Trial Outcomes & Findings for MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and Venlafaxine XR for Treatment of Menopausal Symptoms (NCT NCT01418209)
NCT ID: NCT01418209
Last Updated: 2014-08-27
Results Overview
Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 4 study assessment to produce a mean daily frequency for week 4.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
339 participants
Primary outcome timeframe
Week 4
Results posted on
2014-08-27
Participant Flow
Participant milestones
| Measure |
Low-dose 17-ß-Estradiol With Progesterone Taper
Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably. The 8 week estradiol treatment is followed 14 days (2 weeks) of progesterone taper (as medroxy-progesterone 10 mg/day).
|
Venlafaxine XR
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Overall Study
STARTED
|
97
|
96
|
146
|
|
Overall Study
COMPLETED
|
95
|
93
|
142
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
4
|
Reasons for withdrawal
| Measure |
Low-dose 17-ß-Estradiol With Progesterone Taper
Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably. The 8 week estradiol treatment is followed 14 days (2 weeks) of progesterone taper (as medroxy-progesterone 10 mg/day).
|
Venlafaxine XR
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
1
|
|
Overall Study
Did not provide hot flash diary data
|
1
|
3
|
3
|
Baseline Characteristics
MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and Venlafaxine XR for Treatment of Menopausal Symptoms
Baseline characteristics by cohort
| Measure |
Low-dose 17-ß-estradiol With Progesterone Taper
n=97 Participants
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=96 Participants
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=146 Participants
Placebo: The placebo is an inactive pill that looks like the active medication.
|
Total
n=339 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.9 years
STANDARD_DEVIATION 4.1 • n=99 Participants
|
54.8 years
STANDARD_DEVIATION 3.7 • n=107 Participants
|
54.3 years
STANDARD_DEVIATION 3.8 • n=206 Participants
|
54.6 years
STANDARD_DEVIATION 3.8 • n=7 Participants
|
|
Sex: Female, Male
Female
|
97 Participants
n=99 Participants
|
96 Participants
n=107 Participants
|
146 Participants
n=206 Participants
|
339 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
97 participants
n=99 Participants
|
96 participants
n=107 Participants
|
146 participants
n=206 Participants
|
339 participants
n=7 Participants
|
|
Body Mass Index (BMI)
|
28.5 kg/m^2
STANDARD_DEVIATION 6.5 • n=99 Participants
|
29.3 kg/m^2
STANDARD_DEVIATION 6.9 • n=107 Participants
|
27.6 kg/m^2
STANDARD_DEVIATION 6.8 • n=206 Participants
|
28.3 kg/m^2
STANDARD_DEVIATION 6.8 • n=7 Participants
|
|
Smoking
Never
|
50 participants
n=99 Participants
|
54 participants
n=107 Participants
|
70 participants
n=206 Participants
|
174 participants
n=7 Participants
|
|
Smoking
Past
|
30 participants
n=99 Participants
|
27 participants
n=107 Participants
|
50 participants
n=206 Participants
|
107 participants
n=7 Participants
|
|
Smoking
Current
|
17 participants
n=99 Participants
|
14 participants
n=107 Participants
|
24 participants
n=206 Participants
|
55 participants
n=7 Participants
|
|
Smoking
Missing
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
2 participants
n=206 Participants
|
3 participants
n=7 Participants
|
|
Alcohol use (drinks/week)
<7
|
71 participants
n=99 Participants
|
77 participants
n=107 Participants
|
117 participants
n=206 Participants
|
265 participants
n=7 Participants
|
|
Alcohol use (drinks/week)
>=7
|
21 participants
n=99 Participants
|
13 participants
