Table 2. Open in new tab Re-analysis of...

Outcome	Exposure (early) vs. non exposure	Included studies (cohorts)	Metric	Total sample	Reported summary ES (95% CI)—random-effect model	Re-analyzed summary ES (95% CI) DL method	Re-analyzed summary ES (95% CI) HS method Random-effect model	Heterogeneity I² (%)	Egger’s P-value	PAF (95% CI)	95% prediction interval	GRADE (certainty of evidence)
T2DM/IGT	Not early	23 (23)	OR	1 185 444	1.39 (1.25–1.55)	1.32 (1.28, 1.35)	1.39 (1.26, 1.53)	0.98 (0.86, 1.12)	1.31 (1.20, 1.44)	87.28	0.21226	3.01 (1.96, 4.22)	(0.90, 2.14)	High
GDM	Not early	5 (5)	RR	48 535	1.31 (1.05, 1.56)	1.36 (1.20, 1.53)	1.36 (1.15, 1.60)	1.34 (1.14, 1.58)	1.36 (1.10, 1.67)	33.23	0.85991	3.48 (0.99, 6.28)	(0.93, 1.99)	Moderate
HOMA-IR	Average	5 (1)	WMD	7925	0.40 (0.28, 0.52)	0.39 (0.28, 0.51)	0.39 (0.28, 0.51)	0.42 (0.21, 0.69)	0.41 (0.29, 0.58)	0	0.75369		(0.18, 0.41)	Moderate
Fasting insulin (uIU/mL)	Average	9 (4)	WMD	17 020	1.28 (1.13, 1.43)	1.30 (1.24, 1.36)	1.28 (1.23, 1.44)	2.00 (0.91, 3.09)	1.29 (1.21, 1.38)	8.12	0.67836		(0.99, 1.65)	Moderate
Obesity	Not early	5 (5)	OR	54 006	2.00 (1.79, 2.24)	1.97 (1.83, 2.12)	2.00 (1.79, 2.24)	1.93 (1.69, 2.22)	1.97 (1.73, 2.23)	35.02	0.83040	8.84 (6.80, 10.95)	(1.50, 2.67)	Moderate
Adult BMI (≥40 years)	Not early	6 (6)	SMD	121 943	0.29 (0.28, 0.31)	0.30 (0.28, 0.31)	0.32 (0.28, 0.35)	0.29 (0.27, 0.30)	0.30 (0.28, 0.32)	36.32	0.08680		(0.28, 0.36)	Moderate
Adult BMI (<40 years)	Not early	4 (4)	SMD	124 728	0.39 (0.37, 0.40)	0.39 (0.37, 0.40)	0.40 (0.37, 0.43)	0.39 (0.37, 0.40)	0.39 (0.36, 0.43)	53.25	0.44684		(0.32, 0.48)	Moderate
Hypertension	Not early	17 (10)	OR	1 682 689	1.25 (1.17, 1.34)	1.34 (1.31, 1.36)	1.25 (1.17, 1.34)	1.41 (1.36, 1.47)	1.34 (1.27, 1.41)	84.69	0.04860	3.29 (2.63, 3.94)	(0.99, 1.58)	Moderate
Systolic blood pressure	Not early	8 (4)	RMD	15 064	0.8 (−1.52, 3.12)	1.27 (0.59, 1.96)	0.80 (−1.52, 3.12)	2.50 (1.58, 3.42)	1.27 (−1.05, 3.60)	87.56	0.5613		(−6.63, 9.17)	Moderate
Diastolic blood pressure	Not early	8 (4)	RMD	15 064	0.14 (−1.17, 1.46)	0.68 (0.24, 1.12)	0.14 (−1.17, 1.46)	1.40 (0.79, 2.01)	0.70 (−0.69, 2.10)	84.272	0.3030		(−3.73, 5.13)	Moderate
Asthma	Not early	7 (7)	OR	22 859	1.37 (1.15, 1.64)	1.31 (1.19, 1.44)	1.37 (1.15, 1.64)	1.25 (1.10, 1.43)	1.31 (1.09, 1.57)	54.88	0.38546	3.01 (0.89, 5.39)	(1.07, 1.32)	Low
Endometriosis	Not early	16 (7)	RR	885 390	1.34 (1.16, 1.54)	1.22 (1.16, 1.29)	1.34 (1.16, 1.54)	1.18 (1.06, 1.31)	1.22 (1.09, 1.37)	71.95	0.32131	2.15 (0.89, 3.57)	(3.55, 10.51)	Moderate
Metabolic Syndrome	Late menarche	11 (3)	RR	37 543	1.62 (1.40, 1.88)	1.56 (1.43, 1.71)	1.62 (1.40, 1.88)	1.48 (1.03, 2.12)	1.56 (1.33, 1.83)	57.14	0.16761	5.30 (3.20, 7.66)	(1.04, 2.53)	High
Death from all causes	Median	5 (5)	HR	152 747	1.18 (1.08, 1.29)	1.11 (1.07, 1.15)	1.18 (1.08, 1.29)	1.09 (1.05, 1.13)	1.11 (1.03, 1.19)	57.53	0.04461	1.09 (0.30, 1.87)	(0.90, 1.13)	High
Death from ischemic heart disease	Median	5 (5)	HR	97 963	1.22 (0.95, 1.56)	1.19 (1.04, 1.37)	1.18 (1.02, 1.36)	0.82 (0.47, 1.43)	1.19 (0.87, 1.63)	59.28	0.71765	1.87 (−1.32, 5.93)	(0.56, 2.64)	Low
Death from stroke	Median	5 (5)	HR	91 051	1.05 (0.94, 1.19)	1.05 (0.94, 1.19)	1.05 (0.94, 1.19)	0.99 (0.83, 1.18)	1.05 (0.89, 1.25)	0	0.37610	0.50 (−1.11, 2.44)	(0.86, 1.29)	Moderate
Death from cardiovascular disease	Median	4 (4)	HR	362 106	1.05 (0.90, 1.21)	1.03 (1.93, 1.15)	1.04 (0.90, 1.21)	0.94 (0.74, 1.2)	1.03 (0.82, 1.30)	43.10	0.35284	0.30 (−1.83, 2.91)	(0.40, 2.69)	Moderate
Ovarian cancer	Late menarche	25 (5)	RR	1 022 451	1.18^b(1.03, 1.33)	1.17 (1.08, 1.27)	1.17 (1.03, 1.33)	1.14 (0.88, 1.47)	1.17 (1.04, 1.31)	42.23	0.86570	1.67 (0.40, 3.01)	(0.79, 1.76)	Moderate
Endometrial cancer	Oldest	8 (8)	RR	874 188	1.47^b(1.24, 1.72)	1.40 (1.25, 1.57)	1.47 (1.24, 1.74)	1.39 (1.11, 1.72)	1.40 (1.17, 1.68)	41.90	0.13885	3.85 (1.67, 6.37)	(0.97, 2.24)	High
Depression	Not early	3 (3)	RR	4945	1.33 (1.02, 1.73)	1.26 (1.07, 1.47)	1.33 (1.02, 1.73)	1.15 (0.94, 1.4)	1.26 (0.75, 2.11)	54.55	0.31109	2.53 (−2.56, 10.00)	(0.08, 21.52)	Very low
Breast cancer^a	Not early	117 (35)	RR	103 574		1.12 (1.09, 1.15)	1.19 (1.06, 1.33)							Very high

