Reproductive Axis after Discontinuation of Gonadotropin-Releasing Hormone Analog Treatment of Girls with Precocious Puberty: Long Term Follow-Up Comparing Girls with Hypothalamic Hamartoma to Those with Idiopathic Precocious Puberty

• Published in: The journal of clinical endocrinology and metabolism 1999-01, Vol.84 (1), p.44-49
• Main Authors: Feuillan, Penelope P., Jones, Janet V., Barnes, Kevin, Oerter-Klein, Karen, Cutler, Gordon B.
• Format: Article
• Language: English
• Subjects: Adolescent; Biological and medical sciences; Child; Child, Preschool; Estradiol - blood; Female; Follicle Stimulating Hormone - blood; Follow-Up Studies; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - therapeutic use; Gynecology. Andrology. Obstetrics; Hamartoma - drug therapy; Hamartoma - physiopathology; Humans; Hypothalamic Diseases - drug therapy; Hypothalamic Diseases - physiopathology; Luteinizing Hormone - blood; Medical sciences; Pregnancy; Puberal and climacteric disorders (male and female); Puberty, Precocious - drug therapy; Puberty, Precocious - physiopathology; Reproduction - drug effects; Triptorelin Pamoate - analogs & derivatives
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.84.1.5409

Although the GnRH agonist analogs have become an established treatment for precocious puberty, there have been few long term studies of reproductive function and general health after discontinuation of therapy. To this end, we compared peak LH and FSH after 100 μg sc GnRH, estradiol, mean ovarian volume (MOV), age of onset and frequency of menses, body mass (BMI), and incidence of neurological and psychiatric problems in 2 groups of girls: those with precocious puberty due to hypothalamic hamartoma (HH; n = 18) and those with idiopathic precocious puberty (IPP; n = 32) who had been treated with deslorelin (4–8 μg/kg·day, sc) or histrelin (10μ g/kg·day, sc) for 3.1–10.3 yr and were observed at 1, 2, 3, and 4–5 yr after discontinuation of treatment. The endocrine findings were also compared to those in 14 normal perimenarcheal girls. There were no differences between the HH and IPP groups in age or bone age at the start of treatment, at the end of treatment, or during GnRH analog therapy. We found that whereas the peak LH level was higher in HH than in IPP girls before (165.5 ± 129 vs. 97.5 ± 55.7; P < 0.02) and at the end (6.8 ± 6.0 vs. 3.9 ± 1.8 mIU/mL; P < 0.05) of therapy, this difference did not persist at any of the posttherapy time points. LH, FSH, and estradiol rose into the pubertal range by 1 yr posttherapy in both HH and IPP. However, the mean posttherapy peak LH levels in both HH and IPP groups tended to be lower than normal, whereas the peak FSH levels were not different from normal, so that the overall posttherapy LH/FSH ratio was decreased compared to that in the normal girls (HH, 2.7 ± 0.3; IPP, 2.6 ± 0.1; normal, 5.2 ± 4.8; P < 0.05). The MOV was larger in HH than IPP at the end of treatment (3.7 ± 3.5 vs. 2.0 ± 1.2 mL; P < 0.05) and tended to increase in both groups over time to become larger than that in normal girls by 4–5 yr posttherapy (HH, 14.9 ± 12.9; IPP, 7.6 ± 2.2; normal, 5.4 ± 2.5 mL; P < 0.05). Whereas the onset of spontaneous menses varied widely in both groups, once menses had started, the HH group had a higher incidence of oligomenorrhea. Pelvic ultrasonography revealed more than 10-mm hypoechoic regions in 4 HH patients, 15 IPP patients, and 3 normal girls, all of whom were reporting regular menses. Live births of normal infants were reported by 2 HH and 2 IPP patients, and elective terminations of pregnancy were reported by 1 HH and 2 IPP patients. BMI was greater than normal in HH and IPP both before treatment and at all po