Vasomotor hot flushes and 24-hour ambulatory blood pressure in normotensive women: A placebo-controlled trial on post-menopausal hormone therapy

Figures & data

Figure 1. Flow chart of the study.

Table I. Base-line characteristics. The groups were comparable in pertinent variables except for the hot flush weekly weighted score and time since menopause. The free estradiol index was calculated as (estradiol (nanomoles/L)/sex hormone-binding globulin (nanomoles/L)) × 100. Data are presented as mean ± standard error of mean.

	Transdermal estradiol		Oral estradiol		Oral estradiol and MPA		Placebo
	Asymptomatic n = 19	Symptomatic n = 18	Asymptomatic n = 20	Symptomatic n = 17	Asymptomatic n = 19	Symptomatic n = 18	Asymptomatic n = 19	Symptomatic n = 17
Hot flush weekly weighted score	6.6 ± 1.9^a	162.0 ± 15.4^a	6.4 ± 1.6^a	163.9 ± 14.3^a	6.3 ± 1.7^a	167.7 ± 21.2^a	9.2 ± 2.5^a	156.1 ± 11.0
Age (years)	52.8 ± 0.3	51.6 ± 0.7	52.5 ± 0.4	52.4 ± 0.5	52.3 ± 0.6	52.6 ± 0.5	52.8 ± 0.5	51.9 ± 0.5
Body mass index (kg/m^2)	22.9 ± 0.5	22.2 ± 0.4	23.3 ± 0.4	23.7 ± 0.7	23.0 ± 0.4	23.0 ± 0.6	23.0 ± 0.6	22.6 ± 0.6
Serum thyroid-stimulating hormone (mU/L)	1.9 ± 0.2	1.9 ± 0.2	2.0 ± 0.2	2.3 ± 0.4	2.2 ± 0.2	2.2 ± 0.3	2.0 ± 0.2	2.2 ± 0.2
Time since last menstruation (months)	22.0 ± 2.2	16.6 ± 2.9	23.4 ± 1.9	20.6 ± 2.5	17.1 ± 2.2	16.9 ± 2.4	23.9 ± 2.4^b	13.7 ± 1.8^b
Serum follicle-stimulating hormone (U/L)	76.8 ± 5.1	65.8 ± 5.9	85.7 ± 8.2	68.0 ± 5.6	79.3 ± 8.0	67.1 ± 5.4	69.4 ± 4.4	69.2 ± 5.4
Serum estrone (picomoles/L)	123.6 ± 21.2	137.2 ± 13.1	104.4 ± 8.3	147.2 ± 27.7	133.2 ± 20.8	129.7 ± 12.5	127.1 ± 15.9	119.8 ± 12.0
Serum estradiol (picomoles/L)	60.0 ± 17.9	96.7 ± 21.3	45.0 ± 7.1	81.2 ± 27.1	65.8 ± 15.5	70.6 ± 16.2	66.8 ± 13.2	79.4 ± 19.3
Serum sex hormone-binding globulin (nanomoles/L)	77.1 ± 8.6	78.8 ± 7.4	66.8 ± 6.6	55.9 ± 5.3	67.3 ± 6.6	65.0 ± 6.1	74.9 ± 7.5	63.2 ± 5.1
Free estradiol index (%)	0.08 ± 0.02	0.14 ± 0.03	0.08 ± 0.01	0.14 ± 0.03	0.10 ± 0.02	0.11 ± 0.02	0.10 ± 0.02	0.13 ± 0.03

^aP < 0.001 for the difference between asymptomatic and symptomatic women.

^bP = 0.024 for the difference between asymptomatic and symptomatic women.

n = number of subjects at base-line; MPA = medroxyprogesterone acetate.

Table II. Hemodynamic variables in the different study groups at base-line. Data presented as mean ± standard error of mean. There were no differences between the groups (P-value > 0.05).

