MicroRNA as Biomarkers for Development of Metabolic Syndrome in Women With Polycystic Ovary Syndrome

The aim of this study is to explore the microRNA profile in serum of women with Polycystic Ovary Syndrome and investigate the correlation between the microRNA profile and markers of metabolic syndrome.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome; Insulin Resistance

Detailed Description

The study consist of 2 parts:

1. A cross-sectional study of a cohort of women with PCOS with analysis of materials from the established biobank. (the PICOLO cohort) Data and blood samples from 266 women with PCOS was collected from January 2010 - February 2013 as a part of the PICOLO collaboration: "PCOS, infertility, Cardiovascular and Obstetric risk markers and Long-term Outcome" at Holbaek Fertility Clinic and at Herlev Hospital.

   Serum samples will be analysed with Reverse Transcript polymerase chain Reaction (RT-qPCR) for selected microRNAs.

2. A follow-up study of local participants from the PICOLO study. 90 of the participants were recruited at Holbaek Fertility Clinic.

Following tests will be performed at reexamination, in order to describe the clinical phenotype: Health interview, anthropometrics, acne score, Ferriman-Gallway score, blood pressure, Transvaginal ultrasound of uterus and ovaries, insulin Resistance (IR) assessed with Oral glucose Tolerance test (OGTT), Venous blood for hormone analysis and lipid status.

MicroRNA analysis with Taqman microRNA array will be performed on serum samples.

Detection and treatment of women with PCOS is a challenge due to the variability of the syndrome. If MiRNA could serve as marker of metabolic syndrome, it would be possible to detect and follow the women of greater risk at an earlier stage, and thereby preventing morbidity.

• Study Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• Denmark
  • Holbaek, Denmark, 4300
    • Fertility Clinic,Department of Gynecology and Obstetrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Local Participants from the PICOLO study, performed at Holbæk Hospital between 2010 and 2013

Description

Inclusion Criteria:

• Women between 18 and 40 years when included in the PICOLO study
• PCOS based on the Rotterdam 2003 consensus criteria

Exclusion Criteria:

• Contraceptive pills within 8 weeks from examination,
• endocrinological disease (i.e. type 1 diabetes thyroid dysfunction),
• Severe endometriosis (stage III and IV)
• Premature ovarian insufficiency,
• Breastfeeding women and
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Women with Polycystic Ovary Syndrome; Participants of the PICOLO study Inclusion criteria: Women aged 18-40 years when included in the PICOLO-cohort, PCOS based on the Rotterdam 2003 consensus criteria Exclusion criteria: Contraceptive pills within 6 weeks from examination, endocrinological disease (i.e. diabetes, thyroid dysfunction), endometriosis and premature ovarian insufficiency, breastfeeding women and pregnancy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MicroRNA profile	The change in relative expression of MicroRNA in women with PCOS will be assessed, using TaqMan microRNA arrays, comparing serum samples from baseline from an existing biobank with serum samples from a follow up visit.	MicroRNA analysis will be performed on serum from baseline visit (biobank material) and on serum obtained from a follow-up visit 5 years after baseline. The participants will be examined for 2 hours at follow up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Resistance and Type 2 Diabetes	Insulin Resistance will be assessed by Oral glucose Tolerance test (OGTT). Venous blood samples and measurement of glucose, serum insulin and C-peptid will be collected at -5, 0, 30 and 120 min after a 75 g glucose load. Impaired glucose tolerance will be assessed by calculation of BIGTTs1(insulin sensitivity index) and BIGTTAIR(Acute insulin response)	The participants will be examined for 2 hours, at a follow-up visit 5 years after the baseline visit.
Blood Pressure	Evaluated > 140/90 mmHg	The participants will be examined for 2 hours, at a follow-up visit 5 years after the baseline visit.
Abdominal obesity	Waist-Hip Ratio. Elevated > 0,85	The participants will be examined for 2 hours, at a follow-up visit 5 years after the baseline visit.
Overweight	Defined: BMI > 25 kg/m2	The participants will be examined for 2 hours, at a follow-up visit 5 years after the baseline visit.
Dyslipidemia	Defined as triglycerides > 1,7mmol/L, Total cholesterol > 5,0, LDL > 3,0 or HDL<1,0 mmol/L	The participants will be examined for 2 hours, at a follow-up visit 5 years after the baseline visit.
PCOS status	Evaluated by Rotterdam (2003) criteria: 1. Polycystic Ovaries:Number of antral follicles >12, ovarian volume (length*depth*width/2) > 10 mL 2) Clinical (evaluated by Ferriman Gallway score) or biochemical signs of hyperandrogenism ( Free Testosterone > 0.034 nmol/Lor total testosterone >1.8 nmol/L) 3.Oligo or amenorrhea ´(>35 days between bleedings)	The participants will be examined for 2 hours, at a follow-up visit 5 years after the baseline visit.

Collaborators and Investigators

• Sponsor: Holbaek Sygehus
• Investigators: Principal Investigator: Anne Lis M Englund, DsMC, Fertility Clinic, Dept. of Gynecology and Obstetrics, Holbæk Hospital

Publications and helpful links

General Publications

• Udesen PB, Sorensen AE, Joglekar MV, Hardikar AA, Wissing MLM, Englund AM, Dalgaard LT. Levels of circulating insulin cell-free DNA in women with polycystic ovary syndrome - a longitudinal cohort study. Reprod Biol Endocrinol. 2019 Apr 5;17(1):34. doi: 10.1186/s12958-019-0478-7.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2016
• Primary Completion (Actual): May 23, 2017
• Study Completion (Actual): May 23, 2017

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: May 4, 2017
• First Posted (Actual): May 5, 2017

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Hyperinsulinism; Polycystic Ovary Syndrome; Syndrome; Metabolic Syndrome; Insulin Resistance
• Other Study ID Numbers: SJ-525

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No