Nutritional and Metabolic Correlates of Ovarian Morphology in Women With Polycystic Ovary Syndrome

Sponsor

Cornell University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01927471

Collaborator

University of Rochester (Other)

360

Enrollment

Locations

135

Duration (Months)

120

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators would like to determine how aspects of metabolism and age influence ovarian function. The purpose of the study is to understand how nutrition and metabolism relate to follicle development in women with regular cycles, irregular cycles, or polycystic ovary syndrome (PCOS). We also plan to identify lifestyle factors associated with PCOS and understand how diet and activity levels impact features of PCOS.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome (PCOS) Menstrual Irregularity

Detailed Description

In the ovaries, eggs rest in fluid filled sacs called follicles. When follicles grow they form small fluid-filled cysts that can be easily seen when we use ultrasound to view the ovaries. In women with regular menstrual cycles, groups of follicles grow and regress 2 to 3 times during their cycle (usually over a 28- day period). Several of these follicles grow to a stage where they begin to develop the potential to ovulate - but in general only one follicle is chosen to ovulate. Thus, at any given time during the menstrual cycle, numerous fluid-filled follicles can be visualized in a woman's ovaries at various stages of development using transvaginal ultrasonography. In women with absent or infrequent menstrual cycles, very little is known about the growth patterns of their follicles and how factors such as metabolic hormones, might play a role in the failure to ovulate. Being underweight or overweight increases your chances of having irregular or absent menstrual cycles and a history of abnormal reproductive function compounds your risks for chronic diseases such as infertility, diabetes, hypertension, atherosclerosis and certain cancers. This is particularly the case for women with PCOS that have menstrual cycles that appear to worsen or improve depending on their body weight and metabolic status. Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 6-12% of reproductive-aged women within the general population. The hallmark features of PCOS are menstrual irregularity, increased levels of androgens, and polycystic ovaries. The current diagnostic criteria require 2 out of 3 of these features to be present for the diagnosis, therefore a number of phenotypes of PCOS exist. However, the metabolic and reproductive differences across the phenotypic spectrum of PCOS are not well understood. Women with PCOS characteristically have polycystic ovaries, where up to 10 times more follicles are present in the ovary at any given time. Further, the follicle-size populations and overall distribution throughout the ovary varies in women - follicles may be situated around the periphery of the ovary or may be distributed throughout the ovary. Presumably these small follicles are arrested in development - but emerging data from the Lujan laboratory suggest that this is not the case. Rather, follicles continue to grow in a dynamic pattern during these prolonged periods of anovulation. By comparing follicle populations, reproductive hormones and markers of metabolism in women with regular cycles, women with irregular cycles, and women with a history of PCOS, the researchers plan to identify what factors might explain why fertility potential and long-term health are compromised in some women but not in others. By including women at both early and late stages of their reproductive potential, the researchers will also be able to assess what influence age has on these factors. The ultimate goal of this research is to understand how nutrition and metabolism regulate follicle development in women so we can better develop lifestyle and drug therapies to help women preserve their fertility and long-term health. Since obesity has recently become the leading cause of infertility in North America, these studies are especially important.

Current research has failed to thoroughly examine the relationships between dietary intake, energy expenditure and PCOS. The purpose of this proposed study is to identify lifestyle factors associated with PCOS. Through dietary intake and energy expenditure data, the researchers plan to examine potential lifestyle differences between PCOS and healthy women, as well as between BMI classifications within women with PCOS. The Research Team will also be able to evaluate the diet quality according to the USDA Dietary Guidelines for Americans of all women included in the study. The Research Team is also interested in the relationships between biological markers and lifestyle endpoints in women with and without PCOS. Previous literature has shown there are biological marker differences between those with and without PCOS. By examining these relationships, researchers may further understand whether PCOS status is associated with lifestyle parameters.

To accomplish these objectives, the investigators plan to recruit 120 women with regular menstrual cycles and 240 women with irregular menstrual cycles, with or without PCOS (sub-grouped into 120 women with irregular menstrual cycles and 120 women with a history of PCOS). Their goal is to recruit an equal number of women in each group such that they are matched for age (18 - 48 years old) and body mass index (BMI; Normal weight = 18 - 24.9 kg/m2; Overweight = 25 - 29.9 kg/m2; Obese ≥ 30kg/m2). Women will be included in the PCOS sub-group if they have a confirmed PCOS diagnosis from their primary care provider. Ultrasound scans of the ovaries will be assessed for the total number, size, and distribution of follicles using both two- and three-dimensional imaging techniques. Participants will have blood samples collected determine serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, progesterone, anti-müllerian hormone (AMH), and inhibin

