Postmenopausal hormone therapy and coronary heart disease in early postmenopausal women

Figures & data

Table I. Outcomes of observational studies (number of participants ≥ 5000 or follow-up ≥ 5 years) in which the effects of long-term hormone therapy have been assessed.

	Population; follow-up	Main outcome measure	Results
Leisure World (47,48)	n = 8841; 5.7 years	Cardiac death n = 149	ET: RR 0.59, P = 0.002
		Death due to stroke n = 63	ET: RR 0.53 (95% CI 0.31–0.91)
Sourander et al. (49)	n = 7944; 8 years	Cardiac death n = 258	HT: RR 0.21 (95% CI 0.08–0.59)
		Death due to stroke n = 51	HT: RR 0.16 (95% CI 0.02–1.18)
Swedish cohort (81)	n = 9236; 8 years	Myocardial infarction n = 213	ET: RR 0.75 (95% CI 0.56–0.99); EPT: RR 0.69 (95% CI 0.45–0.90)
		Stroke n = 289	ET: RR 0.91 (95% CI 0.71–1.17); EPT: RR 0.81 (95% CI 0.61–1.10)
Nurses’ Health Study (17)	n = 70,533; 20 years	Coronary heart disease n = 1253	ET: RR 0.55 (95% CI 0.45–0.68); EPT: RR 0.64 (95% CI 0.49–0.85)
		Stroke n = 767	ET: RR 1.18 (95% CI 0.95–1.46); EPT: RR 1.45 (95% CI 1.10–1.92)
WHI Observational Study (82)	n = 53,054; 5.5 years	Coronary heart disease n = 158	EPT: HR 0.87 (95% CI 0.72–1.05)
		Stroke n = 123	EPT: HR 0.86 (95% CI 0.70–1.07)
OSTPRE (83)	n = 11,667; 6.7 years	Cardiac death n = 58	HT ≤ 5 years: RR 0.79 (95% CI 0.36–1.73)
			HT > 5 years: RR 2.16 (95% CI 0.93–4.98)
California Teachers Cohort Study (51)	n = 71,237; 5.7 years	Cardiac death n = 1391	HT: HR 0.84, 95% CI (0.74–0.95)

Table II. Secondary prevention trials on hormone therapy with number of participants ≥ 100 or follow-up ≥ 1 year.

Secondary prevention trials	Population	Treatment	Main outcome	Results
HERS 1998, 2002 (18,25)	n = 2763–2321; mean age: 68; established CHD	4.1 to 6.8 years; CEE 0.625 mg + MPA 2.5 mg	MI or death	No benefit or harm
ERA 2000 (84)	n = 309; mean age: 66; established CHD	3.2 years; CEE 0.625 mg ± MPA 2.5 mg	Angiography: change in coronary lumen diameter	No benefit or harm
PHOREA 2001 (85)	n = 321; mean age: 59; CIMT ≥ 1 mm	11 months; oral estradiol 1 mg ± gestodene 0.025 mg	Ultrasound: change in CIMT	No benefit or harm
PHASE 2002 (86)	n = 255; mean age: 66; established CHD	30.8 months transdermal estradiol 2 mg ± 4 mg cyclic NETA	Unstable angina, proven MI, or cardiac death	No benefit or harm
WAVE 2002 (87)	n = 423; mean age: 65; established CHD	2.8 years; CEE 0.625 mg ± MPA 2.5 mg, and/or vitamin C or E	Angiography: change in coronary lumen diameter	No benefit or harm
ESPRIT 2002 (26)	n = 1017; mean age: 62; previous MI	2 years oral estradiol 2 mg	MI or death	No benefit or harm
WELL-HART 2003 (88)	n = 226; mean age: 64; established CHD	3.3 years oral estradiol 1 mg ± MPA 2.5 mg	Angiography: change in coronary stenosis	No benefit or harm
WHISP 2006 (89)	n = 100; mean age: 69; acute coronary event < 28 days	1 year oral estradiol 1 mg ± NETA 0.5 mg	Death, MI, stroke, CVD admissions	Non-significant reduction in CVD events

CEE = conjugated equine estrogens; CHD = coronary heart disease; CIMT = carotid intima-media thickness; CVD = cardiovascular disease; MI = myocardial infarction; MPA = medroxyprogesterone acetate; NETA = norethindrone acetate; ± with or without; + with.

Table III. Hazard ratios (95% CI) for major outcomes in the HERS (18) and WHI-trials (19,28) associated with HT use. Statistically significant results are in italics.

	HERS 1998 (18)	WHI-EP 2002 (19)	WHI-E 2004 (28)
CHD events	1.30 (0.77–2.19)	1.29 (1.02–1.63)	0.91 (0.75–1.12)
Stroke	1.23 (0.89–1.70)	1.41 (1.07–1.85)	1.39 (1.10–1.77)
Pulmonary embolism	2.79 (0.89–8.75)	2.31 (1.39–3.25)	1.34 (0.87–2.06)
Deep vein thrombosis	3.18 (1.43–7.04)	2.07 (1.49–2.87)	1.47 (1.04–2.08)
Breast cancer	1.30 (0.77–2.19)	1.26 (1.00–1.59)	0.77 (0.59–1.01)
Death	1.08 (0.84–1.38)	0.98 (0.82–1.18)	1.04 (0.88–1.22)
Hip fracture	1.10 (0.49–2.50)	0.66 (0.45–0.98)	0.61 (0.41–0.91)
Colorectal cancer	0.69 (0.32–1.49)	0.63 (0.43–0.92)	1.08 (0.75–1.55)

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