Preoperative Oestrogen in Postmenopausal Women With Pelvic Organ Prolapse

Study Overview
=================
Brief Summary
-----------------
Introduction With increasing age the incidence of pelvic organ prolapse (POP) rises and will increase substantially in the future according to forecasting studies. It is possible that oestrogens, alone or in combination with other forms of therapy, may assist in the management of POP by increasing collagen synthesis and thereby improving the strength of the weakened vaginal epithelium. Yet, studies investigating the effect of topical oestrogen and its impact on POP associated symptoms, both self-reported improvement and observations of objective improvement, are lacking. Objective To evaluate the subjective efficacy concerning prolapse associated complaints measured by the German pelvic floor questionnaire (domain POP: POP-score) after preoperative use of local oestrogen compared to preoperative placebo treatment in postmenopausal women with symptomatic pelvic organ prolapse. Further variables of interest are POP-score after 3 months, differences regarding the objective prolapse quantification system (POP-Q), surgical outcome and tissue operability assessed by the surgeon. Methods In this prospective, randomized, double-blind, placebo-controlled, multicenter study the investigators aim to include 120 postmenopausal women with symptomatic pelvic organ prolapse and indicated operative procedure. An analysis of covariance will be computed with the depending variable POP-score after 6 weeks and the independent variables group (verum versus placebo) and Pop-Score at baseline.

Official Title
-----------------
Preoperative Locally Applied Oestrogen in Postmenopausal Women With Pelvic Organ Prolapse: Changes in Subjective and Objective Outcome - a Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Study

Conditions
-----------------
Pelvic Organ Prolapse

Intervention / Treatment
-----------------
* Drug: Linoladiol Estradiol
* Other: Placebo vaginal cream


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Postmenopausal women Able to read, understand and sign informed consent Able to apply a vaginal cream Symptomatic pelvic organ prolapse with planned and indicated prolapse surgical repair Exclusion Criteria: Suspicion or history of breast cancer or other oestrogen responsive malignancies (endometrial cancer) unexplained abnormal vaginal bleeding history of deep vein thrombosis inherited or acquired blood clotting disorders (eg, APC resistance, Antithrombin III deficiency) transient ischaemic attack, myo- cardial infarction or ischaemic heart disease Hypersensitivity to oestrogen Unable to read and sign informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, Placebo-controlled
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linoladiol Estradiol<br>Linoladiol Estradiol cream 6 weeks before surgery of pelvic organ prolapse | Drug: Linoladiol Estradiol<br>* Linoladiol Estradiol Initial dose (week 1): 1 application (2g Linoladiol = 0.2mg Estradiol) every day for the first week Maintenance dose 1 (week 2) : 1 application (2g Linoladiol = 0.2mg Estradiol) every 48 hours the following week. Maintenance dose 2 (week 3-6): 1 application (2g Linoladiol = 0.2mg Estradiol) twice per week the following 4 weeks. Route of administration: intravaginally by means of a calibrated applicator before retiring at night Duration: 6 weeks<br>* Other names: Montavit ATC Code G03CA03;|
| Placebo Comparator: Placebo<br>Placebo cream 6 weeks before surgery of pelvic organ prolapse | Other: Placebo vaginal cream<br>* Initial dose (week 1): 1 application every day for the first week Maintenance dose 1 (week 2) : 1 application every 48 hours the following week. Maintenance dose 2 (week 3-6): 1 application twice per week the following 4 weeks. Route of administration: intravaginally by means of a calibrated applicator before retiring at night Duration: 6 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| subjective prolapse associated symptoms (measured with the validated German pelvic floor questionnaire) | treatment efficacy of preoperative vaginally administered oestrogen in postmenopausal women with symptomatic pelvic organ prolapse in comparison to placebo, measured by a subjective questionnaire. 42 questions. Range 0 to 3 points for each question. Lower values represent a better outcome | change from baseline POP Score at 6 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| operative time in minutes | effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo | up to 1 week postoperative | 
| length of stay in days | effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo | up to 1 week postoperative | 
| intraoperative blood loss in ml | effect of preoperative vaginally administered oestrogen on postoperative outcome in comparison to placebo | up to 1 week postoperative | 
| blood circulation of the tissue (good, regular, scarce, no blood circulation) | differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation | on day of surgery | 
| separability of the tissue layers (good, regular, scarce, not possible) | differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation | on day of surgery | 
| easy separation from the bladder (yes/no) | differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation | on day of surgery | 
| easy opening of the Douglas cavity (Yes/no) | differences in tissue operability between the two groups assessed by means of a questionnaire which is filled in by the surgeon after the operation | on day of surgery | 
| subjective (all domains of the pelvic floor questionnaire) outcome 3 months postoperative | possible differences regarding subjective outcome parameters between intervention and placebo-group 3 months after operation. 42 questions. Range 0 to 3 points for each question. Lower values represent a better outcome. | 3 months postoperative | 
| objective (POP-Q score) outcome 3 months postoperative | possible differences regarding objective outcome parameters between intervention and placebo-group 3 months after operation. POP-Q Score (Score between 0 and 4). The POP- quantification system consists of six defined points of measurement (Aa, Ba, C,D,Ap,Bp) and three other landmarks (GH,TVL, PB). Each is measured in centimeters above the hymen (negative number) or below the hymen (positive number). | 3 months postoperative | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Local Oestrogen