Introduction
Methods
Criteria for considering studies for this review
Types of studies
Types of participants
Types of interventions
Types of outcome measures
Search methods for identification of studies
Data collection and analysis
Selection of studies
Data extraction
Assessment of risk of bias in retained studies
Assessment of heterogeneity
Measures of intervention effect and data synthesis
Results
Results of the search
Description of studies
Participants | |
– Number of randomized participants: 12–439 | |
– Mean age: 15.5–71.0 years | |
– Mean BMI: 19.9–39.0 kg/m2
| |
– Hormonal groups: | |
– Pre-menopausal: n = 10 | |
– Peri-menopausal: n = 1 | |
– Post-menopausal: n = 13 | |
– Polycystic ovary syndrome (PCOS): n = 12 | |
– Per-partum: n = 1 | |
– Post-partum: n = 2 | |
– Unspecified: n = 1 | |
Interventions | |
– Type of exercise: | |
– Endurance: n = 17 | |
– Resistance: n = 6 | |
– Endurance and resistance: n = 11 | |
– Yoga/Tai chi: n = 2 | |
– Free choice or education to exercise: n = 4 | |
– Modality | |
– Supervision/monitoring | |
– Direct or indirect supervision ± monitored exercise: n = 25 | |
– Monitored only exercise: n = 3 | |
– Mix of supervised and not supervised exercises: n = 4 | |
– No supervision: n = 5 | |
– Unknown: n = 3 | |
– Group sessions: | |
– Exercise within group sessions: n = 5 | |
– Unknown: n = 35 | |
– Intensity: | |
– Light: n = 1 | |
– Moderate: n = 9 | |
– High: n = 19 | |
– Unknown: n = 11 | |
– Frequency: | |
– <3 days/week: n = 5 | |
– 3 to <5 days/week: n = 21 | |
– ≥5 days/week: n = 10 | |
– Unknown: n = 4 | |
– Total duration: | |
– <3 months: n = 2 | |
– 3 to <6 months: n = 20 | |
– 6 to <12 months: n = 9 | |
– ≥12 months: n = 9 | |
– Co-intervention: | |
– No co-intervention: n = 23 | |
– Diet: n = 12 | |
– Other: n = 8 | |
Comparators | |
– No intervention: n = 19 | |
– Diet: n = 6 | |
– Other interventions: n = 19 |
Risk of bias in retained studies
Effects of interventions
Primary outcomes
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Total estradiol: 21 studies evaluated circulating concentrations of total estradiol (Fig. 2). Data from three studies [31, 42, 53] were not included in the meta-analysis (incomplete or unsuitable data; see Additional file 1: Table S2). The overall effect of interventions including physical activity was a decrease of total estradiol concentrations (n = 18, SMD = −0.12, 95 % CI: −0.20 to −0.03, I 2 = 0 %). Subgroup analyses indicated that this effect was more pronounced when studies did not include a cointervention, when the intervention group was compared with a nonintervention group, when participants were overweight (baseline BMI between 25 and 30 kg/m2), and when the intervention resulted in substantial weight loss. This effect was particularly noticeable for resistance exercise, high-intensity exercise, exercise performed 3–5 hours per week, for interventions that included supervised and nonsupervised sessions, and for exercise performed in group sessions (see Additional file 1: Table S4). The only study reporting a statistically significant intervention effect was judged to be at low bias risk [40, 41], and when excluded the overall effect was no longer significant (SMD = −0.06, 95 % CI: −0.16 to 0.03, I 2 = 0 %). The funnel plot was roughly symmetrical, suggesting a low risk of publication bias (Additional file 1: Figure S2).×
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Free estradiol: five studies evaluated circulating concentrations of free estradiol (Fig. 2). Interventions including physical activity resulted in an overall decrease of free estradiol concentrations (n = 5, SMD = −0.20, 95 % CI: −0.31 to −0.09, I 2 = 0 %). None of these studies included a cointervention or resistance exercise. The observed effect was more pronounced when the intervention group was compared with a nonintervention group, when the participants’ BMI was less than 30 kg/m2, and for interventions involving high-intensity exercise. This effect seemed to be independent of hormonal group, weight loss after intervention, amount of exercise per week, and intervention modality (see Additional file 1: Table S4). With the exclusion of Friedenreich et al.’s study [40, 41], the overall effect remained significant (SMD = −0.17, 95 % CI: −0.30 to −0.04, I 2 = 0 %). However, a gap in the left bottom corner of the funnel plot graph may indicate a substantial risk of bias (Additional file 1: Figure S3).
