), describing how well measurements in infancy correlate with those in adulthood. RESULTS: Serum testosterone concentration in infancy was positively associated with adult total sperm count. Median (IQR) total sperm count was 84 (54-138) million spermatozoa for boys in T1, 141 (81-286) million spermatozoa in T2, and 193 (56-287) million spermatozoa in T3. We found the highest ICC for FSH (0.41; 95% CI, 0.26-0.57), while ICCs for inhibin B, SHBG, penile length, and testis volume ranged between 0.24 and 0.27. ICCs for LH and for total and free testosterone were lower and statistically nonsignificant. CONCLUSION: Serum testosterone in infancy was a predictor of adult total sperm count. Other reproductive hormones and genital measures showed good correlation between infancy and adulthood, suggesting that an individual's reproductive setpoint starts shortly after birth in boys and persists until adulthood.

Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function.

OBJECTIVES: Longitudinal assessment of testicular function after pediatric hematopoietic stem cell transplantation (HSCT) is needed to guide clinical follow-up. We investigated dynamics in male reproductive hormones after pediatric HSCT, focusing on pubertal timing and associations with testosterone deficiency and azoospermia in adulthood. METHODS: This retrospective, longitudinal study included 39 survivors median 19 years after pediatric HSCT. Serum concentrations of LH, testosterone, FSH, and inhibin B from the time of HSCT, during puberty, and into adulthood were analyzed. Pubertal timing (rise in LH and testosterone) was compared to a reference cohort of 112 healthy boys. Associations between reproductive hormone levels during puberty and adult testicular function (including semen quality) were investigated. RESULTS: Pubertal induction with testosterone was needed in 6/26 patients who were prepubertal at HSCT. In the remaining patients, pubertal timing was comparable to the reference cohort. However, 9/33 patients (without pubertal induction) developed testosterone deficiency in early adulthood, which was associated with higher LH levels from age 14 to 16 years. Azoospermia in adulthood was found in 18/26 patients without testosterone substitution. Higher FSH and lower inhibin B levels from mid-pubertal age were associated with azoospermia in adulthood, in patients being prepubertal at HSCT. CONCLUSION: Our results indicate a substantial risk of deterioration in testicular function after pediatric HSCT, despite normal pubertal timing. Although reproductive hormone levels from mid-puberty indicated adult testicular function, prolonged follow-up into adulthood is needed in these patients, including clinical examination, reproductive hormone analysis, and semen sample for patients interested in their fertility potential.