The following metabolic parameters will be assessed: (1) 75-gram oral glucose tolerance test to characterize glucose and insulin dynamics at 0, 30, 60, 90, and 120 minutes post-glucose ingestion; (2) dual X-ray absorptiometry (DXA) scan to quantify body fat and lean muscle distribution; (3) vitals and anthropometry assessment to measure waist and hip circumference, height, weight, blood pressure, and heart rate, and (4) fasting blood tests to detect serum concentrations of androgens (i.e., total testosterone, androstenedione, free androgen index) and serum markers of metabolic syndrome (i.e., lipids and hemoglobin A1C). Participants will complete a food frequency questionnaire, a semi-structured dietary interview, and physical activity questionnaire. A researcher may also provide participants with an accelerometer to wear for a week. Participants may also elect to participate in an optional subcutaneous fat biopsy.

Study Design

Study Type:

Observational

Anticipated Enrollment :

360 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Nutritional and Metabolic Correlates of Ovarian Morphology in Women With Polycystic Ovary Syndrome

Study Start Date :

Sep 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Regular menstrual cycles Adult women will be assigned to this category if they report a history of regular menstrual cycles. We will aim to recruit 120 women in this category.
Irregular menstrual cycles, no PCOS Adult women will be assigned to this category if they report a history of irregular menstrual cycles, without a pre-existing diagnosis of PCOS. We will aim to recruit 120 women in this category.
Irregular menstrual cycles, with PCOS Adult women will be assigned to this category if they report a history of irregular menstrual cycles with a pre-existing diagnosis of PCOS by a physician. We will aim to recruit 120 women in this category.

Outcome Measures

Primary Outcome Measures

Follicle number per ovary [1 day]
The number and size of all follicles in each ovary will be assess by ultrasonography for each participant with regular menstrual cycles, irregular menstrual cycles and PCOS.
Insulin sensitivity [1 day]
Insulin sensitivity will be determined by administration of an oral glucose tolerance test and compared across groups.

Secondary Outcome Measures

Ovarian Volume [1 day]
The size of each ovary will be determined by ultrasonography for each participant and compared across groups.
Anti-Müllerian hormone [1 day]
Circulating AMH levels in the serum will be determined for each participant and compared across groups.
LH-FSH ratio [1 day]
The ratio of circulating LH to FSH concentrations in the serum will be determined for each participant and compared across groups.
Androgen concentrations [1 day]
Total testosterone, androstenedione and free androgen index concentrations in serum will be determined and compared across groups.
Menstrual Cycle Length [1 day]
Average menstrual cycle length as determined by self-reported history will be determined and compared across groups.
Hirsutism [1 day]
Degree of hirsutism as judged by the Ferriman-Gallwey scale will be determined and compared across groups.
Serum markers of metabolic syndrome [1 day]
Lipids, glucose and HbA1C concentrations will be determined and compared across groups.
Blood Pressure [1 day]
Blood pressure will be determined and compared across groups.
Body mass index [1 day]
The ratio of weight to height will be determined and compared across groups.
Waist-to-hip ratio [1 day]
The ratio of waist circumference to hip circumference will be determined and compared across groups.
Body fat distribution [1 day]
Percentage and distribution of fat and lean mass as assessed using DXA technology will be compared across groups.
Differences in diet composition between women with and without PCOS [1 week]
A food frequency questionnaire will be administered to assess diet composition for the last three months
Differences in energy expenditure between women with and without PCOS [1 week]
Participants will be asked to wear a small accelerometer device to assess physical activity
Subcutaneous fat biopsy (optional) [1 day]
Subcutaneous fat biopsies will be conducted to assess differences in fat cell populations (major site of reproductive hormone synthesis) between groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 48 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Between 18 and 48 years
BMI ≥ 18 kg/m2

Either:

Regular menstrual cycles (21-35 days);
Irregular menstrual cycles (>36 days); or
Previous diagnosis of PCOS from a primary care provider
If 21 years of age or older, must have had a healthy pelvic exam w/in the past 2 years

Exclusion Criteria:

Current use of medication(s) known or suspected to interfere with reproductive function (eg. oral contraceptives) or insulin sensitivity
Pregnant or breastfeeding
Not otherwise healthy
Significant weight changes within the last three months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Human Metabolic Research Unit, Cornell University	Ithaca	New York	United States	14853
2	Strong Fertility Center	Rochester	New York	United States	14623
3	CRC at University of Rochester Medical Center	Rochester	New York	United States	14642