Nutritional and Metabolic Correlates of Ovarian Morphology in Women With Polycystic Ovary Syndrome
Condition: Polycystic Ovary Syndrome (PCOS); Menstrual Irregularity
MeSH terms: Polycystic Ovary Syndrome; Syndrome; Menstruation Disturbances
Study type: Observational

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.
    

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
      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.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Women must be able to transport to Cornell University and University of Rochester. Eligible
        participants are between 18-48 years with a BMI of 18 kg/m2 or higher. Women are screened
        and enrolled following consent based on their response to our advertisements. Enrollment is
        restricted to the geographical area.
      
Biospecimen description: 
      Blood serum, subcutaneous fat
    
Keywords: Menstrual cycles; Ultrasound; Ovary; Polycystic Ovary Syndrome (PCOS); Physical activity; Diet