Trial Outcomes & Findings for Efficacy and Safety Study for the Treatment of Dysfunctional Uterine Bleeding (NCT NCT00293059)

NCT ID: NCT00293059

Last Updated: 2013-11-27

Results Overview

Up to 8 criteria had to be met for complete response during 90-day period. No bleeding episodes (BE) \>7 days, no \>4 BE, no BE with MBL \>=80 mL, no \>1 BE increase from baseline, no increase from baseline in an individual participant's total number of bleeding days and total number of bleeding days not \>24 days. Additionally, for participants included with prolonged bleeding: decrease between maximum duration during run-in and efficacy \>=2 days excessive bleeding: MBL associated with each episode decreased by \>=50% from average of qualifying episodes during run-in.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 190 participants
• Primary outcome timeframe: during a time period of 90 days under treatment
• Results posted on: 2013-11-27

Participant Flow

The date of first participant, first visit was 14 Dec 2005. The date of last participant, last visit was 21 May 2008.

A total of 1077 participants were screened for inclusion into the study; 887 participants failed screening. The remaining 190 participants were randomized; 120 participants were randomized to the estradiol valerate/dienogest group and 70 participants to the placebo group.

Participant milestones

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo Matching placebo to be taken orally daily
Overall Study STARTED	120	70
Overall Study Subjects Received Treatment	119	66
Overall Study Cycle 1/Treatment Day 28	115	64
Overall Study Cycle 3/Treatment Day 84	100	55
Overall Study Cycle 7/Treatment Day 196	113	62
Overall Study COMPLETED	85	51
Overall Study NOT COMPLETED	35	19

Reasons for withdrawal

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo Matching placebo to be taken orally daily
Overall Study Adverse Event	12	4
Overall Study Lack of Efficacy	2	0
Overall Study Lost to Follow-up	2	3
Overall Study Pregnancy	1	1
Overall Study Protocol Violation	2	0
Overall Study Withdrawal by Subject	11	5
Overall Study Participant moved out of state	1	0
Overall Study Participant stopped study drug	1	0
Overall Study Noncompliant - sanitary pads collection	0	1
Overall Study missing	3	5

Baseline Characteristics

Efficacy and Safety Study for the Treatment of Dysfunctional Uterine Bleeding

Baseline characteristics by cohort

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=120 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=70 Participants Matching placebo to be taken orally daily	Total n=190 Participants Total of all reporting groups
Age Continuous	36.9 Years STANDARD_DEVIATION 7.5 • n=5 Participants	37.0 Years STANDARD_DEVIATION 6.7 • n=7 Participants	36.9 Years STANDARD_DEVIATION 7.2 • n=5 Participants
Sex: Female, Male Female	120 Participants n=5 Participants	70 Participants n=7 Participants	190 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index (BMI)	26.3 kg/m^2 STANDARD_DEVIATION 3.6 • n=5 Participants	25.8 kg/m^2 STANDARD_DEVIATION 3.6 • n=7 Participants	26.1 kg/m^2 STANDARD_DEVIATION 3.6 • n=5 Participants
excessive bleeding	91 participants n=5 Participants	60 participants n=7 Participants	151 participants n=5 Participants
prolonged bleeding	26 participants n=5 Participants	12 participants n=7 Participants	38 participants n=5 Participants
frequent bleeding	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
prolonged and frequent bleeding	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
prolonged and excessive bleeding	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants
frequent and excessive bleeding	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
prolonged, frequent and excessive bleeding	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: during a time period of 90 days under treatment

Population: The intent-to-treat (ITT) group consisted of all randomized participants.

Up to 8 criteria had to be met for complete response during 90-day period. No bleeding episodes (BE) >7 days, no >4 BE, no BE with MBL >=80 mL, no >1 BE increase from baseline, no increase from baseline in an individual participant's total number of bleeding days and total number of bleeding days not >24 days. Additionally, for participants included with prolonged bleeding: decrease between maximum duration during run-in and efficacy >=2 days excessive bleeding: MBL associated with each episode decreased by >=50% from average of qualifying episodes during run-in.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=120 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=70 Participants Matching placebo to be taken orally daily
Proportion of Participants With no Dysfunctional Uterine Bleeding (DUB) Symptoms	0.292 Proportion of participants	0.029 Proportion of participants

SECONDARY outcome

Timeframe: during a time period of 90 days under treatment

Population: The ITT population consisted of all randomized participants who enrolled with prolonged bleeding.

