Evidence ‘weak’ on long-term safety of gonadotropin-releasing hormone in early puberty
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Gonadotropin-releasing hormone analogue therapy is linked to improvement in final adult height and reduced BMI in central precocious puberty, but evidence for other key outcomes is “weak” to indicate benefits or adverse effects, data show.
“Gonadotrophin-releasing hormone analogue has been a treatment choice for central precocious puberty since the mid-1980s, and its effects on hypothalamic-pituitary-gonadal axis suppression has been generally recognized,” Xiao-Ping Luo, MD, PhD, professor and chair of the department of pediatrics at Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, and colleagues wrote in the study background. “However, the long-term efficacy and safety of gonadotrophin-releasing hormone analogue treatment remain unclear, and some studies have reported contradictory findings.”
In a systematic review and meta-analysis, Luo and colleagues analyzed data from 98 studies with 5,475 participants with idiopathic central precocious puberty, who experienced the onset of secondary sex characteristics before age 8 years in girls or age 9 years in boys (98.5% girls). Studies (18 randomized comparative studies; 81 single-arm studies) reported long-term outcomes (duration of at least 6 months) among participants who received any dosage regimen of gonadotropin-releasing hormone (GnRH) analogue therapy, compared with those who received no treatment or placebo, or GnRH therapy plus growth hormone. Primary outcomes were final adult height, target height, BMI and risk for overweight or obesity, and the incidence of polycystic ovary syndrome among girls and androgen excess among boys.
The findings were published in Clinical Endocrinology.
Across studies, the average age of central precocious puberty onset ranged from 4.5 to 8 years; average age of GnRH analogue treatment initiation ranged from 5 to 9.3 years.
Evidence-based comparative studies (n = 242) showed that GnRH treatment increased final adult height (mean difference, 4.83 cm; 95% CI, 2.32-7.34) and decreased BMI (mean difference, 1.01 kg/m²; 95% CI, 1.64 to 0.37) in girls with idiopathic central precocious puberty compared with no treatment.
The incidence of PCOS did not differ with vs. without GnRH treatment.
“The evidence for other long-term outcomes was very weak to deduce the effects of GnRH analogue treatment,” the researchers wrote. “Further, limited evidence is available on its effects in boys.”
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