# Delayed Puberty: Causes and Consequences, Genotypes and Phenotypes

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $507,370

## Abstract

Project Summary/Abstract
 This project seeks to enhance our understanding of the clinical features, long-term consequences, and
genetic underpinnings of delayed puberty, a common condition that affects 2-3% of adolescents. While
delayed puberty has been reported to have negative effects on final height, bone mineral density, and self-
esteem in adulthood, it remains unclear which patients with delayed puberty are at greatest risk for these
outcomes. Furthermore, we have limited understanding of the physiological and genetic mechanisms that
underlie delayed puberty.
 This project treats delayed puberty not as a single, monolithic entity, but as a clinical phenotype that can be
produced by at least two mechanisms. One mechanism is a global slowing of the developmental program that
regulates not just the timing of puberty but also the pace of childhood growth and skeletal maturation; this
global slowing is often called constitutional delay of growth and puberty (CDGP). The other mechanism is a
delay in pubertal timing in the absence of other delays in growth or skeletal maturation, producing an isolated
delay in pubertal timing. These mechanisms are not mutually exclusive, and both could potentially contribute to
delayed puberty in an individual.
 The first Aim of this project explores the clinical heterogeneity in delayed puberty by reviewing clinical
records of delayed puberty patients and identifying correlations between variables using univariate and
multivariate analyses. Aim 1 will also use latent class analysis, an unbiased, data-driven method, to identify
distinct subgroups within delayed puberty.
 The second Aim of this project assesses adults with a history of delayed puberty to determine if these
adults have impairments in height, bone mineral density, self-esteem, or sperm counts (in men) compared to
healthy control adults who had normal pubertal timing. The Aim further assesses whether these outcomes
differ for the different subgroups of delayed puberty identified in Aim 1 and/or across predictor variables such
as sex, body mass index, and prior treatment with sex steroids.
 The third Aim of this project seeks to identify the genetic causes of delayed puberty by examining the
contributions of both rare variants (identified through whole-exome sequencing) and common variants
(identified through genotyping of single-nucleotide polymorphisms). This Aim will also link these genetic causes
to the subgroups of delayed puberty identified in Aim 1 and the adult outcomes examined in Aim 2.
 By identifying the pathophysiologic mechanisms and genetic causes underlying delayed puberty, as well as
the clinical outcomes associated with these factors, these studies will improve our understanding of a common
pediatric condition and may lead to new insights into the mysteries of how the pace of childhood growth and
the timing of puberty are determined.

## Key facts

- **NIH application ID:** 10137980
- **Project number:** 5R01HD090071-05
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Yee-Ming Chan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $507,370
- **Award type:** 5
- **Project period:** 2017-04-11 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137980

## Citation

> US National Institutes of Health, RePORTER application 10137980, Delayed Puberty: Causes and Consequences, Genotypes and Phenotypes (5R01HD090071-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10137980. Licensed CC0.

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