Prolonged bleeding was defined as 2 or more bleeding episodes, each lasting 8 or more days in a 90-day period. Participants were considered cured if they had no bleeding episodes lasting more than 7 days and the decrease between the maximum duration during the run-in phase and the maximum duration during the efficacy phase was at least 2 days.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=26 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=12 Participants Matching placebo to be taken orally daily
Proportion of Participants Cured From Prolonged Bleeding	0.154 Proportion of participants	0.083 Proportion of participants

SECONDARY outcome

Timeframe: during a time period of 90 days under treatment

Population: The ITT population consisted of all randomized participants who enrolled with frequent bleeding.

Frequent bleeding was defined as greater than 5 bleeding episodes, with a minimum of 20 bleeding days overall in a 90-day period. Participants were considered cured if they had no more than 4 bleeding episodes and the total number of bleeding days did not exceed 24 days and there was no increase in the total number of bleeding days in the efficacy phase as compared to the run-in phase.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=4 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=2 Participants Matching placebo to be taken orally daily
Proportion of Participants Cured From Frequent Bleeding	0.250 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: during a time period of 90 days under treatment

Population: The ITT population consisted of all randomized participants who enrolled with excessive bleeding.

Excessive bleeding was defined as 2 or more bleeding episodes each with blood loss volume of 80 mL or more in a 90-day period. Participants were considered cured if (1) the blood loss volume associated with each episode was less than 80 mL and (2) the blood loss volume associated with each bleeding episode represented a decrease of at least 50% from the average of the qualifying bleeding episodes, where the qualifying bleeding episodes were those with a blood loss volume ≥ 80 mL (per episode) that occurred during the run-in phase.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=91 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=60 Participants Matching placebo to be taken orally daily
Proportion of Participants Cured From Excessive Bleeding	0.385 Proportion of participants	0.05 Proportion of participants

SECONDARY outcome

Timeframe: from baseline up to treatment day 84

Population: ITT, excluding participants with missing data

The investigators assessed the participants' change in DUB symptoms at day 84 (visit 7) compared with admission to the study according to a scale of 1 (very much improved) to 7 (very much worse), using the following information: central laboratory data, physical examination, e-diary data, and participant interview. Improvement was defined as being classified as a score of 3 or less.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=100 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=55 Participants Matching placebo to be taken orally daily
Proportion of Participants With Improvement in the Investigator's Global Assessment Scale at Treatment Day 84	0.880 Proportion of participants	0.509 Proportion of participants

SECONDARY outcome

Timeframe: from baseline up to treatment day 196

Population: ITT, excluding participants with missing data

The investigators assessed the participants' change in DUB symptoms at day 196 (visit 11) compared with admission to the study according to a scale of 1 (very much improved) to 7 (very much worse), using the following information: central laboratory data, physical examination, e-diary data, and participant interview. Improvement was defined as being classified as a score of 3 or less.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=114 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=62 Participants Matching placebo to be taken orally daily
Proportion of Participants With Improvement in the Investigator's Global Assessment Scale at Treatment Day 196	0.807 Proportion of participants	0.419 Proportion of participants

SECONDARY outcome

Timeframe: from baseline up to treatment day 84

Population: ITT, excluding participants with missing data

Participants assessed their overall improvement at day 84 (visit 7) compared with their condition at admission to the study on a scale of 1 (very much improved) to 7 (very much worse). Improvement was defined as being classified as a score of 3 or less.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=85 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Proportion of Participants With Improvement in the Participant's Overall Assessment Scale at Treatment Day 84	0.835 Proportion of participants	0.426 Proportion of participants

