Clinical trial NCT03306849: Ultrasonographic Evaluation of Anovulatory Disorders in Lean and Overweight Women
Official title: Ultrasonographic Evaluation of Anovulatory Disorders in Lean and Overweight Women
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Menstrual Cycle Abnormal
PCOS
Overweight
Obesity
Lead sponsor: Cornell University
Sponsor class: OTHER
Collaborators: name: Weill Medical College of Cornell University
First posted: 2017-10-11
Enrollment: 59
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women must be able to transport to Weill Cornell University. Eligible participants are between 18-45 years with a BMI of 18.5 kg/m2 or higher. Women are screened and enrolled following consent based on their response to our advertisements. Women are recruited from the general population. Enrollment is restricted to the geographical area.

Brief summary: The investigators would like to determine whether ultrasound features of the ovaries can be used to reliably diagnose different types of anovulatory disorders in women across all body types. The study will also try to establish whether ultrasound features of the ovary can reflect the degree of reproductive and metabolic problems that a woman with irregular or absent periods might be experiencing.

Detailed description: This study is being conducted in order to determine if ultrasound features of the ovaries can be used to reliably diagnose different types of anovulatory disorders in women across all body types. The study will also try to establish whether ultrasound features of the ovary can reflect the degree of reproductive and metabolic problems that a woman with irregular or absent periods might be experiencing. In this way, the researchers can help to maximize the information that can be received when using ultrasound to evaluate patients with concerns over irregular menstrual cycles and/or infertility.

The ovaries are the site of egg production and normally release one egg every month. The process of releasing an egg is called ovulation. The act of releasing an egg is the body's way of ensuring a woman's fertility each month during her reproductive years. There are a number of reasons why ovulation may not occur regularly in women. Some of these reasons are believed to relate to male hormone production (i.e. androgens), body composition, nutrition and overall metabolic health. However, the precise ways in which these factors affect ovulation are unknown.

The researchers plan to evaluate how the ovaries look and function in a large group of women. Their goal is to recruit both lean and overweight women to this study and include both women that have regular, predictable menstrual cycles as well as those that have infrequent or absent menstrual cycles. The researchers will include women with irregular cycles due to increased androgen production, or hyperandrogenic anovulation - as well as those that have irregular cycles but normal androgen levels or normoandrogenic anovulation. The researchers will use ultrasound to collect information on how the ovaries look and function, and then relate the features of the ovaries to body composition, reproductive and metabolic hormones as well as nutritional factors. Because features of the ovaries are expected to be different in lean and overweight women, the researchers hope to develop ultrasound criteria that will help healthcare providers to diagnosis specific ovulation problems in women across all body sizes. Together, this research will help to better understand the complex relationship between nutrition, metabolism and reproductive health in women.

To accomplish these objectives, the investigators plan to recruit 50 women with regular menstrual cycles, 50 women with normoandrogenic anovulation, and 50 women with hyperandrogenic anovulation. Their goal is to recruit an equal number of women in each group who are lean (BMI; Normal weight = 18.5 - 24.9 kg/m2) and overweight or obese (BMI; Overweight = 25 - 29.9 kg/m2; Obese \>= 30kg/m2). 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. 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 and physical activity questionnaire. A researcher may also provide participants with an accelerometer to wear for a week.

Eligibility criteria: Inclusion Criteria:

* Aged 18-45 years
* At least 2y post-menarche
* BMI \>18.5kg/m2
* Good visibility of the ovaries on ultrasound

Either:

* Regular menstrual cycles (21-35 days);
* Irregular menstrual cycles (\>35 days); or
* Previous diagnosis of PCOS from a primary care provider

Exclusion Criteria:

* Weight \>300lbs
* Currently pregnant or breast feeding
* History of ovarian surgery
* Use of medications or supplements known or suspected to interfere with reproductive function and/or glucose and lipid metabolism in the past 3 months
* Evidence of reproductive aging as assessed by the principal criteria of STRAW+10 stages

Primary outcomes:
measure: Follicle number per ovary
timeFrame: 1 day
Secondary outcomes:
measure: Follicle number per cross section
timeFrame: 1 day
measure: Ovarian volume
timeFrame: 1 day
measure: Stromal echogenicity on ultrasound
timeFrame: 1 day
measure: Ovarian area-stromal area ratio
timeFrame: 1 day
measure: LH-FSH ratio
timeFrame: 1 day
measure: Hirsutism Score
timeFrame: 1 day
measure: Androgen concentrations
timeFrame: 1 day
measure: Menstrual Cycle Length
timeFrame: 1 day
measure: Serum markers of metabolic syndrome
timeFrame: 1 day
measure: Blood Pressure
timeFrame: 1 day
measure: Body mass index
timeFrame: 1 day
measure: Waist-to-hip ratio
timeFrame: 1 day
measure: Body fat distribution
timeFrame: 1 day
measure: Insulin sensitivity
timeFrame: 1 day
measure: Differences in diet composition assessed via food frequency questionnaire
timeFrame: 1 day
measure: Differences in energy expenditure assessed via a waist-worn accelerometer
timeFrame: 1 week
Other outcomes:
Locations:
city: New York
country: United States
facility: Clinical and Translational Science Center
state: New York
Study officials:
affiliation: Cornell University
name: Marla E Lujan, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Steven Spandorfer, MD
role: PRINCIPAL_INVESTIGATOR
References: