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MNT: Weight Management (2015)

Nybacka Å, Carlström K, Ståhle A, Nyrén S, Hellström PM, Hirschberg AL. Randomized comparison of the influence of dietary management and/or physical exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome. Fertil Steril. 2011; 96 (6): 1,508-1,513. doi:10.1016/j.fertnstert.2011.09.006. PubMed ID: 21962963
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To compare the effects of dietary management and exercise on ovarian function and endocrine and metabolic parameters in overweight PCOS patients.
Inclusion Criteria:
  • Diagnosis of PCOS including all three criteria according to the Rotterdam Consensus (i.e., oligo- or anovulation, hyperandrogenism and polycystic ovaries (PCO) on ultrasound)
  • Age: 18 years to 40 years
  • Body mass index (BMI): Greater than 27kg/m2
  • Absence of hormonal treatment for the past three months
  • No pregnancy, lactation or change in weight during the past year.
Exclusion Criteria:
  • The presence of other disease or a different endocrine disorder
  • An eating disorder
  • Smoking
  • Continuous medication including insulin-sensitizing drugs.
Description of Study Protocol:


  • Recruited by clinical referral or advertisement in the local newspaper
  • Telephone screening was done using a standardized telephone questionnaire
  • Those who seemed suitable were scheduled for a visit with a physician.


  • Randomized four-month intervention involving lifestyle modification
  • Subjects were also followed for at least one year after termination of the programs.

Blinding Used

None mentioned.


  • Randomly assigned (permuted-block method; 10 blocks and a block size of six) to one of three groups:
    • Dietary management
    • Exercise
    • Diet and exercise.
  • Intervention lasted four months with monthly visits
  • At least one year after termination of the programs, the women were contacted by letter and invited to participate in a follow-up visit at the clinic. Those who did not respond were reminded by another letter or a telephone call.

Statistical Analysis

  • All values are presented as mean, SD and 95% confidence interval (CI) or as median and interquartile range (25th to 75th percentiles)
  • Using a mixed model in SAS, repeated measurements of the different parameters taken before and after the interventions were compared
  • The factors in the model were group (diet, exercise, and diet + exercise), time (before and after) and group x time interaction
  • Logistic regression analysis was used to evaluate the relationship between improved menstrual pattern, as well as confirmed ovulation and the measurements of body composition, endocrinologic, gynecologic and metabolic parameters
  • Within each block of parameters, stepwise logistic regression analyses were performed and the significant variables this obtained then were included in a final stepwise logistic model
  • Before these analyses, certain of the variables were log-transformed to compensate for their positively skewed distributions
  • P<0.05 was considered to be statistically significant
  • A power calculation revealed that 3x15 subjects would provide 80% power to detect a difference in means of BMI of 1.5kg/m2 within the groups and a difference in means of at least 2.0 between the groups, assuming that the common standard deviation is 1.7, with a 0.5 two-sided significance level.
Data Collection Summary:

Timing of Measurements

  • Immediately before the study, after four months of intervention (end of study) and at the time of the long-term follow-up, each patient underwent a general health exam involving determination of blood pressure, weight, height and waist-to-hip ratio (WHR), blood sampling, gynecologic examination and determination of body composition
  • In a resting and fasting state at 8:00 a.m., a blood sample was collected from a peripheral vein and the serum separated by centrifugation and stored at -70°C, pending analysis for hormones, binding proteins and glucose.

Dependent Variables

  • Gynecologic exams, including transvaginal ultrasound
    • Ovarian parameters evaluated were the maximal number of follicles in one plane and the volumes of the largest follicle and of the entire ovary
    • Menstrual bleedings were recorded and ovulation confirmed on the basis of an elevation in the serum level of progesterone during the luteal phase of the menstrual cycle.
  • Body composition: The patients were examined by dial energy X-ray absorptiometry (DXA) using a Lunar Prodigy Advance whole body scanner
  • Biochemical measurements
    • Serum testosterone (T), 17 beta-estradiol (E2), 17 alpha-hydroxyprogresterone (17OHP) and insulin were determined by radioimmunoassay, serum FSH, LH, SHBG, DHEAS; insulin-like growth factor (IGF) I were determined by direct chemiluminescence enzyme immunoassay; serum IGF-I-binding protein (IGFBP) I was determined by immunoradiometric assay, using commercial kits
    • Glucose was assayed using the YSI 2300 Stat Plus Glucose & Lactate Analyzer. As a measure of insulin resistance, the homeostasis model assessment (HOMA) index was calculated using the formula [(insulin, m[U/L) x (glucose, mg/L)]/405.
    • Apparent concentrations of free testosterone (fT) were calculated from the levels of total T and SHBG, using a fixed concentration of albumin (40g per L). The ratio between total T and SHBG (T-to-SHBG ratio, "free androgen index") was also calculated.

Independent Variables

  • Diet program
    • Individually designed diets by a dietitian
    • Recommended that total daily caloric intake be reduced by at least 600kcal per day compared to before the intervention, while maintaining a well balanced diet containing 55% to 60% carbohydrates, 25% to 30% fat (10% saturated fat) and 10% to 15% protein
    • A strict schedule of three main meals and two to three snacks was also introduced
    • Food intake was assessed by self-reporting once every 24 hours during the four days both immediately before and at the end of the intervention
    • Monthly follow-up with the dietitian was scheduled for discussion of the goals achieved as well as setting up new goals for the next month.
  • Exercise program
    • Individually adjusted and overseen by a physical therapist
    • Designed to enhance both the type (endurance, aerobic or weight training depending on each of the subjects' preferences) and the level of physical activity to a level conforming to each individual patient's capacity, goals and interest at the beginning of this intervention
    • Physical activity was assessed with the use of pedometers during the four days immediately before and at the end of the program
    • Monthly follow-up with the physical therapist was scheduled for discussion of the goals achieved as well as setting up new goals for the next month.
  • Diet + Exercise program combined
    • Both programs previously mentioned
    • Monthly follow-up with the dietitian and physical therapist was scheduled for discussion of the goals achieved as well as setting up new goals for the next month.

Control Variables

Gynecologic exams, including transvaginal ultrasound were performed by the same investigator.

Description of Actual Data Sample:

Initial N

57 subjects.

Attrition (Final N)

43 subjects

  • Five were lost from the Dietary Group
  • Two were lost from the Exercise Group
  • Seven were lost from the Diet + Exercise Combined Group
    • 10 patients dropped out for personal reasons
    • Four were excluded for various medical reasons.


  Diet Exercise Diet and Exercise
N 14 17 12
Age, years 29.3±5.9 31.8±4.9 31.1±4.7

Not described.

Other Relevant Demographics

  Diet Exercise Diet and Exercise
N 14 17 12
FSH, U/L 4.2±1.5 4.6±2.0 4.4±1.6
LH, U/L 9.4±4.8 8.2±3.5 7.3±3.2
T, ng/ml 0.51±0.22 0.44±0.18 0.47±0.21
SHBG, mg/L 2.2±0.8 2.4±0.8 2.1±1.0
T/SHBG ratio 0.26±0.14 0.21±0.12 0.27±0.18
fT, pg/ml 14.7±6.5 12.4±5.9 14.1±7.4
DHEAS, mcg/dL 239±88 181±81 206±103
17OHP, ng/ml 0.86±0.20 0.93±0.40 0.86±0.33
E2, pg/ml 43 (37-46) 41 (39 - 54) 41 (34 - 59)
IGF-I, mcg/L 171±45 165±48 162±53
IGFBP-1, mcg/L 4.2 (3.3-5.6) 5.0 (2.9-9.9) 3.1 (2.4-7.6)
Insulin, mIU/L 15 (14-20) 13 (11-22) 19 (14-32)
Glucose, mg/dL 82.9±6.8 84.6±7.4 86±9.0
HOMA Index 3.1 (2.9-4.1) 2.8 (2.3-4.7) 4.3 (3.3-6.7)
Caloric Intake over 24 Hours 2,264±491 2,042±399 2,081±424
Steps per Day 7,542 (6,075-8,911) 7,723 (5,036-9,598) 7,130 (4,594-9,442)


  Diet Exercise Diet and Exercise
N 14 17 12
Body Weight, kg 94.1±15.0 95.0±11.8 104.5±23.4
Height, cm 165±4 165±6 164±8
BMI, kg/m2 34.7±5.0 34.9±5.3 38.8±7.9
WHR 0.89±0.07 0.89±0.06 0.86±0.07
Total Fat, % 45.7±4.0 44.7±3.2 46.1±5.8
Lean Body Mass, kg 48.0±6.1 49.2±4.7 52.3±8.0


Stockholm, Sweden.

Summary of Results:

Key Findings

Change in body composition, endocrinological and metabolic data for the subjects in the three different intervention groups

Diet Exercise Diet and Exercise
Caloric Intake per 24 Hours -502 (-784 to -220) -267 (-538 to 5.3) -491 (-798 to -185)
Steps per Day 1,890 (-252 to 4,033) 2,003 (147 to 3,859) 3,555 (1,463 to 5,647)
BMI, kg/m2 -1.74 (-2.66 to -0.81) -0.85 (-1.69 to -0.02) -1.90 (-2.90 to -0.90)
Total Fat, % -1.66 (-3.29 to -0.02) -1.35 (-2.83 to 0.14) -0.84 (-2.61 to 0.92)
Upper Body Fat, kg -1.29 (-2.71 to 0,13) -1.57 (-2.86 to -0.28) -1.26 (-2.80 to 0.27)
Lower Body Fat, kg -1,055 (-1,787 to -322) -482 (-1,146 to 183) -1,616 (-2,407 to -825)
Upper/Lower Body Fat 0.01 (-0.08 to 0.10) -0.05 (-0.14 to 0.03) 0.08 (-0.02 to 0.18)
Lean Body Mass, kg -1.34 (-2.72 to 0.02) 0.30 (-0.94 to 1.55) -2.66 (-4.14 to -1.18)
fT, pg/ml -3.66 (-6.12 to -1.20) -0.39 (-2.54 to 1.76) -1.50 (-4.10 to 1.06)
T/SHBG Ratio -0.08 (-0.12 to -0.03) -0.01 (-0.05 to 0.03) -0.05 (-0.09 to -0.00)
IGF-1, mcg/L 17.1 (0.3 to 33.9) 2.6 (-12.1 to 17.3) 5.0 (-12.5 to 22.5)
IGFBP-1, mcg/L 0.32 (0.01 to 0.64) 0.09 (-0.18 to 0.37) 0.06 (-0.27 to 0.38)
Insulin, mIU/L -2.85 (-7.33 to 1.62) -2.47 (-1.35 to 6.29) -3.45 (-8.20 to 1.29)
Glucose, mg/L -3.17 (-7.14 to 0.81) 0.43 (-3.06 to 3.92) -2.89 (-7.04 to 1.27)
HOMA Index -0.74 (-1.76 to 0.29) 0.57 (0.31 to 1.44) -0.90 (-1.98 to 0.19)

Other Findings

  • After four months of intervention, the self-reported 24-hour caloric intake was significantly reduced in the Dietary and Combined Groups (P<0.001 and P<0.01, respectively), as well as to a lesser extent in the Exercise Group (P<0.01)
  • The number of steps per day was significantly enhanced in the Exercise and Combined Groups (P<0.05 and P<0.01, respectively), but not in the Dietary Group
  • There was an overall decrease in BMI (P<0.001) with no significant differences between groups
  • The weight loss was most pronounced in the Dietary (-6%) and the Combined (-5%) Groups (both P<0.001) than in the Exercise Group (-3%; P<0.05)
  • The overall reduction in percentage total body fat was also significant (P<0.01), although this decrease was significant only for the Dietary Group (P<0.05)
  • There was a general decrease in both upper body fat [P<0.01; significant only for the Exercise Group (P<0.05)] and lower body fat [P<0.001; significant for both Dietary (P<0.01) and Combined (P<0.001) Groups]
  • The overall change in total lean body mass (P<0.01) was associated with a significant difference between the groups (P<0.05). For the Combined Group, there was a significant decrease (P<0.001) and there was a similar tendency in the case of the Dietary Group (P=0.054), but not for the Exercise Group.
  • Overall, fT (P<0.05) was decreased, but this was significant only in the Dietary Group (P<0.01)
  • The general lowering of the T/SHBG-ratio (P<0.01) was associated with significant decreases in this parameter for both the Dietary and Combined Groups (P<0.01 and P<0.05, respectively)
  • Mean serum levels of IGF-I and IGFBP-I, in all of the patients combined, tended to rise (P=0.08 and P=0.08, respectively), with significant elevations in the case of the Dietary Group (P<0.05 and P<0.05, respectively)
  • Of all 43 subjects, 30 women (69%; 95% CI, 54% to 83%; P<0.05) exhibited an improved menstrual pattern, shifting from oligo-amenorrhea to regular menstruation, with similar improvement in the three intervention groups
  • Of those having improved menstrual pattern, ovulation was detected in 15 of the 43 women (35%; 95% CI. 21% to 51%; P=0.06), with no significant between-group difference
  • Stepwise logistic regression (involving body composition, endocrinologic, gynecologic and metabolic parameters) revealed that the strongest predictor of an improved menstrual pattern was a lower T-value before treatment (R2=0.30; P<0.01) and a high serum level of IGFBP-1 after treatment predicted ovulation (R2=0.25; P<0.05)
  • At the time of the long-term follow-up [33 (19-56) months after termination of the intervention], 21 patients (seven in each group) came to be examined. A total of 10 women declined to come and the others could not be reached. The mean change in BMI after termination of the program was -0.4kg/m2 (95% CI, -4.0 to 3.2) for the Dietary Group, -0.05kg/m2 (95% CI, -5.8 to 5.7) for the Exercise Group and -1.6kg/m2 (95% CI, -4.8 to 1.6kg/m2 for the Combined Group.
Author Conclusion:
  • Properly managed diet and exercise, alone or in combination, are equally effective in improving reproductive function in overweight or obese women with PCOS, despite the minor weight loss associated with exercise
  • The underlying mechanism appears to involve enhanced insulin sensitivity, as reflected in the high serum level of IGFBP-1 in the ovulatory women
  • Lifestyle modification is suggested as the first line of treatment to improve reproductive and metabolic health in overweight or obese patients with PCOS and the supportive individualized dietary and exercise programs used here may have long-term beneficial effects.
Funding Source:
Other: Swedish Research Counsil, Karolinska Institute, Stockholm City Council, AM Thomer Fund
Reviewer Comments:
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? ???
  6.6. Were extra or unplanned treatments described? ???
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? Yes
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? N/A
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes