Modification of blood pressure in postmenopausal women: role of hormone replacement therapy

Figures & data

Table 1 Clinical trials investigating the effect of estrogens on blood pressure of normotensive postmenopausal women

Source of trial	Year of trial	Age of subjects	Number of subjects	Route of administration of estrogens	Estrogens administered	BP measurement mode	Effects of estrogens
WHI^Citation58	2004	63.6	∼10,000	Oral	CEE 0.625 mg	Office	↑ systolic BP
Wren^Citation59	1981	52	160	Oral	E1 sulphate + CEE 0.625 mg	24-h	↓ BP ↑ BP
EPAT^Citation61	2008	61	222	Oral	E2 1 mg	Office	↑ systolic BP in younger ↓ diastolic BP in older
Akkad^Citation63	1997	30–59	90	Transdermal Oral	E2 0.05 mg E2 + E3 + E1	24-h	↓ nocturnal systolic BP ↓ diastolic BP =24-h BP
Cardoso^Citation62	2011	45–60	47	Oral	E2V 1 mg	24-h	↑ systolic BP ↑ diastolic BP
Vongpatanasin^Citation64	2001	53	12	Transdermal Oral	E2 0.2 mg CEE 0.625 mg	24-h	↓ 24-h BP =24-h BP
Cagnacci^Citation65	1999	53.5	18	Transdermal	E2 0.05 mg	24-h	↓ nocturnal systolic BP ↓ nocturnal diastolic BP ↓ nocturnal mean BP
Driul^Citation66	2005	51.3	46	Transdermal	E2 0.05 mg	24-h	↓ diurnal diastolic BP ↓ nocturnal diastolic BP

Abbreviations: 24-h, 24-hour; BP, blood pressure; CEE, conjugated equine estrogen; EPAT, Estrogen in the Prevention of Atherosclerosis Trial; E1, estrone; E2, estradiol; E2V, oral estradiol valerate; E3, estriol; WHI, Women’s Health Initiative; ↓, decrease; ↑, increase; =, no change.

Table 2 Clinical trials investigating the effects of hormone therapy on blood pressure of normotensive postmenopausal women

Source of trial	Year of trial	Number of subjects	Age of subjects	Route of administration of HT	Estrogens administered	Progestins administered	Mode of BP measurement	Effects of hormone therapy
Hassager^Citation69	1988	875	Earlier in PMW	Oral	E2	NETA	Office	↓ diastolic BP
			Later in PMW	Transdermal	E2	CPA		= BP
				Oral	E2 0.05 mg	MP 200 mg
					E2	NETA
PEPI^Citation70	1995	875	45–64	Oral	CEE 0.625 mg	–	Office	↑ systolic BP
					CEE 0.625 mg	MPA 10 mg		= diastolic BP
					CEE 0.625 mg	MPA 200 mg
DOPS^Citation71	2002	1,006	45–58	Oral	E2 2 mg	–	Office	= diastolic BP
					E2 2 mg	NETA 1 mg		= systolic BP
WHI^Citation73	2000	90,755	50–79	Oral	CEE 0.625 mg	MPA 2.5 mg	Office	↑ systolic BP
								= diastolic BP
HERS^Citation74	2002	2,763	67	Oral	CEE 0.625 mg	MPA 2.5 mg	Office	↑ systolic BP
van Ittersum^Citation75	1998	29	52	Oral	E2 1mg	DYD 5–10 mg	24-h	↓ systolic BP
								↓ diastolic BP
Harvey^Citation76	1999	24	47–60	Oral	E1 sulphate 0.625 mg	MPA 10 mg	24-h	↓ nocturnal BP
					E1 sulphate 2.5 mg
					EE 0.02 mg
Sorensen^Citation77	2000	16	55	Oral	E2 4 mg	NETA 1 mg	24-h	↓ systolic BP
								↓ diastolic BP
Manwaring^Citation78	2000	17	N/A	Oral	CEE 0.625 mg	MPA 5 mg	24-h	↓ systolic BP
					CEE 0.625 mg
Cacciatore^Citation79	2001	73	45–57	Oral	E2 2 mg	NETA 1 mg	24-h	↓ diastolic 24-h
				Transdermal	E2 0.05 mg	NETA 50 μg		↓ systolic 24-h
Paakari^Citation80	1996	63	N/A	Oral	E2	NETA	24-h	↓ systolic BP
				Transdermal
Pripp^Citation81	1999	59	59	Oral	CEE 0.625 mg	MPA 5 mg	24-h	↓ systolic BP
				Transdermal	E2 0.05 mg			↓ diastolic BP
Zacharieva^Citation82	2002	28	45–55	Oral	E2V 2 mg	CPA 2 mg	24-h	↓ sytolic BP
				Transdermal	E2 0.05 mg			↓ diastolic BP
Seely^Citation83	1999	15	56	Transdermal	E2 0.1 mg	P 300 mg	24-h	↓ nocturnal systolic BP
					E2 0.1 mg			↓ nocturnal diastolic BP
								↓ nocturnal mean BP
Deuringer^Citation87	2000	416	N/A	Transdermal	E2 0.05 mg	NETA 1 mg	Office	= diastolic BP
						CMA 2 mg		= systolic BP
Mueck^Citation88	1997	159	N/A	Oral	E2	CMA 0.5, 1, 2,	Office	= diastolic BP
						3 mg		= systolic BP
Mueck^Citation89	1998	N/A	N/A	Oral	E2	DNG 0.5, 1, 2,	Office	= diastolic BP
						3, 4 mg		= systolic BP
Mueck^Citation90	2001	52	55	Oral	E2V	–	Office	= diastolic BP
					E2V	DNG		= systolic BP
van der Mooren^Citation91	1996	563	N/A	Oral	E2 2 mg	DYD 5, 10, 15,	Office	↓ diastolic BP
						20 mg		↓ systolic BP
Kessel^Citation92	2001	52	52	Oral	E2 1–2 mg	DYD 5–20 mg	Office	= diastolic BP
								= systolic BP
Harvey^Citation93	2001	20	53	Oral	CEE 0.625 mg	MPA 2.5, 5,	24-h	↓ diurnal diastolic BP
						10 mg		↓ diurnal mean BP
White^Citation95	2005	213	45–58	Oral	E2 1 mg	DRSP 3 mg	24-h	↓ systolic BP
White^Citation96	2006	750	45–75	Oral	E2 1 mg	DRSP 2 mg	24-h	↓ systolic BP
					E2 1 mg	DRSP 3 mg		↓ systolic BP
White^Citation97	2006	748	56	Oral	E2 1 mg	DRSP 1, 2, 3 mg	24-h	↓ early morning systolic BP
Gambacciani^Citation98	2011	52	53	Oral	E2 1 mg	DRSP 2 mg	Office	= diastolic BP
								= systolic BP in normotensive
								↓ systolic BP in hypertensive
Battaglia^Citation99	2009	30	48–56	Oral	E2 1 mg	DRSP 2 mg	Office	=24-h BP
					E2 1 mg	NETA 0.5 mg		= daytime BP
								= nocturnal BP

