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. 2019 Sep 12;52(11):1205–1223. doi: 10.1002/eat.23158

Table 2.

Overview table over all 94 fitted inverse‐variance weighted random‐effects meta‐analyses comparing female or male anorexia nervosa (AN) patients and healthy controls (CO) pretreatment, posttreatment, and after weight recovery and additional meta‐analyses estimating the change in female AN patients before and after treatment

Female Number of participants Meta‐analysis Heterogeneity Small study effects
Pretreatment outcome k AN CO Min Max MD Unit 95% CI p Q τ 2 I 2 95% CI p T&S Copas 95% CI p N unpub Reference values
Weight 36 1,444 1,536 −26.60 −4.00 −15.64 kg −16.98, −14.30 1.27 × 10−115 5.59 × 10−114 13.41 84.6% 79.6%, 88.4% 4.12 × 10−30 0.76
Height 26 1,499 1,255 −0.05 0.03 −0.01 m −0.02, 0.00 .01 0.02 0.0001 66.7% 49.7%, 77.9% 6.86 × 10−7 0.12
Body mass index 56 2,742 2,302 −9.90 −2.10 −5.81 kg/m2 −6.25, −5.38 3.22 × 10−154 2.83 × 10−152 2.43 93.4% 92.2%, 94.5% 2.27 × 10−140 0.10 18.5–24.9 kg/m2
Fat mass 40 2,193 1,720 −20.50 −1.54 −8.80 kg −9.81, −7.79 4.58 × 10−65 1.01 × 10−63 9.64 96.0% 95.3%, 96.7% 2.97 × 10−181 0.59
Body fat percentage 44 2,179 1803 −24.60 −5.50 −13.84 % −15.10, −12.58 1.87 × 10−102 5.49 × 10−101 15.84 92.8% 91.2%, 94.1% 1.40 × 10−98 0.31 20%–25%
Visceral adipose tissue 2 44 115 −1.02 −0.21 −0.62 kg −1.41, 0.18 .13 0.18 0.32 99.0% 97.9%, 99.5% 1.67 × 10−22
Subcutaneous adipose tissue 2 44 115 −10.71 −7.70 −9.26 kg −12.21, −6.31 7.46 × 10−10 3.28 × 10−9 4.24 93.5% 78.9%, 98.0% 8.63 × 10−5
Trunk fat mass 4 72 88 −4.50 −2.40 −3.51 kg −4.58, −2.43 1.65 × 10−10 8.07 × 10−10 0.88 73.8% 26.7%, 90.7% .009 0.83
Trunk body fat percentage 7 199 245 −5.65 6.40 1.77 % −1.46, 5.01 .28 0.36 16.72 91.1% 84.2%, 95.0% 1.36 × 10−12 0.96
Extremity body fat percentage 5 129 124 −9.00 0.53 −5.40 % −8.38, −2.43 3.74 × 10−4 8.03 × 10−4 8.47 71.5% 27.8%, 88.7% 7.25 × 10−3 0.37
Fat‐free mass 37 2,319 1879 −12.16 0.20 −4.98 kg −5.85, −4.12 1.36 × 10−29 1.99 × 10−28 5.92 90.5% 87.9%, 92.5% 1.22 × 10−58 0.51
Fat‐free mass percentage 9 562 528 −0.10 20.47 12.29 % 8.12, 16.47 8.03 × 10−9 3.21 × 10−8 39.60 99.6% 99.6%, 99.7% .00 0.21
Trunk fat‐free mass percentage 3 124 133 −2.41 0.20 −0.19 % −0.66, 0.27 .42 0.52 0.00 55.8% 0.0%, 87.4% .10
Extremity fat‐free mass percentage 3 124 133 −1.84 −1.00 −1.53 % −2.03, −1.03 2.11 × 10−9 8.84 × 10−9 0.00 0.0% 0.0%, 81.7% .57
Bone mineral content (whole body) 6 585 358 −0.70 −0.11 −0.16 kg −0.19, −0.12 3.10 × 10−21 2.73 × 10−20 0.00 58.2% 0.0%, 83.1% .04 0.08