n=107 Participants
|
27 participants
n=206 Participants
|
61 participants
n=7 Participants
|
|
Alcohol use (drinks/week)
Missing
|
5 participants
n=99 Participants
|
6 participants
n=107 Participants
|
2 participants
n=206 Participants
|
13 participants
n=7 Participants
|
|
Marital status
Never married / Divorced / Widowed
|
38 participants
n=99 Participants
|
40 participants
n=107 Participants
|
49 participants
n=206 Participants
|
127 participants
n=7 Participants
|
|
Marital status
Married / living with partner
|
58 participants
n=99 Participants
|
56 participants
n=107 Participants
|
96 participants
n=206 Participants
|
210 participants
n=7 Participants
|
|
Marital status
Missing
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
2 participants
n=7 Participants
|
|
Education
<College graduate
|
48 participants
n=99 Participants
|
48 participants
n=107 Participants
|
70 participants
n=206 Participants
|
166 participants
n=7 Participants
|
|
Education
College graduate
|
49 participants
n=99 Participants
|
48 participants
n=107 Participants
|
75 participants
n=206 Participants
|
172 participants
n=7 Participants
|
|
Education
Missing
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
1 participants
n=7 Participants
|
|
Menopause status
Perimenopausal
|
14 participants
n=99 Participants
|
16 participants
n=107 Participants
|
22 participants
n=206 Participants
|
52 participants
n=7 Participants
|
|
Menopause status
Postmenopausal
|
74 participants
n=99 Participants
|
72 participants
n=107 Participants
|
110 participants
n=206 Participants
|
256 participants
n=7 Participants
|
|
Menopause status
Indeterminate
|
9 participants
n=99 Participants
|
8 participants
n=107 Participants
|
14 participants
n=206 Participants
|
31 participants
n=7 Participants
|
|
Years since final menstrual period (postmenopausal only)
0 - 5
|
35 participants
n=99 Participants
|
39 participants
n=107 Participants
|
68 participants
n=206 Participants
|
142 participants
n=7 Participants
|
|
Years since final menstrual period (postmenopausal only)
6 - 10
|
23 participants
n=99 Participants
|
20 participants
n=107 Participants
|
29 participants
n=206 Participants
|
72 participants
n=7 Participants
|
|
Years since final menstrual period (postmenopausal only)
> 10
|
16 participants
n=99 Participants
|
13 participants
n=107 Participants
|
13 participants
n=206 Participants
|
42 participants
n=7 Participants
|
|
Years since final menstrual period (postmenopausal only)
Not postmenopausal
|
23 participants
n=99 Participants
|
24 participants
n=107 Participants
|
36 participants
n=206 Participants
|
83 participants
n=7 Participants
|
|
Vasomotor symptom (VMS) number of participants with number of hot flashes / day
< 6
|
36 participants
n=99 Participants
|
36 participants
n=107 Participants
|
67 participants
n=206 Participants
|
139 participants
n=7 Participants
|
|
Vasomotor symptom (VMS) number of participants with number of hot flashes / day
6 - < 9
|
32 participants
n=99 Participants
|
31 participants
n=107 Participants
|
39 participants
n=206 Participants
|
102 participants
n=7 Participants
|
|
Vasomotor symptom (VMS) number of participants with number of hot flashes / day
9 - < 12
|
11 participants
n=99 Participants
|
15 participants
n=107 Participants
|
19 participants
n=206 Participants
|
45 participants
n=7 Participants
|
|
Vasomotor symptom (VMS) number of participants with number of hot flashes / day
>= 12
|
18 participants
n=99 Participants
|
14 participants
n=107 Participants
|
21 participants
n=206 Participants
|
53 participants
n=7 Participants
|
|
