Effects of intravaginal conjugated oestrogen on pessary continuation for pelvic organ prolapse: multicentre, randomised, double blind, placebo controlled trial

Abstract

Objective: To examine the effect of vaginal oestrogen cream on pessary continuation rates in pelvic organ prolapse.

Design: Multicentre, randomised, double blind, placebo controlled trial.

Setting: 12 academic medical centres in China (May 2020-June 2023).

Participants: Postmenopausal women with symptomatic pelvic organ prolapse ≥stage 2 and successfully fitted with ring pessaries were randomly assigned in a 1:1 ratio to receive oestrogen cream or placebo cream.

Interventions: One gram of conjugated oestrogen cream (0.625 mg/g) or placebo cream was inserted vaginally every night for the first two weeks after successful pessary fitting followed by twice weekly for 12 months.

Main outcome measures: The primary outcome was the pessary continuation rate with satisfaction, which was defined as the proportion of participants who continued using the pessary and reported a response of very much better or much better on the Patient Global Impression of Improvement questionnaire at 12 months. Secondary outcomes included self-reported pelvic floor symptoms and adverse events. All analyses were based on a modified intention-to-treat approach, including participants who had at least one visit.

Results: Of 420 postmenopausal women randomised, 411 had at least one visit and were included in the modified intention-to-treat analysis (208 in the vaginal oestrogen group and 203 in the placebo group). The mean age of participants was 66 years. Pessary continuation rate with satisfaction did not differ significantly between the oestrogen group and the placebo group (181/208 (87.0%) v 176/203 (86.7%); risk difference 0.3%, 95% confidence interval -6.2% to 6.9%; P=0.92). Excessive discharge (34/208 (16.3%) v 52/203 (25.6%); -9.3%, -17.1% to -1.4%), vaginal erosion or ulcer (4/208 (1.9%) v 14/203 (6.9%); -5.0%, -8.9% to -1.0%), and vaginal bleeding (3/208 (1.4%) v 13/203 (6.4%); -5.0%, -8.7% to -1.2%) were less common in the vaginal oestrogen group.

Conclusions: Oestrogen cream did not improve the continuation rate of ring pessary use with satisfaction. Use of oestrogen cream might be associated with a lower risk of common adverse events. The clinical decision to use vaginal oestrogen should take into account its benefits and risks and the patient's personal preferences.

Trial registration: ClinicalTrials.gov NCT04393194.

Fig 1

Flowchart. *Five patients were randomised but subsequently found not to meet inclusion or exclusion criteria—two patients had endometrial polyps, one patient had a postvoid residual urine volume >300 mL, one patient resumed menstruation after two months of treatment, one patient used self-administered oestrogen before receiving intervention. †Five patients discontinued pessary use because of adverse events in oestrogen group—one patient had vulvar itching, two patients felt pain and discomfort, one patient stopped because of urinary incontinence, one had vaginal bleeding. ‡Six patients discontinued treatment because of adverse events in oestrogen group—two for severe vulvar itching, one for rashes, one for recurrent urinary infection, one for increased discharge, and one for feeling of pelvic heaviness. §One patient discontinued pessary use because of incomplete urination in the placebo group. ¶Five patients discontinued treatment because of adverse events in placebo group—one for rashes, one for dizziness, one for severe vulvar itching, one for vaginal bleeding, and one for thrombosis. mITT=modified intention-to-treat analysis—population defined as patients who met the inclusion and exclusion criteria, had undergone randomisation, and had at least one visit. PP1=first per protocol analysis—population defined as patients who belonged to mITT population and were at least 50% adherent to vaginal cream for ≥3months. PP2=second per protocol analysis—population defined as patients who belonged to mITT population and were at least 50% adherent to vaginal cream for complete 12 months. One patient used self-purchased oestrogen after three month intervention and was excluded from per protocol population