Outcome

Exposure (early) vs. non exposure

Included studies (cohorts)

Metric

Total sample

Reported summary ES (95% CI)—random-effect model

Re-analyzed summary ES (95% CI) DL method

Re-analyzed summary ES (95% CI) HS method Random-effect model

Heterogeneity I² (%)

Egger’s P-value

PAF (95% CI)

95% prediction interval

GRADE (certainty of evidence)

Fixed-effect model

Random-effect model

Largest study

T2DM/IGT

Not early

23 (23)

1 185 444

1.39 (1.25–1.55)

1.32 (1.28, 1.35)

1.39 (1.26, 1.53)

0.98 (0.86, 1.12)

1.31 (1.20, 1.44)

87.28

0.21226

3.01 (1.96, 4.22)

(0.90, 2.14)

High

GDM

Not early

5 (5)

48 535

1.31 (1.05, 1.56)

1.36 (1.20, 1.53)

1.36 (1.15, 1.60)

1.34 (1.14, 1.58)

1.36 (1.10, 1.67)

33.23

0.85991

3.48 (0.99, 6.28)

(0.93, 1.99)

Moderate

HOMA-IR

Average

5 (1)

WMD

7925

0.40 (0.28, 0.52)

0.39 (0.28, 0.51)

0.42 (0.21, 0.69)

0.41 (0.29, 0.58)

0.75369

(0.18, 0.41)

Moderate

Fasting insulin (uIU/mL)

Average

9 (4)

WMD

17 020

1.28 (1.13, 1.43)

1.30 (1.24, 1.36)

1.28 (1.23, 1.44)

2.00 (0.91, 3.09)

1.29 (1.21, 1.38)

8.12

0.67836

(0.99, 1.65)

Moderate

Obesity

Not early

5 (5)

54 006

2.00 (1.79, 2.24)

1.97 (1.83, 2.12)

2.00 (1.79, 2.24)

1.93 (1.69, 2.22)

1.97 (1.73, 2.23)

35.02

0.83040

8.84 (6.80, 10.95)

(1.50, 2.67)

Moderate

Adult BMI (≥40 years)

Not early

6 (6)

SMD

121 943

0.29 (0.28, 0.31)

0.30 (0.28, 0.31)

0.32 (0.28, 0.35)

0.29 (0.27, 0.30)

0.30 (0.28, 0.32)

36.32

0.08680

(0.28, 0.36)

Moderate

Adult BMI (<40 years)

Not early

4 (4)

SMD

124 728

0.39 (0.37, 0.40)

0.40 (0.37, 0.43)

0.39 (0.37, 0.40)

0.39 (0.36, 0.43)

53.25

0.44684

(0.32, 0.48)

Moderate

Hypertension

Not early

17 (10)

1 682 689

1.25 (1.17, 1.34)

1.34 (1.31, 1.36)

1.25 (1.17, 1.34)

1.41 (1.36, 1.47)

1.34 (1.27, 1.41)

84.69

0.04860

3.29 (2.63, 3.94)

(0.99, 1.58)

Moderate

Systolic blood pressure

Not early

8 (4)

RMD

15 064

0.8 (−1.52, 3.12)

1.27 (0.59, 1.96)

0.80 (−1.52, 3.12)

2.50 (1.58, 3.42)

1.27 (−1.05, 3.60)

87.56

0.5613

(−6.63, 9.17)

Moderate

Diastolic blood pressure

Not early

8 (4)

RMD

15 064

0.14 (−1.17, 1.46)

0.68 (0.24, 1.12)

0.14 (−1.17, 1.46)

1.40 (0.79, 2.01)

0.70 (−0.69, 2.10)

84.272

0.3030

(−3.73, 5.13)

Moderate

Asthma

Not early

7 (7)

22 859

1.37 (1.15, 1.64)

1.31 (1.19, 1.44)

1.37 (1.15, 1.64)

1.25 (1.10, 1.43)

1.31 (1.09, 1.57)

