Long-term clinical outcomes in females with precocious puberty treated with gonadotropin-releasing hormone analogues

Abstract

To evaluate long-term anthropometric, metabolic, reproductive, and bone mineral density (BMD) outcomes in girls with central precocious puberty (CPP) treated with Gonadotropin-Releasing Hormone analogues (GnRHa). In this retrospective cohort with cross-sectional follow-up assessment, 82 of 265 eligible females (30.9%) with central precocious puberty or central hypothalamic-pituitary-gonadal axis activation who had received GnRHa participated in long-term evaluation. Anthropometric outcomes, insulin sensitivity indices (HOMA-IR and QUICKI), hormonal profile, BMD, and reproductive outcomes including polycystic ovary syndrome (PCOS) were assessed. Analyses used available cases for each outcome; missing values were not imputed. The mean age at final evaluation was 17.61 ± 4.3 years, and mean GnRHa treatment duration was 3.14 ± 1.9 years. Mean height at final follow-up was 159.85 ± 6.5 cm; the mean difference from baseline predicted adult height was 1.98 cm (95% CI, -0.37 to 4.34; P = 0.097). The distribution of BMI categories did not change significantly from baseline to final follow-up. Mean HOMA-IR and QUICKI were 3.76 ± 1.82 and 0.319 ± 0.025, respectively; among adults, 14/28 (50.0%) met each prespecified adult-derived threshold for reduced insulin sensitivity. PCOS was identified in 15/67 participants (22.4%). Mean lumbar and femoral BMD Z-scores were -0.25 ± 1.23 and -0.55 ± 1.03, respectively. Among participants who completed long-term follow-up, attained height was comparable at the group level with predicted adult and mid-parental height, and mean BMD Z-scores were within age- and sex-referenced ranges. PCOS and PCOS-related features were observed, while insulin sensitivity indices were associated with adiposity. Because only 30.9% of eligible patients participated and there was no untreated comparison group, these findings describe the evaluated cohort and should not be interpreted as causal effects of GnRHa treatment.