Table 3.

Associations between menopausal factors and menopausal hormone therapy (MHT) use among post-menopausal women and risk of intrahepatic cholangiocarcinoma in the Liver Cancer Pooling Project and the UK Biobank.

	Liver Cancer Pooling Project					UK Biobank					Combined
Age at menopause	No. non-Cases (N = 722,150)a	No. ICC Cases (N = 154)a	HRb	95% CI		No. non-Cases (N = 209,464)a	No. ICC Cases (N = 44)a	HRc	95% CI		HR	95% CI
Natural menopause
<45	35,745	7	0.82	0.37–1.81		11,273	14	1.21	0.38–3.84		0.93	0.48–1.79
45–49	89,227	15	0.68	0.38–1.23		29,137	4	0.62	0.21–1.77		0.67	0.40–1.11
50–54	159,706	42		Referent		63,253			Referent			Referent
≥55	35,001	7	0.67	0.30–1.49		20,114	7	1.53	0.61–3.85		0.96	0.52–1.75
p for trend				0.84					0.59
Surgical menopause
Bilateral oophorectomyd	54,645	12	0.84	0.43–1.63		687	0	–			–
Hysterectomyd	100,694	36	2.25	1.38–3.65		15,809	5	1.11	0.39–3.13		1.98	1.27–3.09
Missing	131,173	30				7837	5
Fertile Duration
All women, per year increase	341,659	80	1.02	0.97–1.07		135,777	34	0.97	0.91–1.03		1.00	0.96–1.04
Menopausal hormone therapy (MHT)
Never	259,833	65		Referent		136,849	23		Referent			Referent
Ever use	340,563	83	1.12	0.80–1.56		72,057	21	1.05	0.56–1.96		1.10	0.82–1.49
Missing	5,795	1				556	0
Timing of use
Never	241,746	63		Referent		136,849	23		Referent			Referent
Former	81,684	22	0.92	0.56–1.50		63,593	19	1.05	0.55–2.01		0.97	0.65–1.43
Current	227,895	59	1.26	0.87–1.84		8464	2	1.04	0.24–4.47		1.25	0.87–1.78
Missing	54,866	5				556	0
Duration of use
None	130,549	36		Referent		136,849	23		Referent			Referent
<5 years	55,378	11	0.79	0.42–1.52		23,845	5	0.84	0.31–2.26		0.80	0.47–1.37
5–9 years	37,442	12	1.30	0.66–2.55		16,452	2	0.45	0.10–1.97		1.09	0.59–2.02
10+ years	66,548	16	0.72	0.35–1.47		13,717	7	1.53	0.62–3.76		0.97	0.55–1.70
Missing	231,499	58				18,599	7
p for trend				0.64					0.05
MHT typee
None	153,760	35		Referent		136,849	23		Referent			Referent
Oestrogen only	125,090	38	1.44	0.90–2.31		2708	1	1.45	0.19	10.85	1.44	0.91–2.28
Combination	100,318	22	1.01	0.58–1.76		5735	1	0.79	0.11–5.95		0.99	0.58–1.69
Other MHT	15,982	1	0.34	0.05–2.54
Missing	196,844	44				64,149	19
MHT pill usagee
None	87,966	24		Referent		136,849	23		Referent			Referent
Used pills	118,376	36	1.06	0.63–1.79		6,501	2	1.34	0.31–5.76		1.09	0.67–1.78
Other MHT	8,467	1	0.55	0.07–4.10		1879	0	–
Missing	377,185	79				64,233	19

^aNumbers are for women with non-missing covariates.

^bAdjusted for age (continuous), alcohol (g/day: none, ≤1.08, >1.08–3.58, >3.58–13.54, >13.54), BMI (kg/m²: <25, 25–29.9, ≥30), diabetes (yes, no), race (white, other), smoking (never, former, current), parent cohort study, menopausal status (pre-, post-menopausal), and education (<high school, high school, some college/vocational, college, graduate degree).

^cAdjusted for age (continuous), alcohol (never, former, current light/occasional (<16 g/day), current heavy (≥16 g/day)), BMI (kg/m²: <25, 25–29.9, ≥30), smoking (never, former, current), menopausal status (pre-, post-menopausal), and education (<secondary school, secondary school, college, graduate degree).

^dReference group for oophorectomy and hysterectomy is females who had natural menopause aged between 50 and 54 years old.

^eInformation on MHT type and pill usage only available for current MHT users at baseline in the UK Biobank.