Bone mineral density (whole body) 15 1,000 593 −0.41 0.04 −0.07 g/cm2 −0.11, −0.04 1.64 × 10−4 3.61 × 10−4 0.005 80.3% 68.3%, 87.7% 1.30 × 10−9 0.002 −0.03 −0.06, −0.01 0.02 9
Bone mineral density (lumbar spine) 12 871 682 −0.27 0.01 −0.14 g/cm2 −0.18, −0.10 4.22 × 10−13 2.32 × 10−12 0.004 83.2% 72.0%, 89.9% 9.28 × 10−10 0.87
Bone mineral density (femoral neck) 11 1,109 723 −0.28 0.03 −0.14 g/cm2 −0.18, −0.09 4.16 × 10−10 1.93 × 10−9 0.004 85.9% 76.5%, 91.5% 2.98 × 10−11 0.81
Bone mineral density (hip) 7 945 406 −0.15 0.03 −0.13 g/cm2 −0.15, −0.11 3.52 × 10−46 6.20 × 10−45 0.0002 52.0% 0.0%, 79.6% .05 0.22
Total body water 6 342 254 −6.82 −2.60 −4.77 L −6.13, −3.41 5.92 × 10−12 3.06 × 10−11 1.95 78.3% 52.1%, 90.1% 3.36 × 10−4 0.72 3.3–3.6 L
Resting energy expenditure 3 99 128 −536.00 −296.37 −393.95 kcal/day −531.04, −256.86 1.78 × 10−8 6.53 × 10−8 12,736.55 85.9% 59.0%, 95.2% 8.30 × 10−4
Fasting glucose 7 111 107 −26.49 −7.21 −11.44 mg/dl −15.95, −6.93 6.71 × 10−7 2.21 × 10−6 28.76 73.9% 44.2%, 87.8% 8.04 × 10−4 0.03 −7.01 −9.61, −4.40 <0.0001 11 <140 mg/dl
Fasting insulin 9 222 221 −42.01 7.83 −19.23 pmol/L −31.68, −6.77 .002 0.004 282.08 91.2% 85.5%, 94.6% 3.43 × 10−16 0.40 <173.6 pmol/L
Ghrelin 4 123 83 15.00 217.50 149.20 pmol/L 54.59, 243.81 .002 0.004 7,872.55 88.3% 72.4%, 95.0% 1.19 × 10−5 0.61 114.4–154 pmol/L
Adiponectin 4 104 88 −7.30 7.28 1.37 μg/ml −4.36, 7.11 .64 0.73 30.55 86.6% 67.4%, 94.4% 5.62 × 10−5 0.52 4–37 μg/ml
Leptin 19 771 544 −14.10 −0.46 −7.90 ng/ml −9.72, −6.08 1.55 × 10−17 1.22 × 10−16 14.25 94.1% 92.0%, 95.6% 6.47 × 10−54 0.04 −7.20 −8.44, −5.96 <0.0001 5 3.3–18.3 ng/ml
Testosterone 4 99 98 −18.23 18.30 −1.35 ng/dl −16.03, 13.33 .86 0.90 144.92 69.4% 11.9%, 89.4% .02 0.91 23–75 ng/dl
Thyroid‐stimulating hormone 5 188 196 −0.80 0.30 −0.06 μIU/ml −0.40, 0.27 .72 0.79 0.08 55.5% 0.0%, 83.6% .06 0.30 0.4–4.8 μIU/L
Free triiodothyronine 8 251 215 −2.14 −0.73 −1.32 pmol/L −1.64, −1.00 1.09 × 10−15 6.85 × 10−15 0.17 85.7% 73.7%, 92.2% 2.41 × 10−8 0.14 3.5–9.5 pmol/L
Free thyroxine 4 173 177 −3.40 −2.19 −2.60 pmol/L −3.26, −1.93 2.09 × 10−14 1.23 × 10−13 0.19 36.8% 0.0%, 78.2% .19 0.88 13–27 pmol/L
Insulin‐like growth factor 1 9 233 186 −140.30 −41.00 −95.86 ng/ml −117.93, −73.8 1.67 × 10−17 1.22 × 10−16 747.86 72.2% 45.3%, 85.8% 3.50 × 10−4 0.91 130–450 ng/ml
Cortisol 7 209 167 50.00 232.00 131.92 nmol/L 86.26, 177.58 1.49 × 10−8 5.70 × 10−8 2,649.65 72.6% 40.9%, 87.3% .001 0.85 170–635 nmol/L (8:00 a.m.)
