An interventional study of Commercial Weight Loss Program in Weight Loss, Anovulation and Amenorrhea, sponsored by Cornell University. Completed at 1 site in United States. Open to female participants aged 18 Years to 35 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-02-03.
Sponsored by Cornell University · Not applicable, Interventional, and Basic science
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).
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.
75 studies on the registry are indexed under Anovulation; 7 are open to participants now.
This study's enrollment of 79 is close to the median of 80 across 52 interventional studies indexed under Anovulation.
Browse Anovulation studies →Cornell University is the lead sponsor of 103 studies on the registry; 16 are open to participants now.
Compared within Anovulation, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Weight Loss. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 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.
Behavioral: Commercial 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.
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
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
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
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
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
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
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
Change From Baseline BMI
Change in BMI from baseline to the end of a hypocaloric dietary intervention.
Time frame: Up to 7 months
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.
| Milestone | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Started | 42 | 37 |
| Completed | 34 | 24 |
| Not completed | 8 | 13 |
| Withdrew: Physician decision | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 2 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Pregnancy | 0 | 2 |
| Withdrew: Poor vein access and/or ultrasound image quality | 4 | 8 |
| Withdrew: Exclusionary medication | 2 | 0 |
| Milestone | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Started | 34 | 24 |
| Completed | 30 | 18 |
| Not completed | 4 | 6 |
| Withdrew: Adverse event | 1 | 0 |
| Withdrew: Physician decision | 1 | 0 |
| Withdrew: Withdrawal by investigator - poor compliance | 1 | 2 |
| Withdrew: Research restrictions (covid) | 1 | 2 |
| Withdrew: Poor vein access and/or ultrasound image quality | 0 | 1 |
| Withdrew: Participant initiated an exclusionary medication. | 0 | 1 |
| Milestone | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Started | 30 | 18 |
| Completed | 18 | 14 |
| Not completed | 12 | 4 |
| Withdrew: Lost to follow-up | 12 | 2 |
| Withdrew: Pregnancy | 0 | 1 |
| Withdrew: Exclusionary medication | 0 | 1 |
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.
| Participants | Irregular Cycles (With or Without Additional Features of PCOS) |
|---|---|
| Responders | 12 |
| Non-Responders | 18 |
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.
| Follicle number per ovary | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Change From Baseline Follicle Number Per Ovary | -5 ± 14 | -9 ± 11 |
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
| ng/dL | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Change in Total testosterone (ng/dL) | 20 ± 52 | -5 ± 8 |
| Change in AMH (ng/dL) | 0.32 ± 2.77 | -0.38 ± 2.91 |
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.
| HOMA-IR score | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Change From Baseline Metabolic Status (HOMA-IR) | -1.3 ± 2.5 | -0.9 ± 0.8 |
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.
| Percent body fat | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Change From Baseline Total Percent Body Fat | -1.8 ± 1.6 | -1.6 ± 4.3 |
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.
| cm^3 | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Change From Baseline Ovarian Volume | -1.9 ± 2.8 | 0.9 ± 2.0 |
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.
| free androgen index | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Change From Baseline Free Androgen Index (FAI) | 2 ± 9 | -1 ± 1 |
Change in BMI from baseline to the end of a hypocaloric dietary intervention.
| kg/m^2 | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| Change From Baseline BMI | -2.8 ± 1.5 | -3.8 ± 1.9 |
Collected over Adverse event data were collected over 13 months (including up to 7 months of baseline and dietary intervention, plus a single follow-up visit 6 months later).. Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Irregular Cycles (With or Without Additional Features of PCOS) | 0/42 (0%) | 0/42 (0%) | 10/42 (23.8%) |
| Regular Cycles | 0/37 (0%) | 0/37 (0%) | 2/37 (5.4%) |
| Event | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles |
|---|---|---|
| 2 hour blood glucose value of 140-199 mg/dLEndocrine disorders | 6/42 | 1/37 |
| Fasting blood glucose value of >120 mg/dLEndocrine disorders | 3/42 | 0/37 |
| Bloating and gastrointestinal discomfortMetabolism and nutrition disorders | 1/34 | 0/24 |
| Hypertrophic scarring at venipuncture siteSkin and subcutaneous tissue disorders | 0/42 | 1/37 |
This table includes baseline characteristics for all participants who completed either the 12-wk or 24-wk hypocaloric dietary intervention, depending on date of enrollment (the study was amended in 2018 to increase the duration of the dietary intervention from 12 to 24 weeks). Regular menstrual cycles were defined as 21-35 days based on self-reported menstrual cycle data from the year leading up to enrollment.
| Age, Continuous(years) | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles | Total |
|---|---|---|---|
| Mean | 28 ± 5 | 31 ± 3 | 29 ± 4 |
| Sex: Female, Male(Participants) | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles | Total |
|---|---|---|---|
| Female | 30 | 18 | 48 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles | Total |
|---|---|---|---|
| Hispanic or Latino | 5 | 1 | 6 |
| Not Hispanic or Latino | 24 | 17 | 41 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Race (NIH/OMB)(Participants) | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 5 | 0 | 5 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 2 |
| White | 23 | 16 | 39 |
| More than one race | 0 | 1 | 1 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(participants) | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles | Total |
|---|---|---|---|
| United States | 30 | 18 | 48 |
| Body Mass Index(kg/m*m) | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles | Total |
|---|---|---|---|
| Mean | 37 ± 6 | 37 ± 7 | 37 ± 6 |
| Menstrual Cycle Length(days) | Irregular Cycles (With or Without Additional Features of PCOS) | Regular Cycles | Total |
|---|---|---|---|
| Mean | 84 ± 67 | 30 ± 2 | 65 ± 59 |
PDFs hosted by the registry, ClinicalTrials.gov.
The record gives a start of Jan 2013, a primary completion of Dec 2023 and a completion of Dec 2023. It does not say whether these dates are actual or estimated.
Results were first posted in Feb 2025, 1 year 1 month after primary completion.
How these figures are worked out, and which studies are left out of them.
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