Study Details Factors Negatively Impacting Time to Menarche in Central Precocious Puberty

A new study from investigators in the department of pediatric endocrinology at the Icahn School of Medicine at Mount Sinai is providing clinicians with an overview of factors that could negatively influence time to menarche following gonadotropin-releasing hormone agonist (GnRHa) in women with central precocious puberty (CPP).

Citing a dearth of research on the topic, investigators carried out a retrospective chart review of more than 3 dozen females with CPP and provide insight into multiple factors, including Tanner stage of breast development and change in bone age, that were negatively associated with the time interval to menarche.

“Few studies have evaluated auxological factors that can predict the time interval to menarche after treatment cessation. The aims of this study were to evaluate the time interval to menarche after GnRHa discontinuation and to identify factors that contribute to timing of menarche,” wrote investigators.

With GnRHa the most commonly used treatment for CPP, the current study was created by investigators described as a lack of studies detailing factors associated with a negative influence on time interval to menarche following treatment cessation. Led by Vickie Wu, MD, a pediatric endocrinologist at the Icahn School of Medicine at Mount Sinai, investigators designed their study as a retrospective chart review of records from women with idiopathic CPP treated with GnRHa from May 2005-November 2017 at an academic pediatric endocrinology clinic.

During this time period, 450 female patients were diagnosed with CPP. Of these, 67 were treated with GnRHa and had documented menarche in their medical record. After exclusion of patients with coexisting endocrinopathies and those with CPP and an identified etiology, 39 patients were identified for inclusion in the analysis. Of note, diagnostic criteria for CPP used min the study were breast development before 8 years of age, measurable pubertal luteinizing hormone (LH) and/or estradiol concentrations at baseline or in response to GnRH stimulation test, and significant bone age advancement.

The mean treatment duration for the 39 patients included in the study was 2.2±1.4 years. At the start of GnRHa treatment, the mean chronologic age of the cohort was 9.4±1.6 years, the mean bone age was 11.2±1.3 years, the mean height was 139.0±9.5 cm, and mean weight was 39.5±10.6 kg. At the end of treatment, the mean chronologic age was 11.6±1.2 years and the mean bone age was 12.5±0.9 years. The difference between bone age and chronologic age at the start of treatment was 1.8±1.4 years and the difference at the end of treatment was 0.9±1.2 years.

Results of the investigators’ analysis indicated menarche occurred at a mean of 12.6±1.1 years, which was a mean of 1.04±0.5 years following treatment discontinuation. Investigators noted 54% of patients reached menarche by 1 year after the end of treatment and 44% reached by 2 years. Further analysis suggested bone age at start of treatment, Tanner stage of breast development at start of treatment, and change in bone age from start to end of treatment were all negatively associated with time interval to menarche (P for all <.05).

Investigators noted a greater change in bone age during treatment was significantly associated with a shorter interval to menarche after adjustment for initial bone age (β=-0.25; 95% CI, -0.44 to -0.07; P=.009). Additionally, results incited advanced bone age and advanced Tanner stage prior to the start of treatment were associated with decreased time interval to menarche.

“In conclusion, the time from the end of treatment to menarche ranged from 0.5 to 1.5 years. The factors negatively associated with the time interval to menarche were Tanner stage of breast development at treatment onset, bone age at treatment onset, and change in bone age,” wrote investigators. “These data provide clinical correlates that assist providers during anticipatory guidance of patients after treatment of CPP with GnRHa.”

Investigators cautioned clinicians to consider the limitations of their study when interpreting the results. Limitations noted by investigators included the relatively small sample size and the lack of an untreated control group who could be followed until menarche.

This study, “Clinical findings influencing time to menarche post gonadotropin-releasing hormone agonist therapy in central precocious puberty,” was published in the Annals of Pediatric Endocrinology & Metabolism.