Estradiol 11 278 231 −72.41 −1.86 −40.83 pg/ml −55.43, −26.23 4.22 × 10−8 1.49 × 10−7 526.46 99.1% 98.9%, 99.3% 9.60 × 10−237 0.87 20–50 pg/ml
Male Number of participants Meta‐analysis Heterogeneity Small study effects
Pretreatment k AN CO Min Max MD Unit 95% CI p Q τ 2 I 2 95% CI p T&S Copas 95% CI p N unpub Reference values
Weight 2 32 34 −18.50 −11.33 −15.48 kg −22.42, −8.54 1.22 × 10−5 1.80 × 10−05 17.94 69.8% 0.0%, 93.2% .07
Height 3 42 44 −0.03 0.00 −0.02 m −0.04, 0.01 .13 0.13 0.00 0.0% 0.0%, 82.7% .55
Body mass index 4 68 92 −9.00 −3.70 −5.48 kg/m2 −7.87, −3.09 6.92 × 10−06 1.80 × 10−05 5.58 94.2% 88.2%, 97.1% 3.65 × 10−11 0.89 18.5–24.9 kg/m2
Fat mass 3 42 44 −8.70 −3.03 −5.87 kg −8.98, −2.75 2.22 × 10−04 2.70 × 10−04 6.77 87.2% 63.5%, 95.5% 4.17 × 10−04
Body fat percentage 4 68 92 −9.70 −2.40 −7.49 % −10.79, −4.19 8.76 × 10−06 1.80 × 10−05 9.84 85.7% 64.8%, 94.2% 1.07 × 10−04 0.70 12%–14%
Fat‐free mass 3 42 44 −10.20 −5.25 −9.37 kg −12.47, −6.27 3.30 × 10−09 2.00 × 10−08 0.00 0.0% 0.0%, 66.3% .73
Female Number of participants Meta‐analysis Heterogeneity Small study effects
Posttreatment k AN CO Min Max MD Unit 95% CI p Q τ 2 I 2 95% CI p T&S Copas 95% CI p N unpub Reference values
Weight 12 398 492 −16.60 0.60 −4.92 kg −8.03, −1.81 1.92 × 10−3 0.004 27.82 92.6% 89%, 95.1% 1.82 × 10−26 0.15
Height 2 146 141 −0.01 0.01 0.00 m −0.02, 0.02 .79 0.84 .22
Body mass index 18 722 809 −5.50 0.20 −2.35 kg/m2 −3.28, −1.42 6.79 × 10−7 2.21 × 10−6 3.81 97.6% 97.0%, 98.1% 3.96 × 10−138 0.04 −2.10 −2.53, −1.67 <.0001 5 18.5–24.9 kg/m2
Fat mass 15 589 617 −6.89 1.70 −2.37 kg −3.75, −0.98 8.29 × 10−4 0.002 6.65 94.6% 92.5%, 96.1% 5.45 × 10−47 0.73
Body fat percentage 14 530 617 −14.29 2.40 −3.15 % −5.61, −0.70 .01 0.02 19.77 89.0% 83.3%, 92.7% 5.37 × 10−19 0.05 −2.50 −4.27, −0.73 .006 3 20%–25%
Trunk body fat percentage 6 179 224 −8.24 12.30 5.84 % −0.14, 11.83 .06 0.09 53.72 94.4% 90.4%, 96.8% 7.59 × 10−18 0.03 11.99 9.54, 14.44 <.0001 52
Extremity body fat percentage 5 129 124 −10.00 0.10 −6.37 % −9.52, −3.23 7.24 × 10−5 1.82 × 10−4 10.48 78.1% 47.5%, 90.9% .001 0.08
Fat‐free mass 12 634 697 −4.80 0.20 −1.82 kg −2.57, −1.08 1.72 × 10−6 5.41 × 10−6 0.98 60.2% 25.0%, 78.9% .004 0.61
Fat‐free mass percentage 6 239 299 −1.00 14.29 2.83 % −1.89, 7.55 .24 0.32 33.35 93.5% 88.5%, 96.3% 3.89 × 10−15 0.08
Trunk fat‐free mass percentage 3 124 133 −1.09 0.90 −0.40 % −1.57, 0.77 .50 0.60 0.85 77.9% 28.8%, 93.2% .01
