TABLE 4.

Incidence of breast-related adverse events of interest

	1 mg E2/100 mg P4 (n = 415)	0.5 mg E2/100 mg P4 (n = 424)	0.5 mg E2/50 mg P4 (n = 421)	0.25 mg E2/50 mg P4 (n = 424)	Placebo (n = 151)
AEs, n (%)
Breast cancera	2 (0.5)	2 (0.5)	1 (0.2)	1 (0.2)	0 (0.0)
[95% CI]	[0.1-1.7]	[0.1-1.7]	[0.0-1.3]	[0.0-1.3]	[0.0-2.4]
P valueb	>0.9999	>0.9999	>0.9999	>0.9999
Benign breast neoplasm	4 (1.0)	5 (1.2)	4 (1.0)	3 (0.7)	1 (0.7)
[95% CI]	[0.3-2.4]	[0.4-2.7]	[0.3-2.4]	[0.1-2.1]	[0.0-3.6]
P-valueb	>0.9999	>0.9999	>0.9999	>0.9999
Breast calcifications	3 (0.7)	0 (0.0)	0 (0.0)	1 (0.2)	0 (0.0)
[95% CI]	[0.1-2.1]	[0.0-0.9]	[0.0-0.9]	[0.0-1.3]	[0.0-2.4]
P valueb	0.5685			>0.9999
Breast cyst	1 (0.2)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
[95% CI]	[0.0-1.3]	[0.0-0.9]	[0.0-0.9]	[0.0-0.9]	[0.0-2.4]
P valueb	>0.9999
Breast mass	0 (0.0)	1 (0.2)	0 (0.0)	0 (0.0)	0 (0.0)
[95% CI]	[0.0-0.9]	[0.0-1.3]	[0.0-0.9]	[0.0-0.9]	[0.0-2.4]
P valueb		>0.9999
TEAEs, n (%)
Breast tenderness	45 (10.8)	19 (4.5)	25 (5.9)	10 (2.4)	1 (0.7)
[95% CI]	[8.0-14.2]	[2.7-6.9]	[3.9-8.6]	[1.1-4.3]	[0.0-3.6]
P-valueb	<0.0001	0.0348	0.0052	0.3035
Breast pain	9 (2.2)	2 (0.5)	1 (0.2)	2 (0.5)	0 (0.0)
[95% CI]	[1.0-4.1]	[0.1-1.7]	[0.0-1.3]	[0.1-1.7]	[0.0-2.4]
P-valueb	0.1215	>0.9999	>0.9999	>0.9999
Breast discomfort	3 (0.7)	1 (0.2)	0 (0.0)	0 (0.0)	0 (0.0)
[95% CI]	[0.1-2.1]	[0.0-1.3]	[0.0-0.9]	[0.0-0.9]	[0.0-2.4]
P valueb	0.5685	>0.9999
Breast swelling	2 (0.5)	0 (0.0)	2 (0.5)	0 (0.0)	0 (0.0)
[95% CI]	[0.1-1.7]	[0.0-0.9]	[0.1-1.7]	[0.0-0.9]	[0.0-2.4]
P valueb	>0.9999		>0.9999

AE, adverse event; TEAE, treatment-emergent adverse event; E2, 17β-estradiol; P4, progesterone.

^aBreast cancer includes invasive ductal breast carcinoma.

^bP value was calculated for active dose versus placebo.