ESPE Abstracts

Background and aims: The impact of GnRH treatment on the timing of menarche, menstrual cycle status, and onset of menopause in girls with early/precocious puberty is of clinical interest. This study aims to provide insight into the effects of GnRH treatment on these aspects.

Methods: A comprehensive literature search was conducted on PubMed for English articles published between 2010 and 2023. The focus was on studies, meta-analyses, and prospective and retrospective investigations exploring the effect of GnRH treatment on the timing of menarche, menstrual cycle status, and onset of menopause in girls with early/precocious puberty.

Results: The analysis of various studies revealed significant findings regarding the impact of GnRH treatment on reproductive milestones: Three long-term studies demonstrated that pubertal reactions in central precocious puberty (CPP) patients were restored within 1 year, with most recovering within 6 months after treatment discontinuation. After GnRH treatment cessation, the onset of menarche required an average interval of 0.9-1.5 years, with menarche starting around 12.6-13.6 years old chronologically. In a Korean study, menarche began approximately 14 months post-GnRHa treatment, corresponding to 11.9 years in chronological age and 12.8 years in bone age (similar to normal girls' average age at menarche). The age at CPP diagnosis (< 6, 6-8, or 8:9) did not significantly impact the prepuberty period or onset of menarche post-treatment. In another study, among CPP patients, GnRHa-treated individuals exhibited an average age at menarche of 12 years, showing a delay compared to the untreated group's age of 9.6 years. A study reported regular menstrual cycles in the majority (82/87) of GnRHa-treated patients, with few (5/87) experiencing oligomenorrhea due to excessive exercise, which improved with exercise control. Other investigators found that in adulthood, 80% of CPP patients who received GnRHa treatment maintained normal menstrual cycles. Another long-term follow-up study reported that patients treated with GnRH displayed regular menstrual cycles and no breast or uterine disorders after an average of 12.5 years post-treatment. A pooled study of postmenopausal women from different countries indicated that early menarche (≤11 years) is a risk factor for both premature menopause (FM P <40 years) and early menopause (FMP 40–44 years).

Conclusion: GnRH treatment does not seem to negatively affect the menstrual cycle status. Nevertheless, untreated early puberty increases the risk of premature or early-onset menopause, which can potentially be mitigated by GnRH therapy. These findings shed light on the intricate relationship between GnRH treatment and early/precocious puberty.