Preoperative Oestrogen in Postmenopausal Women With Pelvic Organ Prolapse

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

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.

Study Overview

• Status: Completed
• Conditions: Pelvic Organ Prolapse
• Intervention / Treatment: Drug: Linoladiol Estradiol; Other: Placebo vaginal cream

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Tulln, Austria, 3430
    • Department of Obstetrics and Gynecology, University of Tulln
  • Vienna, Austria, 1090
    • Department of General Gynecology and Gynecologic Oncology of the Medical University Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Linoladiol Estradiol; Linoladiol Estradiol cream 6 weeks before surgery of pelvic organ prolapse	Drug: Linoladiol Estradiol; 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; Other Names: Montavit ATC Code G03CA03
Placebo Comparator: Placebo; Placebo cream 6 weeks before surgery of pelvic organ prolapse	Other: Placebo vaginal cream; 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

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

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Publications and helpful links

General Publications

• European Urogynaecological Association 2021 Annual Meeting | Hybrid Edition. Female Pelvic Med Reconstr Surg. 2022 Apr 1;28(4):244-271. doi: 10.1097/SPV.0000000000001172. No abstract available.
• Weber MA, Kleijn MH, Langendam M, Limpens J, Heineman MJ, Roovers JP. Local Oestrogen for Pelvic Floor Disorders: A Systematic Review. PLoS One. 2015 Sep 18;10(9):e0136265. doi: 10.1371/journal.pone.0136265. eCollection 2015.
• Rahn DD, Good MM, Roshanravan SM, Shi H, Schaffer JI, Singh RJ, Word RA. Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab. 2014 Oct;99(10):3728-36. doi: 10.1210/jc.2014-1216. Epub 2014 Jun 20.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Actual): August 27, 2020
• Study Completion (Actual): August 27, 2020

Study Registration Dates

• First Submitted: July 29, 2018
• First Submitted That Met QC Criteria: December 16, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Local Oestrogen
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Prolapse; Pelvic Organ Prolapse; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: EstrogenPOP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No