Background
Methods
Search methods for identification of studies
Inclusion criteria: 1. Study design: randomised controlled trials and quasi-randomised controlled trials. 2. Types of participants: reproductive-aged women with a diagnosis of polycystic ovary syndrome (PCOS) based on the National Institute of Health (NIH) diagnostic criteria (1990), the Rotterdam ESHRE/ASRM (2003) diagnostic criteria or the AE-PCOS Criteria (2006). We also included trials where the PCOS diagnosis had been verified by a general practitioner or specialist clinician. 3. Comparators: exercise vs usual care/control, exercise combined with diet vs usual care/control, exercise combined with diet vs diet only. Exercise combined with diet vs exercise only, exercise vs diet, exercise combined with pharmaceutical vs pharmaceutical. 4. All outcomes; expected outcomes included: primary outcomes, such as blood pressure, fasting blood glucose, insulin and lipid concentrations; and secondary outcomes, such as body mass index, cardiorespiratory fitness, testosterone, free androgen index and health-related quality of life measures. Exclusion criteria: 1. Study design: case studies, cross sectional and non-randomised controlled trials. 2. Types of participants: males, adolescent females, post-menopausal women, women without PCOS 3. Comparators: women with PCOS vs healthy controls, pharmaceutical vs exercise, pharmaceutical vs diet, diet vs diet, surgical vs any other condition. |
Study (design) | N randomised/analysed | Intervention duration (assessment points) | Participant characteristics (PCOS diagnostic criteria) | Intervention | Outcome measures |
---|---|---|---|---|---|
Almenning et al. [32] (RCT) | HIIT: 10/8 RT: 11/8 CON: 10/9 | 10 wks (baseline, 10 wks) | Age: 27.2 ± 5.5 y BMI: 26.7 ± 6.0 kg/m2 (Rotterdam) | HIIT frequency: 3 times/wk HIIT intensity: 2 d/wk, 4 × 4 mins 90–95% HRmax/3 × 3 mins ~ 70% HRmax. 1 d/wk, 10 × 1 min ‘all-out’/10 × 1 min rest. RT frequency: 3 times/wk RT sets × reps: 3 × 10 RT load: 75% 1-RM | HOMA-IR, FBG, FI, TG, TC, LDL-C, HDL-C VO2 max, RHR, BW, BMI, WC, BF%, FM, FFM, T, SHBG, FAI, hsCRP |
Brown et al. [97] (RCT) | EX: 21/8 CON: 16/12 | 20–24 wks due to varying length of ramp-up phase (baseline, immediately post) | Age: 32.3 ± ns y BMI: 33.0 kg/m2 (NIH) | Exercise: 12-wk moderate-intensity intervention preceded by 8–12-wk ramp-up. Aerobic duration: ~ 228 min/wk (≤ 60 bouts) Aerobic intensity: 40–60% VO2 max | FBG, FI, HOMA-IR, TG, LDL-C, HDL-C, VO2 max, BW, BMI, WC, FT, SBP, DBP |
Bruner et al. [98] (RCT) | EX + DIET: 7/7 DIET: 5/5 | 12 wks (baseline, 12 weeks) | Age: 30.7 ± 4.6 y BMI: 36.6 ± 6.0 kg/m2 (Rotterdam) | Exercise frequency: 3 times/wk Aerobic intensity: 70–85% HRmax Aerobic duration: 30 mins (+ 10-min warm-up) RT sets × reps: 2–3 × 10–15 RT load: not specified Diet: 1 h/wk of nutritional counselling | FI, QUICKI, VO2 max, BW, BMI, WC, T, SHBG, FAI |