Extremity fat‐free mass percentage 3 124 133 −1.90 1.20 −0.30 % −1.97, 1.37 .73 0.79 1.93 85.0% 55.7%, 94.9% .001
Bone mineral content (whole body) 2 174 194 −0.09 −0.09 −0.09 kg −0.13, −0.05 5.75 × 10−6 1.63 × 10−5 1.00
Bone mineral density (whole body) 2 74 67 −0.04 −0.01 −0.02 g/cm2 −0.04, 0.01 .20 0.27 .34
Total body water 3 204 159 −6.66 −0.80 −3.71 L −7.07, −0.36 .03 0.05 8.25 95.1% 88.9%, 97.8% 1.59 × 10−9 3.3–3.6 L
Fasting glucose 3 45 41 −8.83 5.41 −1.78 mg/dl −8.98, 5.42 .63 0.73 28.75 66.9% 0.0%, 90.5% .05 <140 mg/dl
Fasting insulin 3 46 74 −4.90 9.72 8.31 pmol/L −2.26, 18.87 .12 0.17 0 0.0% 0.0%, 64.8% .74 <173.6 pmol/L
Ghrelin 2 33 61 −89.00 105.00 7.34 pmol/L −182.77, 197.45 .94 0.96 17,674.47 93.9% 80.6%, 98.1% 4.98 × 10−5 114.4–154 pmol/L
Leptin 5 72 113 −9.18 −0.40 −3.91 ng/ml −7.37, −0.45 .03 0.05 12.07 81.3% 56.6%, 92% 2.59 × 10−4 0.17 3.3–18.3 ng/ml
Free triiodothyronine 2 33 63 −1.00 −0.90 −0.91 pmol/L −1.36, −0.47 5.26 × 10−5 1.40 × 10−4 .88 3.5–9.5 pmol/L
Female Number of participants Meta‐analysis Heterogeneity Small study effects
Pretreatment/posttreatment k AN CO Min Max MD Unit 95% CI p Q τ 2 I 2 95% CI p T&S Copas 95% CI p N unpub Reference values
Weight 12 398 436 4.30 16.00 9.93 kg 8.17, 11.68 1.44 × 10−28 2.11 × 10−27 7.54 80.0% 65.0%, 88.0% 1.35 × 10−7 0.32
Height 2 146 146 0.00 0.01 0.00 m −0.01, 0.02 .67 0.75 .53
Body mass index 18 722 807 1.16 6.40 3.39 kg/m2 2.71, 4.08 4.19 × 10−22 4.10 × 10−21 1.99 95.0% 94.0%, 97.0% 8.54 × 10−68 0.37 18.5–24.9 kg/m2
Fat mass 15 589 636 −0.86 8.90 6.39 kg 5.13, 7.65 2.79 × 10−23 3.07 × 10−22 5.42 95.0% 93.0%, 96.0% 7.66 × 10−49 0.68
Body fat percentage 14 530 530 3.85 15.70 10.41 % 7.96, 12.87 9.23 × 10−17 6.25 × 10−16 19.21 93.0% 90.0%, 95.0% 2.07 × 10−32 0.40 20%–25%
Trunk body fat percentage 6 179 179 −2.59 6.20 4.16 % 2.07, 6.25 9.67 × 10−5 2.30 × 10−4 4.08 59.0% 0.0%, 83.0% 3.25 × 10−2 0.08
Extremity body fat percentage 5 129 129 −1.10 −0.43 −0.95 % −2.61, 0.71 .26 0.34 0 0.0% 0.0%, 0.0% 1.00 0.83
Fat‐free mass 12 634 719 0.00 6.90 2.98 kg 1.74, 4.22 2.35 × 10−6 6.89 × 10−6 3.87 93.0% 89.0%, 95.0% 4.57 × 10−27 0.66
Fat‐free mass percentage 6 239 239 −13.92 0.10 −9.00 % −13.63, −4.37 1.38 × 10−4 3.11 × 10−4 31.68 99.0% 99.0%, 99.0% 9.94 × 10−112 0.49
Trunk fat‐free mass percentage 3 124 124 −0.73 1.32 0.17 % −1.06, 1.40 .79 0.84 0.78 72.3% 6.5%, 91.8% .03
