GnRHa ‘effective and safe’ for early fast puberty in girls

medwireNews: Gonadotropin-releasing hormone analogue (GnRHa) therapy offers a similar benefit to girls with early fast puberty (EFP) as it does to those with central precocious puberty (CPP), the results of an observational study suggest.

“We found in this large cohort that GnRHa treatment in girls with EFP was [as] effective and safe as in those with CPP”, say Shlomit Shalitin and colleagues, from the Schneider Children’s Medical Center of Israel in Petah Tikva.

As described in Pediatric Research, the team collated medical records for 231 girls with EFP and 144 girls with CPP who were treated with GnRHa therapy at a tertiary endocrine clinic between 2007 and 2021, and followed-up for height, weight and pubertal stage every 4–6 months for at least 1 year. The majority (92%) of patients in both the EFP and CPP groups received a fixed GnRHa dose of 3.75 mg every 28 days.

As expected, girls with EFP were significantly older at the onset of puberty than those with CPP (median 8.5 vs 7.0 years), began GnRHa therapy at a significantly later age (median 9.3 vs 8.0 years) and ended treatment at a significantly older age (median 10.9 vs 10.0 years). The median duration of treatment was also significantly shorter in the EFP than CPP arm (1.5 vs 2.8 years).

At initiation, the majority of girls with EFP were at Tanner stage 3 (64.3%), with a similar proportion at Tanner stage 2 (15.0%) and 4 (17.2%), whereas among girls with CPP, most were at Tanner stage 3 (50.7%) or 2 (42.3%).

Girls with EFP had a significantly higher mean BMI-standard deviation score (SDS) than those with CPP throughout follow-up. Although the EFP group had a significantly higher BMI-SDS at the end of treatment than at the start, the investigators found that this difference was “transient” and no longer significant at the time of last follow-up (0.96 vs 0.76 and 0.91, respectively).

Both patient populations had a significantly lower median height SDS at their last follow-up than at the time they started or ended GnRHa therapy. And the mean height SDS at all three timepoints was significantly higher than the mean mid-parental height SDS for girls regardless of their diagnosis.

Girls with EFP took a significantly shorter median time to achieve a decrease in the ratio of bone age to chronological age than their CPP counterparts (1.25 vs 1.75 years). All other clinical and laboratory parameters were comparable between the groups, the researchers say, including median time from GnRHa initiation to clinical response (0.42 vs 0.33 years) or suppression of basal serum luteinising hormone and oestrogen (0.42 vs 0.46 years).

Median age of menarche after discontinuing GnRHa therapy was similar in the EFP and CPP groups (12.0 vs 11.8 years), as was the rate of menstrual irregularities (18.7 vs 20.3%). The researchers note such irregularities might point to the development of polycystic ovary syndrome, although they emphasize that prior studies have not found a link to suggest that GnRHa therapy “predisposes” to either irregularities or the syndrome.

Shalitin and co-authors conclude that “treatment with GnRHa did not compromise the genetic [adult height] and did not cause long-lasting obesity both in girls with EFP and in those with CPP.”

They advise: “When deciding whether to start GnRHa treatment, factors such as early age at menarche and the psychological condition of the child should be considered both in girls with CPP and EFP.

“Thus, together with the low rate of adverse effects of treatment, GnRHa therapy may be suggested for

use also in girls who have psychosocial difficulties in coping with EFP.”

Nevertheless, the investigators caution that a “prospective randomized controlled trial is required to examine the psychological impact of GnRHa treatment of variant early puberty.”

By Lynda Williams

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group

Pediatr Res 2023; doi:10.1038/s41390-023-02879-6
Martin Savage
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