Baselines in Reproductive Disorders

NCT00456274 | Unknown DMC

• 1 other identifier: 1999P-003770
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to explore the way in which gonadotropins (pituitary hormones) are released into the body. The knowledge acquired in this study will be used for the diagnosis and treatment of reproductive endocrine disorders. We seek to investigate the baseline characteristics of the GnRH-induced gonadotropin pulsations of patients with the following diagnoses:

• Hypothalamic Amenorrhea (HA)
• Idiopathic hypogonadotropic hypogonadism (IHH)
• Polycystic ovarian disease (PCOD)
• Acquired hypogonadotropic hypogonadism (AHH)
• Premature Ovarian Failure (POF) \*\*WE ARE CURRENTLY RECRUITING ONLY SUBJECTS WITH A DIAGNOSIS OF IHH.\*\* This has been an extremely productive and pivotal protocol in the studies of female reproductive physiology and pathophysiology and continues to be critical for defining the neuroendocrine abnormalities in patients with reproductive disorders. In some cases, it is also helpful in the planning of subsequent therapy if so desired. It is important to note that minors have been included in this protocol, as many patients are extremely anxious to know more about their neuroendocrine disorder. With minors who would like to know if their disorder is correctable, this protocol may be followed up with administration of pulsatile gonadotropin-releasing hormone (GnRH).

Conditions

Amenorrhea; Hypogonadotropic Hypogonadism; Kallmann's Syndrome

Keywords

Hypothalamic Amenorrhea; Idiopathic hypogonadotropic hypogonadism; Acquired hypogonadotropic hypogonadism; Kallmann's Syndrome; Amenorrhea; Gonadotropin Releasing Hormone

Outcome Measures

Primary Outcomes (1)

• Number of luteinizing hormone (LH) and FAS (free alpha subunit) pulses

  8-12 hours

Secondary Outcomes (2)

• Amplitude of LH and FAS pulses

  8-12 hours

• Inter-pulse interval for LH and FAS pulses

  8-12 hours

Study Arms (1)

1

OTHER

Procedure: Frequent baseline blood sampling

Interventions

Frequent baseline blood sampling PROCEDURE

3 ml of blood sampled every 10 minutes for a total of 8-12 hours

1

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy women between the ages of 16-45 years
• Negative pregnancy test
• On no gonadal steroid preparations for at least 3 months, with the exception of the idiopathic hypogonadotropic hypogonadism (IHH) group, they should be off gonadal steroid for at least 4 weeks
• The following test will be performed if they had not been done in the last 2 months
• Normal blood count
• Normal thyroid function test

You may not qualify if:

• Hemoglobin levels less than 11 gm/dL
• Positive pregnancy test
• Abnormal thyroid function
• Abnormal MRI (IHH)

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (14)

• Clarke IJ. Variable patterns of gonadotropin-releasing hormone secretion during the estrogen-induced luteinizing hormone surge in ovariectomized ewes. Endocrinology. 1993 Oct;133(4):1624-32. doi: 10.1210/endo.133.4.8404603.

  PMID: 8404603 BACKGROUND

• Wilson RC, Kesner JS, Kaufman JM, Uemura T, Akema T, Knobil E. Central electrophysiologic correlates of pulsatile luteinizing hormone secretion in the rhesus monkey. Neuroendocrinology. 1984 Sep;39(3):256-60. doi: 10.1159/000123988.

  PMID: 6504270 BACKGROUND

• Nett TM, Adams TE. Further studies on the radioimmunoassay of gonadotropin-releasing hormone: effect of radioiodination, antiserum and unextracted serum on levels of immunoreactivity in serum. Endocrinology. 1977 Oct;101(4):1135-44. doi: 10.1210/endo-101-4-1135. No abstract available.

  PMID: 332491 BACKGROUND

• Adams JM, Taylor AE, Schoenfeld DA, Crowley WF Jr, Hall JE. The midcycle gonadotropin surge in normal women occurs in the face of an unchanging gonadotropin-releasing hormone pulse frequency. J Clin Endocrinol Metab. 1994 Sep;79(3):858-64. doi: 10.1210/jcem.79.3.7521353.

  PMID: 7521353 BACKGROUND

• Filicori M, Flamigni C, Crowley WF, Jr. The critical role of blood sampling frequency in the estimation of episodic luteinizing hormone secretion in normal women. In: Crowley Jr WF, Hofler JG (eds) The Episodic Secretion of Hormones. New York: Churchill Livingston.5-13, 1987.