Extremity fat‐free mass percentage 3 124 124 −0.90 3.04 1.01 % −1.08, 3.10 .34 0.43 2.83 84.6% 54.2%, 94.8% .002
Bone mineral content (whole body) 2 174 174 0.05 0.07 0.05 kg 0.02, 0.09 .006 0.01 .74
Bone mineral density (whole body) 2 74 74 −0.01 0.01 0.01 g/cm2 −0.02, 0.03 .64 0.73 .53
Total body water 3 204 251 0.16 1.80 0.58 L −0.24, 1.40 .17 0.23 0.18 30.8% 0.0%, 92.8% .24 3.3–3.6 L
Fasting glucose 3 45 45 5.23 16.22 9.51 mg/dl 2.68, 16.35 .006 0.01 23.25 66.3% 0.0%, 90.3% .05 <140 mg/dl
Fasting insulin 3 46 84 9.03 38.19 15.92 pmol/L 1.89, 29.95 .03 0.05 42.79 24.2% 0.0%, 92.1% .27 <173.6 pmol/L
Ghrelin 2 33 71 −112.50 −104.00 −107.76 pmol/L −161.47, −54.05 8.41 × 10−5 2.06 × 10−4 .88 114.4–154 pmol/L
Leptin 5 72 110 1.10 5.50 2.83 ng/ml 1.22, 4.44 5.79 × 10−4 0.001 2.41 71.0% 26.0%, 89.0% .008 0.42 3.3–18.3 ng/ml
Free triiodothyronine 2 33 71 0.80 0.80 0.80 pmol/L 0.39, 1.21 1.33 × 10−4 3.08 × 10−4 1.00 3.5–9.5 pmol/L
Female Number of participants Meta‐analysis Heterogeneity Small study effects
Weight‐recovered k AN CO Min Max MD Unit 95% CI p Q τ 2 I 2 95% CI p T&S Copas 95% CI p N unpub Reference values
Weight 11 305 530 −8.70 1.65 −1.83 kg −3.68, 0.02 .05 0.08 5.80 66.4% 36.4%, 82.2% .001 0.95
Height 6 174 341 −0.03 −0.01 −0.01 m −0.03, 0.00 .02 0.03 0.00 0.0% 0.0%, 0.0% .94 0.51
Body mass index 12 398 660 −2.80 0.50 −0.68 kg/m2 −1.38, 0.02 .06 0.09 1.17 93.3% 90.2%, 95.5% 1.16 × 10−29 0.84 18.5–24.9 kg/m2
Fat mass 12 323 563 −6.30 1.70 −0.76 kg −1.75, 0.22 .13 0.18 1.82 63.0% 31.0%, 80.1% .002 0.47
Body fat percentage 10 392 463 −2.32 2.40 −0.03 % −1.09, 1.02 .95 0.96 1.06 39.0% 0.0%, 70.9% .10 0.44 14%–25%
Visceral adipose tissue 2 37 18 0.10 0.24 0.19 kg 0.03, 0.35 .02 0.03 .42
Subcutaneous adipose tissue 2 37 18 −0.52 −0.42 −0.50 kg −1.81, 0.82 .46 0.56 .95
Trunk body fat percentage 5 147 207 −3.30 12.30 5.86 % −0.83, 12.54 .09 0.13 55.17 96.3% 93.7%, 97.8% 1.75 × 10−22 0.28
Extremity body fat percentage 3 81 89 −10.00 20.09 0.53 % −18.65, 19.71 .96 0.96 285.64 99.4% 99.1%, 99.6% 7.45 × 10−72
Fat‐free mass 9 381 645 −2.10 −0.30 −1.27 kg −1.79, −0.75 1.81 × 10−6 5.49 × 10−6 0.03 0.0% 0.0%, 39.7% .79 0.54
Fat‐free mass percentage 4 206 256 −1.00 0.00 0.00 % −0.06, 0.06 .95 0.96 0.00 0.0% 0.0%, 70.9% .66 0.35
Trunk fat‐free mass percentage 2 105 113 −1.11 −0.88 −0.91 % −1.33, −0.49 2.29 × 10−5 6.30 × 10−5 .72
Extremity fat‐free mass percentage 2 105 113 −0.27 1.59 0.56 % −1.25, 2.37 .54 0.64 1.49 86.2% 45.0%, 96.5% .01
