Effects of E4/DRSP on self-reported physical and emotional premenstrual and menstrual symptoms: data from the phase 3 clinical trial in Europe and Russia

Figures & data

Table 1. Demographic characteristics of participants who completed the MDQ at baseline and at end of treatment in the Europe/russia phase 3 trial with E4/DRSP (N = 1398).

Characteristic	n (%) or mean ± standard deviation
Age (years)	27.2 ± 6.9
18 − 25	700 (50.1)
26–35	511 (36.6)
36–50	187 (13.4)
BMI (kg/m^2)	23.0 ± 3.5
< 25	1,073 (76.8)
25.0 to 29.9	242 (17.3)
≥ 30	83 (5.9)
Race
Asian	9 (0.6)
Black	3 (0.2)
Other^a	3 (0.2)
White	1,383 (98.9)
Smoking Status
Former Smoker	62 (4.4)
Never Smoker	1,117 (79.9)
Current Smoker	219 (15.7)
Hormonal contraceptive use
Starters^b	531 (38.0)
Switchers^c	867 (62.0)
Age (years) by past contraceptive use
Starters	27.8 ± 7.1
Switchers	26.9 ± 6.8
BMI (kg/m^2) by past contraceptive use
Starters	23.0 ± 3.7
Switchers	23.0 ± 3.3

BMI: body mass index; DRSP: drospirenone; E4: estetrol; MDQ: menstruation distress questionnaire; n: number.

^aIncludes America Indian or Alaska Native, Native Hawaiian or other Pacific Islanders and Other.

^bNo past hormonal contraceptive use or use >3 months before initiating study drug.

^cPast hormonal contraceptive use within 3 months before initiating study drug.

Table 2. Mean baseline, EoT and change from baseline for menstrual and premenstrual MDQ t-scores in the Europe/russia phase 3 trial with E4/DRSP.

Domain	Phase	Score range	N^a	Baseline	EoT	CfB	p-value^b
Pain	Premenstrual	35-125	1,395	45.0 ± 11.1	44.7 ± 11.6	−0.2 ± 11.1	0.45
	Menstrual	31-120	1,394	45.2 ± 13.5	43.8 ± 13.8	−1.4 ± 13.3	<0.0001
Water retention	Premenstrual	32-120	1,395	44.0 ± 13.3	43.4 ± 13.4	−0.6 ± 14.2	0.12
	Menstrual	32-126	1,394	44.4 ± 14.1	44.0 ± 14.8	−0.3 ± 15.2	0.40
Impaired concentration	Premenstrual	40-157	1,394	45.4 ± 10.4	45.3 ± 10.5	−0.1 ± 10.7	0.76
	Menstrual	39-159	1,393	44.7 ± 10.5	44.8 ± 11.6	0.1 ± 11.5	0.69
Negative Affect	Premenstrual	34-103	1,395	43.4 ± 11.8	42.7 ± 11.8	−0.7 ± 11.5	0.03
	Menstrual	33-109	1,394	43.6 ± 12.9	42.5 ± 13.1	−1.1 ± 13.2	0.002

Data presented as mean ± standard deviation.

^aOnly includes participants who completed the MDQ at baseline and at end of treatment.

^bTwo-sided paired t-test with α set at 0.05.

CfB: change from baseline; DRSP: drospirenone; E4: estetrol; EoT: end of treatment; MDQ: menstruation distress questionnaire; N: number.

Figure 1. Mean baseline and EoT premenstrual [A] and menstrual [B] MDQ t-scores for starters and switchers in the Europe/Russia phase 3 trial with E4/DRSP.

Table 3. Mean baseline, EoT and change from baseline for premenstrual and menstrual MDQ t-scores in the Europe/russia phase 3 trial with E4/DRSP - starters and switchers.

Starters^a (n = 531)
Domain	Phase	Score range	n^b	Baseline	EoT	CfB	p-value^c
Pain	Premenstrual	35-125	530	45.5 ± 12.2	44.1 ± 11.8	−1.4 ± 11.3	0.0045
	Menstrual	31-120	530	46.2 ± 15.0	42.7 ± 14.1	−3.5 ± 13.0	<0.0001
Water retention	Premenstrual	32-120	531	46.8 ± 15.5	43.4 ± 13.9	−3.3 ± 14.8	<0.0001
	Menstrual	32-126	530	46.9 ± 15.8	43.5 ± 15.1	−3.4 ± 15.0	<0.0001
Impaired concentration	Premenstrual	40-157	530	46.5 ± 11.9	45.6 ± 11.5	−0.9 ± 11.5	0.08
	Menstrual	39-159	530	46.1 ± 11.8	45.6 ± 13.0	−0.5 ± 12.5	0.33
Negative Affect	Premenstrual	34-103	530	45.3 ± 13.5	42.8 ± 12.4	−2.5 ± 12.2	<0.0001
	Menstrual	33-109	530	45.2 ± 14.4	42.5 ± 14.4	−2.7 ± 13.6	<0.0001
Switchers^d (n = 867)
Domain	Phase	Score range	n^b	Baseline	EoT	CfB	p-value^c
Pain	Premenstrual	35-125	865	44.6 ± 10.4	45.1 ± 11.4	0.5 ± 10.9	0.18
	Menstrual	31-120	864	44.5 ± 12.5	44.4 ± 13.5	−0.1 ± 13.4	0.78
Water retention	Premenstrual	32-120	864	42.3 ± 11.4	43.4 ± 13.1	1.1 ± 13.5	0.02
	Menstrual	32-126	864	42.8 ± 12.7	44.3 ± 14.7	1.5 ± 15.1	0.003
Impaired concentration	Premenstrual	40-157	864	44.7 ± 9.4	45.1 ± 9.8	0.4 ± 10.1	0.25
	Menstrual	39-159	863	43.9 ± 9.5	44.4 ± 10.6	0.5 ± 10.8	0.16
Negative Affect	Premenstrual	34-103	865	42.2 ± 10.5	42.7 ± 11.4	0.5 ± 11.0	0.21
	Menstrual	33-109	864	42.7 ± 11.8	42.6 ± 12.3	−0.1 ± 12.9	0.76

Data presented as mean ± standard deviation.

^aStarters: participants who had not used hormonal contraception within 3 months prior to E4/DRSP initiation.

^bOnly includes participants who completed the MDQ at baseline and at end of treatment.

^cTwo-sided paired t-test with α set at 0.05.

^dSwitchers: participants who had used hormonal contraceptives within 3 months prior to E4/DRSP initiation.

CfB: change from baseline, DRSP: drospirenone; E4: estetrol; EoT: end of treatment; MDQ: menstruation distress questionnaire; N: number.

Figure 2. Shift analysis for premenstrual and menstrual symptom scores for Painful or tender Breasts in the physical domain ‘Water Retention’ for starters and switchers who completed the MDQ at baseline and at end of treatment in the Europe/Russia phase 3 trial with E4/DRSP.

Figure 3. Shift analysis for premenstrual and menstrual symptom scores for Mood Swings in the emotional domain ‘Negative Affect’ for starters and switchers who completed the MDQ at baseline and at end of treatment in the Europe/Russia phase 3 trial with E4/DRSP.

Figure 4. Shift analysis for premenstrual and menstrual symptom scores for Irritability in the emotional domain ‘Negative Affect’ for starters and switchers who completed the MDQ at baseline and at end of treatment in the Europe/Russia phase 3 trial with E4/DRSP.

Table 4. Overview of shift analysis with % of participants remaining stable, improving and worsening and % of participants with severe or strong symptoms at baseline for premenstrual and menstrual symptoms in the Europe/Russia phase 3 trial with E4/DRSP - starters and switchers.

