The Genetics of Polycystic Ovarian Syndrome

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Corrine Welt, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00166569
First received: September 9, 2005
Last updated: September 26, 2011
Last verified: September 2011
  Purpose

The goal of this study is to determine the genetic basis of polycystic ovary syndrome (PCOS). We will first look for genes in the Icelandic population, where large family trees are known and it is easier to search for genes. We will then determine whether these same genes are important in U.S. PCOS patients.


Condition
Polycystic Ovary Syndrome

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: The Genetics of Polycystic Ovarian Syndrome

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Estimated Enrollment: 2700
Study Start Date: January 2003
Detailed Description:

Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders in women. Its marked phenotypic variability, puzzling list of associated conditions, and hence potential risk to a woman's health over her lifecycle clearly remain a clinical investigational, genetic, and therapeutic challenge. To a great extent, this variability can be attributed to the marked genetic and environmental heterogeneity of the populations studied. We plan to address many of these long-term clinical research obstacles by delineating the genetic basis of PCOS in a unique investigational venue, the Icelandic population. Studying the Icelandic population has the following advantages: a) the population's relative genetic and environmental homogeneity; b) the remarkably rich genealogic database; and c) the centralized healthcare information. In this unusual venue, clustering of large numbers of PCOS families with known relationships is possible. Their relative homogeneity and genealogic characteristics can reduce genetic variance and hence be used to map the genetic basis for PCOS more efficiently than in more heterogeneous populations. As the genes responsible for PCOS emerge, this protocol will also determine phenotype/genotype correlations in Iceland, contrasting them with US women, and assess their long-term medical consequences.

Each female subject will be asked to arrive fasting in the morning. Women with PCOS will be asked to arrive at least 10 days from their last menstrual period, while women with regular menstrual cycles will be seen within the first 14 days after their menstrual period starts. All subjects will be asked to fill out an extensive questionnaire. Subjects will then undergo further history, physical exam and laboratory exams. Blood will be drawn at baseline for DNA (the material in the cell that holds the genes), fasting blood glucose and insulin, HbA1C, total and fractionated cholesterol, triglycerides, testosterone, androstenedione, DHEAS, SHBG and 17-OH Progesterone. Additional blood will be drawn at 10 and 20 minutes for measurement of LH and FSH, which are pulsatile. An oral glucose tolerance test will be optional. A standardized transvaginal ultrasound will be performed to look at the ovaries in all female subjects. This can be done over the abdomen with a full bladder if the patient prefers.

Male family members will also undergo a history, physical and laboratory exams in an identical manner to that of their female family members with the addition that specific notice of their hair distribution will be made. PCOS subjects who are on oral contraceptives or other hormonal medication may have cholesterol, insulin, glucose, triglycerides and HbA1C labs drawn, whereas subjects on insulin sensitizing agents will not have any blood drawn for these tests. These subjects will undergo an ultrasound and DNA sampling.

All hormone blood samples from Icelandic and Boston subjects will be examined in Boston. All DNA testing will be performed in the Genotyping Core of deCODE, a company in Iceland. Therefore, all DNA samples from Iceland and Boston will be analyzed in Iceland. The Boston blood samples will be coded and sent to the DeCODE genotyping facility. The investigators in Boston will retain the link between the code and the subject information in a locked area in the office. The names of subjects will not be disclosed to deCODE.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Women with PCOS age 18 to 40 years, sampled from the population and controls without PCOS.

Criteria

Inclusion Criteria:

  • Inclusion Criteria-PCOS Probands: 1) Aged 18 yrs or above 2) Oligomenorrhea or amenorrhea (<9 menses/yr); 3) clinical and/or biochemical evidence of hyperandrogenemia; 4) normal TSH and prolactin <25 ng/mL; 5) on no hormonal or insulin sensitizing medication for at least 3 months and have not taken Provera for at least ten days prior to enrollment. If the subject has previously had hormone levels drawn and processed in the Reproductive Endocrine Laboratory, it is not necessary to discontinue hormonal or insulin sensitizing medication.

A second group of PCOS probands with a documented diagnosis of PCOS will also be recruited. These subjects will meet all of the criteria above except that they will be on hormonal medication.

Inclusion Criteria-Female Unaffected Relatives: 1) Aged at 18 yrs or above; 2) Regular menstrual cycles 21-35 days or history of regular menstrual cycles in the past if menopausal; 3) no clinical or biochemical evidence of hyperandrogenism; 4) normal TSH and prolactin <25 ng/mL; 5) on no hormonal or insulin sensitizing medication for at least 3 months.

Inclusion Criteria-Male Relatives: 1) Aged 18 yrs or above; 2) normal TSH and prolactin <25 ng/mL; 5) on no hormonal or insulin sensitizing medication for at least 3 months.

Inclusion Criteria-Control Subjects: All control subjects will meet the criteria outlined for the female unaffected relatives. In Iceland, control subjects will be recruited from the Icelandic national registry, matched by age and sex to PCOS subjects and their family members. They will otherwise be recruited at random. In Boston, control subjects will be recruited from email and newspaper listings.

Exclusion Criteria:

  • Exclusion Criteria PCOS Probands: Subjects will not have 1) late onset congenital adrenal hyperplasia as defined by a fasting 17OH progesterone level <200 ng/mL or a cortrosyn stimulated 17 OH progesterone level <500 ng/mL.

Exclusion Criteria (Female unaffected relatives): None. Exclusion Criteria Male Relatives: None. Exclusion Criteria-Control Subjects: Control subjects chosen at random will be excluded if they are already participating in the study as a PCOS subject or are a first degree family member of the PCOS subject.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00166569

Contacts
Contact: Candace Keefe, BA 617-643-2308 ckeefe1@partners.org
Contact: Corrine K Welt, MD 617-726-8437 cwelt@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Candace Keefe, BA    617-643-2308    ckeefe1@partners.org   
Contact: Corrine K Welt, MD    617-726-8437    cwelt@partners.org   
Principal Investigator: William F Crowley, Jr., MD         
Sub-Investigator: Corrine K Welt, MD         
Sub-Investigator: Cindy Ta, MD         
Sponsors and Collaborators
Investigators
Principal Investigator: William F Crowley, Jr., MD
  More Information

No publications provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Corrine Welt, Associate Professor of Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00166569     History of Changes
Other Study ID Numbers: 5U01HD44417-03
Study First Received: September 9, 2005
Last Updated: September 26, 2011
Health Authority: United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Polycystic Ovary Syndrome

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Syndrome
Adnexal Diseases
Cysts
Disease
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Neoplasms
Ovarian Cysts
Ovarian Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 23, 2014