Bone mineral content (whole body) 2 134 161 −0.23 −0.09 −0.10 kg −0.18, −0.03 .008 0.01 0.001 12.9% NA%, NA% .28
Bone mineral density (lumbar spine) 2 31 210 −0.09 −0.04 −0.08 g/cm2 −0.12, −0.04 6.28 × 10−5 1.63 × 10−4 .39
Bone mineral density (femoral neck) 2 31 210 −0.11 −0.05 −0.10 g/cm2 −0.15, −0.04 5.31 × 10−4 0.001 .40
Leptin 2 13 30 −1.30 −0.40 −0.43 ng/ml −2.41, 1.55 .67 0.75 .87 3.3–18.3 ng/ml

To correct for multiple comparison, we calculated FDR‐adjusted Q values. To test for small study effects or publication bias, we performed a Thompson and Sharp (T&S) test. A p value below .05 indicated small study effects or publication bias. In this case, a Copas model was fitted to adjust the original meta‐analysis (Agüera et al., 2015; Bachmann et al., 2014; Benninghoven, Raykowski, Solzbacher, Kunzendorf, & Jantschek, 2007; Bratland‐Sanda et al., 2010; Bredella et al., 2012, 2008; Chudecka & Lubkowska, 2016; de Alvaro et al., 2007; Dellava et al., 2009; Delporte et al., 2003; de Mateo Silleras et al., 2013; Diamanti et al., 2007; DiVasta et al., 2007, 2011; Dostálová et al., 2009; El Ghoch et al., 2012, 2015; El Ghoch, Calugi, et al., 2017; El Ghoch, Milanese, et al., 2014; El Ghoch, Pourhassan, et al., 2017; Estour et al., 2017; Faje et al., 2014; Fazeli et al., 2010; Fernández‐Soto et al., 2013; Galusca et al., 2015; Germain et al., 2010, 2007, 2016; Gniuli et al., 2001; Grinspoon et al., 1996, 2001; Guo et al., 2013; Haas et al., 2018, 2005; Iacopino et al., 2003; Karczewska‐Kupczewska et al., 2010; Karlsson et al., 2000; Kaválková et al., 2012; Kerruish et al., 2002; Kirchengast & Huber, 2004; Konstantynowicz et al., 2011; Kosmiski et al., 2014; Maïmoun et al., 2018; Marra et al., 2019; Mayer et al., 2009, 2005; Mika, Herpertz‐Dahlmann, Heer, & Holtkamp, 2004; Misra et al., 2013; Moreno, Djeddi, & Jaffrin, 2008; Mörkl et al., 2017; Nakahara et al., 2007; Nakai et al., 1999; Prioletta et al., 2011; Rigaud et al., 2010; Scalfi, Marra, Caldara, Silvestri, & Contaldo, 1999; Scalfi et al., 2002; Schneider et al., 1998; Schorr et al., 2019; Singhal et al., 2018; Tagami et al., 2004; Tanaka et al., 2003; Tonhajzerova et al., 2019; Weinbrenner et al., 2004; Wu et al., 2019).

Abbreviations: 95% CI, 95% confidence interval; AN, anorexia nervosa; CO, controls; Copas, Copas model; k, number of studies; MD, mean difference; T&S, Thompson & Sharp; N unpub, number of potentially unpublished studies.