Hormonal Regulation of Puberty and Fertility
|First Received Date ICMJE||January 13, 2012|
|Last Updated Date||April 21, 2017|
|Start Date ICMJE||December 15, 2011|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||The main outcome is the identification of novel GnRH secretory patterns or non-reproductive phenotypic characteristics in individuals representing the complete spectrum of idiophatic hypogonadism.|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01511588 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Secondary outcomes are the recognition of specific pubertal phenotypes, as well as discovery of the roles of newly identified genes contributing to IHH in GnRH development and biology, for those subjects who also enroll in our genetics protocol.|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Hormonal Regulation of Puberty and Fertility|
|Official Title ICMJE||Hormonal Regulation of Puberty and Fertility|
- The body produces gonadotropin-releasing hormone (GnRH) about every 2 hours. GnRH travels through the bloodstream to the pituitary gland, where it stimulates the gland to produce hormones called gonadotropins. These hormones stimulate the testicles or ovaries. The testicles produce testosterone and develop sperm. The ovaries produce estrogen and prepare for ovulation. Normal estrogen and testosterone levels are required for puberty. Some people, however, have either low levels or total lack of GnRH. This can cause problems with puberty and fertility. Researchers want to study people with low or no GnRH to better understand how it affects puberty and fertility.
- To study disorders of GnRH production.
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. GnRH secretion is fully active during the neonatal period, quiescent throughout most of childhood, and is reactivated at the time of puberty to induce sexual maturation and subsequent fertility. 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. In addition, non-reproductive phenotypes of this spectrum have been identified in some individuals, including anosmia, auditory defects, skeletal and renal anomalies.
Defining the physiology of GnRH is critical to understanding the clinical heterogeneity of isolated GnRH deficiency, particularly in light of emerging gene discoveries that elucidate genotype-phenotype correlations. Careful human phenotyping of patients with mutations in genes known to cause IHH has provided insight into developmental pathways involved in the ontogeny of GnRH neurons, but the neuroendocrine regulation of this system is not well understood.
Here, we propose the addition of the NIH as the second site to an existing protocol at Massachusetts General Hospital to phenotypically characterize subjects with IHH. We plan to admit males and females 14 years of age or older with clinical signs suggestive of IHH for comprehensive phenotyping to include neuroendocrine profiling via an LH pulsatility study, as well as identification of other non-reproductive findings. Combining our effort with the established protocol and recruitment mechanisms at MGH will allow us to maximize the number of subjects with this rare disorder that can be evaluated.
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, as well as other unknown aspects of GnRH biology, which may be illuminated through the non-reproductive characteristics of these patients. Examining the baseline 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.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case-Only
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||200|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Since hypogonadotropic hypogonadism is a rare condition, with an incidence of 1/10,000 to 1/86,000 for isolated GnRH deficiency (34, 35), this protocol remains open to enrollment so that we may study all subjects that are both qualified and interested in participating.
Males or females who are greater than or equal to 14 years old with clinical findings of HH as outlined above will be included. In certain circumstances, a patient under the age of 14 years may be considered for baseline evaluation if there is sufficient evidence suggestive of HH, such as any two of the following: anosmia, history of cryptorchidism or microphallus.
-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:
|Ages||14 Years and older (Child, Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01511588|
|Other Study ID Numbers ICMJE||120050
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|
|Study Sponsor ICMJE||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|
|Collaborators ICMJE||Massachusetts General Hospital|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||December 14, 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP