Trial Outcomes & Findings for Low-dose Hormone Therapy for Relief of Vasomotor Symptoms (NCT NCT00446199)

NCT ID: NCT00446199

Last Updated: 2015-05-06

Results Overview

Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Absolute change calculated as week 12 number of moderate to severe hot flushes minus baseline number.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 735 participants
• Primary outcome timeframe: Baseline until 12 weeks of treatment
• Results posted on: 2015-05-06

Participant Flow

The study was conducted at 79 centers in the United States from 26 Mar 2007 (date of first participant's first visit) to 03 Nov 2008 (date of last participant's last visit)

2457 Screened; 1722 Screen Failures; 735 randomized; 726 treated (Safety Analysis Set, SAF); 710 Full Analysis Set (FAS, randomized subjects with Baseline vasomotor symptom (VMS) data, took ≥1 study dose plus ≥1 VMS data day postdose); 569 Per Protocol Set (PPS, all subjects in FAS with ≥75% study drug compliance and no major protocol violations).

Participant milestones

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Overall Study STARTED	183	184	185	183
Overall Study Participants Received Treatment	181	183	182	180
Overall Study Baseline and Postdose VMS Data Available	178	177	179	176
Overall Study COMPLETED	160	164	158	153
Overall Study NOT COMPLETED	23	20	27	30

Reasons for withdrawal

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Overall Study Adverse Event	7	4	6	4
Overall Study Lost to Follow-up	4	5	2	6
Overall Study Protocol Violation	1	2	1	3
Overall Study Withdrawal by Subject	2	5	9	10
Overall Study Site termination	2	0	0	1
Overall Study Randomization in Error	2	0	1	1
Overall Study Lack of Efficacy	1	0	0	1
Overall Study Non-compliant with study drug	1	0	5	0
Overall Study Non-compliant with visit schedule	1	1	1	2
Overall Study Hormone fear	0	0	0	1
Overall Study Lost interest in study participation	0	1	0	0
Overall Study In-/Exclusion criterion violated	2	1	2	1
Overall Study Move	0	1	0	0

Baseline Characteristics

Low-dose Hormone Therapy for Relief of Vasomotor Symptoms

Baseline characteristics by cohort

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=178 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=177 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=179 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=176 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).	Total n=710 Participants Total of all reporting groups
Age, Continuous	53.8 years STANDARD_DEVIATION 5.61 • n=5 Participants	53.5 years STANDARD_DEVIATION 5.77 • n=7 Participants	53.3 years STANDARD_DEVIATION 6.05 • n=5 Participants	53.4 years STANDARD_DEVIATION 6.46 • n=4 Participants	53.5 years STANDARD_DEVIATION 5.97 • n=21 Participants
Sex: Female, Male Female	178 Participants n=5 Participants	177 Participants n=7 Participants	179 Participants n=5 Participants	176 Participants n=4 Participants	710 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Number of participants with hysterectomy/oophorectomy hysterectomized	98 Participants n=5 Participants	91 Participants n=7 Participants	98 Participants n=5 Participants	99 Participants n=4 Participants	386 Participants n=21 Participants
Number of participants with hysterectomy/oophorectomy oophorectomized	61 Participants n=5 Participants	61 Participants n=7 Participants	63 Participants n=5 Participants	59 Participants n=4 Participants	244 Participants n=21 Participants
Body Mass Index (BMI)	29.070 kg/sqm STANDARD_DEVIATION 6.0636 • n=5 Participants	28.190 kg/sqm STANDARD_DEVIATION 5.6965 • n=7 Participants	29.080 kg/sqm STANDARD_DEVIATION 5.7410 • n=5 Participants	27.882 kg/sqm STANDARD_DEVIATION 5.7859 • n=4 Participants	28.543 kg/sqm STANDARD_DEVIATION 5.8370 • n=21 Participants
Years since last menstruation at baseline	9.913 years STANDARD_DEVIATION 8.6719 • n=5 Participants	8.784 years STANDARD_DEVIATION 7.9947 • n=7 Participants	9.214 years STANDARD_DEVIATION 8.1892 • n=5 Participants	9.509 years STANDARD_DEVIATION 8.9693 • n=4 Participants	9.355 years STANDARD_DEVIATION 8.4560 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline until 12 weeks of treatment

Population: Full analysis set (Intention to Treat (ITT)) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.

Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Absolute change calculated as week 12 number of moderate to severe hot flushes minus baseline number.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=177 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=175 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=178 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=176 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value)	-54.515 Hot Flushes per week Interval -324.6 to 60.82	-54.125 Hot Flushes per week Interval -215.9 to 9.03	-44.389 Hot Flushes per week Interval -145.4 to 91.25	-30.020 Hot Flushes per week Interval -485.3 to 55.91

PRIMARY outcome

Timeframe: Baseline until 4 weeks of treatment

Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.

Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Absolute change calculated as week 4 number of moderate to severe hot flushes minus baseline number.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=177 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=174 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=177 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=176 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Median Value)	-46.868 Hot Flushes per week Interval -276.63 to 60.82	-37.596 Hot Flushes per week Interval -162.15 to 35.0	-31.621 Hot Flushes per week Interval -141.44 to 37.91	-15.109 Hot Flushes per week Interval -666.33 to 27.17

PRIMARY outcome

Timeframe: Baseline until 12 weeks of treatment

Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.

Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Daily score is calculated as [(2 x number of moderate hot flushes) + (3 x number of severe hot flushes)] / (total number of moderate to severe hot flushes on that day). Range = 0 (lowest severity) to 3 (highest severity). Absolute change calculated as week 12 severity of moderate to severe hot flushes minus baseline severity.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=177 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=175 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=178 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=176 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value)	-1.9294 Scores on a scale Interval -3.0 to 0.48	-1.000 Scores on a scale Interval -3.0 to 0.443	-0.2638 Scores on a scale Interval -3.0 to 0.337	-0.0698 Scores on a scale Interval -3.0 to 0.542

PRIMARY outcome

Timeframe: Baseline until 4 weeks of treatment

Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.

Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Daily score is calculated as [(2 x number of moderate hot flushes) + (3 x number of severe hot flushes)] / (total number of moderate to severe hot flushes on that day). Range = 0 (lowest severity) to 3 (highest severity). Absolute change calculated as week 4 severity of moderate to severe hot flushes minus baseline severity.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=177 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=174 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=177 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=176 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Median Value)	-0.2905 Scorese on a scale Interval -3.0 to 0.383	-0.1821 Scorese on a scale Interval -2.8 to 1.267	-0.0651 Scorese on a scale Interval -2.898 to 0.38	0.0000 Scorese on a scale Interval -3.0 to 0.516

SECONDARY outcome

Timeframe: Baseline until 12 weeks of treatment

Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.

Vaginal pH determined following speculum examination using vaginal pH paper and recorded on case report form (CRF). Absolute change calculated as week 12 pH minus baseline pH.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=167 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=169 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=169 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=158 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 12 in Vaginal pH	-0.63 (pH) Standard Deviation 0.874	-0.63 (pH) Standard Deviation 0.935	-0.66 (pH) Standard Deviation 0.967	-0.06 (pH) Standard Deviation 0.698

SECONDARY outcome

Timeframe: Baseline until 12 weeks of treatment

Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.

Calculated as (percentage of superficial cells) + 0.5 * (percentage of intermediate cells). Absolute change calculated as week 12 value minus baseline value.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=161 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=170 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=164 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=157 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 12 in Vaginal Maturation Value	10.07 Percentages of cells Standard Deviation 28.638	11.71 Percentages of cells Standard Deviation 29.185	7.69 Percentages of cells Standard Deviation 25.627	-2.41 Percentages of cells Standard Deviation 20.923

SECONDARY outcome

Timeframe: After 12 weeks of treatment

Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.

Subjects self-assessed symptom severity

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=172 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=171 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=172 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=164 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' none	83 participants	70 participants	71 participants	70 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' mild	59 participants	52 participants	62 participants	47 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' moderate	24 participants	38 participants	29 participants	35 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Dryness' severe	6 participants	11 participants	10 participants	12 participants

SECONDARY outcome

Timeframe: After 12 weeks of treatment

Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.

Subjects self-assessed symptom severity

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=172 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=171 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=172 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=164 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' none	152 participants	140 participants	146 participants	128 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' mild	20 participants	24 participants	21 participants	22 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' moderate	0 participants	3 participants	5 participants	11 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal and/or Vulvar Irritation/Itching' severe	0 participants	4 participants	0 participants	3 participants

SECONDARY outcome

Timeframe: After 12 weeks of treatment

Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.

Subjects self-assessed symptom severity

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=172 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=171 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=170 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=162 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' none	166 participants	169 participants	167 participants	153 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' mild	6 participants	2 participants	1 participants	9 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' severe	0 participants	0 participants	1 participants	0 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Dysuria' moderate	0 participants	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: After 12 weeks of treatment

Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.

Subjects self-assessed symptom severity

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=166 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=165 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=162 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=152 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' none	128 participants	132 participants	127 participants	118 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' mild	21 participants	22 participants	21 participants	19 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' moderate	13 participants	7 participants	11 participants	11 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Pain Associated With Sexual Activity' severe	4 participants	4 participants	3 participants	4 participants

SECONDARY outcome

Timeframe: After 12 weeks of treatment

Population: Full analysis set. Numbers differ from the complete full analysis set due to missing data.

Subjects self-assessed symptom severity

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=166 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=165 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=162 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=153 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' none	164 participants	162 participants	159 participants	151 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' mild	2 participants	2 participants	3 participants	2 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' moderate	0 participants	1 participants	0 participants	0 participants
Symptoms of Vulvar and Vaginal Atrophy: Severity of Symptom 'Vaginal Bleeding Associated With Sexual Activity' severe	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: After 12 weeks of treatment

Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.

Subjects self-assessed presence or absence of symptom

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=173 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=171 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=172 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=163 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Urogenital Symptoms: Number of Participants With Symptom 'Frequent Urination'	45 participants	56 participants	62 participants	57 participants

SECONDARY outcome

Timeframe: After 12 weeks of treatment

Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.

Subjects self-assessed presence or absence of symptom

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=172 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=170 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=172 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=164 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Urogenital Symptoms: Number of Participants With Symptom 'Involuntary Urination When Laughing or Coughing'	70 participants	53 participants	53 participants	48 participants

SECONDARY outcome

Timeframe: After 12 weeks of treatment

Population: Full analysis set (ITT). Numbers differ from the complete full analysis set due to missing data.

Subjects self-assessed presence or absence of symptom; and if present recorded average number of times per night: 1; 2 to 4; more than 4.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=173 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=171 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=172 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=164 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Urogenital Symptoms: Number of Participants With Symptom 'Urination at Night'	99 participants	114 participants	114 participants	111 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline until 12 weeks of treatment

Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.

Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Absolute change calculated as week 12 number of moderate to severe hot flushes minus baseline number.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=177 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=175 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=178 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=176 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 12 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value)	-60.331 Hot Flushes per week Standard Deviation 37.5217	-55.317 Hot Flushes per week Standard Deviation 30.2311	-41.783 Hot Flushes per week Standard Deviation 32.6122	-31.916 Hot Flushes per week Standard Deviation 44.4507

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline until 4 weeks of treatment

Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.

Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Absolute change calculated as week 4 number of moderate to severe hot flushes minus baseline number.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=177 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=174 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=177 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=176 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 4 in Weekly Frequency of Moderate to Severe Hot Flushes (Mean Value)	-48.810 Hot Flushes per week Standard Deviation 35.7876	-38.989 Hot Flushes per week Standard Deviation 27.7812	-32.633 Hot Flushes per week Standard Deviation 28.1349	-24.195 Hot Flushes per week Standard Deviation 54.7480

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline until 12 weeks of treatment

Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.

Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Daily score is calculated as [(2 x number of moderate hot flushes) + (3 x number of severe hot flushes)] / (total number of moderate to severe hot flushes on that day). Range = 0 (lowest severity) to 3 (highest severity). Absolute change calculated as week 12 severity moderate to severe hot flushes minus baseline severity.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=177 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=175 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=178 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=176 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 12 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value)	-1.4473 Scores on a scale Standard Deviation 1.11616	-1.2141 Scores on a scale Standard Deviation 1.08299	-0.7822 Scores on a scale Standard Deviation 1.03497	-0.3873 Scores on a scale Standard Deviation 0.76950

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline until 4 weeks of treatment

Population: Full analysis set (ITT) with last observation carried forward approach (LOCF). Numbers differ from the complete full analysis set due to missing Week 1 data.

Subjects record daily on the diary cards the frequency and severity of hot flushes during the treatment period as none, mild, moderate or severe. Daily score is calculated as [(2 x number of moderate hot flushes) + (3 x number of severe hot flushes)] / (total number of moderate to severe hot flushes on that day). Range = 0 (lowest severity) to 3 (highest severity). Absolute change calculated as week 4 severity moderate to severe hot flushes minus baseline severity.

Outcome measures

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=177 Participants One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=174 Participants One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=177 Participants One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle).	Placebo n=176 Participants Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Change From Baseline to Week 4 in Weekly Mean Daily Severity of Moderate to Severe Hot Flushes (Mean Value)	-0.8347 scores on a scale Standard Deviation 1.02226	-0.5859 scores on a scale Standard Deviation 0.89106	-0.4033 scores on a scale Standard Deviation 0.73774	-0.1926 scores on a scale Standard Deviation 0.63585

Adverse Events

0.5mg DRSP / 0.5mg E2 (BAY86-4891)

Serious events: 0 serious events

Other events: 80 other events

Deaths: 0 deaths

0.25mg DRSP / 0.5mg E2 (BAY86-4891)

Serious events: 1 serious events

Other events: 75 other events

Deaths: 0 deaths

Estradiol (E2 0.3mg)

Serious events: 3 serious events

Other events: 68 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=181 participants at risk One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=183 participants at risk One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=182 participants at risk One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle)	Placebo n=180 participants at risk Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Infections and infestations Salpingitis	0.00% 0/181	0.55% 1/183	0.00% 0/182	0.00% 0/180
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/181	0.00% 0/183	0.00% 0/182	0.56% 1/180
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/181	0.00% 0/183	0.55% 1/182	0.00% 0/180
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oropharyngeal cancer stage unspecified	0.00% 0/181	0.00% 0/183	0.55% 1/182	0.00% 0/180
Reproductive system and breast disorders Ovarian cyst	0.00% 0/181	0.00% 0/183	0.55% 1/182	0.00% 0/180
Reproductive system and breast disorders Uterine polyp	0.00% 0/181	0.00% 0/183	0.55% 1/182	0.00% 0/180

Other adverse events

Measure	0.5mg DRSP / 0.5mg E2 (BAY86-4891) n=181 participants at risk One tablet \[0.5mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	0.25mg DRSP / 0.5mg E2 (BAY86-4891) n=183 participants at risk One tablet \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 3 cycles (28 days per cycle).	Estradiol (E2 0.3mg) n=182 participants at risk One tablet \[17β-estradiol (E2 0.3mg)\] per day taken orally for 3 cycles (28 days per cycle)	Placebo n=180 participants at risk Matching placebo tablet per day taken orally for 3 cycles (28 days per cycle).
Gastrointestinal disorders Nausea	2.8% 5/181	3.3% 6/183	3.3% 6/182	1.1% 2/180
Gastrointestinal disorders Abdominal pain	1.1% 2/181	4.4% 8/183	2.7% 5/182	0.56% 1/180
Gastrointestinal disorders Diarrhoea	1.1% 2/181	2.2% 4/183	1.1% 2/182	0.56% 1/180
Gastrointestinal disorders Abdominal distension	2.2% 4/181	0.00% 0/183	1.6% 3/182	0.56% 1/180
Gastrointestinal disorders Vomiting	2.8% 5/181	0.00% 0/183	0.00% 0/182	0.00% 0/180
General disorders Oedema peripheral	1.1% 2/181	2.2% 4/183	0.00% 0/182	0.56% 1/180
Infections and infestations Vaginitis bacterial	3.9% 7/181	1.6% 3/183	3.8% 7/182	3.9% 7/180
Infections and infestations Nasopharyngitis	2.2% 4/181	3.3% 6/183	2.2% 4/182	3.3% 6/180
Infections and infestations Urinary tract infection	2.8% 5/181	2.2% 4/183	1.6% 3/182	2.8% 5/180
Infections and infestations Upper respiratory tract infection	3.3% 6/181	1.6% 3/183	2.2% 4/182	1.7% 3/180
Infections and infestations Vulvovaginal mycotic infection	1.1% 2/181	2.7% 5/183	2.2% 4/182	0.56% 1/180
Infections and infestations Vulvovaginal candidiasis	1.1% 2/181	2.7% 5/183	0.55% 1/182	0.00% 0/180
Investigations Low density lipoprotein increased	2.2% 4/181	3.8% 7/183	3.8% 7/182	5.0% 9/180
Investigations C-reactive protein increased	1.1% 2/181	3.3% 6/183	1.6% 3/182	2.2% 4/180
Investigations Blood glucose increased	2.2% 4/181	1.1% 2/183	1.6% 3/182	2.2% 4/180
Investigations Blood cholesterol increased	1.1% 2/181	1.6% 3/183	2.2% 4/182	1.1% 2/180
Investigations Blood triglycerides increased	2.2% 4/181	1.1% 2/183	0.55% 1/182	1.7% 3/180
Investigations Weight decreased	2.2% 4/181	1.1% 2/183	1.1% 2/182	1.1% 2/180
Investigations Weight increased	1.1% 2/181	2.2% 4/183	0.55% 1/182	1.7% 3/180
Investigations Gamma-glutamyltransferase increased	1.7% 3/181	1.1% 2/183	0.00% 0/182	2.2% 4/180
Musculoskeletal and connective tissue disorders Back pain	3.9% 7/181	1.1% 2/183	2.2% 4/182	1.7% 3/180
Musculoskeletal and connective tissue disorders Pain in extremity	2.2% 4/181	2.2% 4/183	0.55% 1/182	3.9% 7/180
Musculoskeletal and connective tissue disorders Arthralgia	3.3% 6/181	2.7% 5/183	1.6% 3/182	0.56% 1/180
Nervous system disorders Headache	4.4% 8/181	6.0% 11/183	5.5% 10/182	5.0% 9/180
Psychiatric disorders Mood swings	2.2% 4/181	1.1% 2/183	1.1% 2/182	0.56% 1/180
Reproductive system and breast disorders Cervical dysplasia	1.1% 2/181	4.4% 8/183	2.7% 5/182	3.9% 7/180
Reproductive system and breast disorders Breast tenderness	6.6% 12/181	3.3% 6/183	0.55% 1/182	0.00% 0/180
Reproductive system and breast disorders Endometrial hypertrophy	2.2% 4/181	1.6% 3/183	2.7% 5/182	2.8% 5/180
Reproductive system and breast disorders Postmenopausal haemorrhage	2.2% 4/181	1.1% 2/183	0.55% 1/182	0.56% 1/180
Reproductive system and breast disorders Breast pain	2.2% 4/181	0.00% 0/183	0.55% 1/182	0.56% 1/180
Vascular disorders Hypertension	0.00% 0/181	0.55% 1/183	2.2% 4/182	2.8% 5/180

Additional Information

Therapeutic Area Head

BAYER

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee (A) PI will provide copy to Sponsor at least (30) days prior to date of planned submission or presentation. Sponsor will have thirty (30) days to review and provide feedback. If proposed publication presents material adverse effect on the confidentiality of Sponsor's information, then PI shall delay or prevent such publication. (B) In a multi-center trial, the investigative data will be pooled and published as a collaborative effort with consent from all parties including the Sponsor.
• Publication restrictions are in place

Restriction type: OTHER