Guzick et al. [99] (RCT) | EX + DIET: 6/6 CON: 6/6 | 12 wks (baseline, 12 weeks) | Age: 31.7 ± 10.0 y BMI: ns (NIH) | Exercise frequency: 5 times/wk Exercise intensity: 1050–4200 kJ/wk Diet: VLCD (8 wks) with calories increased over final 4 wks (4200–5040 kJ/d). ‘Optifast’ used to supplement diet | FBG, FI, BW, WHR, T, SHBG, FT, LH, FSH |
Hoeger et al. [100] (RCT) | LS + PLA: 11/6 PLA: 9/7 LS + MF: 9/5 MF: 9/5 | 48 wks (baseline, 24 wks, 48 wks) | Age: 28.5 ± 5.2 y BMI: 39.0 ± 6.1 kg/m2 (NIH) | Exercise programme: Individualised to achieve 150 min per week Diet: Individualised healthy balanced meal plan to achieve 500–1000 kcal deficit per day Metformin: 850 mg 2 times/day | BW, T, SHBG, FAI |
Konopka et al. [102] (RCT) | EX: 12/12 CON: 13/13 | 12 wks (baseline, 12 wks) | Age: 35 ± 5.0 y BMI: 33.0 ± 5.0 kg/m2 (Rotterdam) | Exercise frequency: 5 times/wk Exercise intensity: 65% VO2 peak Exercise duration: 60 min | FBG, FI, HOMA-IR, BMI, BW, FM, FFM, E2 |
Nasrekani et al. [104] (RCT) | EX: 10/10 CON: 10/10 | 12 wks (baseline, 12 wks) | Age: 30.4 ± 5.9 y BMI: 28.3 ± 6.2 kg/m2 (Rotterdam) | Exercise frequency: 3 times/wk Exercise intensity: 40–65% HRmax Exercise duration: 25–30 min | VO2 max, BW, BMI, FSH, LH |
(RCT) | EX: 19/17 EX + DIET: 19/12 DIET: 19/14 | 4 months (baseline, 4 months) | Age: 30.8 ± 5.2 y BMI: 36.0 ± 6.2 kg/m2 (Rotterdam) | Exercise programme: Individualised to meet individuals’ capacity, goals and interest. Diet: ≥ 600 kcal/day reduction maintaining 55–60% CHO, 25–30% fat and 10–15% protein. | FBG, FI, HOMA-IR, BW, BMI, WHR, BF%, FFM, T, SHBG, FT, E2, FSH, LH |
Petranyi et al. [107] (QRCT) | LS + MF: 29/29 MF: 27/27 | 6 months (baseline, 6 months) | Age: 29 ± ns y BMI: 27.2 ± 6.9 kg/m2 (Rotterdam) | Exercise programme: recommendation to increase physical activity levels. Specifics unclear. Diet: low glycaemic index diet with caloric restriction for those who are obese. Metformin: 500 mg 3 times/day | BMI, WHR |
Roessler et al. [34] (Randomised crossover) | EX: 8/7 CON: 9/7 | 16 wks (baseline, 8 wks, 16 wks) | Age: 31.7 ± 7.9 y BMI: 36.3 ± 7.2 kg/m2 (Rotterdam) | Exercise frequency: 3 times/wk (2 × cycle, 1 × walk) Exercise intensity: following 2-week ramp, cycling 20–180 s 80–100% HRmax/rest 25–180 s 45–65% HRmax. Walking 3–5 min 80–90% HRmax/1 min 50–60% HRmax. Exercise duration: 45 min (+ 10 min warm-up). Control: Group counselling sessions (2 h, 1 time/wk) focussing on barriers and motivation. | VO2 max, BW, BMI, WC |
(RCT) | EX: 15/14 CON: 15/13 | 16 wks (baseline, 16 wks) | Age: 26.0 ± 5.0 y BMI: 32.8 ± 4.6 kg/m2 (Rotterdam) | Exercise frequency: 3 times/wk Exercise intensity: 60–85% HRmax Exercise duration: 40 min (+ 5 min) | SBP, DBP, FI, BMI, RHR, VO2 max, T, FSH, LH |
Saremi et al. [109] (RCT) | EX: 11/11 CON: 11/11 | 8 wks (baseline, 8 wks) | Age: 35.2 ± 4.4 y BMI: 28.3 ± 4.3 kg/m2 (Rotterdam) | Exercise frequency: 3 times/wk Exercise intensity: 40–65% HRmax Exercise duration: 30 min | FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, VO2 peak, BW, BMI, BF%, WC, WHR |
