A randomized controlled pilot study was performed with a sample of extremely preterm infants to evaluate the impact of postnatal estradiol and progesterone replacement on postnatal bone mineral accretion. Twenty-five of 30 infants in the pilot study survived, and of these, 24 infants were available for the follow-up examination at a median chronological age of 18.1 months (minimum-maximum, 17.0--20.6) corresponding to a corrected age of 14.8 months (minimum-maximum, 12.9--17.4). Somatic growth data and bone mineralization showed no differences between the hormone-treated and control group infants. The deviation of the skeletal age from the corrected age was 0.0 months (minimum-maximum, -7.7 to 7.4) for hormone-treated infants compared with -1.7 months (minimum-maximum, -7.5 to 5.9) for the control group. The Bayley scales mental and psychomotor developmental indexes were 89 (minimum-maximum, 71--107) and 101 (minimum-maximum, 49--121) for the hormone-treated infants and 93 (minimum-maximum, 49--111) and 71 (minimum-maximum, 49--121) for the control group infants, respectively (mental developmental index, P = 1.0; psychomotor developmental index, P = 0.14). The normal psychomotor development in the hormone-treated infants compared with the below average development in the control group infants is encouraging and indicates the potentially important integrative role of sex steroids for the developing brain. Larger studies on the effects of the postnatal replacement of estradiol and progesterone in extremely preterm infants are warranted.