  BACKGROUND

• Hall JE, Lavoie HB, Marsh EE, Martin KA. Decrease in gonadotropin-releasing hormone (GnRH) pulse frequency with aging in postmenopausal women. J Clin Endocrinol Metab. 2000 May;85(5):1794-800. doi: 10.1210/jcem.85.5.6612.

  PMID: 10843154 BACKGROUND

• Whitcomb RW, O'Dea LS, Finkelstein JS, Heavern DM, Crowley WF Jr. Utility of free alpha-subunit as an alternative neuroendocrine marker of gonadotropin-releasing hormone (GnRH) stimulation of the gonadotroph in the human: evidence from normal and GnRH-deficient men. J Clin Endocrinol Metab. 1990 Jun;70(6):1654-61. doi: 10.1210/jcem-70-6-1654.

  PMID: 1693373 BACKGROUND

• Crowley WF, Taylor AE, Martin KA, Whitcomb RW, Finkelstein JS, Hall JE. 1994 Use of the free alpha subunit (FAS) of glycoprotein secreting hormones as a surrogate marker of GnRH secretion in the human. In: Glycoprotein Hormones: Structure, Function and Clinical Implications. JW Lusbader, LD Puett, R Ruddon (eds), Serono Symposia, UAS pp. 253-63.

  BACKGROUND

• Sharpless JL, Supko JG, Martin KA, Hall JE. Disappearance of endogenous luteinizing hormone is prolonged in postmenopausal women. J Clin Endocrinol Metab. 1999 Feb;84(2):688-94. doi: 10.1210/jcem.84.2.5433.

  PMID: 10022439 BACKGROUND

• Kourides IA, Weintraub BD, Re RN, Ridgway EC, Maloof F. Thyroid hormone, oestrogen, and glucocorticoid effects on two different pituitary glycoprotein hormone alpha subunit pools. Clin Endocrinol (Oxf). 1978 Dec;9(6):535-42. doi: 10.1111/j.1365-2265.1978.tb01511.x. No abstract available.

  PMID: 747894 BACKGROUND

• Hall JE, Whitcomb RW, Rivier JE, Vale WW, Crowley WF Jr. Differential regulation of luteinizing hormone, follicle-stimulating hormone, and free alpha-subunit secretion from the gonadotrope by gonadotropin-releasing hormone (GnRH): evidence from the use of two GnRH antagonists. J Clin Endocrinol Metab. 1990 Feb;70(2):328-35. doi: 10.1210/jcem-70-2-328.

  PMID: 2105329 BACKGROUND

• Hall JE, Martin KA, Whitney HA, Landy H, Crowley WF Jr. Potential for fertility with replacement of hypothalamic gonadotropin-releasing hormone in long term female survivors of cranial tumors. J Clin Endocrinol Metab. 1994 Oct;79(4):1166-72. doi: 10.1210/jcem.79.4.7962290.

  PMID: 7962290 BACKGROUND

• Perkins RB, Hall JE, Martin KA. Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability, and response to neurotransmitter modulation. J Clin Endocrinol Metab. 1999 Jun;84(6):1905-11. doi: 10.1210/jcem.84.6.5823.

  PMID: 10372685 BACKGROUND

• Hayes FJ, McNicholl DJ, Schoenfeld D, Marsh EE, Hall JE. Free alpha-subunit is superior to luteinizing hormone as a marker of gonadotropin-releasing hormone despite desensitization at fast pulse frequencies. J Clin Endocrinol Metab. 1999 Mar;84(3):1028-36. doi: 10.1210/jcem.84.3.5579.

  PMID: 10084591 BACKGROUND

Related Links

• MGH Reproductive Endocrine Research Studies

MeSH Terms

Conditions

Amenorrhea; Hypogonadism; Kallmann Syndrome; Idiopathic Hypogonadotropic Hypogonadism

Condition Hierarchy (Ancestors)

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

Study Officials

• Janet E Hall, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Shaw, MD

CONTACT

617-726-1895; nshaw@partners.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician

Study Record Dates

• First Submitted: April 2, 2007
• First Posted: April 4, 2007
• Study Start: September 1, 1999
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: August 4, 2014

Record last verified: 2014-07

Locations

US (1)