Table 4.

Overall and subgroup analyses of early age at natural menopause with all-cause and cardiovascular mortality.

Group	Studies (n)	All-cause mortality		Cardiovascular mortality
Effect-size estimate		HR (95% CI); P	I 2	HR (95% CI); P	I 2
Overall analyses
Mortality (unadjusted)	15/18	1.12 (1.05-1.19); <0.001	65.3%	1.04 (1.00-1.13); 0.385	61.7%
Mortality (adjusted)	15/18	1.08 (1.03-1.14); 0.002	45.6%	1.01 (0.95-1.09); 0.682	42.1%
Subgroup analyses
By country
America	7/6	1.05 (0.96-1.15); 0.268	51.5%	1.06 (0.96-1.16); 0.235	0.0%
Europe	NA/2	NA	NA	0.85 (0.71-1.01); 0.060	48.3%
Asia	8/10	1.11 (1.03-1.18); 0.004	46.7%	1.05 (0.97-1.14); 0.228	37.1%
By follow-up
<13.8 years	6/7	1.09 (1.00-1.18); 0.047	57.7%	1.02 (0.95-1.10); 0.560	20.6%
≥13.8 years	9/11	1.08 (1.01-1.16); 0.036	40.0%	1.01 (0.90-1.14); 0.811	54.0%
Dose-response analysis
<40 years	7/6	1.10 (1.01-1.21); 0.034	60.7%	1.09 (1.00-1.19); 0.045	0.0%
40-44 years	4/3	1.12 (0.96-1.31); 0.145	49.2%	1.07 (0.90-1.27); 0.464	0.0%
45-49 years	4/9	1.05 (1.00-1.10); 0.051	0.0%	0.97 (0.88-1.07); 0.539	60.8%
Effect-size estimate		RR (95% CI); P	I 2	RR (95% CI); P	I 2
Overall analyses
Mortality (unadjusted)	2/NA	1.03 (1.00-1.06); 0.026	28.2%	NA	NA
Mortality (adjusted)	16/3	1.05 (1.01-1.08); 0.005	60.7%	1.08 (0.77-1.51); 0.652	0.0%
Subgroup analyses
By country
America	12/3	1.08 (1.02-1.15); 0.010	68.8%	1.08 (0.77-1.51); 0.652	0.0%
Europe	4/NA	1.03 (1.01-1.08); 0.010	0.0%	NA	NA
Asia	NA/NA	NA	NA	NA	NA
By follow-up
<16.5 years	8/8	1.21 (1.03-1.41); 0.020	76.0%	1.08 (0.77-1.51); 0.652	0.0%
≥16.5 years	3/NA	1.08 (0.77-1.51); 0.652	0.0%	NA	NA
Dose-response analysis
<40 years	5/1	1.34 (1.08-1.66); 0.007	75.3%	1.26 (0.56-2.85); 0.579	NA
40-44 years	5/1	1.03 (0.96-1.10); 0.377	52.7%	1.04 (0.54-2.00); 0.906	NA
45-49 years	6/1	1.02 (1.01-1.04); 0.004	0.0%	1.05 (0.67-1.64); 0.830	NA

HR: hazard ratio; RR: relative risk; 95% CI: 95% confidence interval; NA: not available.