This study aimed to evaluate the age at menarche in girls treated with gonadotropin-releasing hormone agonist (GnRHa) therapy for central precocious puberty (CPP) or early and fast puberty (EFP). The associations between the timing of menarche and different clinical and anthropometric factors were also investigated. This was a retrospective single-centre cohort study. This retrospective observational study analysed data from 112 girls who were treated with GnRHa between 2019 and 2024 and subsequently reached menarche following treatment cessation (CPP: 33; EFP: 79). The study examined demographic characteristics, anthropometric measurements at the start and end of treatment, bone age (BA), the bone age/ chronological age (BA/CA) ratio, hormone levels, and age at menarche. Changes before and after treatment were assessed, and subgroups were established on the basis of the interval between treatment cessation and menarche (< 12 months vs. ≥ 12 months) to evaluate potential differences in outcomes. The mean age at menarche was 11.75 ± 0.49 years, and the mean duration between treatment discontinuation and menarche was 12.22 ± 5.07 months. No significant difference was found in the timing of menarche between the CPP and EFP groups (p > 0.05). When the CPP and EFP groups before and after treatment were compared, the height SDS and BA/CA decreased during treatment, whereas the estimated adult height increased (p < 0.05). In patients in whom menarche occurred within 12 months following treatment discontinuation, the BMI SDS at the start and end of treatment, bone age at the end of treatment, and BA/CA at the end of treatment significantly increased (p < 0.05). In logistic regression analysis, baseline BMI SDS (OR: 1.99; 95% CI 1.15–3.42; p = 0.013) and end-of-treatment bone age (OR: 3.71; 95% CI 1.53–8.99; p = 0.004) were identified as independent risk factors for early menarche. Age at menarche showed a positive correlation with duration of treatment and age at treatment cessation, and negative correlations with baseline and end-of-treatment BMI SDS, bone age, and Tanner stage (p < 0.05). Conclusions: In this single-center cohort, menarche typically occurred approximately one year after cessation of GnRHa therapy, with similar timing in terms of CPP and EFP. A higher BMI SDS and more advanced skeletal maturation at treatment initiation and discontinuation were independently associated with earlier pubertal recovery, although their overall contribution to variability was modest. These findings suggest that careful clinical and auxological monitoring during treatment may help guide the appropriate timing of treatment discontinuation and assist clinicians in anticipating the subsequent timing of menarche. However, given the retrospective design, causal inferences cannot be established.<Table Float="No" ID="Taba"> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> What is Known: • The interval to menarche after GnRH agonist discontinuation is variable and influenced by pubertal and auxological characteristics. • Evidence on predictors of menarche timing, especially in early fast puberty, remains limited. </entry> </row> <row> <entry align="left" colname="c1"> What is New: • Higher BMI SDS and more advanced skeletal maturation at treatment cessation are associated with earlier menarche after GnRHa therapy. • This study provides comparative insights between central precocious puberty and early fast puberty, helping to inform clinical decision-making on treatment cessation. </entry> </row> </tbody> </tgroup> </Table>

Menarche timing after GnRHa treatment in cases of central precocious puberty or early and fast puberty

期刊论文
发表日期：

2026年4月13日

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Duygu Deligozoglu,
Gonul Buyukyilmaz,
Irem Gokdemir,
Pinar Kocaay,
Derya Tepe,
Mehmet Boyraz,
Fatih Gurbuz

摘要

This study aimed to evaluate the age at menarche in girls treated with gonadotropin-releasing hormone agonist (GnRHa) therapy for central precocious puberty (CPP) or early and fast puberty (EFP). The associations between the timing of menarche and different clinical and anthropometric factors were also investigated. This was a retrospective single-centre cohort study. This retrospective observational study analysed data from 112 girls who were treated with GnRHa between 2019 and 2024 and subsequently reached menarche following treatment cessation (CPP: 33; EFP: 79). The study examined demographic characteristics, anthropometric measurements at the start and end of treatment, bone age (BA), the bone age/ chronological age (BA/CA) ratio, hormone levels, and age at menarche. Changes before and after treatment were assessed, and subgroups were established on the basis of the interval between treatment cessation and menarche (< 12 months vs. ≥ 12 months) to evaluate potential differences in outcomes. The mean age at menarche was 11.75 ± 0.49 years, and the mean duration between treatment discontinuation and menarche was 12.22 ± 5.07 months. No significant difference was found in the timing of menarche between the CPP and EFP groups (p > 0.05). When the CPP and EFP groups before and after treatment were compared, the height SDS and BA/CA decreased during treatment, whereas the estimated adult height increased (p < 0.05). In patients in whom menarche occurred within 12 months following treatment discontinuation, the BMI SDS at the start and end of treatment, bone age at the end of treatment, and BA/CA at the end of treatment significantly increased (p < 0.05). In logistic regression analysis, baseline BMI SDS (OR: 1.99; 95% CI 1.15–3.42; p = 0.013) and end-of-treatment bone age (OR: 3.71; 95% CI 1.53–8.99; p = 0.004) were identified as independent risk factors for early menarche. Age at menarche showed a positive correlation with duration of treatment and age at treatment cessation, and negative correlations with baseline and end-of-treatment BMI SDS, bone age, and Tanner stage (p < 0.05). Conclusions: In this single-center cohort, menarche typically occurred approximately one year after cessation of GnRHa therapy, with similar timing in terms of CPP and EFP. A higher BMI SDS and more advanced skeletal maturation at treatment initiation and discontinuation were independently associated with earlier pubertal recovery, although their overall contribution to variability was modest. These findings suggest that careful clinical and auxological monitoring during treatment may help guide the appropriate timing of treatment discontinuation and assist clinicians in anticipating the subsequent timing of menarche. However, given the retrospective design, causal inferences cannot be established.

What is Known:

• The interval to menarche after GnRH agonist discontinuation is variable and influenced by pubertal and auxological characteristics.

• Evidence on predictors of menarche timing, especially in early fast puberty, remains limited.

What is New:

• Higher BMI SDS and more advanced skeletal maturation at treatment cessation are associated with earlier menarche after GnRHa therapy.

• This study provides comparative insights between central precocious puberty and early fast puberty, helping to inform clinical decision-making on treatment cessation.