Saremi et al. [110] (RCT) | EX + PLA: 10/10 CON: 10/10 EX + CAL: 10/10 | 8 wks (baseline, 8 wks) | Age: 27.1 ± 5.1 y BMI: 25.5 ± 2.7 kg/m2 (Rotterdam) | Exercise frequency: 3 times/wk RT sets x reps: 1–2 × 15–20 RT load: 40–60% 1-RM | FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, BW, BMI |
(RCT) | EX: 34/22 CON: 17/13 ACU: 33/24 | 16 wks (baseline, 16 wks, 32 wks) | Age: 30 ± 4.4 y BMI: 28.1 ± 7.3 kg/m2 (Rotterdam) | Exercise frequency: 3 times/wk Exercise intensity: HR ≥ 120 BPM Exercise duration: 30–45 min Low-frequency electroacupuncture: 14 × 30 min treatments over 16 wks | SBP, DBP, FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, BMI, WHR, T, FT, SHBG, FAI, LH, FSH, VO2 max, BMI, E2 |
(RCT) | AET + DIET: 31/18 AET + RT + DIET: 33/20 DIET: 30/14 | 20 weeks (baseline, 10 wks, 20 wks) | Age: 29.3 ± 6.8 y BMI: 36.1 ± 4.8 kg/m2 (Rotterdam) | Exercise frequency: 5 times/wk (3 × aerobic, 2 × RT in combined exercise group) Aerobic intensity: 60–65% HRmax progressed to 75–80% HRmax by study end Aerobic duration: 25–30 min progressed to 45 mins by study end RT sets × reps: 3 × 12 RT load: 50–60% 1-RM progressed to 65–75% 1-RM after 2 wks Diet: energy restricted high protein diet (5000–6000 kJ/day) | SBP, DBP, FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, BW, BF%, FM, FFM, WC, T, SHBG, FAI, PCOS-Q |
Turan et al. [117] (RCT) | EX: 16/14 CON: 16/16 | 8 wks (baseline, 8 wks) | Age: 24.5 ± 2.8 y BMI: 21.9 ± 3.5 kg/m2 (Rotterdam) | Exercise frequency: 3 times/wk Exercise duration: 50–60 min Aerobic intensity: 65–70% HRmax RT sets x reps: 1 × 15 RT load: 5–6 on RPE for RT scale | SBP, DBP, FBG, HOMA-IR, FI, TG, TC, HDL-C, LDL-C, BMI, WC, RHR, VO2 max, T, FT, E2, LH, FSH |
Vigorito et al. [118] (RCT) | EX: 45/45 CON: 45/45 | 3 months (baseline, 3 months) | Age: 21.8 ± 2.1 y BMI: 29.4 ± 3.2 kg/m2 (Rotterdam) | Exercise frequency: 3 times/wk Exercise intensity: 60–70% VO2 max Exercise duration: 30 min | SBP, DBP, FBG, FI, TG, TC, LDL-C, HDL-C, VO2 max, RHR, BMI, WC, E2, T, FT, SHBG, FAI, LH, FSH, CRP |
Vizza et al. [119] (RCT) | EX: 8/7 CON: 7/6 | 12 wks (baseline, 12 wks) | Age: 27 ± 5.0 y BMI: 37.8 ± 11.4 kg/m2 | Exercise frequency: 4 times/wk (2 × RT, 2 home-based) RT sets × reps: 2–3 × 8–12 RT load: Progressed with strength gains Home-based: Callisthenics, 3 sets of 10 reps | FBG, FI, HOMA-IR, BW, BMI, WC, FM, FFM, BF%, hsCRP, T, SHBG, FAI, PCOS-Q, SF-36 |
Assessment of risk of bias in included studies
Strategy for data synthesis
Investigation of heterogeneity
Assessment of reporting biases
Subgroup analysis
Sensitivity analysis
Results
Description of included studies
Search results
Eligible studies design and attrition
Participant characteristics of included studies
Intervention and comparison details
Characteristics of the outcome measures
Assessment of risk of bias in included studies
Effects of interventions: Exercise versus control
Outcome | References | Change from baseline | Immediately post-intervention values | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
N
| MD | Lower 95% CI | Upper 95% CI | I2 (%) |
N
