. 2020 Apr 15;30(4):519–530. doi: 10.1089/thy.2019.0426

Table 5.

Effect Modification of Menopausal Hormone Therapy TYPE (Stratified Analysis)

Any MHT use duration
	N (%)	No. of invasive breast cancer cases	Incidence^a	No. of years used MHT	Age-adjusted HR [95% CI]	Fully adjusted HR [95% CI]
Full model—all
No thyroid dx	111,740	6769	41.68	4.57 (7.10)	Ref.	Ref.
Hyperthyroid dx	1695	114	47.26	5.49 (7.80)	1.11 [0.92–1.34]	1.12 [0.93–1.36]
Any hypothyroid dx with no medication	7815	501	43.77	5.81 (7.99)	1.05 [0.96–1.15]	0.97 [0.89–1.07]
Any hypothyroid dx with medications	12,872	753	40.47	6.98 (8.81)	0.95 [0.88–1.02]	0.89 [0.83–0.97]
Duration of any MHT use: none
No thyroid dx	50,560	2746	38.66	0 (0)	Ref.	Ref.
Hyperthyroid dx	708	40	41.56	0 (0)	1.07 [0.78–1.47]	1.10 [0.79–1.54]
Any hypothyroid dx with no medication	2963	180	43.09	0 (0)	1.13 [0.97–1.32]	1.03 [0.88–1.21]
Any hypothyroid dx with medications	4324	204	33.50	0 (0)	0.87 [0.75–1.00]	0.80 [0.69–0.93]
Duration of MHT use: <5 years
No thyroid dx	25,248	1502	39.44	1.93 (1.29)	Ref.	Ref.
Hyperthyroid dx	353	27	53.45	1.90 (1.27)	1.36 [0.93–2.00]	1.40 [0.96–2.051]
Any hypothyroid dx with no medication	1792	115	42.81	1.94 (1.27)	1.08 [0.89–1.31]	1.01 [0.83–1.23]
Any hypothyroid dx with medications	2772	156	38.07	1.98 (1.30)	0.96 [0.81–1.14]	0.93 [0.78–1.09]
Duration of MHT use: 5 years or more
No thyroid dx	35,927	2521	47.32	12.86 (7.25)	Ref.	Ref.
Hyperthyroid dx	634	47	49.77	13.63 (7.39)	1.00 [0.74–1.35]	1.01 [0.75–1.37]
Any hypothyroid dx with no medication	3060	206	44.96	13.71 (7.62)	0.94 [0.81–1.08]	0.90 [0.78–1.05]
Any hypothyroid dx with medications	5776	393	46.69	14.61 (8.10)	0.95 [0.85–1.05]	0.93 [0.83–1.03]

Unopposed estrogen (E)
	N (%)	No. of invasive breast cancer cases	Incidence^b	No. of years used E	Age-adjusted HR [95% CI]	Fully adjusted HR [95% CI]
Full model—all
No thyroid dx	111,740	6769	41.68	3.18 (6.77)	Ref.	Ref.
Hyperthyroidism dx	1695	114	47.26	4.07 (7.70)	1.11 [0.92–1.34]	1.12 [0.93–1.36]
Any hypothyroidism dx with no meds	7815	501	43.77	4.18 (7.83)	1.05 [0.96–1.15]	0.97 [0.89–1.07]
Any hypothyroidism dx with meds	12,872	753	40.47	5.27 (8.77)	0.95 [0.88–1.03]	0.89 [0.83–0.97]
Duration of unopposed estrogen use: none
No thyroid dx	74,496	4599	42.53	0 (0)	Ref.	Ref.
Hyperthyroidism dx	1073	69	45.44	0 (0)	1.04 [0.81–1.32]	1.05 [0.82–1.35]
Any hypothyroidism dx with no meds	4764	319	45.81	0 (0)	1.08 [0.97–1.22]	0.98 [0.87–1.11]
Any hypothyroidism dx with meds	7196	429	41.15	0 (0)	0.95 [0.86–1.05]	0.87 [0.78–0.96]
Duration of unopposed estrogen use: <5 years
No thyroid dx	14,509	815	38.61	1.83 (1.26)	Ref.	Ref.
Hyperthyroidism dx	204	18	62.52	1.79 (1.27)	1.62 [1.01–2.58]	1.62 [1.01–2.58]
Any hypothyroidism dx with no meds	1058	60	38.86	1.79 (1.21)	1.01 [0.77–1.31]	0.94 [0.72–1.22]
Any hypothyroidism dx with meds	1682	95	39.41	1.92 (1.30)	0.99 [0.80–1.23]	0.93 [0.75–1.15]
Duration of unopposed estrogen use: 5 years or more
No thyroid dx	22,732	1355	40.87	14.47 (7.92)	Ref.	Ref.
Hyperthyroidism dx	418	27	44.57	15.64 (7.78)	1.06 [0.72–1.57]	1.07 [0.73–1.58]
Any hypothyroidism dx with no meds	1993	122	41.53	15.44 (8.24)	0.99 [0.82–1.20]	0.96 [0.79–1.16]
Any hypothyroidism dx with meds	3994	229	39.69	16.18 (8.58)	0.95 [0.83–1.10]	0.91 [0.79–1.05]

Estrogen+progestogen
	N (%)	No. of invasive breast cancer cases	Incidence^c	No. of years used E + P	Age-adjusted HR [95% CI]	Fully adjusted HR [95% CI]
Full model—all
No thyroid dx	111,740	6769	41.68	1.43 (3.70)	Ref.	Ref.
Hyperthyroid dx	1695	114	47.26	1.62 (3.70)	1.11 [0.92–1.34]	1.12 [0.93–1.36]
Any hypothyroid dx with no medication	7815	501	43.77	1.81 (4.06)	1.05 [0.96–1.15]	0.97 [0.89–1.07]
Any hypothyroid dx with medications	12,872	753	40.47	1.94 (4.39)	0.95 [0.88–1.03]	0.89 [0.83–0.97]
Duration of estrogen+progestogen use: none
No thyroid dx	82,101	4476	38.39	0 (0)	Ref.	Ref.
Hyperthyroid dx	1218	69	40.84	0 (0)	1.07 [0.84–1.36]	1.09 [0.85–1.40]
Any hypothyroid dx with no medication	5525	330	41.75	0 (0)	1.09 [0.98–1.22]	1.01 [0.90–1.14]
Any hypothyroid dx with medications	9042	459	35.79	0 (0)	0.93 [0.84–1.02]	0.87 [0.79–0.96]
Duration of estrogen+progestogen use: <5 years
No thyroid dx	15,204	1026	42.98	1.94 (1.28)	Ref.	Ref.
Hyperthyroid dx	234	22	63.56	1.93 (1.25)	1.41 [0.92–2.18]	1.51 [0.98–2.34]
Any hypothyroid dx with no medication	1126	80	45.41	1.99 (1.27)	1.03 [0.82–1.30]	0.98 [0.78–1.23]
Any hypothyroid dx with medications	1822	113	40.27	1.94 (1.27)	0.93 [0.76–1.13]	0.89 [0.73–1.09]
Duration of estrogen+progestogen use: 5 years or more
No thyroid dx	14,432	1267	57.75	9.82 (4.72)	Ref.	Ref.
Hyperthyroid dx	243	23	61.12	9.45 (4.42)	0.99 [0.64–1.53]	0.98 [0.64–1.51]
Any hypothyroid dx with no medication	1164	91	51.13	10.21 (4.78)	0.88 [0.71–1.09]	0.85 [0.68–1.05]
Any hypothyroid dx with medications	2008	181	60.86	10.67 (5.38)	0.99 [0.84–1.16]	0.95 [0.81–1.12]

^{^a}

Incidence per 10,000 person-years follow-up.

MHT use × thyroid group interaction p = 0.346.

Fully adjusted model includes age, race/ethnicity, body mass index, smoking, alcohol intake, duration of menopausal hormone replacement therapy, history of hysterectomy/oophorectomy, parity history and numbers, age at menarche, age at menopause, family history of breast cancer, mammogram ever, and breastfeeding.

^{^b}

Incidence per 10,000 person-years follow-up.

Unopposed estrogen duration × thyroid group interaction p = 0.747.

^{^c}

Incidence per 10,000 person-years follow-up.

E + P use × thyroid group interaction p = 0.497.

dx, diagnosis.