Introduction: 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%. Conclusion: Infant gonadotropin concentrations accurately predict spontaneous later thelarche and menarche for persons with TS.

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.

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.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

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.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data are available from the authors upon reasonable request.