Age at starting vasomotor symptoms (VMS), years of age
< 50
|
47 participants
n=99 Participants
|
51 participants
n=107 Participants
|
73 participants
n=206 Participants
|
171 participants
n=7 Participants
|
|
Age at starting vasomotor symptoms (VMS), years of age
>= 50
|
48 participants
n=99 Participants
|
44 participants
n=107 Participants
|
71 participants
n=206 Participants
|
163 participants
n=7 Participants
|
|
Age at starting vasomotor symptoms (VMS), years of age
Missing
|
2 participants
n=99 Participants
|
1 participants
n=107 Participants
|
2 participants
n=206 Participants
|
5 participants
n=7 Participants
|
|
Insomnia Severity Index (ISI) Score
|
11.0 units on a scale
STANDARD_DEVIATION 6.3 • n=99 Participants
|
11.7 units on a scale
STANDARD_DEVIATION 6.0 • n=107 Participants
|
10.4 units on a scale
STANDARD_DEVIATION 5.8 • n=206 Participants
|
11.0 units on a scale
STANDARD_DEVIATION 6.0 • n=7 Participants
|
|
Insomnia Severity Index (ISI) Score
No clinically significant insomnia (<= 7)
|
28 participants
n=99 Participants
|
26 participants
n=107 Participants
|
52 participants
n=206 Participants
|
106 participants
n=7 Participants
|
|
Insomnia Severity Index (ISI) Score
Subthreshold insomnia (8 - 14)
|
40 participants
n=99 Participants
|
39 participants
n=107 Participants
|
54 participants
n=206 Participants
|
133 participants
n=7 Participants
|
|
Insomnia Severity Index (ISI) Score
Clinical insomnia (moderate, 15 - 21)
|
21 participants
n=99 Participants
|
25 participants
n=107 Participants
|
32 participants
n=206 Participants
|
78 participants
n=7 Participants
|
|
Insomnia Severity Index (ISI) Score
Clinical insomnia (severe, >= 22)
|
5 participants
n=99 Participants
|
5 participants
n=107 Participants
|
4 participants
n=206 Participants
|
14 participants
n=7 Participants
|
|
Insomnia Severity Index (ISI) Score
Missing
|
3 participants
n=99 Participants
|
1 participants
n=107 Participants
|
4 participants
n=206 Participants
|
8 participants
n=7 Participants
|
|
Pittsburgh Sleep Quality Index (PSQI) Score
|
7.6 units on a scale
STANDARD_DEVIATION 3.6 • n=99 Participants
|
7.6 units on a scale
STANDARD_DEVIATION 3.2 • n=107 Participants
|
7.3 units on a scale
STANDARD_DEVIATION 3.5 • n=206 Participants
|
7.5 units on a scale
STANDARD_DEVIATION 3.4 • n=7 Participants
|
|
Pittsburgh Sleep Quality Index (PSQI) Score
Good quality sleep (< 5)
|
23 participants
n=99 Participants
|
14 participants
n=107 Participants
|
30 participants
n=206 Participants
|
67 participants
n=7 Participants
|
|
Pittsburgh Sleep Quality Index (PSQI) Score
Moderate sleep quality (5 - < 8)
|
21 participants
n=99 Participants
|
35 participants
n=107 Participants
|
46 participants
n=206 Participants
|
102 participants
n=7 Participants
|
|
Pittsburgh Sleep Quality Index (PSQI) Score
Poor sleep quality (>= 8)
|
46 participants
n=99 Participants
|
40 participants
n=107 Participants
|
65 participants
n=206 Participants
|
151 participants
n=7 Participants
|
|
Pittsburgh Sleep Quality Index (PSQI) Score
Missing
|
7 participants
n=99 Participants
|
7 participants
n=107 Participants
|
5 participants
n=206 Participants
|
19 participants
n=7 Participants
|
|
Patient Health Questionnaire (PHQ-9) Depression Score
|
3.9 units on a scale
STANDARD_DEVIATION 4.4 • n=99 Participants
|
3.0 units on a scale
STANDARD_DEVIATION 2.9 • n=107 Participants
|
3.4 units on a scale
STANDARD_DEVIATION 3.7 • n=206 Participants
|
3.4 units on a scale
STANDARD_DEVIATION 3.7 • n=7 Participants
|
|
PHQ-9 Depression Score
No depression (0 - 4)
|
68 participants
n=99 Participants
|
70 participants
n=107 Participants
|
108 participants
n=206 Participants
|
246 participants
n=7 Participants
|
|
PHQ-9 Depression Score
Mild depression (5 - 9)
|
18 participants
n=99 Participants
|
23 participants
n=107 Participants
|
23 participants
n=206 Participants
|
64 participants
n=7 Participants
|
|
PHQ-9 Depression Score
Moderate depression (>= 10)
|
11 participants
n=99 Participants
|
3 participants
n=107 Participants
|
15 participants
n=206 Participants
|
29 participants
n=7 Participants
|
|
Generalized Anxiety Disorder 7 (GAD-7) Score
|
3.0 units on a scale
STANDARD_DEVIATION 4.3 • n=99 Participants
|
2.2 units on a scale
STANDARD_DEVIATION 3.0 • n=107 Participants
|
2.4 units on a scale
STANDARD_DEVIATION 3.4 • n=206 Participants
|
2.5 units on a scale
STANDARD_DEVIATION 3.6 • n=7 Participants
|
|
Generalized Anxiety Disorder 7 (GAD-7) Score
No anxiety (0 - 4)
|
73 participants
n=99 Participants
|
76 participants
n=107 Participants
|
116 participants
n=206 Participants
|
265 participants
n=7 Participants
|
|
Generalized Anxiety Disorder 7 (GAD-7) Score
Mild anxiety (5 - 9)
|
15 participants
n=99 Participants
|
17 participants
n=107 Participants
|
19 participants
n=206 Participants
|
51 participants
n=7 Participants
|
|
Generalized Anxiety Disorder 7 (GAD-7) Score
Moderate anxiety (>= 10)
|
9 participants
n=99 Participants
|
3 participants
n=107 Participants
|
11 participants
n=206 Participants
|
23 participants
n=7 Participants
|
|
Vasomotor Symptoms (VMS) as number of hot flashes
|
8.5 Number of hot flashes per day
STANDARD_DEVIATION 5.7 • n=99 Participants
|
8.2 Number of hot flashes per day
STANDARD_DEVIATION 5.5 • n=107 Participants
|
7.7 Number of hot flashes per day
STANDARD_DEVIATION 4.8 • n=206 Participants
|
8.1 Number of hot flashes per day
STANDARD_DEVIATION 5.3 • n=7 Participants
|
|
Severity of Hot Flashes
|
1.1 units on a scale
STANDARD_DEVIATION 0.5 • n=99 Participants
|
1.0 units on a scale
STANDARD_DEVIATION 0.5 • n=107 Participants
|
1.0 units on a scale
STANDARD_DEVIATION 0.4 • n=206 Participants
|
1.0 units on a scale
STANDARD_DEVIATION 0.5 • n=7 Participants
|
|
Bothersomeness of Hot Flashes
|
2.1 units on a scale
STANDARD_DEVIATION 0.5 • n=99 Participants
|
2.0 units on a scale
STANDARD_DEVIATION 0.5 • n=107 Participants
|
2.0 units on a scale
STANDARD_DEVIATION 0.5 • n=206 Participants
|
2.0 units on a scale
STANDARD_DEVIATION 0.5 • n=7 Participants
|
|
Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS)
|
36.9 units on a scale
STANDARD_DEVIATION 23.8 • n=99 Participants
|
36.8 units on a scale
STANDARD_DEVIATION 23.4 • n=107 Participants
|
32.8 units on a scale
STANDARD_DEVIATION 21.3 • n=206 Participants
|
35.1 units on a scale
STANDARD_DEVIATION 22.6 • n=7 Participants
|
PRIMARY outcome
Timeframe: Week 4Population: Intention-to-treat, i.e., all participants with follow-up data were included.
Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 4 study assessment to produce a mean daily frequency for week 4.
Outcome measures
| Measure |
Low-dose 17-ß-estradiol With Progesterone Taper
n=91 Participants
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=93 Participants
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=139 Participants
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Frequency of Hot Flashes (Vasomotor Symptom [VMS] Frequency) -- Week 4
|
5.3 number of hot flashes per day
Interval 4.2 to 6.5
|
5.1 number of hot flashes per day
Interval 4.1 to 6.0
|
5.8 number of hot flashes per day
Interval 4.9 to 6.7
|
PRIMARY outcome
Timeframe: Week 8Population: Intention-to-treat, i.e., all participants with follow-up data were included.
