Pelvic ultrasound and pubertal attainment in girls with sexual precocity: the pivotal role of uterine volume in predicting the timing of menarche

Abstract

Introduction: Among girls assessed for pubertal precocity, pelvic ultrasound (pUS) may represent a pivotal tool to predict the time expected to elapse between sonographic assessment and the onset of menarche (T_US-M). Accordingly, the present analysis is meant to define the statistical relationship between sonographic parameters and T_US-M, in order to identify the most reliable predictor of the timing of menarche.

Methods: Retrospective, multicenter analysis. Girls assessed for sexual precocity and showing sonographic and clinical findings consistent with pubertal onset upon referral were considered eligible. Patients treated with GnRH analogues were excluded and only those who had subsequently achieved complete and spontaneous pubertal attainment and for whom the exact date of menarche was available were included. Overall, we enrolled 184 girls from five tertiary care Italian Centers.

Results: The time elapsed (months) between baseline endocrine assessment and spontaneous achievement of menarche showed a negative statistically significant correlation (p<0.0001) with LH (r:-0.61), FSH (r:-0.59), estradiol (r:-0.52) and stimulated LH values (r:-0.58). Among pUS parameters, ovarian volume (r:-0.17 left, -0.30 right) and uterine body-to-cervix ratio (r:-0.18) poorly correlated with T_US-M, while uterine diameters (r:-0.61 longitudinal, -0.64 anteroposterior) and volume (r:-0.70) achieved a highly statistical significance (p<0.0001). Uterine volume (UV) showed a negative logarithmic relationship with T_US-M and represented the most reliable predictor of the timing of menarche in uni- and multivariable analyses (p <0.001). ROC analyses identified the UV thresholds that best predict the onset of menarche within 18, 12 and 6 months, respectively: 3.76, 6.02 and 8.80 ml.

Conclusion: The logarithm of UV shows the best statistical performance in predicting the timing of menarche in girls assessed for pubertal precocity. Accordingly, we developed a user-friendly online application that provides clinicians with an estimation of the months expected to elapse before menarche, based on the UV recorded upon pUS.

Keywords: GnRH analogues; age of menarche; pelvic ultrasound; precocious puberty; uterine volume.

Figure 1

Statistical relationship between the time elapsed between sonographic/biochemical assessment and menarche (T_US-M, dependent variable) and the following independent variables: unstimulated LH (A), LH peak following GnRH administration (B), unstimulated FSH (C) and estradiol values (D). The most-fitting correlation statistical pattern is logarithmic for all the independent variables assessed.

Figure 2

Matrix of the correlation coefficients between couples of biochemical and/or sonographic variables. (A) reports the Pearson’s coefficients for all the couples of variables. (B) displays a graphical equivalence for each correlation, represented as a filled circle. The greater the coefficient, the more intense is the color of each circle, with red representing negative correlations and blue positive ones. In addition, the diameter of each circle shows an inverse relationship with the p value of the specific correlation assessed. Overall, larger and darker circles represent more statistically significant and strong correlations, while transparent and small-sized circles indicate weaker and poorly statistically significant relationships between the variables assessed. T_US-M – time elapsed between ultrasound/biochemical evaluation and menarche.

Figure 3

Statistical relationship between T_US-M, (time elapsed from pelvic ultrasound and menarche, dependent variable) and the following sonographic parameters: uterine volume (A, logarithmic function), uterine longitudinal diameter (B, linear function), uterine transversal diameter (C, linear function) and anteroposterior diameter (D, linear function).

Figure 4

Receiver operator characteristic (ROC) curves designed to define the best cut-off points for the three uterine sonographic parameters assessed (uterine volume, longitudinal and anteroposterior diameters). Accordingly, we defined the threshold values that display the best statistical accuracy in predicting the onset of menarche by pre-defined time intervals (6,12 and 18 months). Patients with uterine parameters exceeding these thresholds are expected to achieve menarche within the corresponding time span with the most satisfactory combination of sensitivity and specificity.

Figure 5

Kaplan-Meier model reporting the survivorship trendlines (event: onset of menarche) in the whole study population (A) and in specific subcohorts of patients classified with reference to the threshold values identified by the ROC curves reported above. The survivorship curves report the biological behavior of subclasses of patients showing different uterine volume (B), longitudinal uterine diameter (C) and anteroposterior diameter (D).