| MD | Lower 95% CI | Upper 95% CI | I2 (%) | ||
SBP (mmHg) | 158 | − 2.93 | − 7.06 | 1.20 | 50 | 158 | 2.02 | − 6.82 | 10.86 | 87 | |
DBP (mmHg) | 158 | − 2.19 | − 5.23 | 0.85 | 46 | 158 | − 0.82 | − 3.49 | 1.84 | 31 | |
FBG (mg/dL) | 263 | − 1.08 | − 2.47 | 0.30 | 16 | 238 | − 1.69 | − 4.35 | 0.97 | 37 | |
FI (μIU/mL) | 263 | − 2.44** | − 4.24 | − 0.64 | 91 | 238 | − 2.11** | − 3.49 | − 0.73 | 40 | |
HOMA-IR | 173 | − 0.57** | − 0.99 | − 0.14 | 87 | 148 | − 0.22 | − 0.80 | 0.36 | 69 | |
TC (mg/dL) | 225 | − 5.88** | − 9.92 | − 1.83 | 35 | 225 | − 6.35** | − 10.76 | − 1.95 | 0 | |
LDL-C (mg/dL) | 225 | − 7.39*** | − 9.83 | − 4.95 | 0 | 225 | − 6.68** | − 11.66 | − 1.70 | 0 | |
HDL-C (mg/dL)▲ | 225 | 0.29 | − 1.46 | 2.04 | 52 | 225 | 1.87 | − 1.59 | 5.33 | 65 | |
TG (mg/dL) | 225 | − 4.78*** | − 7.52 | − 2.05 | 3 | 225 | − 1.97 | − 7.36 | 3.42 | 18 | |
VO2 max (ml/kg/min)▲ | 229 | 3.84*** | 2.87 | 4.81 | 17 | 184 | 5.01*** | 3.48 | 6.54 | 42 | |
RHR (bpm) | 156 | − 2.65 | − 5.55 | 0.25 | 51 | 156 | − 3.26*** | − 4.93 | − 1.59 | 0 | |
BMI (kg/m2) | 331 | − 0.49 | − 1.04 | 0.06 | 66 | 272 | − 1.02** | − 1.81 | − 0.23 | 0 | |
Body Mass (kg) | 139 | − 1.25 | − 3.27 | 0.76 | 33 | 128 | − 0.48 | − 4.86 | 3.91 | 0 | |
WC (cm) | 221 | − 2.62*** | − 4.13 | − 1.11 | 53 | 221 | − 2.33 | − 5.23 | 0.58 | 15 | |
WHR | 101 | − 0.03 | − 0.08 | 0.02 | 0 | 101 | − 0.04 | − 0.08 | 0.01 | 19 | |
Body Fat (%) | 60 | − 1.39* | − 2.61 | − 0.18 | 30 | 60 | − 3.28 | − 7.39 | 0.83 | 22 | |
Fat Mass (kg) | 63 | − 1.70 | − 3.93 | 0.53 | 70 | 38 | 5.14 | − 14.39 | 24.68 | 65 | |
FFM (kg)▲ | 63 | 0.46 | − 0.89 | 1.81 | 58 | 38 | 4.99 | − 7.31 | 17.28 | 75 | |
Testosterone (nmol/L) | 203 | − 0.09 | − 0.24 | 0.06 | 0 | 169 | − 0.08 | − 0.35 | 0.19 | 37 | |
SHBG (nmol/L) | 173 | 7.51 | − 8.01 | 23.04 | 89 | 139 | 4.03 | − 18.57 | 26.63 | 66 | |
Free T (pg/mL) | 74 | − 0.43 | − 1.74 | 0.88 | 76 | 41 | 0.33 | − 0.10 | 0.77 | 0 | |
FAI | 139 | 0.24 | − 0.55 | 1.04 | 0 | 139 | 0.68 | − 1.09 | 2.44 | 46 | |
FG | 135 | − 0.63 | − 2.08 | 0.81 | 0 | 101 | − 0.75 | − 2.03 | 0.54 | 0 | |
Oestradiol (pmol/L) | 190 | − 13.94 | − 54.53 | 26.64 | 65 | 120 | 0.27 | − 11.27 | 11.80 | 0 | |
DHEA-S (μmol/L) | 70 | − 0.60 | − 1.58 | 0.39 | 0 | 36 | − 0.20 | − 1.87 | 1.46 | 0 | |
LH (IU/L) | 185 | − 0.30 | − 2.54 | 1.95 | 72 | 151 | − 0.66 | − 2.39 | 1.06 | 43 | |
FSH (IU/L) | 185 | 0.23 | − 0.08 | 0.53 | 0 | 151 | − 0.01 | − 0.40 | 0.37 | 0 | |
LH/FSH ratio | 41 | − 0.02 | − 0.38 | 0.33 | 0 | 41 | 0.32 | − 0.22 | 0.86 | 37 | |
PG (nmol/L) | 115 | − 0.72 | − 2.53 | 1.09 | 74 | – | – | – | – | – | |
Prolactin (ng/mL) | 110 | − 0.05 | − 0.71 | 0.61 | 0 | 110 | 0.20 | − 0.27 | 0.68 | 0 | |
hsCRP (mg/L) | 38 | − 0.41 | − 1.19 | 0.37 | 0 | 38 | 0.67 | − 1.31 | 2.65 | 0 | |
AMH (ng/mL) | 67 | − 0.67 | − 1.65 | 0.32 | 0 | 67 | 0.48 | − 1.89 | 2.84 | 0 | |
Adiponectin (μg/mL) | 70 | − 0.20 | − 1.04 | 0.64 | 0 | – | – | – | – | – |
Primary outcomes
Blood pressure
Exercise compared to usual care for women with PCOS | ||||||