Measured by self-report diary twice daily (day and night). The day and night frequencies were summed to produce a single number of hot flashes per day. The single number of hot flashes per day were summed and averaged for one week prior to the week 8 study assessment to produce a mean daily frequency for week 8.
Outcome measures
| Measure |
Low-dose 17-ß-estradiol With Progesterone Taper
n=92 Participants
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=89 Participants
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=137 Participants
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Frequency of Hot Flashes (Daily Vasomotor Symptom [VMS] Frequency) -- Week 8
|
3.9 number of hot flashes per day
Interval 2.9 to 4.9
|
4.4 number of hot flashes per day
Interval 3.5 to 5.3
|
5.5 number of hot flashes per day
Interval 4.7 to 6.3
|
SECONDARY outcome
Timeframe: Week 4Population: Intention-to-treat, i.e., all participants with follow-up data were included.
Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS severity for week 4.
Outcome measures
| Measure |
Low-dose 17-ß-estradiol With Progesterone Taper
n=81 Participants
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=86 Participants
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=134 Participants
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Severity of Hot Flashes -- Week 4
|
0.7 units on a scale
Interval 0.6 to 0.9
|
0.7 units on a scale
Interval 0.5 to 0.8
|
0.8 units on a scale
Interval 0.7 to 0.9
|
SECONDARY outcome
Timeframe: Week 8Population: Intention-to-treat, i.e., all participants with follow-up data were included.
Measured by self-report diary twice daily (day and night) for 7 days. Severity ratings ranged from 0 to 3 with lower numbers being less severe and higher numbers being more severe. Data from the day and night severity ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS severity for week 8.
Outcome measures
| Measure |
Low-dose 17-ß-estradiol With Progesterone Taper
n=73 Participants
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=86 Participants
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=133 Participants
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Severity of Hot Flashes -- Week 8
|
0.6 units on a scale
Interval 0.4 to 0.7
|
0.6 units on a scale
Interval 0.4 to 0.7
|
0.7 units on a scale
Interval 0.6 to 0.8
|
SECONDARY outcome
Timeframe: Week 4Population: Intention-to-treat, i.e., all participants with follow-up data were included.
Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 4 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 4.
Outcome measures
| Measure |
Low-dose 17-ß-estradiol With Progesterone Taper
n=82 Participants
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=88 Participants
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=135 Participants
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Bothersomeness of Hot Flashes -- Week 4
|
1.6 units on a scale
Interval 1.4 to 1.7
|
1.6 units on a scale
Interval 1.4 to 1.7
|
1.7 units on a scale
Interval 1.6 to 1.8
|
SECONDARY outcome
Timeframe: Week 8Population: Intention-to-treat, i.e., all participants with follow-up data were included.
Measured by self-report diary twice daily (day and night) for 7 days. Bothersomeness ratings ranged from 0 to 3 with lower numbers being less bothersome and higher numbers being more bothersome. Data from the day and night bothersomeness ratings were averaged for a single daily score. The single daily scores for the week prior to the week 8 study assessment were summed and averaged to produce a mean daily VMS bothersomeness for week 8.
Outcome measures
| Measure |
Low-dose 17-ß-estradiol With Progesterone Taper
n=73 Participants
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=86 Participants
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=133 Participants
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Bothersomeness of Hot Flashes -- Week 8
|
1.4 units on a scale
Interval 1.2 to 1.6
|
1.4 units on a scale
Interval 1.3 to 1.6
|
1.6 units on a scale
Interval 1.5 to 1.7
|
SECONDARY outcome
Timeframe: Week 4Population: Intention-to-treat, i.e., all participants with follow-up data were included.
The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference.
