Birth Weight in Relation to Sex Steroid Status and Body Composition in Young Healthy Male Siblings

Context: Sex steroid concentrations have a strong genetic determination, but environmental factors and body composition play an important role. From studies in children with intrauterine growth restriction, low birth weight has been associated with altered gonadotropin concentrations.

Objective: We aim to investigate sex steroid concentrations in healthy young brothers in relation to birth weight (normal gestational age), body composition, and parental steroid concentrations.

Design And Setting: We conducted a cross-sectional, population-based sibling pair study with inclusion of parental data.

Participants: A total of 677 men (25-45 yr old) were included in this study, with 296 independent pairs of brothers and 122 fathers.

Main Outcomes: We measured testosterone, estradiol, leptin, adiponectin, IGF-I (immunoassays), and free steroid hormones (calculated) in relation to birth weight and changes in body composition (dual-energy x-ray absorptiometry).

Results: Birth weight was associated with serum testosterone (P = 0.0004) and SHBG (P = 0.0001), independent from weight, age, or fat mass, whereas no association with (free) estradiol, LH, or FSH was found. Paternal testosterone (P = 0.02), estradiol (P = 0.04), and SHBG (P = 0.0004) were associated with the respective sex steroid concentrations in the brothers. Weight increase (population rank) during life, was associated with lower testosterone (-15%; P < 0.001), independent from current weight and with higher free estradiol concentrations (+8%; P = 0.002), whereas weight decrease was associated with higher testosterone (+13%; P < 0.001).

Conclusion: Birth weight and paternal steroid concentrations are associated with testosterone concentrations, independent from adult weight. These findings support the concept of in utero programming across the range of birth weight.