	Transdermal estradiol		Oral estradiol		Oral estradiol and MPA		Placeb
	Asymptomatic n = 19	Symptomatic n = 18	Asymptomatic n = 20	Symptomatic n = 17	Asymptomatic n = 19	Symptomatic n = 18	Asymptomatic n = 19	Symptomatic n = 17
Systolic blood pressure (mmHg)
24-hour	113.2 ± 2.0	116.1 ± 3.1	116.5 ± 2.1	118.7 ± 2.1	117.2 ± 1.8	115.1 ± 1.9	112.8 ± 2.1	116.1 ± 2.2
Day-time	117.6 ± 2.2	121.0 ± 3.2	121.4 ± 2.3	124.0 ± 2.2	121.8 ± 1.9	119.4 ± 2.0	117.1 ± 2.1	120.1 ± 2.4
Night-time	98.6 ± 16	103.1 ± 3.0	100.1 ± 2.0	104.4 ± 2.5	102.9 ± 1.9	102.2 ± 2.1	98.8 ± 2.3	103.1 ± 2.1
Diastolic blood pressure (mmHg)
24-hour	74.4 ± 1.3	75.2 ± 1.7	75.1 ± 1.5	75.1 ± 1.6	76.8 ± 1.2	76.0 ± 1.2	74.4 ± 1.5	76.0 ± 1.7
Day-time	77.6 ± 1.5	79.4 ± 1.7	78.8 ± 1.6	79.1 ± 1.7	80.4 ± 1.2	79.8 ± 1.2	77.7 ± 1.6	79.5 ± 1.8
Night-time	62.8 ± 1.0	64.2 ± 1.7	62.6 ± 1.5	63.7 ± 1.5	65.7 ± 1.5	65.5 ± 1.5	62.8 ± 1.7	65.0 ± 1.6
Heart rate (beats/minute)
24-hour	70.4 ± 1.8	68.4 ± 1.4	67.0 ± 0.8	71.2 ± 2.2	70.2 ± 1.7	65.7 ± 2.1	69.4 ± 1.5	72.2 ± 1.6
Day-time	74.1 ± 1.9	72.6 ± 1.6	70.1 ± 1.0	75.1 ± 2.5	73.8 ± 1.8	68.8 ± 2.2	72.5 ± 1.6	75.8 ± 1.7
Night-time	58.1 ± 1.6	57.1 ± 1.6	56.6 ± 1.1	61.4 ± 1.9	59.7 ± 2.1	56.6 ± 1.8	59.1 ± 1.5	60.8 ± 1.8
Absolute dipping (mmHg)	−19.1 ± 1.6	−17.9 ± 1.6	−21.3 ± 1.7	−19.6 ± 2.1	−18.9 ± 1.3	−17.2 ± 2.1	−18.3 ± 1.4	−17.1 ± 1.3
Relative dipping (%)	−16.0 ± 1.2	−14.7 ± 1.2	−17.4 ± 1.2	−15.8 ± 1.6	−15.5 ± 1.0	−14.2 ± 1.8	−15.6 ± 1.1	−14.1 ± 1.0

n = number of subjects at base-line; MPA = medroxyprogesterone acetate.

Table III. The levels of estrogens after 6 months of hormonal treatment, and percentual changes from base-line. Data presented as mean ± standard error of mean.

	Transdermal estradiol n = 36	Oral estradiol n = 34	Oral estradiol and MPA n = 34	Placebo n = 35
Estrone (pmol/L)	384.3 ± 39.2^a	2 034.1 ± 208.1^a,b	1 608.8 ± 169.3^a,b	169.5 ± 37.9
Percentage change	251.1 ± 40.9^a	1 883.3 ± 260.6^a,b	1 329.3 ± 170.0^a,b	60.8 ± 41.6
Estradiol (pmol/L)	204.2 ± 29.5^a	213.5 ± 17.4^a	173.8 ± 14.8^a	70.6 ± 17.8
Percentage change	400.3 ± 114.9^a	468.8 ± 74.7^a	321.3 ± 54.l^a	50.3 ± 38.6
Free estradiol index	0.23 ± 0.03^a	0.18 ± 0.01^a	0.19 ± 0.02^a	0.10 ± 0.03
Percentage change	320.7 ± 100.9^a	160.3 ± 27.7^a	182.0 ± 35.2^a	42.8 ± 30.5

^a = P < 0.001 compared to placebo,

^b = P < 0.001 for transdermal estradiol versus oral estradiol with or without medroxyprogesterone acetate.

n = number of subjects at base-line; MPA = medroxyprogesterone acetate.