Domain	Symptom	Stage	Starters (n = 531)				Switchers (n = 867)
			Severe/strong symptoms at baseline	Change from baseline			Severe/strong symptoms at baseline	Change from baseline
				Stable	Improving	Worsening		Stable	Improving	Worsening
Pain	Muscle stiffness	Premenstrual	2.3%	81.3%	10.8%	8.0%	0.5%	81.8%	6.6%	11.6%
		Menstrual	3.6%	76.7%	14.2%	9.1%	0.9%	79.6%	7.9%	12.5%
	Headache	Premenstrual	3.0%	63.3%	19.3%	17.4%	5.1%	60.4%	21.0%	18.6%
		Menstrual	4.2%	62.4%	19.8%	17.8%	7.0%	57.5%	26.1%	16.4%
	Cramps	Premenstrual	4.5%	63.6%	21.9%	14.5%	2.9%	63.8%	17.8%	18.4%
		Menstrual	16.4%	50.4%	35.7%	14.0%	11.0%	53.7%	24.4%	21.9%
	Backache	Premenstrual	5.1%	66.0%	21.6%	12.5%	3.5%	64.0%	17.1%	18.8%
		Menstrual	10.4%	59.5%	28.5%	11.9%	7.1%	58.5%	21.3%	20.2%
	Fatigue	Premenstrual	7.2%	60.6%	21.8%	17.6%	5.0%	53.2%	21.2%	25.6%
		Menstrual	10.2%	57.8%	25.2%	17.0%	7.5%	48.3%	25.2%	26.5%
	General aches and pain	Premenstrual	2.3%	73.9%	14.2%	11.9%	1.4%	75.4%	13.0%	11.6%
		Menstrual	5.5%	66.9%	21.6%	11.6%	2.7%	68.0%	16.7%	15.3%
Water retention	Weight gain	Premenstrual	3.6%	67.2%	17.0%	15.8%	1.4%	72.2%	11.1%	16.7%
		Menstrual	3.0%	68.3%	18.2%	13.5%	1.7%	71.6%	10.3%	18.1%
	Skin blemish or disorder	Premenstrual	4.7%	68.7%	20.5%	10.7%	4.1%	60.1%	15.7%	24.2%
		Menstrual	5.5%	70.9%	18.9%	10.2%	3.6%	60.4%	16.1%	23.5%
	Painful or tender breasts	Premenstrual	11.5%	49.4%	34.5%	16.0%	5.2%	58.3%	23.3%	18.4%
		Menstrual	9.6%	51.2%	33.3%	15.5%	4.2%	59.3%	20.7%	19.9%
	Swelling	Premenstrual	8.5%	53.5%	29.7%	16.8%	3.2%	63.8%	18.5%	17.7%
		Menstrual	10.0%	55.4%	28.7%	15.9%	5.1%	60.4%	19.7%	19.9%
Negative Affect	Loneliness	Premenstrual	4.2%	74.9%	15.8%	9.2%	0.9%	79.3%	9.6%	11.1%
		Menstrual	4.4%	75.4%	15.0%	9.7%	1.5%	80.0%	9.6%	10.4%
	Anxiety	Premenstrual	3.0%	72.3%	16.8%	10.9%	1.3%	80.0%	8.6%	10.6%
		Menstrual	2.8%	73.5%	16.4%	10.0%	1.0%	78.8%	9.3%	11.9%
	Mood swings	Premenstrual	13.8%	49.5%	33.5%	17.0%	7.1%	53.4%	22.8%	23.8%
		Menstrual	12.8%	47.9%	34.9%	17.2%	6.8%	49.1%	26.5%	24.2%
	Crying	Premenstrual	4.9%	68.7%	20.0%	11.3%	2.9%	73.7%	14.0%	12.3%
		Menstrual	4.3%	69.6%	19.5%	11.0%	2.8%	72.2%	14.7%	13.1%
	Irritability	Premenstrual	11.5%	53.1%	31.0%	15.9%	6.5%	52.0%	23.4%	24.7%
		Menstrual	13.2%	49.1%	35.5%	15.5%	7.4%	47.5%	27.5%	25.0%
	Tension	Premenstrual	4.9%	66.0%	19.6%	14.3%	2.4%	67.2%	14.2%	18.5%
		Menstrual	4.9%	67.7%	19.8%	12.5%	2.9%	68.1%	15.9%	16.0%
	Feeling sad or blue	Premenstrual	4.3%	70.5%	19.1%	10.4%	2.1%	67.5%	16.3%	16.2%
		Menstrual	4.7%	69.2%	19.3%	11.5%	2.7%	64.2%	19.0%	16.8%
	Restlessness	Premenstrual	2.1%	81.3%	9.2%	9.4%	0.3%	80.8%	9.7%	9.5%
		Menstrual	2.1%	78.8%	10.6%	10.6%	1.7%	78.8%	11.1%	10.1%
Impaired concentration	Insomnia	Premenstrual	3.2%	78.6%	12.9%	8.5%	1.7%	81.4%	8.4%	10.2%
		Menstrual	4.5%	80.0%	11.9%	8.1%	2.1%	79.7%	10.4%	9.8%
	Forgetfulness	Premenstrual	1.9%	80.5%	9.9%	9.7%	1.3%	80.7%	9.0%	10.3%
		Menstrual	2.8%	76.9%	12.3%	10.8%	1.3%	79.8%	9.2%	11.0%
	Confusion	Premenstrual	0.0%	91.5%	4.5%	4.0%	0.7%	91.8%	3.8%	4.4%
		Menstrual	0.0%	89.4%	5.7%	4.9%	0.5%	90.8%	4.1%	5.1%
	Poor Judgement	Premenstrual	0.8%	90.7%	4.9%	4.3%	0.5%	91.7%	4.4%	3.9%
		Menstrual	0.8%	90.4%	4.5%	5.1%	0.2%	92.2%	3.8%	3.9%
	Difficulty concentrating	Premenstrual	1.7%	77.9%	12.3%	9.8%	1.2%	78.4%	9.6%	12.0%
		Menstrual	1.3%	73.2%	13.6%	13.2%	1.2%	78.7%	9.4%	11.9%
	Distractibility	Premenstrual	1.1%	76.0%	14.5%	9.4%	1.2%	77.1%	10.8%	12.2%
		Menstrual	1.7%	73.2%	15.5%	11.3%	1.2%	78.8%	10.3%	10.9%
	Minor accidents	Premenstrual	0.8%	89.4%	7.4%	3.2%	0.1%	91.7%	4.5%	3.8%
		Menstrual	0.4%	87.9%	7.4%	4.7%	0.3%	91.5%	4.3%	4.2%
	Poor motor coordination	Premenstrual	0.8%	91.7%	4.2%	4.2%	0.1%	93.1%	3.4%	3.6%
		Menstrual	0.4%	89.0%	5.9%	5.1%	0.2%	92.5%	3.1%	4.4%

Bold ≤60% of participants stable and ≥10% of participants with severe or strong symptoms at baseline.

Bold italic ≤60% of participants stable and <10% of participants with severe or strong symptoms at baseline.

Underlined: ≥10% difference between improvement and worsening.

DRSP: drospirenone; E4: estetrol.