An observational study in Genetic Disorder, Infertility and Hypogonadism, sponsored by National Institute of Environmental Health Sciences (NIEHS). Recruiting at 2 sites in United States. Open to participants aged 6 Weeks to 120 Years. Per ClinicalTrials.gov, last updated 2026-10-26.
Sponsored by National Institute of Environmental Health Sciences (NIEHS) · Observational
Background:
- During puberty, children begin to develop into adults. Problems with the hormones released during puberty can affect the reproductive system. Some people have low hormone levels that severely delay or prevent puberty. Others start puberty abnormally early. Other people may have a normal puberty but develop reproductive disorders later in life. Researchers want to study people with reproductive disorders to learn more about how these disorders may be inherited.
Objectives:
- To learn how reproductive system disorders may be inherited.
Eligibility:
Design:
The key initiating factors for reproductive development remain among the great mysteries of pediatric and reproductive endocrinology. The onset of puberty is initiated by pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. The neuroendocrine events leading to increased GnRH secretion and the resultant onset of puberty remain largely unknown.
Isolated deficiency of GnRH results in the rare clinical syndrome of idiopathic hypogonadotropic hypogonadism (IHH), where decreased secretion of GnRH results in impaired gonadotropin secretion. The resultant hypogonadism presents with delayed, incomplete, or absent sexual maturation. Human and animal models have identified a number of genes responsible for IHH, but more than half of patients with clinical evidence of the disorder do not have a detectable mutation. In addition, there is significant clinical heterogeneity among affected individuals, including members of the same family harboring the same mutations. Careful human phenotyping of such patients and families has expanded our understanding of this spectrum of disorders to include oligo-digenic inheritance, as well as reversibility of the condition, and has provided insight into developmental pathways involved in the ontogeny of GnRH neurons. In particular, hypogonadotropic hypogonadism (HH) exists along a genetic and phenotypic spectrum that includes milder forms of GnRH dysregulation, precocious and delayed puberty, and onset of reproductive dysfunction after puberty.
Genetic analysis of subjects with unknown mutations is likely to yield important insights into additional pathways involved in the regulation of GnRH secretion. Here, we propose a genetic investigation of subjects with IHH to characterize further the phenotypic effects of previously described genetic variants, as well as to identify novel genes involved in congenital GnRH deficiency. We will use candidate gene and whole exome approaches, as well as linkage analysis.
This protocol will utilize the disease model of IHH to increase our understanding of the physiology of GnRH secretion, including the neuroendocrine regulation of GnRH pulsatility. Examining the genetic characteristics of subjects with isolated GnRH deficiency will reveal insights into the mechanisms underlying the reawakening of the hypothalamic-pituitary-gonadal axis at puberty, providing opportunities for new diagnostic capabilities and therapeutic interventions for disorders of puberty and fertility.
583 studies on the registry are indexed under Genetic Diseases, Inborn; 157 are open to participants now.
This study's planned enrollment of 850 is above the median of 151 across 239 observational studies indexed under Genetic Diseases, Inborn.
Browse Genetic Diseases, Inborn studies →National Institute of Environmental Health Sciences (NIEHS) is the lead sponsor of 183 studies on the registry; 18 are open to participants now.
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Primary Clinical, self-referred or physician-referred subjects
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
The essential inclusion criteria include:
EXCLUSION CRITERIA:
Since hypogonadotropic hypogonadism is a rare condition, this protocol remains open to enrollment so that we may study all subjects that are both qualified and interested in participating.
Because HH represents a spectrum, where associated clinical findings may provide phenotypic clues to the assessment of inheritability and underlying physiology, exclusion criteria are very limited:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CPP subjects
IHH, KS, GnRH Deficiency, BAM syndrome (arhinia), HA, CDP subjects
The main outcome is the identification of known and novel genetic variants in individuals representing the complete spectrum of idiopathic hypogonadotropic hypogonadism.
The main outcome is the identification of known and novel genetic variants in individuals representing the complete spectrum of idiopathic hypogonadotropic hypogonadism.
Time frame: Ongoing/exploratory
Phenotypic correlations, made by comparing the results of the genotypic analysis with clinical and/or biochemical characteristics, as well as the discovery of genes worthy of further functional analysis.
Phenotypic correlations, made by comparing the results of the genotypic analysis with clinical and/or biochemical characteristics, as well as the discovery of genes worthy of further functional analysis.
Time frame: Ongoing/exploratory
Plan to share: Undecided — This study does not meet the criteria of a clinical trial, therefore ICMJE does not require a data sharing statement.@@@@@@@@@@@@The study will comply with the NIH Genomic Data Sharing Policy, if in the future, it meets the Policy s criteria for large scale human genomic data.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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