Patient or population: women with PCOS Setting: Intervention: exercise Comparison: usual care | ||||||
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect(95% CI) | № of participants (studies) | Certainty of the evidence(GRADE) | Comments | |
Risk with usual care | Risk with exercise | |||||
Systolic blood pressure (change from baseline) follow-up: range 8 weeks to 16 weeks | The mean systolic blood pressure (change from baseline) ranged from − 2.5 to 1.1 mmHg | The mean systolic blood pressure (change from baseline) in the intervention group was 2.93 mmHg lower (7.06 lower to 1.2 higher) | – | 158 (4 RCTs) | ⨁⨁◯◯ LOW a,b | Exercise may result in little to no difference in systolic blood pressure (change from baseline). |
Diastolic blood pressure (change from baseline)follow-up: range 8 weeks to 16 weeks | The mean diastolic blood pressure (change from baseline) ranged from −3.1 to 2.9 mmHg | The mean diastolic blood pressure (change from baseline) in the intervention group was 2.19 mmHg lower (5.23 lower to 0.85 higher) | – | 158 (4 RCTs) | ⨁⨁◯◯ LOW a,b | Exercise may result in little to no difference in diastolic blood pressure (change from baseline). |
Fasting blood glucose (change from baseline)follow-up: range 8 weeks to 16 weeks | The mean fasting blood glucose (change from baseline) ranged from − 1.3 to 2.6 mg/dL | The mean fasting blood glucose (change from baseline) in the intervention group was 1.08 mg/dL lower (2.47 lower to 0.3 higher) | – | 263 (9 RCTs) | ⨁⨁◯◯ LOW c,d | Exercise may result in little to no difference in fasting blood glucose (change from baseline). |
Fasting insulin (change from baseline) follow-up: range 8 weeks to 16 weeks | The mean fasting insulin (change from baseline) ranged from −4.1 to 2.5 μU/ml | The mean fasting insulin (change from baseline) in the intervention group was 2.44 μU/ml lower (4.42 lower to 0.64 lower) | – | 263 (9 RCTs) | ⨁◯◯◯ VERY LOW e,f,g | Exercise may reduce fasting insulin (change from baseline) but we are very uncertain. |
HOMA-IR (change from baseline)follow-up: range 8 weeks to 16 weeks | The mean HOMA-IR (change from baseline) ranged from − 0.4 to 0.7 | The mean HOMA-IR (change from baseline) in the intervention group was 0.57 lower (0.99 lower to 0.14 lower) | – | 173 (8 RCTs) | ⨁◯◯◯ VERY LOW d,e,h | Exercise may reduce HOMA-IR (change from baseline) but we are very uncertain. |
Total cholesterol (change from baseline) follow-up: range 8 weeks to 16 weeks | The mean total cholesterol (change from baseline) ranged from −8.85 to 6.85 mg/dL | The mean total cholesterol (change from baseline) in the intervention group was 6.48 mg/dL lower (10.5 lower to 2.45 lower) | – | 225 (7 RCTs) | ⨁⨁◯◯ LOW g,i | Exercise may reduce total cholesterol (change from baseline) slightly. |
LDL-C (change from baseline) follow-up: range 8 weeks to 16 weeks | The mean LDL-C (change from baseline) ranged from − 17.7 to 7.03 mg/dL | The mean LDL-C (change from baseline) in the intervention group was 7.51 mg/dL lower (10.01 lower to 5.02 lower) | – | 225 (7 RCTs) | ⨁⨁◯◯ LOW g,i | Exercise may reduce LDL-C (change from baseline) slightly. |