54.88

0.38546

3.01 (0.89, 5.39)

(1.07, 1.32)

Low

Endometriosis

Not early

16 (7)

885 390

1.34 (1.16, 1.54)

1.22 (1.16, 1.29)

1.34 (1.16, 1.54)

1.18 (1.06, 1.31)

1.22 (1.09, 1.37)

71.95

0.32131

2.15 (0.89, 3.57)

(3.55, 10.51)

Moderate

Metabolic Syndrome

Late menarche

11 (3)

37 543

1.62 (1.40, 1.88)

1.56 (1.43, 1.71)

1.62 (1.40, 1.88)

1.48 (1.03, 2.12)

1.56 (1.33, 1.83)

57.14

0.16761

5.30 (3.20, 7.66)

(1.04, 2.53)

High

Death from all causes

Median

5 (5)

152 747

1.18 (1.08, 1.29)

1.11 (1.07, 1.15)

1.18 (1.08, 1.29)

1.09 (1.05, 1.13)

1.11 (1.03, 1.19)

57.53

0.04461

1.09 (0.30, 1.87)

(0.90, 1.13)

High

Death from ischemic heart disease

Median

5 (5)

97 963

1.22 (0.95, 1.56)

1.19 (1.04, 1.37)

1.18 (1.02, 1.36)

0.82 (0.47, 1.43)

1.19 (0.87, 1.63)

59.28

0.71765

1.87 (−1.32, 5.93)

(0.56, 2.64)

Low

Death from stroke

Median

5 (5)

91 051

1.05 (0.94, 1.19)

0.99 (0.83, 1.18)

1.05 (0.89, 1.25)

0.37610

0.50 (−1.11, 2.44)

(0.86, 1.29)

Moderate

Death from cardiovascular disease

Median

4 (4)

362 106

1.05 (0.90, 1.21)

1.03 (1.93, 1.15)

1.04 (0.90, 1.21)

0.94 (0.74, 1.2)

1.03 (0.82, 1.30)

43.10

0.35284

0.30 (−1.83, 2.91)

(0.40, 2.69)

Moderate

Ovarian cancer

Late menarche

25 (5)

1 022 451

1.18^b(1.03, 1.33)

1.17 (1.08, 1.27)

1.17 (1.03, 1.33)

1.14 (0.88, 1.47)

1.17 (1.04, 1.31)

42.23

0.86570

1.67 (0.40, 3.01)

(0.79, 1.76)

Moderate

Endometrial cancer

Oldest

8 (8)

874 188

1.47^b(1.24, 1.72)

1.40 (1.25, 1.57)

1.47 (1.24, 1.74)

1.39 (1.11, 1.72)

1.40 (1.17, 1.68)

41.90

0.13885

3.85 (1.67, 6.37)

(0.97, 2.24)

High

Depression

Not early

3 (3)

4945

1.33 (1.02, 1.73)

1.26 (1.07, 1.47)

1.33 (1.02, 1.73)

1.15 (0.94, 1.4)

1.26 (0.75, 2.11)

54.55

0.31109

2.53 (−2.56, 10.00)

(0.08, 21.52)

Very low

Breast cancer^a

Not early

117 (35)

103 574

1.12 (1.09, 1.15)

1.19 (1.06, 1.33)

