Weight Loss, Anovulation, Amenorrhea, Infertility
Conditions
Keywords
Weight Loss, Polycystic Ovary Syndrome (PCOS), Ovarian Follicle Development, Metabolism
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.
Interventions
BEHAVIORALCommercial Weight Loss Program
Regardless of reproductive history, each participant will be provided with six months of the commercial weight loss program, Nutrisystem® D. Nutrisystem® D is a portion-controlled, low calorie, and low glycemic index meal delivery system that provides 1250-1500 kcal/day. It has been proven to help overweight adults achieve real and sustainable weight loss results. When meals and snacks are consumed as instructed, average weight loss is 1-2 lbs per week or 15-20% body weight by the end of six months. Nutrisystem® D offers a balanced meal plan that is consistent with the nutrition recommendations of the USDA Dietary Guidelines for Americans and American Diabetes Association. Each participant will be encouraged to take a daily multivitamin to help meet her micronutrient needs on the program.
Sponsors
Nutrisystem, Inc.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Ovulatory/Menstrual Function | Up to 7 months | Participants with irregular menstrual cycles at baseline were categorized as responders or non-responders based on any changes they experienced in menstrual cyclicity over the course of the intervention. Responders were defined as participants who shifted towards a more favorable menstrual cycle status over the course of the intervention. Non-responders were defined as participants who experienced no change or a shift to a less favorable menstrual cycle status over the course of the intervention. Menstrual cycle status categories were defined as Amenorrhea (mean cycle length\>90 days; least favorable), Oligomenorrhea (mean cycle length 36-90 days; unfavorable), and Regular (mean cycle length 21-35 days; most favorable). All participants with regular menstrual cycles at baseline maintained regular cycles over the course of the intervention and were therefore not included in this analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Reproductive Hormones | Up to 7 months | Change in reproductive hormones from baseline to the end of a hypocaloric dietary intervention. Blood samples were collected in the morning after an overnight fast during the early follicular phase as confirmed by the absence of a dominant follicle or corpus luteum on ultrasound. Hormones reported include: * Total testosterone: Evaluated by the Brigham Research Assay Core (Harvard) using liquid chromatography tandem mass-spectrometry. Results are reported in ng/dL. * Anti-Müllerian hormone (AMH): Evaluated using the Motive Biosciences (formerly Ansh Labs) picoAMH ELISA. Results are reported in ng/mL |
| Change From Baseline Metabolic Status (HOMA-IR) | Up to 7 months | Change in metabolic status from baseline to the end of a hypocaloric dietary intervention. HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) was used as an indicator of metabolic status. HOMA-IR uses fasting blood glucose and insulin values to approximate insulin resistance. Blood glucose and insulin were measured in the morning after an overnight fast during the early follicular phase as confirmed by the absence of a dominant follicle or corpus luteum on ultrasound. HOMA-IR was calculated by multiplying blood glucose (mg/dL) by insulin (mIU/mL) and dividing by 405. A higher HOMA-IR score is indicative of increased insulin resistance. |
| Change From Baseline Total Percent Body Fat | Up to 7 months | Change in total percent body fat from baseline to the end of a hypocaloric dietary intervention. Body fat was measured using the Hologic Discovery A Dual X-Ray Absorptiometry (DXA) Scanner. |
| Change From Baseline Follicle Number Per Ovary | Up to 7 months | Change in follicle number per ovary (FNPO) from baseline to the end of a hypocaloric dietary intervention. Ovarian images were collected using 3D transvaginal ultrasonography and were assessed for morphological endpoints by trained raters using the 2D offline grid method. FNPO was calculated by summing all 2-9 mm follicles in each ovary. Left and right FNPO were averaged for each participant before baseline to post-intervention changes were calculated. |
| Change From Baseline Free Androgen Index (FAI) | Up to 7 months | Change in FAI from baseline to the end of a hypocaloric dietary intervention. Blood samples were collected in the morning after an overnight fast during the early follicular phase as confirmed by the absence of a dominant follicle or corpus luteum on ultrasound. Free Androgen Index (FAI) is the ratio of total testosterone to sex hormone binding globulin (SHBG), indicating the amount of active testosterone in the blood. SHBG was evaluated by the Cornell Human Nutrition Chemistry Service Laboratory using Immulite 2000 immunoassay. FAI levels of 5 or higher are indicative of PCOS. |
| Change From Baseline BMI | Up to 7 months | Change in BMI from baseline to the end of a hypocaloric dietary intervention. |
| Change From Baseline Ovarian Volume | Up to 7 months | Change ovarian volume (cm\^3) from baseline to the end of a hypocaloric dietary intervention. Ovarian images were collected using 3D transvaginal ultrasonography and were assessed for morphological endpoints by trained raters using the 2D offline grid method. Ovarian volume was calculated using a modified formula for a prolate ellipsoid. Left and right ovarian volumes were averaged for each participant before baseline to post-intervention changes were calculated. |
Countries
United States
Participant flow
Recruitment details
Women ages 18-38 with BMI \>25 kg/m\*m with regular menstrual cycles or irregular menstrual cycles (with or without PCOS). No use of hormonal contraception, fertility therapy, or insulin-sensitizing medication in the 3 months prior to enrollment. All participants completed 4-week baseline evaluation. Participants enrolled before 2018 completed a 12-week hypocaloric dietary intervention. The study was amended in 2018 to increase the duration of the intervention to 24 weeks.
Pre-assignment details
Most participants experienced a lag between enrollment and the start of baseline due to scheduling, med washout, and/or stage of menstrual cycle. Some participants were lost to follow-up during this time. Additionally, the first 2 weeks of baseline were used to assess ovarian ultrasound image quality and vein status to confirm eligibility. Participants were excluded if we could not achieve consistent high quality ovarian ultrasound images and/or successful venipuncture in the first 2 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) Participants who completed the hypocaloric dietary intervention\* and reported irregular menstrual cycles at baseline. Irregular menstrual cycles were defined as mean cycle length \>35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
\*Participants enrolled before 2018 completed a 12-week dietary intervention and participants enrolled 2018 and later completed a 24-week dietary intervention. | 30 |
| Regular Cycles Participants who completed the hypocaloric dietary intervention\* and reported regular menstrual cycles at baseline. Regular menstrual cycles were defined as mean cycle length 21-35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
\*Participants enrolled before 2018 completed a 12-week dietary intervention and participants enrolled 2018 and later completed a 24-week dietary intervention. | 18 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 4-week Baseline Evaluation | Exclusionary medication | 2 | 0 |
| 4-week Baseline Evaluation | Lost to Follow-up | 0 | 1 |
| 4-week Baseline Evaluation | Physician Decision | 1 | 0 |
| 4-week Baseline Evaluation | Poor vein access and/or ultrasound image quality | 4 | 8 |
| 4-week Baseline Evaluation | Pregnancy | 0 | 2 |
| 4-week Baseline Evaluation | Withdrawal by Subject | 1 | 2 |
| 6-month Post-intervention Follow-up | Exclusionary medication | 0 | 1 |
| 6-month Post-intervention Follow-up | Lost to Follow-up | 12 | 2 |
| 6-month Post-intervention Follow-up | Pregnancy | 0 | 1 |
| Hypocaloric Dietary Intervention | Adverse Event | 1 | 0 |
| Hypocaloric Dietary Intervention | Participant initiated an exclusionary medication. | 0 | 1 |
| Hypocaloric Dietary Intervention | Physician Decision | 1 | 0 |
| Hypocaloric Dietary Intervention | Poor vein access and/or ultrasound image quality | 0 | 1 |
| Hypocaloric Dietary Intervention | Research Restrictions (COVID) | 1 | 2 |
| Hypocaloric Dietary Intervention | Withdrawal by Investigator - Poor Compliance | 1 | 2 |
Baseline characteristics
| Characteristic | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles | Total |
|---|---|---|---|
| Age, Continuous | 28 years STANDARD_DEVIATION 5 | 31 years STANDARD_DEVIATION 3 | 29 years STANDARD_DEVIATION 4 |
| Body Mass Index | 37 kg/m*m STANDARD_DEVIATION 6 | 37 kg/m*m STANDARD_DEVIATION 7 | 37 kg/m*m STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 17 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Menstrual Cycle Length | 84 days STANDARD_DEVIATION 67 | 30 days STANDARD_DEVIATION 2 | 65 days STANDARD_DEVIATION 59 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 23 Participants | 16 Participants | 39 Participants |
| Region of Enrollment United States | 30 participants | 18 participants | 48 participants |
| Sex: Female, Male Female | 30 Participants | 18 Participants | 48 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 37 |
| other Total, other adverse events | 10 / 42 | 2 / 37 |
| serious Total, serious adverse events | 0 / 42 | 0 / 37 |
Outcome results
Primary
Change From Baseline Ovulatory/Menstrual Function
Participants with irregular menstrual cycles at baseline were categorized as responders or non-responders based on any changes they experienced in menstrual cyclicity over the course of the intervention. Responders were defined as participants who shifted towards a more favorable menstrual cycle status over the course of the intervention. Non-responders were defined as participants who experienced no change or a shift to a less favorable menstrual cycle status over the course of the intervention. Menstrual cycle status categories were defined as Amenorrhea (mean cycle length\>90 days; least favorable), Oligomenorrhea (mean cycle length 36-90 days; unfavorable), and Regular (mean cycle length 21-35 days; most favorable). All participants with regular menstrual cycles at baseline maintained regular cycles over the course of the intervention and were therefore not included in this analysis.
Time frame: Up to 7 months
Population: This table includes outcome data for all participants who completed either the 12-wk or 24-wk hypocaloric dietary intervention, depending on year of enrollment (participants pre-2018 completed 12 weeks, participants 2018 and later completed 24 weeks). Irregular menstrual cycles were defined as mean cycle length \>35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline Ovulatory/Menstrual Function | Responders | 12 Participants |
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline Ovulatory/Menstrual Function | Non-Responders | 18 Participants |
Secondary
Change From Baseline BMI
Change in BMI from baseline to the end of a hypocaloric dietary intervention.
Time frame: Up to 7 months
Population: This table includes outcome data for all participants who completed either the 12-wk or 24-wk hypocaloric dietary intervention, depending on year of enrollment (participants pre-2018 completed 12 weeks, participants 2018 and later completed 24 weeks). Irregular menstrual cycles were defined as mean cycle length \>35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline BMI | -2.8 kg/m^2 | Standard Deviation 1.5 |
| Regular Cycles | Change From Baseline BMI | -3.8 kg/m^2 | Standard Deviation 1.9 |
Secondary
Change From Baseline Follicle Number Per Ovary
Change in follicle number per ovary (FNPO) from baseline to the end of a hypocaloric dietary intervention. Ovarian images were collected using 3D transvaginal ultrasonography and were assessed for morphological endpoints by trained raters using the 2D offline grid method. FNPO was calculated by summing all 2-9 mm follicles in each ovary. Left and right FNPO were averaged for each participant before baseline to post-intervention changes were calculated.
Time frame: Up to 7 months
Population: This table includes outcome data for all participants who completed either the 12-wk or 24-wk hypocaloric dietary intervention, depending on year of enrollment (participants pre-2018 completed 12 weeks, participants 2018 and later completed 24 weeks). Irregular menstrual cycles were defined as mean cycle length \>35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline Follicle Number Per Ovary | -5 Follicle number per ovary | Standard Deviation 14 |
| Regular Cycles | Change From Baseline Follicle Number Per Ovary | -9 Follicle number per ovary | Standard Deviation 11 |
Secondary
Change From Baseline Free Androgen Index (FAI)
Change in FAI from baseline to the end of a hypocaloric dietary intervention. Blood samples were collected in the morning after an overnight fast during the early follicular phase as confirmed by the absence of a dominant follicle or corpus luteum on ultrasound. Free Androgen Index (FAI) is the ratio of total testosterone to sex hormone binding globulin (SHBG), indicating the amount of active testosterone in the blood. SHBG was evaluated by the Cornell Human Nutrition Chemistry Service Laboratory using Immulite 2000 immunoassay. FAI levels of 5 or higher are indicative of PCOS.
Time frame: Up to 7 months
Population: This table includes outcome data for all participants who completed either the 12-wk or 24-wk hypocaloric dietary intervention, depending on year of enrollment (participants pre-2018 completed 12 weeks, participants 2018 and later completed 24 weeks). Irregular menstrual cycles were defined as mean cycle length \>35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline Free Androgen Index (FAI) | 2 free androgen index | Standard Deviation 9 |
| Regular Cycles | Change From Baseline Free Androgen Index (FAI) | -1 free androgen index | Standard Deviation 1 |
Secondary
Change From Baseline Metabolic Status (HOMA-IR)
Change in metabolic status from baseline to the end of a hypocaloric dietary intervention. HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) was used as an indicator of metabolic status. HOMA-IR uses fasting blood glucose and insulin values to approximate insulin resistance. Blood glucose and insulin were measured in the morning after an overnight fast during the early follicular phase as confirmed by the absence of a dominant follicle or corpus luteum on ultrasound. HOMA-IR was calculated by multiplying blood glucose (mg/dL) by insulin (mIU/mL) and dividing by 405. A higher HOMA-IR score is indicative of increased insulin resistance.