Secondary outcomes
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Other estrogens: the overall effect on estrone circulating concentrations was not significant (n = 4, MD = −1.67, 95 % CI: −3.62 to 0.28, I 2 = 0 %). Few studies reported the effect on the other estrogen and estrogen metabolites, and the overall effect for each of them was not significant (Table 2).Table 2Meta-analysis of secondary outcomesOutcome or subgroupStudies (n)Participants (n)Effect estimate95 % CII 2 (%)Other estrogens (mean difference)Estrone (pg/ml)4973−1.67−3.62, 0.280Estrone sulfate (ng/ml)2393−0.02−0.19, 0.140Estriol (NR)179123.90−249.69, 497.49NAEstrogens – not otherwise specified (pg/ml)28927.80−9.76, 65.3694Estrogen metabolites (standardized mean difference)2-OHE13512−0.03−0.20, 0.15016α-OHE135120.03−0.15, 0.201Total estrogen metabolites concentration (2-OHE1 + 16α-OHE1)1320.37−0.33, 1.07NA2-OHE1:16α-OHE1 ratio2195−0.08−0.36, 0.210Androgens (mean difference)Total testosterone (ng/dl)211939−1.36−3.83, 1.1161Free testosterone (pg/ml)91369−0.18−0.29, −0.070Androstenedione (pg/ml)71187–33.87−64.44, −3.299DHEA (ng/ml)4304−0.08−0.50, 0.350DHEA sulfate (μmol/l)8697−0.31−0.57, −0.060Sex hormone binding protein (mean difference) (nmol/l)1416343.930.98, 6.8775Anthropometric factors (mean difference)Body weight (kg)161737−1.83−2.86, −0.8145Body mass index (kg/m2)201976−0.45−0.87, −0.0365Total body fat (kg)101552−2.11−3.71, −0.5292Percent fat mass (%)131563−1.28−1.95, −0.6154Waist circumference (cm)111274−2.23−2.97, −1.4934
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Androgens: 26 studies reported the effect on circulating concentrations of total testosterone, of which five were not suitable for quantitative synthesis (see Additional file 1: Table S2). The funnel plot was roughly symmetrical (Figure not shown) and the overall effect was a nonstatistically significant decrease of total testosterone (n = 21, MD = −1.36, 95 % CI: −3.83 to 1.11, I 2 = 61 %). Significant effects were observed for free testosterone (n = 9, MD = −0.18 pg/ml, 95 % CI: −0.29 to −0.07, I 2 = 0 %), androstenedione (n = 7, MD = −33.87 pg/ml, 95 % CI: −64.44 to −3.29, I 2 = 9 %), and DHEA sulfate (n = 8, MD = −0.31 μmol/l, 95 % CI: −0.57 to −0.06, I 2 = 0 %). These effects seemed to be independent of hormonal group, BMI at baseline, and weight loss after intervention (see Additional file 1: Tables S5 and S6). The effect on free testosterone was slightly more pronounced for interventions with high-intensity exercise and for resistance exercise. The effect on androstenedione was more noticeable for supervised exercise (see Additional file 1: Table S6). The effect on DHEA was not significant (n = 4, MD = −0.08 ng/ml, 95 % CI: −0.50 to 0.35, I 2 = 0 %).
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SHBG: 19 studies reported the effect on SHBG, of which five were not included in quantitative synthesis. The overall effect was a statistically significant increase in SHBG concentrations (n = 14, MD = 3.93 nmol/l, 95 % CI: 0.98–6.87, I 2 = 75 %). The analysis of the different subgroups indicated that the observed effect mainly reflected the effect in the PCOS hormonal group (n = 8, MD = 6.76 nmol/l, 95 % CI: 5.56–7.96, I 2 = 77 %) (see Additional file 1: Table S6). A gap in the bottom-left corner of the funnel plot graph was observed, indicating some risk of bias (Figure not shown).
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Anthropometric factors: overall, physical activity interventions resulted in statistically significant decreases in body weight, BMI, total fat mass, percent fat mass, and waist circumference (Table 2).
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Hormonal function: the data from the 17 studies reporting hormonal function were not suitable for quantitative synthesis. Overall, there was no significant change in menstrual cycle length of premenopausal women (3 studies) [25, 27, 28]. An improvement in the regularity or the frequency of the menstrual cycle and ovulatory parameters was observed among PCOS participants (11 studies). For postmenopausal women (two studies), there was no significant change in menopausal symptom occurrence [36, 49].