SECONDARY outcome

Timeframe: from baseline up to treatment day 196

Population: ITT, excluding participants with missing data

Participants assessed their overall improvement at day 196 (visit 11) compared with their condition at admission to the study on a scale of 1 (very much improved) to 7 (very much worse). Improvement was defined as being classified as a score of 3 or less.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=85 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Proportion of Participants With Improvement in the Participant's Overall Assessment Scale at Treatment Day 196	0.812 Proportion of participants	0.383 Proportion of participants

SECONDARY outcome

Timeframe: Baseline and reference period of 90 days under treatment

Population: ITT, excluding participants with missing data

Menstrual blood loss was determined using the alkaline hematin method for the 90 days before treatment (baseline) and for 90 days under treatment. A negative value indicates a reduction in blood loss after treatment.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=79 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=46 Participants Matching placebo to be taken orally daily
Change From Baseline in Blood Loss Volume for All Participants to the Reference Period of 90 Days Under Treatment	-353.1 mL Standard Deviation 309.4	-130.4 mL Standard Deviation 338.3

SECONDARY outcome

Timeframe: 28 days

Population: ITT, excluding participants with missing data

Menstrual blood loss volume was determined using the alkaline hematin method after participants were on treatment for one cycle

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=117 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=66 Participants Matching placebo to be taken orally daily
Menstrual Blood Loss Volume for All Participants at Cycle 1	136.5 mL Standard Deviation 141.3	146.9 mL Standard Deviation 133.9

SECONDARY outcome

Timeframe: 28 days

Population: ITT, excluding participants with missing data

Menstrual blood loss volume was determined using the alkaline hematin method after participants were on treatment for 3 cycles

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=104 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=58 Participants Matching placebo to be taken orally daily
Menstrual Blood Loss Volume for All Participants at Cycle 3	59.9 mL Standard Deviation 91.5	139.6 mL Standard Deviation 92.2

SECONDARY outcome

Timeframe: 28 days

Population: ITT, excluding participants with missing data

Menstrual blood loss volume was determined using the alkaline hematin methods after participants were on treatment for 7 cycles

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=86 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=49 Participants Matching placebo to be taken orally daily
Menstrual Blood Loss Volume for All Participants at Cycle 7	41.3 mL Standard Deviation 54.2	113.3 mL Standard Deviation 76.6

SECONDARY outcome

Timeframe: baseline and reference period of 90 days under treatment

Population: ITT, participants with excessive bleeding at baseline

The blood loss volume for participants with excessive bleeding (2 or more bleeding episodes each with blood loss volume of 80 mL or more during the run-in phase) was determined for the 90 days before treatment (ie, run-in phase) and for the 90 days under treatment. A negative value indicates a reduction in blood loss while under treatment compared to before treatment.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=65 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=42 Participants Matching placebo to be taken orally daily
Change From Baseline in Blood Loss Volume for Participants With Excessive Bleeding to the Reference Period of 90 Days Under Treatment	-411.9 mL Standard Deviation 308.5	-152.3 mL Standard Deviation 343.2

SECONDARY outcome

Timeframe: 28 days

Population: ITT, participants with excessive bleeding at baseline

The blood loss volume for participants with excessive bleeding (2 or more bleeding episodes each with blood loss volume of 80 mL or more during the run-in phase) was determined using the alkaline hematin method after participants were on treatment for one cycle.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=90 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=58 Participants Matching placebo to be taken orally daily
Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 1	206.1 mL Standard Deviation 179.8	194.7 mL Standard Deviation 132.2

SECONDARY outcome

Timeframe: 28 days

Population: ITT, participants with excessive bleeding at baseline

The blood loss volume for participants with excessive bleeding (2 or more bleeding episodes each with blood loss volume of 80 mL or more during the run-in phase) was determined using the alkaline hematin method after participants were on treatment for 3 cycles.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=78 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=51 Participants Matching placebo to be taken orally daily
Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 3	67.1 mL Standard Deviation 96.2	147.4 mL Standard Deviation 93.4

SECONDARY outcome

Timeframe: 28 days

Population: ITT, participants with excessive bleeding at baseline

The blood loss volume for participants with excessive bleeding (2 or more bleeding episodes each with blood loss volume of 80 mL or more during the run-in phase) was determined using the alkaline hematin method after participants were on treatment for 7 cycles.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=68 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=42 Participants Matching placebo to be taken orally daily
Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 7	47.5 mL Standard Deviation 58.5	116.9 mL Standard Deviation 77.5

SECONDARY outcome

Timeframe: baseline and reference period of 90 days under treatment

Population: ITT, excluding participants with missing data

The number of bleeding days was determine for the 90 days before treatment (baseline) and for 90 days while under treatment. A negative value indicates a reduction in the number of bleeding days while under treatment compared to baseline.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=79 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=46 Participants Matching placebo to be taken orally daily
Change From Baseline in Number of Bleeding Days to the Reference Period of 90 Days Under Treatment	-5.2 bleeding days Standard Deviation 11.4	-2.0 bleeding days Standard Deviation 6.2

SECONDARY outcome

Timeframe: baseline and reference period of 90 days under treatment

Population: ITT, excluding participants with missing data

A bleeding episode was one that lasted for at least 2 days, and where the bleeding days were separated by no more than 1 bleeding-free day. An episode stopped with 2 consecutive bleeding-free days. The number of episodes was determined for the 90 days before treatment and for the 90 days under treatment. A negative values indicates a reduction from baseline in the number of episodes while under treatment.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=79 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=46 Participants Matching placebo to be taken orally daily
Change From Baseline in Number of Bleeding Episodes to the Reference Period of 90 Days Under Treatment	-0.5 bleeding episodes Standard Deviation 1.5	-0.3 bleeding episodes Standard Deviation 0.9

SECONDARY outcome

Timeframe: baseline and reference period of 90 days under treatment

Population: ITT, excluding participants with missing data

The number of total sanitary protection items used during the 90-day run-in phase before treatment (baseline) and the number of total sanitary protection items used during the 90 days while under treatment was determined. A negative value indicates a reduction in the number of sanitary protection items used while under treatment compared to the number used before treatment.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=79 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=46 Participants Matching placebo to be taken orally daily
Change From Baseline in Number of Sanitary Protection Used at 90 Days of Treatment	-43.6 Sanitary protection products Standard Deviation 40.9	-21.2 Sanitary protection products Standard Deviation 43.2

SECONDARY outcome

Timeframe: baseline and treatment day 84

Population: ITT, excluding participants with missing data

The PGWBI questionnaire consisted of 22 questions that were answered using a 6-grade Likert scale. The minimum overall score was 22 and the maximum was 132. The higher the score, the better the well being of the participant. The observation phase was the last 4 weeks. The following 6 dimensions were derived from the questionnaire: anxiety, depressed mood, positive well-being, self-control, health, and vitality and the highest possible scores were 30, 18, 24, 18, 18, and 24, respectively.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=82 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=44 Participants Matching placebo to be taken orally daily
Change From Baseline in Psychological General Well-Being Index (PGWBI) Scores at Treatment Day 84	-1.0 Scores on a scale Standard Deviation 13.4	-0.7 Scores on a scale Standard Deviation 10.1

SECONDARY outcome

Timeframe: baseline and treatment day 196

Population: ITT, excluding participants with missing data

The PGWBI questionnaire consisted of 22 questions that were answered using a 6-grade Likert scale. The minimum overall score was 22 and the maximum was 132. The higher the score, the better the well being of the participant. The observation phase was the last 4 weeks. The following 6 dimensions were derived from the questionnaire: anxiety, depressed mood, positive well-being, self-control, health, and vitality and the highest possible scores were 30, 18, 24, 18, 18, and 24, respectively.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=81 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=43 Participants Matching placebo to be taken orally daily
Change From Baseline in Psychological General Well-Being Index (PGWBI) Scores at Treatment Day 196	0.7 Scores on a scale Standard Deviation 14.6	1.0 Scores on a scale Standard Deviation 10.1

SECONDARY outcome

Timeframe: baseline and treatment day 84

Population: ITT, excluding participants with missing data

The MFSQ was designed to measure aspects of female sexuality and asked about the participants' sexual experience during the last 4 weeks. Higher scores represent higher, more complete, or better integrated levels of female sexual function. Minimum and maximum possible values are 19 and 133.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=42 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=22 Participants Matching placebo to be taken orally daily
Change From Baseline in McCoy Female Sexuality Questionnaire (MFSQ) Scores at Treatment Day 84	-3.5 Scores on a scale Standard Deviation 12.0	0.8 Scores on a scale Standard Deviation 8.4

SECONDARY outcome

Timeframe: baseline and treatment day 196

Population: ITT, excluding participants with missing data

The MFSQ was designed to measure aspects of female sexuality and asked about the participants' sexual experience during the last 4 weeks. Higher scores represent higher, more complete, or better integrated levels of female sexual function. Minimum and maximum possible values are 19 and 133.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=37 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=24 Participants Matching placebo to be taken orally daily
Change From Baseline in McCoy Female Sexuality Questionnaire (MFSQ) Scores at Treatment Day 196	-2.0 Scores on a scale Standard Deviation 15.9	-0.8 Scores on a scale Standard Deviation 9.1

SECONDARY outcome

Timeframe: baseline and treatment day 84

Population: ITT, excluding participants with missing data

The Health State Classification of the EQ-5D comprised 5 questions addressing mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Participants were asked to indicate their current health state by ticking the most appropriate of 3 statements about each of the questions (ie, no problems, some problems, extreme problems). The best possible answers were (1,1,1,1,1), which equals a valuation score of 1.0. The worst possible answers were (3,3,3,3,3), which equals a valuation score of .594. The change from the baseline score at day 84 is presented.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=86 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Change From Baseline in EuroQoL (Quality of Life) 5 Dimensional Health Questionnaire (EQ-5D) Scores at Treatment Day 84	-0.0035 scores on a scale Standard Deviation 0.2145	-0.0024 scores on a scale Standard Deviation 0.1507

SECONDARY outcome

Timeframe: baseline and treatment day 196

Population: ITT, excluding participants with missing data

The Health State Classification of the EQ-5D comprised 5 questions addressing mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Participants were asked to indicate their current health state by ticking the most appropriate of 3 statements about each of the questions (ie, no problems, some problems, extreme problems). The best possible answers were (1,1,1,1,1), which equals a valuation score of 1.0. The worst possible answers were (3,3,3,3,3), which equals a valuation score of .594. The change from the baseline score at day 196 is presented.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=85 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Change From Baseline in EuroQoL (Quality of Life) 5 Dimensional Health Questionnaire (EQ-5D) Scores at Treatment Day 196	0.0052 Scores on a scale Standard Deviation 0.1504	0.0154 Scores on a scale Standard Deviation 0.1611

SECONDARY outcome

Timeframe: baseline and treatment day 84

Population: ITT, excluding participants with missing data

The visual analogue scale (ie, "thermometer") had endpoints of 100 (best imaginable health state) at the top, and 0 (worst imaginable health state) at the bottom. Participants rated their current health state by drawing a line from the box marked 'your own health state today' to the appropriate point on the thermometer scale. The change from baseline at day 84 is presented.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=85 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Change From Baseline in Visual Analogue Scale (VAS) of the EQ-5D Score at Treatment Day 84	-2.07 Scores on a scale Standard Deviation 11.74	-0.26 Scores on a scale Standard Deviation 10.38

SECONDARY outcome

Timeframe: baseline and treatment day 196

Population: ITT, excluding participants with missing data

The visual analogue scale (ie, "thermometer") had endpoints of 100 (best imaginable health state) at the top, and 0 (worst imaginable health state) at the bottom. Participants rated their current health state by drawing a line from the box marked 'your own health state today' to the appropriate point on the thermometer scale. The change from baseline at day 196 is presented.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=84 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Change From Baseline in Visual Analogue Scale (VAS) of the EQ-5D Score at Treatment Day 196	-0.07 Scores on a scale Standard Deviation 12.86	-0.51 Scores on a scale Standard Deviation 12.90

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked if there was any change in her employment status in the last 12 weeks. The proportion of participants with a change is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=86 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Change in the Employment Status) at Treatment Day 84	0.221 Proportion of participants	0.106 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked how many days and hours they missed from work during the past 12 weeks because of problems associated with DUB, not including the time missed to participate in this study.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=75 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=41 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Days Missed From Work) at Treatment Day 84	0.4 day Standard Deviation 1.84	0.7 day Standard Deviation 1.87

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked to rate on a scale of 0 to 10, how much their DUB affected productivity while working during the past 12 weeks, where 0 represented that DUB had no effect on work and 10 represented that DUB completely prevented her from working.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=78 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=42 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Productivity While Working) at Treatment Day 84	2.38 Scores on a scale Standard Deviation 2.175	3.07 Scores on a scale Standard Deviation 2.088

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked to rate on a scale of 0 to 10 how much DUB affected their ability to do their regular daily activities, other than work at a job, during the past 12 weeks where 0 represented that DUB had no effect on daily activities and 10 represented that DUB completely prevented her from doing daily activities.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=80 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=45 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Regular Daily Activities) at Treatment Day 84	2.81 Scores on a scale Standard Deviation 2.551	3.91 Scores on a scale Standard Deviation 2.466

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked if they had any unscheduled outpatient visits to a hospital because of DUB during the past 12 weeks, not including visits that were due to participation in this study. The proportion of participants with such visits is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=86 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Unscheduled Outpatient Visit at Hospital) at Treatment Day 84	0.012 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked if they had any unscheduled visits to a physician (non-hospital medical care) because of DUB during the past 12 weeks, not including visits that were due to participation in this study. The proportion of participants with such visits is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=85 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Unscheduled Visit to Physician) at Treatment Day 84	0.012 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked if they had any unscheduled procedures (eg, laparoscopy, laboratory tests, ultrasound) because of DUB during the past 12 weeks. The proportion of participants with such procedures is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=86 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Additional Unscheduled Procedures) at Treatment Day 84	0.012 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked if they had received ambulatory services (eg, home help, child care) because of DUB during the past 12 weeks. The proportion of participants who received such services is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=103 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=57 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Received Ambulatory Services) at Treatment Day 84	0.0 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked to specify if they had out-of-pocket expenses because of DUB during the past 12 weeks, including over-the-counter medication (the name of the medication, the number of packages, and the cost per package), co-payments due to prescribed medication, and costs to travel to and from medical appointments. The proportion of participants with such expenses is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=99 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=54 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Out-of-pocket Expenses) at Treatment Day 84	0.323 Proportion of participants	0.407 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 84

Population: ITT, excluding participants with missing data

Participants were asked if they had any medical treatment (eg, prescribed medication, other treatment) because of DUB during the past 12 weeks. The proportion of participants with such treatment is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=85 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=48 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Any Medical Treatment) at Treatment Day 84	0.047 Proportion of participants	0.062 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked if there was any change in employment status in the last 12 weeks. The proportion of participants with a change is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=85 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Change in the Employment Status) at Treatment Day 196	0.129 Proportion of participants	0.213 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked how many days and hours were missed from work during the past 12 weeks because of problems associated with DUB, not including the time missed to participate in this study.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=79 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=42 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Days Missed From Work) at Treatment Day 196	0.2 days Standard Deviation 1.19	0.4 days Standard Deviation 1.51

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked to rate on a scale of 0 to 10, how much DUB affected their productivity while working during the past 12 weeks, where 0 represented that DUB had no effect on work and 10 represented that DUB completely prevented her from working.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=78 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=38 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Productivity While Working) at Treatment Day 196	2.40 Scores on a scale Standard Deviation 2.293	4.03 Scores on a scale Standard Deviation 3.123

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked to rate on a scale of 0 to 10 how much DUB affected their ability to do regular daily activities, other than work at a job, during the past 12 weeks where 0 represented that DUB had no effect on daily activities and 10 represented that DUB completely prevented her from doing her daily activities.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=80 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=42 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Regular Daily Activities) at Treatment Day 196	2.48 Scores on a scale Standard Deviation 2.291	4.10 Scores on a scale Standard Deviation 2.903

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked if they had any unscheduled outpatient visits to a hospital because of DUB during the past 12 weeks, not including visits that were due to participation in this study. The proportion of participants with such visits is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=85 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=46 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Unscheduled Outpatient Visit at Hospital) at Treatment Day 196	0.012 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked if they had any unscheduled visits to a physician (non-hospital medical care) because of DUB during the past 12 weeks, not including visits that were due to participation in this study. The proportion of participants with such visits is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=84 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=45 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Unscheduled Visit to Physician) at Treatment Day 196	0.024 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked if they had any unscheduled procedures (eg, laparoscopy, laboratory tests, ultrasound) because of DUB during the past 12 weeks. The proportion of participants with such procedures is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=84 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=46 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Additional Unscheduled Procedures) at Treatment Day 196	0.024 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked if they had received ambulatory services (eg, home help, child care) because of DUB during the past 12 weeks. The proportion of participants who had received such services is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=81 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=45 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Received Ambulatory Services) at Treatment Day 196	0.012 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked to specify out-of-pocket expenses because of DUB during the past 12 weeks, including over-the-counter medication, co-payments due to prescribed medication, and costs to travel to and from medical appointments. The proportion of participants with such expenses is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=87 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=51 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Out-of-pocket Expenses) at Treatment Day 196	0.241 Proportion of participants	0.314 Proportion of participants

SECONDARY outcome

Timeframe: treatment day 196

Population: ITT, excluding participants with missing data

Participants were asked if they had any medical treatment (eg, prescribed medication, other treatment) because of DUB during the past 12 weeks. The proportion of participants with such treatment is displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=85 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=47 Participants Matching placebo to be taken orally daily
Resource Use Assessment by Use of a Self Administered Questionnaire (Any Medical Treatment) at Treatment Day 196	0.047 Proportion of participants	0.043 Proportion of participants

SECONDARY outcome

Timeframe: baseline and treatment day 196

Population: ITT, excluding participants with missing data

Hematocrit was measured before treatment and after 196 days under treatment. A positive value indicates an increase in hematocrit from baseline at treatment day 196.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=108 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=59 Participants Matching placebo to be taken orally daily
Change From Baseline in Hematocrit (Hct) Concentrations at Treatment Day 196	1.30 Percentage of blood volume Standard Deviation 2.98	0.09 Percentage of blood volume Standard Deviation 3.04

SECONDARY outcome

Timeframe: baseline and treatment day 84

Population: ITT, excluding participants with missing data

Serum ferritin was measured before treatment and after 84 days under treatment. A positive value indicates an increase in serum ferritin from baseline at treatment day 84.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=99 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=54 Participants Matching placebo to be taken orally daily
Change From Baseline in Serum Ferritin Concentration at Treatment Day 84	0.2 ng/mL Standard Deviation 35.6	-1.5 ng/mL Standard Deviation 12.2

SECONDARY outcome

Timeframe: baseline and treatment day 196

Population: ITT, excluding participants with missing data

Serum ferritin was measured before treatment and after 196 days under treatment. A positive value indicates an increase in serum ferritin from baseline at treatment day 196.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=112 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=59 Participants Matching placebo to be taken orally daily
Change From Baseline in Serum Ferritin Concentration at Treatment Day 196	5.3 ng/mL Standard Deviation 37.8	2.0 ng/mL Standard Deviation 11.9

SECONDARY outcome

Timeframe: baseline and treatment day 84

Population: ITT, excluding participants with missing data

Hemoglobin was measured before treatment and after 84 days under treatment. A positive value indicates an increase in hemoglobin from baseline at treatment day 84.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=96 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=53 Participants Matching placebo to be taken orally daily
Change From Baseline in Hemoglobin Concentration at Treatment Day 84	0.22 g/dL Standard Deviation 0.83	0.17 g/dL Standard Deviation 0.62

SECONDARY outcome

Timeframe: baseline and treatment day 196

Population: ITT, excluding participants with missing data

Hemoglobin was measured before treatment and after 196 days under treatment. A positive value indicates an increase in hemoglobin from baseline at treatment day 196.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=108 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=59 Participants Matching placebo to be taken orally daily
Change From Baseline in Hemoglobin Concentration at Treatment Day 196	0.57 g/dL Standard Deviation 1.02	0.20 g/dL Standard Deviation 1.03

POST_HOC outcome

Timeframe: during a time period of 28 days under treatment

Population: Only participants with heavy menstrual bleeding were included in the analysis.

End of Study menstrual blood loss (MBL) ≤ 80 mL and a decrease to a value of ≤ 50% of the Baseline MBL was considered as treatment success.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=88 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=60 Participants Matching placebo to be taken orally daily
Proportion of Participants With Successful Treatment End of study MBL <=80 mL	0.568 Proportion of participants	0.183 Proportion of participants
Proportion of Participants With Successful Treatment Decrease MBL >=50% of baseline MBL	0.568 Proportion of participants	0.217 Proportion of participants
Proportion of Participants With Successful Treatment Successful treatment	0.511 Proportion of participants	0.133 Proportion of participants

POST_HOC outcome

Timeframe: during a time period of 28 days under treatment

Population: Only participants with heavy menstrual bleeding were included in the analysis.

The MBL for each cycle includes intermenstrual bleeding in addition to withdrawal bleeding. Baseline MBL was the mean MBL of measured MBL during three cycles in the run-in Phase. One cycle was defined as 28 days. For this analysis, the run-in Phase was defined by the days 1 to 84 (= 3 cycles each of 28 days). End of Study MBL was measured during Cycle 7 of the Treatment Phase (data imputation and Last Observation Carried Forward was applied).

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=88 Participants A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=60 Participants Matching placebo to be taken orally daily
Change in Absolute Value From Baseline MBL to end-of Study MBL	-114.60 mL Standard Deviation 138.712	-49.944 mL Standard Deviation 117.038

Adverse Events

Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027)

Serious events: 1 serious events

Other events: 46 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=119 participants at risk A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=66 participants at risk Matching placebo to be taken orally daily
Cardiac disorders Myocardial infarction	0.84% 1/119 • Number of events 1	0.00% 0/66
Psychiatric disorders Suicide attempt	0.00% 0/119	1.5% 1/66 • Number of events 1
General disorders Chest pain	0.00% 0/119	1.5% 1/66 • Number of events 1

Other adverse events

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=119 participants at risk A blister card consists of 28 pills taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo	Placebo n=66 participants at risk Matching placebo to be taken orally daily
Blood and lymphatic system disorders Anaemia	1.7% 2/119 • Number of events 3	7.6% 5/66 • Number of events 5
Gastrointestinal disorders Nausea	5.9% 7/119 • Number of events 9	7.6% 5/66 • Number of events 7
Infections and infestations Nasopharyngitis	7.6% 9/119 • Number of events 9	9.1% 6/66 • Number of events 7
Infections and infestations Vaginitis bacterial	5.9% 7/119 • Number of events 8	6.1% 4/66 • Number of events 4
Investigations Weight increased	8.4% 10/119 • Number of events 10	1.5% 1/66 • Number of events 1
Nervous system disorders Headache	5.9% 7/119 • Number of events 8	13.6% 9/66 • Number of events 28
Reproductive system and breast disorders Breast pain	5.0% 6/119 • Number of events 8	0.00% 0/66
Reproductive system and breast disorders Metrorrhagia	5.0% 6/119 • Number of events 7	0.00% 0/66
Skin and subcutaneous tissue disorders Acne	5.0% 6/119 • Number of events 6	0.00% 0/66

Additional Information

Therapeutic Area Head

BAYER

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60