Very high

Outcome	Exposure (early) vs. non exposure	Included studies (cohorts)	Metric	Total sample	Reported summary ES (95% CI)—random-effect model	Re-analyzed summary ES (95% CI) DL method	Re-analyzed summary ES (95% CI) HS method Random-effect model	Heterogeneity I² (%)	Egger’s P-value	PAF (95% CI)	95% prediction interval	GRADE (certainty of evidence)
T2DM/IGT	Not early	23 (23)	OR	1 185 444	1.39 (1.25–1.55)	1.32 (1.28, 1.35)	1.39 (1.26, 1.53)	0.98 (0.86, 1.12)	1.31 (1.20, 1.44)	87.28	0.21226	3.01 (1.96, 4.22)	(0.90, 2.14)	High
GDM	Not early	5 (5)	RR	48 535	1.31 (1.05, 1.56)	1.36 (1.20, 1.53)	1.36 (1.15, 1.60)	1.34 (1.14, 1.58)	1.36 (1.10, 1.67)	33.23	0.85991	3.48 (0.99, 6.28)	(0.93, 1.99)	Moderate
HOMA-IR	Average	5 (1)	WMD	7925	0.40 (0.28, 0.52)	0.39 (0.28, 0.51)	0.39 (0.28, 0.51)	0.42 (0.21, 0.69)	0.41 (0.29, 0.58)	0	0.75369		(0.18, 0.41)	Moderate
Fasting insulin (uIU/mL)	Average	9 (4)	WMD	17 020	1.28 (1.13, 1.43)	1.30 (1.24, 1.36)	1.28 (1.23, 1.44)	2.00 (0.91, 3.09)	1.29 (1.21, 1.38)	8.12	0.67836		(0.99, 1.65)	Moderate
Obesity	Not early	5 (5)	OR	54 006	2.00 (1.79, 2.24)	1.97 (1.83, 2.12)	2.00 (1.79, 2.24)	1.93 (1.69, 2.22)	1.97 (1.73, 2.23)	35.02	0.83040	8.84 (6.80, 10.95)	(1.50, 2.67)	Moderate
Adult BMI (≥40 years)	Not early	6 (6)	SMD	121 943	0.29 (0.28, 0.31)	0.30 (0.28, 0.31)	0.32 (0.28, 0.35)	0.29 (0.27, 0.30)	0.30 (0.28, 0.32)	36.32	0.08680		(0.28, 0.36)	Moderate
Adult BMI (<40 years)	Not early	4 (4)	SMD	124 728	0.39 (0.37, 0.40)	0.39 (0.37, 0.40)	0.40 (0.37, 0.43)	0.39 (0.37, 0.40)	0.39 (0.36, 0.43)	53.25	0.44684		(0.32, 0.48)	Moderate
Hypertension	Not early	17 (10)	OR	1 682 689	1.25 (1.17, 1.34)	1.34 (1.31, 1.36)	1.25 (1.17, 1.34)	1.41 (1.36, 1.47)	1.34 (1.27, 1.41)	84.69	0.04860	3.29 (2.63, 3.94)	(0.99, 1.58)	Moderate
Systolic blood pressure	Not early	8 (4)	RMD	15 064	0.8 (−1.52, 3.12)	1.27 (0.59, 1.96)	0.80 (−1.52, 3.12)	2.50 (1.58, 3.42)	1.27 (−1.05, 3.60)	87.56	0.5613		(−6.63, 9.17)	Moderate
Diastolic blood pressure	Not early	8 (4)	RMD	15 064	0.14 (−1.17, 1.46)	0.68 (0.24, 1.12)	0.14 (−1.17, 1.46)	1.40 (0.79, 2.01)	0.70 (−0.69, 2.10)	84.272	0.3030		(−3.73, 5.13)	Moderate
Asthma	Not early	7 (7)	OR	22 859	1.37 (1.15, 1.64)	1.31 (1.19, 1.44)	1.37 (1.15, 1.64)	1.25 (1.10, 1.43)	1.31 (1.09, 1.57)	54.88	0.38546	3.01 (0.89, 5.39)	(1.07, 1.32)	Low
Endometriosis	Not early	16 (7)	RR	885 390	1.34 (1.16, 1.54)	1.22 (1.16, 1.29)	1.34 (1.16, 1.54)	1.18 (1.06, 1.31)	1.22 (1.09, 1.37)	71.95	0.32131	2.15 (0.89, 3.57)	(3.55, 10.51)	Moderate
Metabolic Syndrome	Late menarche	11 (3)	RR	37 543	1.62 (1.40, 1.88)	1.56 (1.43, 1.71)	1.62 (1.40, 1.88)	1.48 (1.03, 2.12)	1.56 (1.33, 1.83)	57.14	0.16761	5.30 (3.20, 7.66)	(1.04, 2.53)	High
Death from all causes	Median	5 (5)	HR	152 747	1.18 (1.08, 1.29)	1.11 (1.07, 1.15)	1.18 (1.08, 1.29)	1.09 (1.05, 1.13)	1.11 (1.03, 1.19)	57.53	0.04461	1.09 (0.30, 1.87)	(0.90, 1.13)	High
Death from ischemic heart disease	Median	5 (5)	HR	97 963	1.22 (0.95, 1.56)	1.19 (1.04, 1.37)	1.18 (1.02, 1.36)	0.82 (0.47, 1.43)	1.19 (0.87, 1.63)	59.28	0.71765	1.87 (−1.32, 5.93)	(0.56, 2.64)	Low
Death from stroke	Median	5 (5)	HR	91 051	1.05 (0.94, 1.19)	1.05 (0.94, 1.19)	1.05 (0.94, 1.19)	0.99 (0.83, 1.18)	1.05 (0.89, 1.25)	0	0.37610	0.50 (−1.11, 2.44)	(0.86, 1.29)	Moderate
Death from cardiovascular disease	Median	4 (4)	HR	362 106	1.05 (0.90, 1.21)	1.03 (1.93, 1.15)	1.04 (0.90, 1.21)	0.94 (0.74, 1.2)	1.03 (0.82, 1.30)	43.10	0.35284	0.30 (−1.83, 2.91)	(0.40, 2.69)	Moderate
Ovarian cancer	Late menarche	25 (5)	RR	1 022 451	1.18^b(1.03, 1.33)	1.17 (1.08, 1.27)	1.17 (1.03, 1.33)	1.14 (0.88, 1.47)	1.17 (1.04, 1.31)	42.23	0.86570	1.67 (0.40, 3.01)	(0.79, 1.76)	Moderate
Endometrial cancer	Oldest	8 (8)	RR	874 188	1.47^b(1.24, 1.72)	1.40 (1.25, 1.57)	1.47 (1.24, 1.74)	1.39 (1.11, 1.72)	1.40 (1.17, 1.68)	41.90	0.13885	3.85 (1.67, 6.37)	(0.97, 2.24)	High
Depression	Not early	3 (3)	RR	4945	1.33 (1.02, 1.73)	1.26 (1.07, 1.47)	1.33 (1.02, 1.73)	1.15 (0.94, 1.4)	1.26 (0.75, 2.11)	54.55	0.31109	2.53 (−2.56, 10.00)	(0.08, 21.52)	Very low
Breast cancer^a	Not early	117 (35)	RR	103 574		1.12 (1.09, 1.15)	1.19 (1.06, 1.33)							Very high

Outcome

Exposure (early) vs. non exposure

Included studies (cohorts)

Metric

Total sample

Reported summary ES (95% CI)—random-effect model

Re-analyzed summary ES (95% CI) DL method

Re-analyzed summary ES (95% CI) HS method Random-effect model

Heterogeneity I² (%)

Egger’s P-value

PAF (95% CI)

95% prediction interval

GRADE (certainty of evidence)

Fixed-effect model

Random-effect model

Largest study

T2DM/IGT

Not early

23 (23)

1 185 444

1.39 (1.25–1.55)

1.32 (1.28, 1.35)

1.39 (1.26, 1.53)

0.98 (0.86, 1.12)

1.31 (1.20, 1.44)

87.28

0.21226

3.01 (1.96, 4.22)

(0.90, 2.14)

High

GDM

Not early

5 (5)

48 535

1.31 (1.05, 1.56)

1.36 (1.20, 1.53)

1.36 (1.15, 1.60)

1.34 (1.14, 1.58)

1.36 (1.10, 1.67)

33.23

0.85991

3.48 (0.99, 6.28)

(0.93, 1.99)

Moderate

HOMA-IR

Average

5 (1)

WMD

7925

0.40 (0.28, 0.52)

0.39 (0.28, 0.51)

0.42 (0.21, 0.69)

0.41 (0.29, 0.58)

0.75369

(0.18, 0.41)

Moderate

Fasting insulin (uIU/mL)

Average

9 (4)

WMD

17 020

1.28 (1.13, 1.43)

1.30 (1.24, 1.36)

1.28 (1.23, 1.44)

2.00 (0.91, 3.09)

1.29 (1.21, 1.38)

8.12

0.67836

(0.99, 1.65)

Moderate

Obesity

Not early

5 (5)

54 006

2.00 (1.79, 2.24)

1.97 (1.83, 2.12)

2.00 (1.79, 2.24)

1.93 (1.69, 2.22)

1.97 (1.73, 2.23)

35.02

0.83040

8.84 (6.80, 10.95)

(1.50, 2.67)

Moderate

Adult BMI (≥40 years)

Not early

6 (6)

SMD

121 943

0.29 (0.28, 0.31)

0.30 (0.28, 0.31)

0.32 (0.28, 0.35)

0.29 (0.27, 0.30)

0.30 (0.28, 0.32)

36.32

0.08680

(0.28, 0.36)

Moderate

Adult BMI (<40 years)

Not early

4 (4)

SMD

124 728

0.39 (0.37, 0.40)

0.40 (0.37, 0.43)

0.39 (0.37, 0.40)

0.39 (0.36, 0.43)

53.25

0.44684

(0.32, 0.48)

Moderate

Hypertension

Not early

17 (10)

1 682 689

1.25 (1.17, 1.34)

1.34 (1.31, 1.36)

1.25 (1.17, 1.34)

1.41 (1.36, 1.47)

1.34 (1.27, 1.41)

84.69

0.04860

3.29 (2.63, 3.94)

(0.99, 1.58)

Moderate

Systolic blood pressure

Not early

8 (4)

RMD

15 064

0.8 (−1.52, 3.12)

1.27 (0.59, 1.96)

0.80 (−1.52, 3.12)

2.50 (1.58, 3.42)

1.27 (−1.05, 3.60)

87.56

0.5613

(−6.63, 9.17)

Moderate

Diastolic blood pressure

Not early

8 (4)

RMD

15 064

0.14 (−1.17, 1.46)

0.68 (0.24, 1.12)

0.14 (−1.17, 1.46)

1.40 (0.79, 2.01)

0.70 (−0.69, 2.10)

84.272

0.3030

(−3.73, 5.13)

Moderate

Asthma

Not early

7 (7)

22 859

1.37 (1.15, 1.64)

1.31 (1.19, 1.44)

1.37 (1.15, 1.64)

1.25 (1.10, 1.43)

1.31 (1.09, 1.57)

54.88

0.38546

3.01 (0.89, 5.39)

(1.07, 1.32)

Low

Endometriosis

Not early

16 (7)

885 390

1.34 (1.16, 1.54)

1.22 (1.16, 1.29)

1.34 (1.16, 1.54)

1.18 (1.06, 1.31)

1.22 (1.09, 1.37)

71.95

0.32131

2.15 (0.89, 3.57)

(3.55, 10.51)

Moderate

Metabolic Syndrome

Late menarche

11 (3)

37 543

1.62 (1.40, 1.88)

1.56 (1.43, 1.71)

1.62 (1.40, 1.88)

1.48 (1.03, 2.12)

1.56 (1.33, 1.83)

57.14

0.16761

5.30 (3.20, 7.66)

(1.04, 2.53)

High

Death from all causes

Median

5 (5)

152 747

1.18 (1.08, 1.29)

1.11 (1.07, 1.15)

1.18 (1.08, 1.29)

1.09 (1.05, 1.13)

1.11 (1.03, 1.19)

57.53

0.04461

1.09 (0.30, 1.87)

(0.90, 1.13)

High

Death from ischemic heart disease

Median

5 (5)

97 963

1.22 (0.95, 1.56)

1.19 (1.04, 1.37)

1.18 (1.02, 1.36)

0.82 (0.47, 1.43)

1.19 (0.87, 1.63)

59.28

0.71765

1.87 (−1.32, 5.93)

(0.56, 2.64)

Low

Death from stroke

Median

5 (5)

91 051

1.05 (0.94, 1.19)

0.99 (0.83, 1.18)

1.05 (0.89, 1.25)

0.37610

0.50 (−1.11, 2.44)

(0.86, 1.29)

Moderate

Death from cardiovascular disease

Median

4 (4)

362 106

1.05 (0.90, 1.21)

1.03 (1.93, 1.15)

1.04 (0.90, 1.21)

0.94 (0.74, 1.2)

1.03 (0.82, 1.30)

43.10

0.35284

0.30 (−1.83, 2.91)

(0.40, 2.69)

Moderate

Ovarian cancer

Late menarche

25 (5)

1 022 451

1.18^b(1.03, 1.33)

1.17 (1.08, 1.27)

1.17 (1.03, 1.33)

1.14 (0.88, 1.47)

1.17 (1.04, 1.31)

42.23

0.86570

1.67 (0.40, 3.01)

(0.79, 1.76)

Moderate

Endometrial cancer

Oldest

8 (8)

874 188

1.47^b(1.24, 1.72)

1.40 (1.25, 1.57)

1.47 (1.24, 1.74)

1.39 (1.11, 1.72)

1.40 (1.17, 1.68)

41.90

0.13885

3.85 (1.67, 6.37)

(0.97, 2.24)

High

Depression

Not early

3 (3)

4945

1.33 (1.02, 1.73)

1.26 (1.07, 1.47)

1.33 (1.02, 1.73)

1.15 (0.94, 1.4)

1.26 (0.75, 2.11)

54.55

0.31109

2.53 (−2.56, 10.00)

(0.08, 21.52)

Very low

Breast cancer^a

Not early

117 (35)

103 574

1.12 (1.09, 1.15)

1.19 (1.06, 1.33)

Very high

Table 2.

Open in new tab

Re-analysis of effect size using DL method and HS method, heterogeneity, Egger’s P values, population attributable factor, 95% prediction interval and GRADE

Outcome	Exposure (early) vs. non exposure	Included studies (cohorts)	Metric	Total sample	Reported summary ES (95% CI)—random-effect model	Re-analyzed summary ES (95% CI) DL method			Re-analyzed summary ES (95% CI) HS method Random-effect model	Heterogeneity I² (%)	Egger’s P-value	PAF (95% CI)	95% prediction interval	GRADE (certainty of evidence)
Outcome	Exposure (early) vs. non exposure	Included studies (cohorts)	Metric	Total sample	Reported summary ES (95% CI)—random-effect model	Fixed-effect model	Random-effect model	Largest study		Heterogeneity I² (%)	Egger’s P-value	PAF (95% CI)	95% prediction interval	GRADE (certainty of evidence)
T2DM/IGT	Not early	23 (23)	OR	1 185 444	1.39 (1.25–1.55)	1.32 (1.28, 1.35)	1.39 (1.26, 1.53)	0.98 (0.86, 1.12)	1.31 (1.20, 1.44)	87.28	0.21226	3.01 (1.96, 4.22)	(0.90, 2.14)	High
GDM	Not early	5 (5)	RR	48 535	1.31 (1.05, 1.56)	1.36 (1.20, 1.53)	1.36 (1.15, 1.60)	1.34 (1.14, 1.58)	1.36 (1.10, 1.67)	33.23	0.85991	3.48 (0.99, 6.28)	(0.93, 1.99)	Moderate
HOMA-IR	Average	5 (1)	WMD	7925	0.40 (0.28, 0.52)	0.39 (0.28, 0.51)	0.39 (0.28, 0.51)	0.42 (0.21, 0.69)	0.41 (0.29, 0.58)	0	0.75369		(0.18, 0.41)	Moderate
Fasting insulin (uIU/mL)	Average	9 (4)	WMD	17 020	1.28 (1.13, 1.43)	1.30 (1.24, 1.36)	1.28 (1.23, 1.44)	2.00 (0.91, 3.09)	1.29 (1.21, 1.38)	8.12	0.67836		(0.99, 1.65)	Moderate
Obesity	Not early	5 (5)	OR	54 006	2.00 (1.79, 2.24)	1.97 (1.83, 2.12)	2.00 (1.79, 2.24)	1.93 (1.69, 2.22)	1.97 (1.73, 2.23)	35.02	0.83040	8.84 (6.80, 10.95)	(1.50, 2.67)	Moderate
Adult BMI (≥40 years)	Not early	6 (6)	SMD	121 943	0.29 (0.28, 0.31)	0.30 (0.28, 0.31)	0.32 (0.28, 0.35)	0.29 (0.27, 0.30)	0.30 (0.28, 0.32)	36.32	0.08680		(0.28, 0.36)	Moderate
Adult BMI (<40 years)	Not early	4 (4)	SMD	124 728	0.39 (0.37, 0.40)	0.39 (0.37, 0.40)	0.40 (0.37, 0.43)	0.39 (0.37, 0.40)	0.39 (0.36, 0.43)	53.25	0.44684		(0.32, 0.48)	Moderate
Hypertension	Not early	17 (10)	OR	1 682 689	1.25 (1.17, 1.34)	1.34 (1.31, 1.36)	1.25 (1.17, 1.34)	1.41 (1.36, 1.47)	1.34 (1.27, 1.41)	84.69	0.04860	3.29 (2.63, 3.94)	(0.99, 1.58)	Moderate
Systolic blood pressure	Not early	8 (4)	RMD	15 064	0.8 (−1.52, 3.12)	1.27 (0.59, 1.96)	0.80 (−1.52, 3.12)	2.50 (1.58, 3.42)	1.27 (−1.05, 3.60)	87.56	0.5613		(−6.63, 9.17)	Moderate
Diastolic blood pressure	Not early	8 (4)	RMD	15 064	0.14 (−1.17, 1.46)	0.68 (0.24, 1.12)	0.14 (−1.17, 1.46)	1.40 (0.79, 2.01)	0.70 (−0.69, 2.10)	84.272	0.3030		(−3.73, 5.13)	Moderate
Asthma	Not early	7 (7)	OR	22 859	1.37 (1.15, 1.64)	1.31 (1.19, 1.44)	1.37 (1.15, 1.64)	1.25 (1.10, 1.43)	1.31 (1.09, 1.57)	54.88	0.38546	3.01 (0.89, 5.39)	(1.07, 1.32)	Low
Endometriosis	Not early	16 (7)	RR	885 390	1.34 (1.16, 1.54)	1.22 (1.16, 1.29)	1.34 (1.16, 1.54)	1.18 (1.06, 1.31)	1.22 (1.09, 1.37)	71.95	0.32131	2.15 (0.89, 3.57)	(3.55, 10.51)	Moderate
Metabolic Syndrome	Late menarche	11 (3)	RR	37 543	1.62 (1.40, 1.88)	1.56 (1.43, 1.71)	1.62 (1.40, 1.88)	1.48 (1.03, 2.12)	1.56 (1.33, 1.83)	57.14	0.16761	5.30 (3.20, 7.66)	(1.04, 2.53)	High
Death from all causes	Median	5 (5)	HR	152 747	1.18 (1.08, 1.29)	1.11 (1.07, 1.15)	1.18 (1.08, 1.29)	1.09 (1.05, 1.13)	1.11 (1.03, 1.19)	57.53	0.04461	1.09 (0.30, 1.87)	(0.90, 1.13)	High
Death from ischemic heart disease	Median	5 (5)	HR	97 963	1.22 (0.95, 1.56)	1.19 (1.04, 1.37)	1.18 (1.02, 1.36)	0.82 (0.47, 1.43)	1.19 (0.87, 1.63)	59.28	0.71765	1.87 (−1.32, 5.93)	(0.56, 2.64)	Low
Death from stroke	Median	5 (5)	HR	91 051	1.05 (0.94, 1.19)	1.05 (0.94, 1.19)	1.05 (0.94, 1.19)	0.99 (0.83, 1.18)	1.05 (0.89, 1.25)	0	0.37610	0.50 (−1.11, 2.44)	(0.86, 1.29)	Moderate
Death from cardiovascular disease	Median	4 (4)	HR	362 106	1.05 (0.90, 1.21)	1.03 (1.93, 1.15)	1.04 (0.90, 1.21)	0.94 (0.74, 1.2)	1.03 (0.82, 1.30)	43.10	0.35284	0.30 (−1.83, 2.91)	(0.40, 2.69)	Moderate
Ovarian cancer	Late menarche	25 (5)	RR	1 022 451	1.18^b(1.03, 1.33)	1.17 (1.08, 1.27)	1.17 (1.03, 1.33)	1.14 (0.88, 1.47)	1.17 (1.04, 1.31)	42.23	0.86570	1.67 (0.40, 3.01)	(0.79, 1.76)	Moderate
Endometrial cancer	Oldest	8 (8)	RR	874 188	1.47^b(1.24, 1.72)	1.40 (1.25, 1.57)	1.47 (1.24, 1.74)	1.39 (1.11, 1.72)	1.40 (1.17, 1.68)	41.90	0.13885	3.85 (1.67, 6.37)	(0.97, 2.24)	High
Depression	Not early	3 (3)	RR	4945	1.33 (1.02, 1.73)	1.26 (1.07, 1.47)	1.33 (1.02, 1.73)	1.15 (0.94, 1.4)	1.26 (0.75, 2.11)	54.55	0.31109	2.53 (−2.56, 10.00)	(0.08, 21.52)	Very low
Breast cancer^a	Not early	117 (35)	RR	103 574		1.12 (1.09, 1.15)	1.19 (1.06, 1.33)							Very high

Outcome	Exposure (early) vs. non exposure	Included studies (cohorts)	Metric	Total sample	Reported summary ES (95% CI)—random-effect model	Re-analyzed summary ES (95% CI) DL method			Re-analyzed summary ES (95% CI) HS method Random-effect model	Heterogeneity I² (%)	Egger’s P-value	PAF (95% CI)	95% prediction interval	GRADE (certainty of evidence)
Outcome	Exposure (early) vs. non exposure	Included studies (cohorts)	Metric	Total sample	Reported summary ES (95% CI)—random-effect model	Fixed-effect model	Random-effect model	Largest study		Heterogeneity I² (%)	Egger’s P-value	PAF (95% CI)	95% prediction interval	GRADE (certainty of evidence)
T2DM/IGT	Not early	23 (23)	OR	1 185 444	1.39 (1.25–1.55)	1.32 (1.28, 1.35)	1.39 (1.26, 1.53)	0.98 (0.86, 1.12)	1.31 (1.20, 1.44)	87.28	0.21226	3.01 (1.96, 4.22)	(0.90, 2.14)	High
GDM	Not early	5 (5)	RR	48 535	1.31 (1.05, 1.56)	1.36 (1.20, 1.53)	1.36 (1.15, 1.60)	1.34 (1.14, 1.58)	1.36 (1.10, 1.67)	33.23	0.85991	3.48 (0.99, 6.28)	(0.93, 1.99)	Moderate
HOMA-IR	Average	5 (1)	WMD	7925	0.40 (0.28, 0.52)	0.39 (0.28, 0.51)	0.39 (0.28, 0.51)	0.42 (0.21, 0.69)	0.41 (0.29, 0.58)	0	0.75369		(0.18, 0.41)	Moderate
Fasting insulin (uIU/mL)	Average	9 (4)	WMD	17 020	1.28 (1.13, 1.43)	1.30 (1.24, 1.36)	1.28 (1.23, 1.44)	2.00 (0.91, 3.09)	1.29 (1.21, 1.38)	8.12	0.67836		(0.99, 1.65)	Moderate
Obesity	Not early	5 (5)	OR	54 006	2.00 (1.79, 2.24)	1.97 (1.83, 2.12)	2.00 (1.79, 2.24)	1.93 (1.69, 2.22)	1.97 (1.73, 2.23)	35.02	0.83040	8.84 (6.80, 10.95)	(1.50, 2.67)	Moderate
Adult BMI (≥40 years)	Not early	6 (6)	SMD	121 943	0.29 (0.28, 0.31)	0.30 (0.28, 0.31)	0.32 (0.28, 0.35)	0.29 (0.27, 0.30)	0.30 (0.28, 0.32)	36.32	0.08680		(0.28, 0.36)	Moderate
Adult BMI (<40 years)	Not early	4 (4)	SMD	124 728	0.39 (0.37, 0.40)	0.39 (0.37, 0.40)	0.40 (0.37, 0.43)	0.39 (0.37, 0.40)	0.39 (0.36, 0.43)	53.25	0.44684		(0.32, 0.48)	Moderate
Hypertension	Not early	17 (10)	OR	1 682 689	1.25 (1.17, 1.34)	1.34 (1.31, 1.36)	1.25 (1.17, 1.34)	1.41 (1.36, 1.47)	1.34 (1.27, 1.41)	84.69	0.04860	3.29 (2.63, 3.94)	(0.99, 1.58)	Moderate
Systolic blood pressure	Not early	8 (4)	RMD	15 064	0.8 (−1.52, 3.12)	1.27 (0.59, 1.96)	0.80 (−1.52, 3.12)	2.50 (1.58, 3.42)	1.27 (−1.05, 3.60)	87.56	0.5613		(−6.63, 9.17)	Moderate
Diastolic blood pressure	Not early	8 (4)	RMD	15 064	0.14 (−1.17, 1.46)	0.68 (0.24, 1.12)	0.14 (−1.17, 1.46)	1.40 (0.79, 2.01)	0.70 (−0.69, 2.10)	84.272	0.3030		(−3.73, 5.13)	Moderate
Asthma	Not early	7 (7)	OR	22 859	1.37 (1.15, 1.64)	1.31 (1.19, 1.44)	1.37 (1.15, 1.64)	1.25 (1.10, 1.43)	1.31 (1.09, 1.57)	54.88	0.38546	3.01 (0.89, 5.39)	(1.07, 1.32)	Low
