Free α-Subunit Is the Most Sensitive Marker of Gonadotropin Recovery after Treatment of Central Precocious Puberty with the Histrelin Implant

Abstract

Gonadotropin free alpha-subunit (FAS) levels paradoxically increase during GnRH agonist (GnRHa) treatment of central precocious puberty (CPP). The histrelin implant suppresses gonadotropins and estradiol (E(2)) levels for 1 yr, but effects on FAS have not been described. We aimed to determine whether FAS levels remain elevated during treatment with the implant, to assess the dynamics of FAS after removal, and to ascertain the reliability of FAS for monitoring gonadotropin secretion. Ten girls with CPP were studied. In eight, monthly im GnRHa preparations were given until implant insertion. Two naive girls did not receive prior GnRHa. Duration of implant treatment ranged from 18-63 months with repeated implant removals and insertions of new implants. LH, FSH, E(2), and FAS were measured before implant insertion in the two naive patients and during treatment, and in all girls before and after implant removal. FAS levels were 0.2 and 0.4 ng/ml (normal, <0.6 ng/ml) in the two naive girls and increased to 2.4 and 5.1 ng/ml within 2-5 d of insertion. FAS level (mean +/- SD) in all 10 girls during histrelin implant treatment was 1.19 +/- 0.49 ng/ml and rapidly decreased to 0.31 +/- 0.12 ng/ml within 1 wk of implant removal (P < 0.03). In contrast, significant increases in LH (P < 0.05) and FSH (P < 0.02) were observed at 3 wk and E(2) (P < 0.05) at 6 wk after implant removal. Compared to LH, FSH, and E(2), FAS responds more rapidly to implant removal and represents the most sensitive indicator of gonadotropin recovery after histrelin implant treatment.