Table IV. Effect of hormone therapy on ambulatory blood pressure and heart rate in asymptomatic and symptomatic women. Data are presented as absolute changes (mean ± standard error of mean) adjusted for the respective base-line values.

	Transdermal estradiol		Oral estradiol		Oral estradiol and MPA		Placebo
	Asymptomatic n = 19 (18)	Symptomatic n = 18 (18)	Asymptomatic n = 20 (17)	Symptomatic n = 17 (17)	Asymptomatic n = 19 (16)	Symptomatic n = 18 (17)	Asymptomatic n = 19 (19)	Symptomatic n = 17 (16)
Systolic blood pressure (mmHg)
24-hour	−4.3 ± 1.5	−1.2 ± 1.5	3.7 ± 1.2^a	−1.2 ± 1.2^a	0.8 ± 1.5	0.5 ± 1.5	2.2 ± 1.8	−0.5 ± 1.9
Day-time	−4.7 ± 1.5	−1.6 ± 1.5	3.0 ± 1.3^b	−1.9 ± 1.3^b	0.5 ± 1.9	0.3 ± 1.9	3.1 ± 1.8	−0.8 ± 2.0
Night-time	−3.6 ± 1.8	0.3 ± 1.8	3.7 ± 1.9	0.2 ± 1.9	0.9 ± 1.3	1.2 ± 1.3	0.6 ± 1.8	−0.4 ± 2.1
Diastolic blood pressure (mmHg)
24-hour	−2.2 ± 1.0	−0.2 ± 1.0	1.8 ± 0.8^c	−2.1 ± 0.8^c	−1.2 ± 1.1	−1.2 ± 1.0	1.4 ± 1.1	−0.9 ± 1.2
Day-time	−2.0 ± 0.9	−0.2 ± 0.9	1.8 ± 0.9^d	−2.4 ± 0.9^d	−1.0 ± 1.3	−1.6 ± 1.2	2.5 ± 1.1^e	−1.5 ± 1.3^e
Night-time	−2.9 ± 1.3	0.6 ± 1.3	0.3 ± 1.2	−1.7 ± 1.2	−2.0 ± 1.0	−1.1 ± 0.9	0.5 ± 1.1	−0.2 ± 1.2
Heart rate (beats/minute)
24-hour	−0.7 ±1.1	0.9 ± 1.1	−0.4 ± 0.9	−2.1 ± 0.9	0.5 ± 1.3	0.8 ± 1.3	−1.2 ± 1.0	0.6 ± 1.1
Day-time	−1.4 ± 1.3	−1.3 ± 1.3	−1.1 ± 1.0	−2.2 ± 1.1	−0.1 ± 1.4	0.9 ± 1.3	−0.2 ±1.1	0.2 ± 1.2
Night-time	0.9 ± 1.2	2.0 ± 1.2	−0.2 ± 1.3	−2.1 ± 1.3	1.3 ± 1.3	0.8 ± 1.2	0.6 ± 1.0	1.3 ± 1.1
Absolute dipping (mmHg)	1.0 ± 1.2	1.9 ± 1.2	1.0 ± 1.7	1.8 ± 1.0	0.1 ± 1.8	1.2 ± 1.8	−2.2 ± 1.7	0.5 ± 1.7
Relative dipping (%)	0.1 ± 1.0	1.4 ± 1.0	1.1 ± 1.3	1.4 ± 1.4	0.3 ± 1.4	1.0 ± 1.3	−1.2 ± 1.2	0.4 ± 1.4

^aP = 0.010; ^bP = 0.017; ^cP = 0.003; ^dP = 0.003; and ^eP = 0.028 for the differences between asymptomatic and symptomatic women.

n = number of subjects at base-line (at 6 months); MPA = medroxyprogesterone acetate.

Figure 2. Changes in 24-hour systolic and diastolic blood pressures after 6 months of hormone therapy in symptomatic and asymptomatic women. Data presented as mean ± SE adjusted for the respective base-line levels. A P-value <0.05 was considered statistically significant. P-values are corrected with Bonferroni adjustment for multiple comparisons.