Endometriosis	Not early	16 (7)	RR	885 390	1.34 (1.16, 1.54)	1.22 (1.16, 1.29)	1.34 (1.16, 1.54)	1.18 (1.06, 1.31)	1.22 (1.09, 1.37)	71.95	0.32131	2.15 (0.89, 3.57)	(3.55, 10.51)	Moderate
Metabolic Syndrome	Late menarche	11 (3)	RR	37 543	1.62 (1.40, 1.88)	1.56 (1.43, 1.71)	1.62 (1.40, 1.88)	1.48 (1.03, 2.12)	1.56 (1.33, 1.83)	57.14	0.16761	5.30 (3.20, 7.66)	(1.04, 2.53)	High
Death from all causes	Median	5 (5)	HR	152 747	1.18 (1.08, 1.29)	1.11 (1.07, 1.15)	1.18 (1.08, 1.29)	1.09 (1.05, 1.13)	1.11 (1.03, 1.19)	57.53	0.04461	1.09 (0.30, 1.87)	(0.90, 1.13)	High
Death from ischemic heart disease	Median	5 (5)	HR	97 963	1.22 (0.95, 1.56)	1.19 (1.04, 1.37)	1.18 (1.02, 1.36)	0.82 (0.47, 1.43)	1.19 (0.87, 1.63)	59.28	0.71765	1.87 (−1.32, 5.93)	(0.56, 2.64)	Low
Death from stroke	Median	5 (5)	HR	91 051	1.05 (0.94, 1.19)	1.05 (0.94, 1.19)	1.05 (0.94, 1.19)	0.99 (0.83, 1.18)	1.05 (0.89, 1.25)	0	0.37610	0.50 (−1.11, 2.44)	(0.86, 1.29)	Moderate
Death from cardiovascular disease	Median	4 (4)	HR	362 106	1.05 (0.90, 1.21)	1.03 (1.93, 1.15)	1.04 (0.90, 1.21)	0.94 (0.74, 1.2)	1.03 (0.82, 1.30)	43.10	0.35284	0.30 (−1.83, 2.91)	(0.40, 2.69)	Moderate
Ovarian cancer	Late menarche	25 (5)	RR	1 022 451	1.18^b(1.03, 1.33)	1.17 (1.08, 1.27)	1.17 (1.03, 1.33)	1.14 (0.88, 1.47)	1.17 (1.04, 1.31)	42.23	0.86570	1.67 (0.40, 3.01)	(0.79, 1.76)	Moderate
Endometrial cancer	Oldest	8 (8)	RR	874 188	1.47^b(1.24, 1.72)	1.40 (1.25, 1.57)	1.47 (1.24, 1.74)	1.39 (1.11, 1.72)	1.40 (1.17, 1.68)	41.90	0.13885	3.85 (1.67, 6.37)	(0.97, 2.24)	High
Depression	Not early	3 (3)	RR	4945	1.33 (1.02, 1.73)	1.26 (1.07, 1.47)	1.33 (1.02, 1.73)	1.15 (0.94, 1.4)	1.26 (0.75, 2.11)	54.55	0.31109	2.53 (−2.56, 10.00)	(0.08, 21.52)	Very low
Breast cancer^a	Not early	117 (35)	RR	103 574		1.12 (1.09, 1.15)	1.19 (1.06, 1.33)							Very high

BMI, body mass index; CI, confidence interval; DL, Der Simonian and Laird; GDM, gestational diabetes mellitus; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; HR, hazard ratio; HS, Hartung–Knapp–Sidik–Jonkman; IGT, impaired glucose tolerance; OR, odds ratio; RMD, raw mean differences; RR, relative risks; SMD, standard mean differences; T2DM, type 2 diabetes mellitus; WMD, weighted mean differences.

This meta-analysis was included by individual level. We cannot calculate several values such as heterogeneity, Egger’s P values and 95% prediction interval.

The reciprocal of the value presented in the original text was used.

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