Abbreviations: 24-h, 24-hour; BP, blood pressure; CEE, conjugated equine estrogen; CMA, chlormadinone acetate; DNG, dienogest; DOPS, Danish Osteoporosis Prevention Study; DRSP, drospirenone; DYD, dihydrogesterone; EE, ethinylestradiol; E1, estrone; E2, estradiol; E2V, oral estradiol valerate; HERS, Heart and Estrogen/Progestin Replacement Study; HT, hormone therapy; MP, micronized progesterone; MPA, medroxyprogesterone acetate; NETA, norethisterone acetate; P, progesterone; PEPI, Postmenopausal Estrogen/Progestin Intervention; PMW, postmenopausal women; WHI, Women’s Health Initiative ; ↓, decrease; ↑, increase; =, no change; CPA, cyproterone acetate; N/A, not available.

Table 3 Clinical trials investigating the effect of estrogens alone or with hormone therapy on blood pressure of hypertensive postmenopausal women

Source of trial	Year of trial	Number of subjects	Routes of administration	Estrogens	Progestins	Mode of measurement	Effects
Luotola^Citation100	1983	40	Oral	E2 2 mg	–	Office	↓ diastolic BP
				E2 4 mg			↓ systolic BP
Mercuro^Citation101	1998	30	Transdermal	E2 50 μg	–	24-h	↓ diastolic BP
							↓ systolic BP
Kornhauser^Citation104	1997	55	Oral	Estradiol valerate 10 mg	–	Office	↑ systolic BP
			Oral + im	Estradiol valerate 4 mg	Prasterone enanthate 200 mg		↑ diastolic BP
Jespersen^Citation105	1993	24	Oral	E2	–	Office	↓ systolic BP
				E2 + E1	NETA		= diastolic BP
van der Mooren^Citation91	1996	99	Oral	E2	DYD	Office	↑ systolic BP
							↑ diastolic BP
Harvey^Citation106	2000	14	Oral	CEE 0.3, 0.625, 1.25 mg	MPA 10 mg	Office	↓ BP
Mueck^Citation102	2000	13,190	Oral	CEE 0.3, 0.625, 1.25 mg	MPA 10 mg	Office	↓ systolic BP
							↓ diastolic BP
Foidart^Citation108	1991	92	Transdermal +	E2 50 μg	MPA 10 mg	Office	= diastolic BP
			Oral				= systolic BP
Sumino^Citation107	2003	31	Oral	CEE 0.625 mg	MPA 2.5 mg	Office	= BP
Kaya^Citation110	2006	66	Oral	E2 1 mg	DYD 10 mg	24-h	↓ systolic BP
							↓ diastolic BP
							↓ mean BP
Wong^Citation111	2005	34	Oral	E2	Norgestrel	24-h	↓ daily mean BP
Affinito^Citation112	2001	60	Transdermal	E2 50 μg	MPA 10 mg	24-h	↓ diastolic BP
							↓ systolic BP
Szekacs^Citation114	2000	30	Transdermal	E2 50 μg	Norgestrel	24-h	↓ diastolic BP
							↓ systolic BP

Abbreviations: 24-h, 24-hour; BP, blood pressure; CEE, conjugated equine estrogen; DYD, dihydrogesterone; E1, estrone; E2, estradiol; im, intramuscular; MPA, medroxyprogesterone acetate; NETA, norethisterone acetate; ↓, decrease; ↑, increase; =, no change, –, none.

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