HDL-C (change from baseline) follow-up: range 8 weeks to 16 weeks | The mean HDL-C (change from baseline) ranged from − 17.7 to 3.5 mg/dL | The mean HDL-C (change from baseline) in the intervention group was 0.01 mg/dL lower (1.91 lower to 1.89 higher) | – | 225 (7 RCTs) | ⨁⨁◯◯ LOW d,i | Exercise may result in little to no difference in HDL-C (change from baseline). |
Triglycerides (change from baseline) follow-up: range 8 weeks to 16 weeks | The mean triglycerides (change from baseline) ranged from − 1.0 to 8.9 mg/dL | The mean triglycerides (change from baseline) in the intervention group was 4.78 mg/dL lower (7.52 lower to 2.05 lower) | – | 225 (7 RCTs) | ⨁⨁◯◯ LOW g,i | Exercise likely results in a small effect that may not be an important (or unimportant) reduction in triglycerides (change from baseline). |
Fasting blood glucose
Fasting insulin
HOMA-IR
Circulating lipids
Secondary outcomes
Maximal or peak oxygen uptake
Resting heart rate
Body mass and body mass index
Waist and hip circumference and waist-to-hip ratio
Body composition
Androgenic, hormonal, and inflammatory markers
Psychosocial outcomes
Effects of interventions: Exercise and diet versus control
Effects of interventions: Exercise and diet versus diet
Exercise and diet compared to Diet for women with PCOS | ||||||
Patient or population: women with PCOS Setting: Intervention: exercise and diet Comparison: Diet | ||||||
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
Risk with Diet | Risk with exercise and diet | |||||
Fasting blood glucose (change from baseline) follow-up: range 16 weeks to 20 weeks | The mean fasting blood glucose (change from baseline) ranged from − 7.0 to − 3.2 mg/dL | The mean fasting blood glucose (change from baseline) in the intervention group was 2.92 mg/dL higher (0.4 lower to 6.23 higher) | – | 78 (2 RCTs) | ⨁◯◯◯ VERY LOW a,b | We are uncertain about the effect of exercise and diet on fasting blood glucose (change from baseline). |
Fasting insulin (change from baseline) follow-up: range 12 weeks to 20 weeks | The mean fasting insulin (change from baseline) ranged from − 2.9 to − 18.54 μU/ml | The mean fasting insulin (change from baseline) in the intervention group was 2.22 μU/ml higher (3.7 lower to 8.14 higher) | – | 90 (3 RCTs) | ⨁◯◯◯ VERY LOW a,c,d | We are uncertain about the effect of exercise and diet on fasting insulin (change from baseline). |
HOMA-IR (change from baseline) follow-up: range 16 weeks to 20 weeks | The mean HOMA-IR (change from baseline) ranged from − 0.74 to − 0.56 | The mean HOMA-IR (change from baseline) in the intervention group was 0.01 lower (0.45 lower to 0.43 higher) | – | 78 (2 RCTs) | ⨁◯◯◯ VERY LOW a,b | We are uncertain about the effect of exercise and diet on HOMA-IR (change from baseline). |
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; MD: Mean difference | ||||||
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect |