Oestrogen therapy for urinary incontinence in post‐menopausal women

June D Cody; Karen Richardson; Birgit Moehrer; Andrew Hextall; Cathryn MA Glazener

doi:10.1002/14651858.CD001405.pub2

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Analysis 1.1

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 1 Number with incontinence (women's observations).

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Analysis 1.2

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 2 Number with incontinence not improved (women's observations).

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Analysis 1.3

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 3 Incontinence not improved (generic inverse variance) (women's observations).

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Analysis 1.4

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 4 Number with incontinence (objective observations).

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Analysis 1.5

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 5 Number with incontinence not improved (objective observations).

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Analysis 1.6

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 6 Number of pad changes over 24 hours.

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Analysis 1.7

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 7 Pad test weights.

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Analysis 1.8

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 8 Incontinent episodes over 24 hours.

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Analysis 1.9

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 9 Number of voids over 24 hours.

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Analysis 1.10

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 10 Number of nocturnal voids.

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Analysis 1.11

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 11 Number of women with frequency.

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Analysis 1.12

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 12 Number of women with nocturia.

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Analysis 1.13

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 13 Number of women with urgency.

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Analysis 1.14

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 14 Maximum urethral closure pressure (MUCP).

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Analysis 1.15

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 15 Volume at first urge to void.

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Analysis 1.16

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 16 Maximum bladder capacity.

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Analysis 1.17

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 17 Number with adverse effects.

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Analysis 1.18

Comparison 1 Oestrogen versus placebo or no treatment, Outcome 18 Number with bacteriuria.

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Analysis 2.1

Comparison 2 Oestrogen versus other treatments, Outcome 1 Number with incontinence (women's observations).

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Study	Oestrogen	PPA
Oetrogens versus PPA
Beisland 1984#L	9/10 women	10/10 women

Analysis 2.2

Comparison 2 Oestrogen versus other treatments, Outcome 2 Number with incontinence, crossover studies (women's observations).

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Analysis 2.3

Comparison 2 Oestrogen versus other treatments, Outcome 3 Number with incontinence not improved (women's observations).

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Study	Oestrogen	PPA
Oetrogens versus PPA
Beisland 1984#L	6/10 women	2/10 women

Analysis 2.4

Comparison 2 Oestrogen versus other treatments, Outcome 4 Number with incontinence not improved, crossover studies (women's observations).

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Analysis 2.5

Comparison 2 Oestrogen versus other treatments, Outcome 5 Number with incontinence (objective observations).

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Analysis 2.6

Comparison 2 Oestrogen versus other treatments, Outcome 6 Number with incontinence not improved (objective observations).

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Analysis 2.7

Comparison 2 Oestrogen versus other treatments, Outcome 7 Number of pad changes over 24 hours.

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Analysis 2.8

Comparison 2 Oestrogen versus other treatments, Outcome 8 Number of voids over 24 hours.

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Analysis 2.9

Comparison 2 Oestrogen versus other treatments, Outcome 9 Pad test weights.

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Analysis 2.10

Comparison 2 Oestrogen versus other treatments, Outcome 10 Adverse effects.

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Analysis 2.11

Comparison 2 Oestrogen versus other treatments, Outcome 11 Maximum urethral closure pressure (MUCP).

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Study	Oestrogen	PPA
Oetrogens versus PPA
Beisland 1984#L	Mean=41.6, N=10	Mean=47.1, N=10

Analysis 2.12

Comparison 2 Oestrogen versus other treatments, Outcome 12 Maximum urethral closure pressure (MUCP), crossover studies.

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Analysis 3.1

Comparison 3 Oestrogen + other treatments versus placebo, Outcome 1 Number with incontinence not improved (women's observations).

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Analysis 3.2

Comparison 3 Oestrogen + other treatments versus placebo, Outcome 2 Incontinence not improved (generic inverse variance) (women's observations).

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Analysis 3.3

Comparison 3 Oestrogen + other treatments versus placebo, Outcome 3 Incontinent episodes over 24 hours.

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Analysis 3.4

Comparison 3 Oestrogen + other treatments versus placebo, Outcome 4 Number of diurnal voids per 24 hours.

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Analysis 3.5

Comparison 3 Oestrogen + other treatments versus placebo, Outcome 5 Number of nocturnal voids per 24 hours.

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Analysis 3.6

Comparison 3 Oestrogen + other treatments versus placebo, Outcome 6 Pad test weights.

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Analysis 3.7

Comparison 3 Oestrogen + other treatments versus placebo, Outcome 7 Use of drugs for incontinence.

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Analysis 3.8

Comparison 3 Oestrogen + other treatments versus placebo, Outcome 8 Number of women having incontinence surgery.

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Analysis 4.1

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 1 Number with incontinence not improved (women's observations).

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Study	oestr + other drug	oestrogen
oestrogen + PPA vs oestrogen
Ahlstrom 1990#S	17/27	21/26
Kinn 1988#S	14/30	21/30

Analysis 4.2

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 2 Number with incontinence not improved (women's observations) (cross‐over trials).

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Analysis 4.3

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 3 Number of pad changes over 24 hours.

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Analysis 4.4

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 4 Number of voids over 24 hours.

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Analysis 4.5

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 5 Pad test weights.

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Analysis 4.6

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 6 Number of women with frequency.

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Analysis 4.7

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 7 Number of women with nocturia.

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Analysis 4.8

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 8 Number with adverse effects.

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Study	oestrogen + naproxen	oestrogen
oestrogen + PPA vs oestrogen
Blom 1995#S	172 ml (SD 12) N=16	186 ml (SD 12) N=16

Analysis 4.9

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 9 Volume at first urge to void (cross‐over trials).

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Study	oestr + naproxen	oestrogen
oestrogen +other vs oestrogen
Blom 1995#S	316 ml (SD 17) N=16	318 ml (SD 20) N=16

Analysis 4.10

Comparison 4 Oestrogen + other treatments versus oestrogen, Outcome 10 Maximum bladder capacity (cross‐over trials).

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Analysis 5.1

Comparison 5 Oestrogen + other treatments versus other treatments, Outcome 1 Number with incontinence (women's observations).

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Analysis 5.2

Comparison 5 Oestrogen + other treatments versus other treatments, Outcome 2 Number with incontinence not improved (women's observations).

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Analysis 5.3

Comparison 5 Oestrogen + other treatments versus other treatments, Outcome 3 Number of pad changes over 24 hours.

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Analysis 5.4

Comparison 5 Oestrogen + other treatments versus other treatments, Outcome 4 Number of voids over 24 hours.

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Analysis 5.5

Comparison 5 Oestrogen + other treatments versus other treatments, Outcome 5 Pad test weights.

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Analysis 5.6

Comparison 5 Oestrogen + other treatments versus other treatments, Outcome 6 Adverse effects.

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Analysis 6.1

Comparison 6 Different types of oestrogen, Outcome 1 Number with incontinence not improved (women's observations).

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Analysis 6.2

Comparison 6 Different types of oestrogen, Outcome 2 Number of women with nocturia.

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Analysis 6.3

Comparison 6 Different types of oestrogen, Outcome 3 Number of women with dysuria.

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Analysis 6.4

Comparison 6 Different types of oestrogen, Outcome 4 Number of women with urgency.

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Analysis 6.5

Comparison 6 Different types of oestrogen, Outcome 5 Number of women with frequency.

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Analysis 6.6

Comparison 6 Different types of oestrogen, Outcome 6 Number of adverse events.

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Analysis 7.1

Comparison 7 Different routes of administration, Outcome 1 Number of pad changes over 24 hours.

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Analysis 7.2

Comparison 7 Different routes of administration, Outcome 2 Number of voids over 24 hours.

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Analysis 7.3

Comparison 7 Different routes of administration, Outcome 3 Pad test weights.

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Analysis 8.1

Comparison 8 High‐dose versus low‐dose oestrogen, Outcome 1 Number of voids over 24 hours.

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Analysis 8.2

Comparison 8 High‐dose versus low‐dose oestrogen, Outcome 2 Number of nocturnal voids.

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Analysis 8.3

Comparison 8 High‐dose versus low‐dose oestrogen, Outcome 3 Maximum urethral closure pressure (MUCP).

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Analysis 8.4

Comparison 8 High‐dose versus low‐dose oestrogen, Outcome 4 Volume at first urge to void.

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Analysis 8.5

Comparison 8 High‐dose versus low‐dose oestrogen, Outcome 5 Maximum bladder capacity.

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Table 1. Summary of study characteristics: type of oestrogen, route of administration, dose, length of treatment, population

Study ID	Type of Oestrogen	Route of administration	Dose	Length of treatment	Population
Ahlstrom 1990#S	Oestriol	Systemic (oral)	4mg	6 weeks	USI (stress), postmenopausal
Beisland 1984#L	Oestriol	Local (vaginal)	1 mg	8 weeks	UI (stress), postmenopausal
Blom 1995#S	Estradiol	Systemic (transdermal)	0.05 mg	8 weeks	UUI (OAB), elderly
Cardozo 1993 S	Oestriol	Systemic (oral)	3 mg	3 months	UUI (urge), postmenopausal
Cardozo 2001 L	Oestradiol	Vaginal (pessary, Vagifem)	25 µgm	3 months	OAB (urge), postmenopausal
Chompootaweep 1998 SL	A: Ethinyl oestradiol + levonorgestrel B: conjugated equine oestrogen	A: Systemic (oral) B: Local (vaginal cream)	A: 30 mg /250 ng B: 0.625 mg	2 months	UUI (urogenital symptoms), oestrogen deficiency, postmenopausal
Dessole 2004 L	Oestriol	Local (intravaginal ovules)	1‐2 mg	6 months	UI (stress), postmenopausal
Ek 1980#S	Oestradiol	Systemic (oral)	1 mg	6 weeks	USI (stress), postmenopausal
Enzelsberger 1990 L	Oestriol	Local (vaginal)	0.5, 1 or 2 mg	Not stated	UI (urge), OAB
Enzelsberger 1991a L; Enzelsberger 1991b L	Oestriol	Local (vaginal)	1 mg or 3 mg	3 weeks	UI (urge), OAB, postmenopausal
Fantl 1996 S	Conjugated equine oestrogens + medroxyprogesterone	Systemic (oral)	0.625 mg / 10 mg	3 months	UI (stress), postmenopausal
Grady 2001 S	Conjugated oestrogens (premarin) + medroxyprogesterone	Systemic (oral)	0.625 mg / 2.5 mg	up to 4 years	UI (unspecified), postmenopausal, heart disease, age <80 years, with uterus
Henalla 1989 L	Conjugated equine oestrogen	Local (vaginal cream)	1.25 mg	3 months	USI (stress)
Henalla 1990 L	Conjugated equine oestrogen	Local (vaginal cream)	2 gm	6 weeks	USI (stress), postmenopausal
HendrixA (no uterus) S	Conjugated equine oestrogen	Systemic (oral)	0.625 mg	1 year	UI (SUI, UUI, MUI), postmenopausal, prevention of heart disease and hip fracture Without uterus
HendrixB (+ uterus) S	Conjugated equine oestrogen + medroxyprogesterone	Systemic (oral)	0.625 mg / 2.5 mg	1 year	UI (SUI, UUI, MUI), postmenopausal, prevention of heart disease and hip fracture With uterus
Hilton 1990 SL	Oestrogen	Local (intravaginal) Systemic (oral)	2 gm 1.25 mg	1 month	USI (stress), postmenopausal
Ishiko 2001 S	Estriol	Systemic (oral)	1 mg	2 years	SUI (stress), postmenopausal
Jackson 1999 S	Oestradiol	Systemic (oral)	2 mg	6 months	USI (stress), postmenopausal
Judge 1969#	Quinestradiol	Not stated	1 mg	1 month	UI (unspecified), postmenopausal, geriatric inpatients
Kinn 1988#S	Oestriol	Systemic (oral)	4 mg	1 month	USI (stress), postmenopausal
Kurz 1993 L	Oestriol	Local (intravesical)	1 mg	3 weeks	UUI, OAB (urge), postmenopausal
Lose 2000 L	Oestradiol	Local (intravaginal ring, vaginal pessaries)	ring 7.5mg, pessary 0.5 mg	6 months	UI (unspecified), LUT symptoms, postmenopausal
Melis 1997 L	Oestriol	Local (intravaginal)	0.5 mg	3 months	UI, menopausal symptoms
Ouslander 2001 S	Oestrogen + progesterone	Systemic (oral)	0.625 mg / 2.5 mg	6 months	UI (unspecified), nursing home residents
Rufford 2003 S	17‐beta oestradiol	Systemic (implant)	25 mg	6 months	UUI, OAB (urge), postmenopausal
Sacco 1990 L	Oestrogen	Local (cream)	0.5 mg	3 months	USI (stress), postmenopausal
Samsioe 1985 #S	Oestriol	Systemic (oral)	3 mg	3 months	MUI (mixture), postmenopausal
Walter 1978 S	Oestradiol + oestriol	Systemic (oral)	2 mg / 1 mg	4 months (with breaks)	SUI, MUI (stress and mixed), postmenopausal
Walter 1990 S	Oestriol	Systemic (oral)	4 mg	1‐2 months	SUI (stress), postmenopausal
Wilson 1987 S	Piperazine oestrone sulphate	Systemic (oral)	3 mg	3 months (with breaks)	USI (stress), postmenopausal
Zullo 2005 L	Estriol	Local (intravaginal ovules)	1 mg	6 months	SUI (stress), postmenopausal
LUTs = lower urinary tract symptoms; MUI = mixed urinary incontinence; OAB = overactive bladder syndrome; SUI = stress urinary incontinence; UI = urinary incontinence; USI = urodynamic stress incontinence; UUI = urgency urinary incontinence.

Table 1. Summary of study characteristics: type of oestrogen, route of administration, dose, length of treatment, population

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Comparison 1. Oestrogen versus placebo or no treatment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number with incontinence (women's observations) Show forest plot	6	341	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.70, 0.90]

1.1 Systemic administration	4	197	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.70, 0.98]
1.2 Local administration	2	144	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.62, 0.87]
2 Number with incontinence not improved (women's observations) Show forest plot	9	444	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.53, 0.72]

2.1 Systemic administration	5	231	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.58, 0.93]
2.2 Local administration	4	213	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.43, 0.65]
3 Incontinence not improved (generic inverse variance) (women's observations) Show forest plot	10		RR (Fixed, 95% CI)	Subtotals only

3.1 Systemic administration (any incontinence)	6	6151	RR (Fixed, 95% CI)	1.32 [1.17, 1.48]
3.2 Local administration (any incontinence)	4	213	RR (Fixed, 95% CI)	0.74 [0.64, 0.86]
4 Number with incontinence (objective observations) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4.1 Local administration	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Number with incontinence not improved (objective observations) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 Local administration	2	52	Risk Ratio (M‐H, Fixed, 95% CI)	0.6 [0.40, 0.89]
6 Number of pad changes over 24 hours Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

6.1 Systemic administration	3	112	Mean Difference (IV, Fixed, 95% CI)	‐0.12 [‐0.89, 0.66]
7 Pad test weights Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 Systemic administration	3	106	Mean Difference (IV, Fixed, 95% CI)	1.75 [‐5.67, 9.16]
8 Incontinent episodes over 24 hours Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

8.1 Systemic administration	2	82	Mean Difference (IV, Fixed, 95% CI)	0.54 [‐0.50, 1.57]
9 Number of voids over 24 hours Show forest plot	7	237	Mean Difference (IV, Fixed, 95% CI)	‐1.20 [‐1.81, ‐0.60]

9.1 Systemic administration	3	125	Mean Difference (IV, Fixed, 95% CI)	‐0.25 [‐1.22, 0.73]
9.2 Local administration	4	112	Mean Difference (IV, Fixed, 95% CI)	‐1.80 [‐2.58, ‐1.03]
10 Number of nocturnal voids Show forest plot	5	194	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐0.59, ‐0.07]

10.1 Systemic administration	2	112	Mean Difference (IV, Fixed, 95% CI)	‐0.12 [‐0.40, 0.16]
10.2 Local administration	3	82	Mean Difference (IV, Fixed, 95% CI)	‐2.03 [‐2.82, ‐1.24]
11 Number of women with frequency Show forest plot	3	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.59, 1.33]

11.1 Systemic administration	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [0.89, 2.19]
11.2 Local administration	2	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.19, 0.98]
12 Number of women with nocturia Show forest plot	2	79	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.55, 1.42]

12.1 Systemic administration	1	45	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.62, 1.62]
12.2 Local administration	1	34	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.11, 2.38]
13 Number of women with urgency Show forest plot	4	179	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.67, 1.12]

13.1 Systemic administration	2	89	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.83, 1.33]
13.2 Local administration	2	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.38 [0.15, 0.99]
14 Maximum urethral closure pressure (MUCP) Show forest plot	7	291	Mean Difference (IV, Fixed, 95% CI)	3.61 [1.87, 5.35]

14.1 Systemic administration	2	89	Mean Difference (IV, Fixed, 95% CI)	‐1.41 [‐6.24, 3.43]
14.2 Local administration	5	202	Mean Difference (IV, Fixed, 95% CI)	4.35 [2.49, 6.22]
15 Volume at first urge to void Show forest plot	7	269	Mean Difference (IV, Fixed, 95% CI)	18.80 [13.01, 24.60]

15.1 Systemic administration	3	153	Mean Difference (IV, Fixed, 95% CI)	9.09 [‐25.45, 43.62]
15.2 Local administration	4	116	Mean Difference (IV, Fixed, 95% CI)	19.09 [13.21, 24.96]
16 Maximum bladder capacity Show forest plot	7	269	Mean Difference (IV, Fixed, 95% CI)	45.34 [31.86, 58.82]

16.1 Systemic administration	3	153	Mean Difference (IV, Fixed, 95% CI)	7.18 [‐33.26, 47.62]
16.2 Local administration	4	116	Mean Difference (IV, Fixed, 95% CI)	50.11 [35.81, 64.41]
17 Number with adverse effects Show forest plot	3	184	Risk Ratio (M‐H, Fixed, 95% CI)	4.25 [1.50, 12.03]

17.1 Systemic administration	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	13.0 [1.87, 90.21]
17.2 Local administration	2	144	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.32, 5.61]
18 Number with bacteriuria Show forest plot	2	128	Risk Ratio (M‐H, Fixed, 95% CI)	0.45 [0.27, 0.76]

18.1 Systemic administration	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.37, 1.42]
18.2 Local administration	1	88	Risk Ratio (M‐H, Fixed, 95% CI)	0.3 [0.13, 0.68]

Comparison 1. Oestrogen versus placebo or no treatment

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Comparison 2. Oestrogen versus other treatments

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number with incontinence (women's observations) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 oestrogen vs PPA	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Number with incontinence, crossover studies (women's observations) Show forest plot			Other data	No numeric data

2.1 Oetrogens versus PPA			Other data	No numeric data
3 Number with incontinence not improved (women's observations) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 oestrogen vs PPA	2	57	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.63, 1.09]
4 Number with incontinence not improved, crossover studies (women's observations) Show forest plot			Other data	No numeric data

4.1 Oetrogens versus PPA			Other data	No numeric data
5 Number with incontinence (objective observations) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5.1 oestrogen vs PPA	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Number with incontinence not improved (objective observations) Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 oestrogen vs PPA	1	29	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.46, 1.90]
6.2 oestrogen vs PFMT	2	69	Risk Ratio (M‐H, Fixed, 95% CI)	1.62 [1.18, 2.23]
6.3 oestrogen vs electrostimulation	1	49	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.95, 1.75]
7 Number of pad changes over 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

7.1 oestrogen vs PPA	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Number of voids over 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

8.1 oestrogen vs PPA	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Pad test weights Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

9.1 oestrogen vs PPA	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 Adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

10.1 oestrogen vs PPA	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Maximum urethral closure pressure (MUCP) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

11.1 oestrogen vs PFMT	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 oestrogen vs electrostimulation	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
12 Maximum urethral closure pressure (MUCP), crossover studies Show forest plot			Other data	No numeric data

12.1 Oetrogens versus PPA			Other data	No numeric data

Comparison 2. Oestrogen versus other treatments

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Comparison 3. Oestrogen + other treatments versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number with incontinence not improved (women's observations) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 oestrogen + progesterone vs placebo	2	1514	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [1.01, 1.16]
2 Incontinence not improved (generic inverse variance) (women's observations) Show forest plot	3		Relative Risk (Fixed, 95% CI)	Subtotals only

2.1 Systemic administration of oestrogen + progesterone vs placebo	3	10635	Relative Risk (Fixed, 95% CI)	1.11 [1.04, 1.18]
3 Incontinent episodes over 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 oestrogen + progesterone vs placebo	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Number of diurnal voids per 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 oestrogen + progesterone vs placebo	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Number of nocturnal voids per 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 oestrogen + progesterone vs placebo	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Pad test weights Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

6.1 oestrogen + progesterone vs placebo	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Use of drugs for incontinence Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7.1 oestrogen + progesterone vs placebo	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Number of women having incontinence surgery Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

8.1 oestrogen + progesterone vs placebo	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 3. Oestrogen + other treatments versus placebo

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Comparison 4. Oestrogen + other treatments versus oestrogen

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number with incontinence not improved (women's observations) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Oestrogen + PPA vs oestrogen	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Number with incontinence not improved (women's observations) (cross‐over trials) Show forest plot			Other data	No numeric data

2.1 oestrogen + PPA vs oestrogen			Other data	No numeric data
3 Number of pad changes over 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 oestrogen + PPA vs oestrogen	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Number of voids over 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 oestrogen + PPA vs oestrogen	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Pad test weights Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 oestrogen + PPA vs oestrogen	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Number of women with frequency Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6.1 oestrogen + progesterone vs oestrogen	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 oestriol + benzidamine vs oestriol	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Number of women with nocturia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7.1 oestriol + benzidamine vs oestriol	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Number with adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

8.1 Oestrogen + PPA vs oestrogen	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Volume at first urge to void (cross‐over trials) Show forest plot			Other data	No numeric data

9.1 oestrogen + PPA vs oestrogen			Other data	No numeric data
10 Maximum bladder capacity (cross‐over trials) Show forest plot			Other data	No numeric data

10.1 oestrogen +other vs oestrogen			Other data	No numeric data

Comparison 4. Oestrogen + other treatments versus oestrogen

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Comparison 5. Oestrogen + other treatments versus other treatments

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number with incontinence (women's observations) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 oestrogen + PFMT vs PFMT	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 TVT vs TVT + vaginal oestrogen	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Number with incontinence not improved (women's observations) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 oestrogen + PPA vs PPA	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Number of pad changes over 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 oestrogen + PPA vs PPA	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Number of voids over 24 hours Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 oestrogen + PPA vs PPA	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 detrusitol + vaginal oestrogen vs detrusitol m	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Pad test weights Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 oestrogen + PPA vs PPA	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Adverse effects Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6.1 oestrogen + PPA vs PPA	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 oestrogen + PFMT vs PFMT	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 5. Oestrogen + other treatments versus other treatments

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Comparison 6. Different types of oestrogen

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number with incontinence not improved (women's observations) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 oestradiol ring vs oestriol pessary	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Number of women with nocturia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 oestradiol ring vs oestriol pessary	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Number of women with dysuria Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.1 oestradiol ring vs oestriol pessary	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Number of women with urgency Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4.1 oestradiol ring vs oestriol pessary	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 oestrogen cream vs vaginal oestrogen + progesterone	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Number of women with frequency Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5.1 oestradiol ring vs oestriol pessary	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 oestrogen cream vs vaginal oestrogen + progesterone	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Number of adverse events Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6.1 oestradiol ring vs oestriol pessary	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 6. Different types of oestrogen

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Comparison 7. Different routes of administration

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of pad changes over 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

1.1 oestrogen cream vs oestrogen orally	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Number of voids over 24 hours Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.1 oestrogen cream vs oestrogen orally	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Pad test weights Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 oestrogen cream vs oestrogen orally	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 7. Different routes of administration

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Comparison 8. High‐dose versus low‐dose oestrogen

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of voids over 24 hours Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 high dose vs low dose	2	65	Mean Difference (IV, Fixed, 95% CI)	‐1.02 [‐1.87, ‐0.16]
2 Number of nocturnal voids Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

2.1 high dose vs low dose	2	65	Mean Difference (IV, Fixed, 95% CI)	‐1.80 [‐2.36, ‐1.24]
3 Maximum urethral closure pressure (MUCP) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

3.1 high dose vs low dose	2	65	Mean Difference (IV, Fixed, 95% CI)	3.84 [‐5.77, 13.46]
4 Volume at first urge to void Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4.1 high dose vs low dose	2	65	Mean Difference (IV, Fixed, 95% CI)	‐1.56 [‐12.20, 9.08]
5 Maximum bladder capacity Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 high dose vs low dose	2	65	Mean Difference (IV, Fixed, 95% CI)	34.90 [8.35, 61.45]

Comparison 8. High‐dose versus low‐dose oestrogen

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