Hormonal Regulation of Puberty and Fertility

NCT01511588 | Completed

• 2 other identifiers: 12005012-E-0050
• Study Type: observational
• Target: 111
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Endocrine Disease; Infertility; Hypogonadism; Amenorrhea; Adolescents

Keywords

Kallmann Syndrome; Delayed Puberty; GnRH Deficiency; Infertility; Hypogonadotropic Hypogonadism; Natural History; Amenorrhea; Hypogonadism

Outcome Measures

Primary Outcomes (1)

• The main outcome is the identification of novel GnRH secretory patterns or non-reproductive phenotypic characteristics in individuals representing the complete spectrum of idiopathic hypogonadotropic hypogonadism.

  The main outcome is the identification of novel GnRH secretory patterns or non-reproductive phenotypic characteristics in individuals representing the complete spectrum of idiopathic hypogonadotropic hypogonadism.

  At study enrollment

Secondary Outcomes (1)

• 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.

Study Arms (1)

HH patients

Clinical patients with hypogonadotropic hypogonadism (HH)

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Clinical patients with hypogonadotropic hypogonadism (HH)

You may qualify if:

• Since hypogonadotropic hypogonadism is a rare condition, with an incidence of 1/10,000 to 1/86,000 for isolated GnRH deficiency (43, 44), 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 \>= 14 years old with clinical findings of HH as follows will be included (due to substantial variability among patient presentations, this will be based on the clinical judgement of the investigator):
• Failure to go through a normal, age-appropriate, spontaneous puberty and low sex steroid levels in the setting of low/normal gonadotropins; OR
• Normal puberty with subsequent development of low gonadotropin levels.
• A patient under the age of 14 years may be considered for baseline evaluation if there is sufficient evidence suggestive of HH, including, but not limited to any two of the following: anosmia, history of cryptorchidism or microphallus. As above, due to substantial variability among patient presentations, this will be based on the clinical judgement of the Investigator.

You may not qualify if:

• 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
• In some cases, the subjects will be given the option of having the initial evaluation performed at the NIEHS Clinical Research Unit (Durham, NC). The initial evaluation may be completed at one site with completion of the LH pulsatility study and other diagnostic evaluations undertaken at the other site, depending up on logistical considerations for both the patient and the sites.
• All subjects will be provided with a copy of the consent to read over. Time will be given to meet with the subject, describe the study, and review the procedures involved with the study. This will be followed by a time where the prospective subject can express any questions or concerns he/she may have regarding the study and have those issues addressed by one of the investigators. The consent will be signed by the subject and by a designated investigator. A copy of the signed consent will be given to the subject prior to the initiation of any study procedures.
• Children
• For subjects who are children, all provisions regarding obtaining assent from children and consent from their parent/guardian are described in detail in Consent/Assent Procedures, below.
• NIH Staff, and family members of study team members
• NIH staff and family members of study team members may be enrolled in this study as this population meets the study entry criteria. Neither participation nor refusal to participate as a subject in the research will have an effect, either beneficial or adverse, on the participant s employment or position at NIH.
• Every effort will be made to protect participant information, but such information may be available in medical records and may be available to authorized users outside of the study team in both an identifiable and unidentifiable manner.
• The NIH Frequently Asked Questions (FAQs) for Staff Who are Considering Participation in NIH Research will be made available. Please see Consent/Assent Procedures for consent of NIH Staff. NIH employees or staff who participate during work hours will receive a copy of Leave Policy for NIH Employees Participating in NIH Medical Research Studies.

Sponsors & Collaborators

• National Institute of Environmental Health Sciences (NIEHS): lead

Study Sites (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

NIEHS Clinical Research Unit (CRU)

Research Triangle Park, North Carolina, 27709, United States

Location

Related Publications (4)

• Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E. Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone. Science. 1978 Nov 10;202(4368):631-3. doi: 10.1126/science.100883.

  PMID: 100883 BACKGROUND

• Seminara SB, Hayes FJ, Crowley WF Jr. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): pathophysiological and genetic considerations. Endocr Rev. 1998 Oct;19(5):521-39. doi: 10.1210/edrv.19.5.0344. No abstract available.

  PMID: 9793755 BACKGROUND

• Nachtigall LB, Boepple PA, Pralong FP, Crowley WF Jr. Adult-onset idiopathic hypogonadotropic hypogonadism--a treatable form of male infertility. N Engl J Med. 1997 Feb 6;336(6):410-5. doi: 10.1056/NEJM199702063360604.

  PMID: 9010147 BACKGROUND

• Delaney A, Volochayev R, Meader B, Lee J, Almpani K, Noukelak GY, Henkind J, Chalmers L, Law JR, Williamson KA, Jacobsen CM, Buitrago TP, Perez O, Cho CH, Kaindl A, Rauch A, Steindl K, Garcia JE, Russell BE, Prasad R, Mondal UK, Reigstad HM, Clements S, Kim S, Inoue K, Arora G, Salnikov KB, DiOrio NP, Prada R, Capri Y, Morioka K, Mizota M, Zechi-Ceide RM, Kokitsu-Nakata NM, Tonello C, Vendramini-Pittoli S, da Silva Dalben G, Balasubramanian R, Dwyer AA, Seminara SB, Crowley WF, Plummer L, Hall JE, Graham JM, Lin AE, Shaw ND. Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose. J Clin Endocrinol Metab. 2020 May 1;105(5):1538-51. doi: 10.1210/clinem/dgaa065.

  PMID: 32034419 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Endocrine System Diseases; Infertility; Hypogonadism; Amenorrhea; Kallmann Syndrome; Puberty, Delayed

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Gonadal Disorders; Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Natalie D Shaw, M.D.

  National Institute of Environmental Health Sciences (NIEHS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2012
• First Posted: January 18, 2012
• Study Start: April 25, 2012
• Last Updated: May 29, 2026

Record last verified: 2026-03-11

Locations

US (2)