NAFLD in Adolescents and Young Adults With PCOS

Nonalcoholic Fatty Liver Disease (NAFLD), Insulin Resistance and Dyslipidemia in Adolescents and Young Adults With Polycystic Ovary Syndrome (PCOS)

This project focuses on an at-risk adolescent and young adult population who may gain long-term health benefits from detection of risk factors at a young age. The primary aims of this proposal are: 1) To observe whether adolescents and young adults with Polycystic Ovary Syndrome (PCOS) are more likely to have elevated liver fat (>/=4.8%) than controls by studying liver fat deposition measured by magnetic resonance spectroscopy (MRS); 2) To assess the association of percentage liver fat with biomarkers of Non-alcoholic fatty liver disease (NAFLD), dyslipidemia, insulin resistance and body composition in PCOS and controls.

In the proposed study, 40 adolescents and young adults with PCOS and 40 age-comparable control subjects will be evaluated for metabolic disturbances and elevated liver fat using noninvasive and state-of-the-art techniques including MRI, dual-energy x-ray absorptiometry and an oral glucose tolerance test in order to fully assess the metabolic and body composition differences between these groups. This research proposal represents a critical step in understanding the metabolic and cardiovascular comorbidities of PCOS and their relationship to NAFLD. The investigator hopes to use the results generated by this research proposal in order to lay the groundwork for the prevention and treatment of metabolic disorders in adolescents with PCOS. The overarching goal is to decrease and prevent lifelong morbidity associated with this common disorder.

Study Overview

• Status: Active, not recruiting
• Conditions: Polycystic Ovary Syndrome; Metabolic Syndrome; Non-Alcoholic Fatty Liver Disease

Detailed Description

PCOS is a common condition that frequently presents in adolescence and young adulthood and is defined by the presence of hyperandrogenism and ovulatory dysfunction. Affected individuals are at increased risk of insulin resistance, NAFLD and dyslipidemia, which are features associated with the metabolic syndrome, a major public health concern. The associations between PCOS and both insulin resistance and dyslipidemia have been extensively described; however, its association with NAFLD has only recently been noted and superficially studied in adolescents and young adults. Additionally, it has not yet been fully elucidated why seemingly healthy nonobese adolescents with PCOS are predisposed to insulin resistance and its related complications. The susceptibility of certain PCOS patients to developing NAFLD is theorized to be due to the following potentiating factors: insulin resistance, hyperandrogenemia, and a genetic predisposition.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Healthy adolescent girls and young women 14 - 25 years with and without PCOS

Description

Inclusion Criteria:

• All: Healthy; between 14 and 25 years; at least 2 years postmenarche
• PCOS: Clinical hyperandrogenism and/or hyperandrogenemia, menstrual dysfunction (oligomenorrhea or amenorrhea) and exclusion of other known disorders. PCOS will be diagnosed using the NIH 1990 criteria.
• Controls: Regular menses; no clinical hyperandrogenism and/or hyperandrogenemia

Exclusion Criteria:

• Past or present history of a medical disorder or medication known to affect body composition, insulin secretion and sensitivity, or the growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis (eg steroid hormone or thyroid replacement).
• History of current or past pregnancy
• Hormonal contraceptive or metformin use within 3 months of enrollment
• Nonclassical congenital adrenal hyperplasia

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
PCOS subjects; Forty adolescents and young adults between the ages of 14 and 25 years with Polycystic Ovary Syndrome (PCOS) at least two years past menarche.
Control subjects; Forty unaffected adolescents and young adults between the ages of 14 and 25 years at least two years past menarche.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in percentage liver fat between PCOS and controls in adolescents and young adults	To compare percentage liver fat by magnetic resonance spectroscopy between adolescents and young adults with PCOS and controls to determine if there is a difference between these groups.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association of percentage liver fat by magnetic resonance spectroscopy with insulin resistance as measured by HOMA-IR.	The association of percent liver fat with insulin resistance as measured by HOMA-IR will be measured by correlation/regression.	1 day
The association of percentage liver fat by magnetic resonance spectroscopy with triglycerides	The association of percent liver fat with triglycerides will be measured by correlation/regression.	1 day
The association of percentage liver fat by magnetic resonance spectroscopy with visceral adipose tissue (VAT)	The association of percent liver fat with visceral adipose tissue (VAT) will be measured by correlation/regression.	1 day
The association of percentage liver fat by magnetic resonance spectroscopy with total body adipose tissue	The association of percent liver fat with total body adipose tissue will be measured by correlation/regression.	1 day

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Aviva Sopher, MD, MS, MS, Columbia University

Publications and helpful links

General Publications

• Sopher AB, Grigoriev G, Laura D, Cameo T, Lerner JP, Chang RJ, McMahon DJ, Oberfield SE. Anti-Mullerian hormone may be a useful adjunct in the diagnosis of polycystic ovary syndrome in nonobese adolescents. J Pediatr Endocrinol Metab. 2014 Nov;27(11-12):1175-9. doi: 10.1515/jpem-2014-0128.
• Sopher AB, Gerken AT, Blaner WS, Root JM, McMahon DJ, Oberfield SE. Metabolic manifestations of polycystic ovary syndrome in nonobese adolescents: retinol-binding protein 4 and ectopic fat deposition. Fertil Steril. 2012 Apr;97(4):1009-15. doi: 10.1016/j.fertnstert.2012.01.111. Epub 2012 Feb 17.

Helpful Links

• Recruitment Video
• Information about PCOS
• Information about NAFLD

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: July 21, 2015
• First Submitted That Met QC Criteria: July 21, 2015
• First Posted (Estimate): July 23, 2015

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Adolescents; MRI; Metabolic syndrome; Dyslipidemia; Polycystic Ovary Syndrome; MRS; DXA; Hirsutism; Non-Alcoholic Fatty Liver Disease; Amenorrhea; Young Women; Percentage liver fat
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Insulin Resistance; Hyperinsulinism; Liver Diseases; Polycystic Ovary Syndrome; Syndrome; Fatty Liver; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: AAAA7793

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: We will consider this