|
|
Long-term Follow-up of Idiopathic CPP Treated with GnRHa« Back to Volume 24, Issue 2, November 2008 - Table of Contents Pasquino et al evaluated the impact of gonadotropin-releasing hormone analog (GnRHa) treatment on the adult height (AH), BMI, bone mineral density (BMD), and reproductive function of 87 girls with idiopathic central precocious puberty (ICPP). Patients were treated with depot triptorelin at a dose of 100 to 120 mcg/kg every 21 – 25 days for a period of 4.2 ± 1.6 years (range 3 – 7.9) and were then observed for 9.9 ± 2.0 years (range of 4 – 10.6) after discontinuing treatment; 32 untreated girls with ICPP served as controls. The AH of treated girls was 159.8 ± 5.3 cm, significantly higher than predicted adult height (PAH) with a gain in centimeters between PAH and AH of 5.1 ± 4.5. Although, on the whole, BMI increased, BMI SDS for chronological age was not different at the beginning or at the discontinuation of treatment, or years afterwards; patients who were overweight or obese at the beginning of treatment remained so by the end of therapy. Gonadotropin and estradiol levels decreased significantly with GnRHa therapy and rose above pre-treatment levels one year after discontinuation of therapy. Ovarian volumes, were reduced during treatment and increased thereafter, while uterine length was unchanged during therapy and increased one year after discontinuing therapy. Menarche appeared at the age of 13.6 ± 1.1 years after withdrawal of GnRHa at 0.9 ± 0.4 years (range of 0.3 – 2.0); 82 patients had a pattern of regular menses, while 5 had oligomenorrhea due to intensive physical activity (which resolved when this activity was decreased), and 6 girls became pregnant and delivered normal offspring. The BMD calculated both by area and volume were decreased at discontinuation of therapy when compared to controls, but after complete resumption of gonadal activity were not significantly different from controls. The authors concluded that GnRHa treatment of girls with ICCP is safe for the reproductive system, BMD, and BMI and is helpful in reaching an AH close to target height. Editor’s CommentThe long-term follow-up by Pasquino and colleagues of a large cohort of girls with ICPP treated with GnRHa, suggests that this form of therapy is safe—leading to a normal resumption of gonadal function one year after discontinuation of therapy. This was manifested by an increase of gonadotropins and estradiol to normal levels for age, an increase in ovarian and uterine dimensions, appearance of menarche at a mean of 0.9 ± 0.4 years after discontinuation of treatment with the maintenance of a normal menstrual pattern thereafter, and with normal pregnancies and deliveries of healthy offspring in 6 girls. This, as well as previous data1 should assure physicians and parents of the safety of this medication in regard to gonadal function and the future reproductive health of girls with ICPP treated for prolonged periods with GnRHa. Recent data suggest that children with ICPP may have an increased BMI and that GnRHa treatment might contribute to the worsening of this parameter.2 Although, as a whole, BMI increased during therapy, it remained in the same centile or SDS throughout treatment and patients who were already obese or overweight at the beginning, remained so at the end of treatment. There is still controversy regarding the beneficial effect of GnRHa treatment on the AH of treated girls with ICPP.1,2 In this study AH of treated girls was significantly increased when compared to PAH before the beginning of therapy and, as a whole, patients reached or overcame their TH. When the AH height of untreated control subjects was compared to that of treated individuals it was found to be about 5 cm shorter—more than 4 cm below their TH and with no significant gain over their PAH. However, while GnRHa therapy seems helpful in reaching an AH close to TH, it is clear that there is a marked variability in individual response. Another worrisome issue is the effect of suppression of ovarian activity on BMD, both during therapy and long-term.3 Even though this study demonstrated a decrease in bone accretion during GnRHa therapy, bone mineral density calculated both by area and volume seemed to normalize after the complete resumption of ovarian activity and peak bone mass was reached. Although GnRHa therapy has been widely used in the treatment of girls with ICPP for the last 20 years, many doubts in regard to its long-term benefits and safety remain. This long-term follow-up of a large cohort of treated girls may ease concerns. Roberto Lanes, MD References - (linked to
|
Volume 26 Number 1
September 2010
www.GGHjournal.com
ISSN 1932-9032
)