Time frame: Up to 7 months
Population: This table includes outcome data for all participants who completed either the 12-wk or 24-wk hypocaloric dietary intervention, depending on year of enrollment (participants pre-2018 completed 12 weeks, participants 2018 and later completed 24 weeks). Irregular menstrual cycles were defined as mean cycle length \>35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline Metabolic Status (HOMA-IR) | -1.3 HOMA-IR score | Standard Deviation 2.5 |
| Regular Cycles | Change From Baseline Metabolic Status (HOMA-IR) | -0.9 HOMA-IR score | Standard Deviation 0.8 |
Secondary
Change From Baseline Ovarian Volume
Change ovarian volume (cm\^3) from baseline to the end of a hypocaloric dietary intervention. Ovarian images were collected using 3D transvaginal ultrasonography and were assessed for morphological endpoints by trained raters using the 2D offline grid method. Ovarian volume was calculated using a modified formula for a prolate ellipsoid. Left and right ovarian volumes were averaged for each participant before baseline to post-intervention changes were calculated.
Time frame: Up to 7 months
Population: This table includes outcome data for all participants who completed either the 12-wk or 24-wk hypocaloric dietary intervention, depending on year of enrollment (participants pre-2018 completed 12 weeks, participants 2018 and later completed 24 weeks). Irregular menstrual cycles were defined as mean cycle length \>35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline Ovarian Volume | -1.9 cm^3 | Standard Deviation 2.8 |
| Regular Cycles | Change From Baseline Ovarian Volume | 0.9 cm^3 | Standard Deviation 2 |
Secondary
Change From Baseline Reproductive Hormones
Change in reproductive hormones from baseline to the end of a hypocaloric dietary intervention. Blood samples were collected in the morning after an overnight fast during the early follicular phase as confirmed by the absence of a dominant follicle or corpus luteum on ultrasound. Hormones reported include: * Total testosterone: Evaluated by the Brigham Research Assay Core (Harvard) using liquid chromatography tandem mass-spectrometry. Results are reported in ng/dL. * Anti-Müllerian hormone (AMH): Evaluated using the Motive Biosciences (formerly Ansh Labs) picoAMH ELISA. Results are reported in ng/mL
Time frame: Up to 7 months
Population: This table includes outcome data for all participants who completed either the 12-wk or 24-wk hypocaloric dietary intervention, depending on year of enrollment (participants pre-2018 completed 12 weeks, participants 2018 and later completed 24 weeks). Irregular menstrual cycles were defined as mean cycle length \>35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline Reproductive Hormones | Change in Total testosterone (ng/dL) | 20 ng/dL | Standard Deviation 52 |
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline Reproductive Hormones | Change in AMH (ng/dL) | 0.32 ng/dL | Standard Deviation 2.77 |
| Regular Cycles | Change From Baseline Reproductive Hormones | Change in Total testosterone (ng/dL) | -5 ng/dL | Standard Deviation 8 |
| Regular Cycles | Change From Baseline Reproductive Hormones | Change in AMH (ng/dL) | -0.38 ng/dL | Standard Deviation 2.91 |
Secondary
Change From Baseline Total Percent Body Fat
Change in total percent body fat from baseline to the end of a hypocaloric dietary intervention. Body fat was measured using the Hologic Discovery A Dual X-Ray Absorptiometry (DXA) Scanner.
Time frame: Up to 7 months
Population: This table includes outcome data for all participants who completed either the 12-wk or 24-wk hypocaloric dietary intervention, depending on year of enrollment (participants pre-2018 completed 12 weeks, participants 2018 and later completed 24 weeks). Irregular menstrual cycles were defined as mean cycle length \>35 days over the past year, based on self-reported menstrual cycle dates at enrollment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) | Change From Baseline Total Percent Body Fat | -1.8 Percent body fat | Standard Deviation 1.6 |
| Regular Cycles | Change From Baseline Total Percent Body Fat | -1.6 Percent body fat | Standard Deviation 4.3 |