Elevated serum levels of estradiol, dihydrotestosterone, and inhibin B in adult males born small for gestational age

Context: Prenatal growth restriction may affect future fertility in both females and males. Studies have shown that growth-retarded male rats have different sexual behavior and disturbed steroidogenesis. Objective: We hypothesized that adult human males born small for gestational age (SGA) have an altered sex hormone profile. Design, Setting, and Patients: Twenty-five adult males born SGA with median birth weight -2.2 SD scores (SDS) and birth length -2.4 SDS were studied. Median age was 23.1 yr and final height -0.5 SDS. They were compared with 44 male controls with median age 20.5 yr and final height 0.4 SDS. Main Outcome Measure: The primary outcome before the study started was 17 beta-estradiol (E-2) levels in SGA males. Results: The SGA group showed significantly higher median levels of E-2, 17.9 pg/ml (P < 0.001), and dihydrotestosterone (DHT), 0.543 ng/ml (P < 0.05), compared with controls, 12.6 pg/ml and 0.423 ng/ml, respectively. Testosterone (T) levels did not differ between groups. E-2 to T ratio correlated negatively to birth weight (r = -0.40, P < 0.01) and birth length (r = -0.44, P < 0.001). DHT to T ratio correlated negatively to birth weight ( r = -0.51, P < 0.001) and birth length ( r = -0.38, P < 0.01). Males born SGA also had significantly higher median levels of inhibin B, 164 pg/ml ( P < 0.05), compared with controls, 137 pg/ml. Inhibin B correlated negatively to birth length ( r = -0.34, P < 0.01). Conclusion: SGA males of normal stature have higher levels of E2, DHT, and inhibin B than controls, indicating a disturbed steroid synthesis or metabolism. Aromatase activity, calculated as E2 to T ratio, and 5 beta-reductase activity, calculated as DHT to T ratio, is negatively correlated to size at birth.