Table 2 Associations of hormones and SHBG with the risk of invasive breast cancer in pre- and post-menopausal women.

	Cases	Total	HR (95% CI)^a	HR (95% CI)^b	HR (95% CI)^c	HR (95% CI)^d	HR (95% CI)^e	p_{heterogeneity}
Total testosterone, per 0.5 nmol/L increment
Pre-menopausal	527	30,565	1.02 (0.94, 1.12)	1.02 (0.93, 1.12)	1.03 (0.94, 1.12)	1.01 (0.92, 1.11)	1.03 (0.92, 1.16)	0.03
Post-menopausal	2997	133,294	1.19 (1.14, 1.23)	1.19 (1.14, 1.23)	1.17 (1.12, 1.21)	1.16 (1.12, 1.21)	1.18 (1.14, 1.23)
Calculated free testosterone, per 10 pmol/L increment
Pre-menopausal	527	30,565	1.00 (0.89, 1.13)	1.01 (0.89, 1.13)	1.02 (0.90, 1.16)	0.97 (0.84, 1.12)	0.97 (0.78, 1.20)	0.009
Post-menopausal	2997	133,294	1.32 (1.26, 1.39)	1.32 (1.26, 1.39)	1.27 (1.20, 1.33)	1.25 (1.18, 1.32)	1.31 (1.23, 1.40)
SHBG, per 30 nmol/L increment
Pre-menopausal	527	30,565	0.98 (0.88, 1.08)	0.96 (0.87, 1.07)	0.94 (0.84, 1.06)	0.97 (0.86, 1.09)	0.96 (0.79, 1.15)	0.4
Post-menopausal	2997	133,294	0.83 (0.79, 0.87)	0.83 (0.79, 0.88)	0.89 (0.84, 0.94)	0.90 (0.85, 0.95)	0.89 (0.84, 0.94)
IGF-1, per 5 nmol/L increment
Pre-menopausal	527	30,565	1.14 (1.03, 1.25)	1.13 (1.03, 1.24)	1.13 (1.02, 1.24)	1.12 (1.02, 1.24)	1.18 (1.03, 1.36)	0.2
Post-menopausal	2997	133,294	1.07 (1.02, 1.11)	1.06 (1.02, 1.11)	1.08 (1.04, 1.12)	1.05 (1.01, 1.10)	1.07 (1.01, 1.12)
Total oestradiol, per 400 pmol/L increment
Pre-menopausal	527	30,565	1.00 (0.88, 1.14)	0.99 (0.86, 1.13)	0.98 (0.86, 1.13)	0.99 (0.86, 1.13)	–	–
Calculated free oestradiol, per 5 pmol/L increment
Pre-menopausal	527	30,565	1.04 (0.90, 1.20)	1.03 (0.89, 1.19)	1.04 (0.90, 1.20)	1.03 (0.89, 1.19)	–	–

^aHazard ratios stratified for age group, region and deprivation and adjusted for age (underlying time variable).
^bAs above + adjusted for ethnicity, educational level, smoking, alcohol, physical activity, regular menstrual cycle (pre-menopause), parity, age at first birth, time since OCP use, age at menopause (post-menopause), time since HRT use (post-menopause), presence of endocrine disorders and family history of breast cancer.
^cAs above + adjusted for BMI.
^dAs above + adjusted for other hormones and SHBG.
^eAs above + corrected for regression dilution using repeat measures except for total and calculated free oestradiol.

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