Approximately 50% of women aged 50 or over are affected by pelvic organ prolapse (POP), the descent of one or more of the anterior or posterior vaginal wall, the uterus or the apex of the vagina (after hysterectomy). Older age, a larger number of births and a higher body mass index (BMI) are all recognised as being risk factors. Currently, oestrogens are being used in daily clinical practice to treat POP, sometimes in combination with other therapies, without clear supporting evidence. Therefore, the objective of this Cochrane systematic review was to assess the effects of topical or systematic oestrogen therapy, alone or in combination with other treatments, on POP in postmenopausal women.

We searched the Cochrane Incontinence Specialised Register on 20 June 2022 for randomised controlled trials (RCTs), quasi-RCTs, cross-over RCTs or cluster-RCTs of postmenopausal women (defined as one year since last menses) with any grade of POP in any compartment. The key comparisons were: oestrogen therapy alone versus no treatment or placebo; oestrogen therapy alone versus pelvic floor muscle training (PFMT); oestrogen therapy alone versus devices such as vaginal pessaries; and oestrogen therapy alone versus surgery. The primary outcome was subjective cure or improvement of POP symptoms (measured by tools such as the PGI-I or VAS). Key secondary outcomes include improvement or cure of sexual symptoms associated with POP, objective cure or improvement of POP symptoms, generic quality of life measures, patient adherence to the intervention, minor vaginal adverse events and major adverse events.

Two review authors independently screened all titles and abstracts for eligibility; in cases of disagreement, a third review author acted as arbitrator. The same process was followed for full-text screening. The same two review authors also independently extracted all data and critically appraised included studies using Cochrane’s ‘Risk of bias’ tool. Where feasible, we performed random-effects meta-analyses using RevMan Web. If meta-analyses were not feasible, we conducted narrative syntheses based on the principles of synthesis without meta-analysis (SWiM). Had data allowed, the GRADE approach would have been used to assess the certainty of key outcomes for key comparisons.

We identified 14 studies (with a total of 1002 women) as being eligible for the review. We did not identify any studies that addressed our key comparisons. However, three studies assessed oestrogen therapy in conjunction with vaginal pessaries versus vaginal pessaries alone and 11 studies that compared oestrogen therapy in conjunction with surgery versus surgery alone.

One study comparing oestrogen therapy in conjunction with vaginal pessaries versus vaginal pessaries alone reported that slightly more women in the pessary alone group discontinued pessary use. A meta-analysis of three studies suggested that topical oestrogen plus pessary may lead to a reduction in minor adverse vaginal events compared with pessary alone (RR 0.48, 95% CI 0.25 to 0.91; n = 185). Two studies reported that no major adverse events occurred in either the oestrogen therapy plus vaginal pessary group or the vaginal pessary alone group. Subjective cure or improvement of POP symptoms, improvement or cure of sexual symptoms, cure or improvement of POP symptoms and generic quality of life were not measured for this comparison.

At 12 months, two studies that could not be meta-analysed suggested there may be little or no evidence of a difference in subjective improvement of POP symptoms between women who used oestrogen therapy in conjunction with surgery compared with those who had surgery alone. It is uncertain whether topical oestrogen therapy alongside surgery has an effect on sexual symptoms associated with POP compared with surgery alone at 12 months (MD – 0.57, 95% CI -1.98 to 0.85; studies = 2; n = 207). One study reported that there may be little to no evidence of a difference between topical oestrogen therapy alongside surgery and surgery alone in terms of objective cure or improvement of POP symptoms at 12 months (n = 186). There may be little to no difference in adherence to intervention between women who took oestrogen alongside having surgery compared with women who underwent surgery alone (RR 1.07, 95% CI 0.49 to 2.32; studies = 2; n = 114). Due to the 95% CI potentially indicating both benefit or harm, it is uncertain whether oestrogen therapy alongside surgery results in more women experiencing adverse vaginal events compared with surgery alone (RR 2.23, 95% CI 0.74 to 6.79; studies = 4; n = 371). For the same reason, it is uncertain whether using either topical or systemic oestrogen therapy in conjunction with surgery results in fewer women experiencing major adverse events compared with women who undertook surgery alone (RR 1.02, 95% CI 0.39 to 2.66; studies = 5; n = 453). Generic quality of life was not reported for this comparison.

In general, the studies were at a high risk of bias, particularly regarding blinding of participants and personnel, as well as concerns surrounding selective reporting. Many of the included studies also had very few women participating in them.

There is currently insufficient evidence to determine the effects of oestrogen therapy for managing POP in postmenopausal women. Larger, well-designed studies on the effectiveness and cost-effectiveness of using oestrogen therapy are required.

Continence 7S1 (2023) 100852
DOI: 10.1016/j.cont.2023.100852