Clinical trial NCT01785719: Evaluation of Ovarian Morphology and Function in Overweight Women During Weight Loss
Official title: Ultrasound Characterization of Ovarian Follicle Dynamics During Weight Loss
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Weight Loss
Anovulation
Amenorrhea
Infertility
Keywords: Weight Loss
Polycystic Ovary Syndrome (PCOS)
Ovarian Follicle Development
Metabolism
Lead sponsor: Cornell University
Sponsor class: OTHER
Collaborators: name: Nutrisystem, Inc.
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-02-07
Enrollment: 79
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The researchers plan to recruit two cohorts of obese women to the study: (1) those with irregular menstrual cycles and/or PCOS and (2) those with regular menstrual cycles. Both of the cohorts will receive the same intervention.
Primary purpose: BASIC_SCIENCE

Brief summary: The objective of this study is to explore the effects of weight loss on body composition, metabolic status, reproductive hormones, and ovarian follicle development in obese women with regular menstrual cycles versus obese women with irregular menstrual cycles and/or polycystic ovary syndrome (PCOS).

Detailed description: Polycystic ovary syndrome (PCOS) is a complex endocrine condition that impacts one in ten women of reproductive age worldwide. It is characterized by a collection of signs and symptoms, including: (1) oligo- or anovulation, (2) hyperandrogenism, and (3) polycystic ovarian morphology. Because obesity worsens the reproductive and metabolic features of the condition, lifestyle intervention aimed at weight loss is recommended as the first-line therapy in overweight / obese patients. Many studies have shown that modest weight loss (5-10%) can improve symptomology in women with PCOS. Yet, the mechanism whereby weight loss might stimulate ovulation or restore menstrual cyclicity remains unclear.

Hence, the goal of this study is to explore the effects of weight loss on body composition, metabolic status, reproductive hormones, and ovarian follicle development in obese women with regular menstrual cycles versus obese women with irregular menstrual cycles and/or PCOS. The researchers believe that a hypocaloric and low-glycemic index eating pattern, based on the nutrition recommendations of the USDA Dietary Guidelines for Americans and American Diabetes Association, will reduce endocrine and metabolic disturbances and consequently improve ovulatory and menstrual cyclicity in PCOS.

To accomplish this objective, the researchers plan to recruit up to 50 obese (i.e. body mass index \>30 kg/m\*m) women with regular menstrual cycles and up to 50 obese women with irregular menstrual cycles and/or PCOS. Exclusion criteria will include ages \<18 or \>35 y and the use of hormonal contraception, fertility therapy, or insulin-sensitizing medication in the three months prior to enrollment. This study entails one month of data collection during a baseline interval (Month 1) and six months of data collection during a commercial weight loss program (Nutrisystem® D; Month 2 thru Month 7).

Participants will be evaluated every other day (in Months 1 and 7) or twice per week (in Months 2 thru 6) by transvaginal ultrasonography and venipuncture. Ultrasound images of the ovaries will be assessed for the total number and diameter of individual follicles. Serum samples will be assessed for follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone. Participants will also be evaluated at up to four time points using multiple metabolic and behavioral tests. Time points of interest will include: (1) Month 1 (i.e. pre-intervention), (2) after 5% weight loss, (3) after 10% weight loss, and (4) Month 7 (i.e. post-intervention). Assessments and endpoints of interest will include: (1) fasting blood tests (to detect serum androgens and markers of metabolic syndrome); (2) an oral glucose tolerance test (to characterize glucose and insulin dynamics at 0, 30, 60, 90, and 120-minutes post-glucose ingestion); (3) a physical examination (to measure height, weight, waist and hips circumference, blood pressure, heart rate, and hirsutism score); (4) a dual x-ray absorptiometry scan (to quantify total and regional fat and lean mass); and (5) a quality of life questionnaire (to evaluate health-related quality of life).

To evaluate further changes in ovarian morphology, reproductive hormones, metabolic status, and body composition after the intervention, participants will be invited to return to the research unit six months after the study ends. The aforementioned procedures (transvaginal ultrasound scan; fasting blood tests; oral glucose tolerance test; physical examination; dual x-ray absorptiometry scan; and quality of life questionnaire) will be repeated.

Eligibility criteria: Inclusion Criteria:

* BMI ≥ 30.0 kg/m\*m.
* Self-reported history of regular menstrual cycles, irregular menstrual cycles, or PCOS.
* Absence of hormonal contraception, fertility therapy, or insulin-sensitizing medication in the three months prior to enrollment.

Exclusion Criteria:

* Pregnant, breastfeeding, or lactating
* Lack of one or both ovaries and/or uterus
* Previous diagnosis of bleeding disorder(s) or current use of blood thinners/anticoagulants
* Vegan or gluten free
* Soy or peanut allergy

Primary outcomes:
measure: Change From Baseline Ovulatory/Menstrual Function
timeFrame: Up to 7 months
Secondary outcomes:
measure: Change From Baseline Follicle Number Per Ovary
timeFrame: Up to 7 months
measure: Change From Baseline Reproductive Hormones
timeFrame: Up to 7 months
measure: Change From Baseline Metabolic Status (HOMA-IR)
timeFrame: Up to 7 months
measure: Change From Baseline Total Percent Body Fat
timeFrame: Up to 7 months
measure: Change From Baseline Ovarian Volume
timeFrame: Up to 7 months
measure: Change From Baseline Free Androgen Index (FAI)
timeFrame: Up to 7 months
measure: Change From Baseline BMI
timeFrame: Up to 7 months
Other outcomes:
Locations:
city: Ithaca
country: United States
facility: Cornell University - Human Metabolic Research Unit
state: New York
Study officials:
affiliation: Cornell University
name: Marla Lujan, PhD
role: PRINCIPAL_INVESTIGATOR
References: