Infant gonadotropins predict spontaneous puberty in girls with Turner syndrome

Alexandra Sawyer; Samantha Bothwell; Karli Swenson; Sharon Travers; Shanlee Davis

doi:10.1515/jpem-2024-0523

Article

Infant gonadotropins predict spontaneous puberty in girls with Turner syndrome

Alexandra Sawyer , Samantha Bothwell , Karli Swenson , Sharon Travers and Shanlee Davis

Published/Copyright: April 29, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 6

Abstract

Objectives

Hypergonadotropic hypogonadism is a characteristic clinical manifestation of Turner syndrome (TS). While up to 30 and 20 % of people with TS will have spontaneous thelarche and menarche respectively, there is a lack of evidence to predict who will retain sufficient ovarian function to achieve these outcomes. The aim of this study was to determine if follicle-stimulation hormone (FSH) and/or luteinizing hormone (LH) concentrations measured in infancy would accurately predict later spontaneous thelarche or menarche.

Methods

Patients with a diagnosis of Turner syndrome with FSH and/or LH clinically measured prior to three years of age and now ≥10 years of age with documented pubertal assessment were included (n=33). Differences in infant gonadotropin values were determined for patients with vs. without spontaneous thelarche/menarche using Kruskal-Wallis tests. The optimal threshold of infant LH and FSH to predict spontaneous thelarche and menarche was then determined by maximizing the sum of sensitivity and specificity.

Results

The prevalence of spontaneous thelarche and menarche were 21.2 and 15.2 % respectively. An infant LH value greater than 0.5 mIU/mL predicted lack of spontaneous thelarche with an estimated accuracy of 94 % and lack of spontaneous menarche with an estimated accuracy of 96 %. An infant FSH value greater than 37.4 mIU/mL predicted lack of lack of spontaneous thelarche with an accuracy of 97 % and lack of spontaneous menarche with an accuracy of 100 %.

Conclusions

Infant gonadotropin concentrations accurately predict spontaneous later thelarche and menarche for persons with TS.

Keywords: Turner syndrome; infant gonadotropins; FSH; LH; AMH; puberty

Corresponding author: Shanlee Davis, MD, PhD, Associate Professor of Pediatrics, Department of Pediatrics, Section of Endocrinology, University of Colorado SOM, Aurora, CO, USA; and Attending Physician, Department of Pediatric Endocrinology, eXtraOrdinarY Kids Clinic and Research Program, Children’s Hospital Colorado, 13123 East 16th Ave B265, Aurora, CO, 80045, USA, E-mail: Shanlee.davis@cuanschutz.edu

Funding source: NIH/NCATS Colorado CTSA

Award Identifier / Grant number: UM1 TR004399

Acknowledgements

We want to acknowledge the non-profit organization Turner Syndrome Colorado that supports the eXtraOrdinary Kids Turner Syndrome Multidisciplinary Clinic at Children’s Hospital Colorado and all the patients and providers that are a part of that clinic.

Research ethics: This study protocol was reviewed and approved by the Colorado Multiple Institutional Review Board, #16–1631. The study was determined to meet all criteria for a full waiver of informed consent. Contents are the authors’ sole responsibility and do not necessarily represent official NIH views.
Informed consent: Not applicable.
Author contributions: Dr. Sawyer completed data collection and drafted the initial version of the manuscript. Ms. Bothwell completed statistical analysis of data, drafted sections of the manuscript, and critically reviewed and edited the manuscript. Dr. Swenson drafted sections of the manuscript and reviewed and edited the manuscript. Dr. Travers conceptualized and designed this study and reviewed and edited the manuscript. Dr. Davis conceptualized, funded, and oversaw this work, acquired data, guided statistical analysis, and reviewed and edited the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: SD is a site investigator for a clinical trial sponsored by Ascendis Pharma and has received research funding from Turner Syndrome Global Alliance, Turner Syndrome Colorado, Pediatric Endocrine Society, NIH, and Boettcher Foundation. The other authors have no conflicts of interest to declare.
Research funding: This study was supported by department funds and NIH/NCATS Colorado CTSA Grant Number UM1 TR004399 (REDCap). Contents are the authors’ sole responsibility and do not necessarily represent official NIH views. The funder had no role in the design, data collection, data analysis, and reporting of this study.
Data availability: Data are available from the authors upon reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jpem-2024-0523).

Received: 2024-10-30

Revised: 2025-03-03

Accepted: 2025-04-12

Published Online: 2025-04-29

Published in Print: 2025-06-26

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Supplementary Material

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Keywords for this article

Turner syndrome; infant gonadotropins; FSH; LH; AMH; puberty