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

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
B. 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.

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