View Clinical Trial (Medical Research Study)
Hormonal Regulation of Puberty and Fertility
| City: |
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Bethesda |
| State: |
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Maryland |
| Zip Code: |
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20892 |
| Conditions: |
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Endocrine Disease - Infertility - Hypogonadism - Amenorrhea - Adolescents |
| Purpose: |
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Background:
- 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.
Objectives:
- To study disorders of GnRH production.
Eligibility:
- Adult men and women at least 18 years of age with low or no gonadotropin levels.
- Adolescents between 14 and 18 years of age with low or no gonadotropin levels.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine
samples will be collected.
- Participants will have tests to look at their hormone levels. Blood samples may be
collected after taking different drugs, including insulin and cortisone. A 24-hour
urine sample will be collected.
- Participants will have imaging studies to look at bone and brain development. They will
also have ultrasounds of the kidneys, abdomen, and reproductive organs.
- Tests of smell and hearing will be used to look for abnormalities in these senses.
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| Study Summary: |
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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.
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| Criteria: |
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- INCLUSION CRITERIA:
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.
EXCLUSION CRITERIA:
-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:
- Patients who have additional pituitary deficiencies, effectively ruling out isolated
GnRH deficiency, whether these deficiencies are congenital or acquired (e.g.
secondary to malignancy, infection, or irradiation).
- Patients who are taking medications known to cause HH, such as corticosteroids or
continuous opiate administration.
- Pregnancy or lactation
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| NCT ID: |
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NCT01511588 |
| Primary Contact: |
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Principal Investigator
Angela Delaney, M.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Angela Delaney, M.D.
Phone: (301) 496-3025
Email: delaneya@mail.nih.gov
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| Backup Contact: |
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N/A |
| Location Contact: |
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Bethesda, Maryland 20892
United States
For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)
Phone: 800-411-1222
Email: prpl@mail.cc.nih.gov
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 25, 2013 |
| Modifications to this listing: |
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