Accepted Manuscript Title Endometrial changes during ulipristal acetate use a systematic review

Endometrial changes during ulipristal acetate use a systematic review Accepted Manuscript Title Endometrial changes during ulipristal acetate use a systematic review Author Inge De Milliano Dominique.

Accepted Manuscript

Title: Endometrial changes during ulipristal acetate use: a

systematic review

Author: Inge De Milliano Dominique Van Hattum Johannes

C.F Ket Judith A.F Huirne Wouter J.K Hehenkamp

This is a PDF file of an unedited manuscript that has been accepted for publication.

As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Accepted Manuscript

30

31

Accepted Manuscript

443

Accepted Manuscript

24

Tables

444

Table 1 Study characteristics

Number of endometrial biopsies Author,

Ulipristal acetate as a contraceptive

1500µg/day (N=28) or 2500µg/day (N=27)

Vaginal ring No Two 12 week

UPA 30mg once weekly (N=12) or UPA 30mg every 5 days (N=11)

Stratton,

2010

(N=13), 50mg (N=14), 100mg (N=14)

Per os Yes Once at LH+1 or

242 Placebo (N=48) UPA 5mg (N=96) UPA 10 mg (N=98)

Placebo 41.6±5.6 UPA 5mg 41.2±5.9 UPA 10mg 42.0±5.6

Donnez,

2012

PEARL II

Double blind RCT

307 UPA 5mg (N=98)

UPA 5mg 40.1±6.2 UPA 10mg 40.7±6.3

Accepted Manuscript

25

(N=104) Leuprolide acetate (N=101)

Leuprolide acetate 40.3±6.2 Levens,

2008

45.1±5.1 UPA 10mg 42.6±4.8 UPA 20mg 44.3±4.2

Placebo (N=8), UPA 10mg (N=8) or UPA 20mg (N=6) daily

Per os Yes 3 cycles or 90-102

4 courses: N=107

1 course 40.1±6.0

≥ 2 courses 40.5±5.8

4 courses:

40.8±5.5

10 mg daily

NB: Followed by 10mg progestestin norethisterone acetate

or placebo

NB: post UPA medication

10 days

TVUS PEARL III: 1

PEARL III Extension:

1

PEARL III: 0 PEARL III Extension:

0

PEARL III: 1 PEARL III Extension:

41.6±5.4 UPA 10mg 41.1±5.1

5mg or 10mg daily Per os No Two 12 week

courses

Separated by a drug-free interval

Accepted Manuscript

26

452

Table 2 Reported histological changes at any moment during and after ulipristal acetate use

PAEC Simple hyperplasia Adenocarcinoma During treatment Follow-up During treatment Follow-up During treatment Follow-up Ulipristal acetate as a contraceptive

Accepted Manuscript

28

458

Table 3 Reported mean endometrial thickness by TVUS or MRI before, during and after ulipristal acetate use (in mm)

Before treatment (mean±SD) During treatment (mean±SD) After treatment (mean±SD) Ulipristal acetate as a contraceptive

UPA 5mg: 8.22 ± 3.46 UPA 10mg: 8.67 ± 6.12

UPA 5mg: 7.4 ± 4.2 UPA 10mg: 7.9 ± 5.4 Donnez, 2012

PEARL II

N=281

UPA 5mg: 8.9 ± 4.2 UPA 10mg: 8.9 ± 4.3

UPA 5mg: 9.4 ± 5.7*

UPA 10mg: 10.7 ± 5.9*

UPA 5mg: 8.8 ± 4.1 UPA 10mg: 8.5 ± 3.4 Levens, 2008

Course 1:

UPA 5mg: 8.8 ± 4.3 UPA 10mg: 9.5 ± 4.8

Course 2:

UPA 5mg: 8.7 ± 4.9 UPA 10mg: 7.9 ± 4.4

UPA 5mg: 8.5 ± 3.8 UPA 10mg: 8.1 ± 4.3

Accepted Manuscript

30

464

Accepted Manuscript

31

Accepted Manuscript

N=7 Aantal Low risk of bias Aantal Unclear risk of bias Aantal High risk of bias

Random sequence generation (selection bias) 5 71.42857143 2 28.57142857 0 0

Allocation concealment (selection bias) 6 85.71428571 1 14.28571429 0 0

Blinding of participants and personnel (performance bias) 5 71.42857143 1 14.28571429 1 14.28571429

Blinding of outcome assessment (detection bias) 5 71.42857143 1 14.28571429 1 14.28571429

Selective reporting (reporting bias) 3 42.85714286 4 57.14285714 0 0

Figure 3 Overall risk of bias for included cohort studies

N=3 Aantal Low risk of bias Aantal Moderate risk of bias Aantal High risk of bias

Study participation Study attrition Prognostic factor measurement Outcome measurement Study confounding Statistical analysis and reporting

Accepted Manuscript

Low risk of bias Unclear risk of bias High risk of bias

Low risk of bias Moderate risk of bias High risk of bias

Accepted Manuscript

Records identified through database

searching (n = 2699 )

Records excluded (n = 1742 )

Full-text articles assessed for eligibility (n = 33 )

Full-text articles excluded, with reasons (n = 23 )

• No full text available (n = 9)

• Type of study (n = 8)

• Different outcome measure (n = 6) Studies included in

qualitative synthesis (n = 10 )