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Elevated Serum Levels of Estradiol, Dihydrotestosterone, and Inhibin B in Adult Males Born Small for Gestational Age

Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at Göteborg University, S-416 85 Göteborg, Sweden

Address all correspondence and requests for reprints to: Kerstin Allvin, M.D., Göteborg Pediatric Growth Research Center, The Sahlgrenska Academy at Göteborg University, The Queen Silvia Children’s Hospital, S-416 85 Göteborg, Sweden. E-mail: kerstin.allvin{at}vgregion.se.

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 17β-estradiol (E₂) levels in SGA males.

Results: The SGA group showed significantly higher median levels of E₂, 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. E₂ 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-reductase activity, calculated as DHT to T ratio, is negatively correlated to size at birth.

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