Outcome measures
| Measure |
Low-dose 17-ß-estradiol With Progesterone Taper
n=84 Participants
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=83 Participants
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=128 Participants
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 4
|
18.3 units on a scale
Interval 13.8 to 22.8
|
19.8 units on a scale
Interval 15.6 to 23.9
|
24.2 units on a scale
Interval 20.7 to 27.7
|
SECONDARY outcome
Timeframe: Week 8Population: Intention-to-treat, i.e., all participants with follow-up data were included.
The perceived hot flash related daily interference scale (HFRDIS) is a tool for assessing the impact of hot flashes on quality of life. There are 10 questions with each having a score ranging from 0 to 10. The scores from each question are summed for a total score ranging from 0 to 100. Lower numbers indicate less interference and higher numbers indicate more interference.
Outcome measures
| Measure |
Low-dose 17-ß-estradiol With Progesterone Taper
n=92 Participants
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=86 Participants
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=137 Participants
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
Perceived Hot Flash Interference (Hot Flash Related Daily Interference Scale; HFRDIS) -- Week 8
|
14.6 units on a scale
Interval 10.6 to 18.7
|
18.3 units on a scale
Interval 13.8 to 22.7
|
21.5 units on a scale
Interval 18.1 to 24.9
|
Adverse Events
Low-dose 17-ß-estradiol
Serious events: 0 serious events
Other events: 53 other events
Deaths: 0 deaths
Venlafaxine XR
Serious events: 0 serious events
Other events: 65 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 88 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Low-dose 17-ß-estradiol
n=97 participants at risk
Low-dose 17-ß-estradiol: Low-dose 17-ß-estradiol oral (by mouth), 0.5 mg once per day for 8 (eight) weeks. After the 8-week treatment, women with a uterus will receive medroxyprogesterone 10 mg once per day for 2 weeks (14 days). 17-ß-estradiol is approved by the US Food and Drug Administration (FDA) and is indicated for the treatment of menopausal symptoms. ß is the Greek symbol for beta; the symbol and the word are used interchangeably.
|
Venlafaxine XR
n=96 participants at risk
Venlafaxine XR: Venlafaxine oral (by mouth) 37.5 mg once per day for 1 (one) week, then 75 mg once per day for 7 (seven) weeks. Venlafaxine XR should not be taken while also taking monoamine oxidase inhibitors (MAOIs). Venlafaxine XR is approved by the US Food and Drug Administration (FDA) for treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder, and is available by prescription. Venlafaxine XR is not FDA-approved for the treatment of hot flashes, although prior studies have indicated that it is useful for treating hot flashes and vasomotor symptoms. After the 8-week venlafaxine XR study treatment period, women will receive a tapering dose of venlafaxine XR 37.5 mg once per day for 14 days (2 weeks).
|
Placebo
n=146 participants at risk
Placebo: The placebo is an inactive pill that looks like the active medication.
|
|---|---|---|---|
|
General disorders
Any fatigue/arousal symptom
|
23.5%
20/85 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
32.1%
26/81 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
26.0%
33/127 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
|
Nervous system disorders
Any central nervous system symptom
|
23.9%
22/92 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
31.9%
30/94 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
25.4%
36/142 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
|
Gastrointestinal disorders
Any GI symptom
|
24.5%
23/94 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
26.9%
25/93 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
31.0%
44/142 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
|
Reproductive system and breast disorders
Breast tenderness
|
5.6%
5/90 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
0.00%
0/93 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
5.6%
8/142 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
|
Reproductive system and breast disorders
Vaginal secretions
|
2.2%
2/90 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
3.3%
3/90 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
2.2%
3/139 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
|
Musculoskeletal and connective tissue disorders
Any musculoskeletal symptom
|
9.8%
9/92 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
5.3%
5/94 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
9.2%
13/141 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
|
General disorders
Any miscellaneous symptom
|
29.8%
28/94 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
38.3%
36/94 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
30.3%
43/142 • 8 weeks
At 1-, 4, and 8-weeks, potential adverse events were assessed by a Management and Safety Interview. Symptoms data were collected at screening and weeks 4 and 8. Data are reported as newly emergent adverse events.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place