Table 2.

Linear mixed regression analysis with random intercept were performed to assess the effect of sex hormones on Pheno Age, GrimAge, DNAm-based PAI1, and DNAm-based leptin. Sex hormones were standardized and winsorized (highest and lowest 1%) by study. The analyses were performed stratified by sex, and adjusted for age, body mass index (BMI), alcohol intake, smoking packyears, physical activity, the time between visits, cohort study, and blood cell composition based on DNAm. Among women, we also adjusted for time since menopause.

		Men					Females
Outcome	Sex Hormones	Est.	95% LL	95% UL	P	BH-P	Est.	95% LL	95% UL	P	BH-P
Pheno AA	E1	0.26	−0.09	0.61	0.14	0.31	0.06	−0.42	0.54	0.79	0.96
	E2	0.13	−0.15	0.40	0.37	0.67	0.05	−0.32	0.41	0.81	0.96
	SHBG	−0.11	−0.41	0.19	0.47	0.67	−0.40	−0.75	−0.04	0.03	0.22
	TotT	−0.35	−0.64	−0.06	0.02	0.08	0.11	−0.23	0.44	0.54	0.92
	TE ratio	−0.41	−0.70	−0.12	0.01	0.04	−0.12	−0.48	0.23	0.49	0.92
	DHEAS	−0.02	−0.62	0.57	0.94	0.98	0.38	−0.12	0.87	0.14	0.47
Grim AA	E1	0.19	−0.02	0.39	0.07	0.22	0.03	−0.22	0.29	0.80	0.96
	E2	−0.04	−0.21	0.12	0.59	0.71	0.04	−0.15	0.23	0.66	0.96
	SHBG	0.05	−0.13	0.22	0.59	0.71	−0.10	−0.29	0.08	0.28	0.76
	TotT	−0.22	−0.39	−0.05	0.01	0.06	0.00	−0.18	0.18	0.99	0.99
	TE ratio	−0.16	−0.33	0.01	0.07	0.22	−0.14	−0.32	0.05	0.16	0.48
	DHEAS	0.28	−0.08	0.64	0.12	0.30	0.09	−0.16	0.34	0.50	0.92
DNAm PAI1	E1	61	−100	222	0.46	0.67	−67	−270	136	0.52	0.92
	E2	−103	−230	24	0.11	0.30	139	−22	299	0.09	0.37
	SHBG	−478	−614	−343	1E-11	1E-10	−434	−589	−279	1E-07	2E-06
	TotT	−481	−613	−349	2E-12	6E-11	−134	−284	15	0.08	0.37
	TE ratio	−351	−486	−217	4E-07	3E-06	−197	−356	−39	0.02	0.18
	DHEAS	68	−200	335	0.62	0.71	−21	−264	222	0.86	0.96
DNAm LEPTIN	E1	0	−90	89	1.00	1.00	13	−162	187	0.89	0.96
	E2	−28	−101	45	0.44	0.67	28	−106	163	0.68	0.96
	SHBG	−30	−109	50	0.46	0.67	−140	−271	−10	0.04	0.22
	TotT	−26	−103	52	0.52	0.69	42	−82	166	0.50	0.92
	TE ratio	18	−60	95	0.66	0.72	−26	−159	107	0.70	0.96
	DHEAS	−75	−253	104	0.41	0.67	9	−174	193	0.92	0.96

Abbreviations: Est: Effect estimate; LL: Lower Limit; UL: Upper Limit; P: P-value; BH-P: Benjamini-Hochberg adjusted P-value; AA: Age Acceleration; DNAm: DNA-methylation; E1: total estrone; E2: total estradiol; SHBG: Sex Hormone Binding Globulin; TotT: total testosterone; TE ratio: Total testosterone divided by total estradiol concentration