Local oestrogen is recommended for urogenital symptoms in menopausal women.
The recommendation is strong because of large effect size on symptoms, absence of significant harms, and low cost. Treatment may also be beneficial for sexual function.
A Cochrane review [Abstract] 1 included 30 studies with a total of 6 235 patients. The overall quality of the studies was good. Outcome measures varied between the studies. Oestrogenic preparations in the form of creams, tablets and the oestradiol-releasing vaginal ring were all effective in relieving the symptoms of vaginal atrophy when compared to placebo and non-hormonal gel (table T1). There was no evidence of a difference in efficacy between the various intravaginal oestrogenic preparations when compared with each other. There was no difference in adverse effects.
| Outcome | Relative effect(95% CI) | Assumed risk - Placebo | Corresponding risk -Intervention (95% CI) | No of participants (trials) |
|---|---|---|---|---|
| Improvement in symptoms (participant-assessed),oestrogen tablets | OR 12.47 (9.81 to 15.84) | 294 / 1000 | 839 / 1000(803 to 868) | 1638(2) |
| Improvement in symptoms (clinician-assessed), oestrogen tablets | OR 1.03 (0.70 to 1.52) | 697 / 1000 | 699 / 1000(612 to 774) | 528(3) |
| Improvement in symptoms (participant-assessed), oestrogen cream | OR 4.10 (1.88 to 8.93) | 685 / 1000 | 899 / 1000(803 to 951) | 198(2) |
| Improvement in symptoms (clinician-assessed), oestrogen cream | OR 3.29 (1.47 to 7.36) | 646 / 1000 | 857 / 1000(728 to 931) | 153(1) |
A systematic review 2 included 53 studies. Compared with placebo, all vaginal estrogens demonstrated superiority in objective endpoints and subjective endpoints of genitourinary syndrome. Some trials demonstrated superiority versus placebo in urogenital symptoms. No significant difference was observed between various dosages and dosage forms of vaginal estrogen products. Estrogen showed superiority over vaginal lubricants and moisturizers for the improvement of objective clinical endpoints of vulvovaginal atrophy but not for subjective endpoints.
Another systematic review 3 included 20 randomized controlled studies, 8 interventional studies, and 10 observational studies. Collectively, there was no increased risk of endometrial hyperplasia or cancer with low-dose vaginal estrogens. Rates of endometrial cancer and hyperplasia were 0.03% and 0.4%, respectively (20 RCT, n=2983). Overall, reports of endometrial hyperplasia were observed with various doses and durations and appeared sporadic, consistent with endometrial hyperplasia rates in the general population. The Women's Health Initiative Observational Study showed no association (1.3 cases/1000 women-years with vaginal estrogens versus 1.0/1000 women-years for nonuse).
A systematic review 4 including 30 RCTs trials evaluated the effects of hormone therapy (HT) for urinary symptoms in 32 204 perimenopausal and postmenopausal women. Urinary symptoms included dysuria, urgency, frequency, recurrent urinary tract infections (UTIs), and urge and stress incontinence. 6 trials compared vaginal estrogens (estriol cream, estradiol tablet, estradiol releasing ring, estriol ovule, estrogen cream) with placebo or no treatment for 3-8 months. Vaginal estrogen effectively reduced urinary frequency, urgency, urge and stress incontinence, and recurrent urinary track infections. Because of the heterogeneity in symptoms and outcome measures assessed, a meta-analysis was not possible.
A Danish observational study 5 included a cohort of postmenopausal women, diagnosed 1997-2004 with early-stage invasive estrogen receptor-positive nonmetastatic breast cancer (BC), who received no treatment or 5 years of adjuvant endocrine therapy. Among 8461 women who had not received vaginal estrogen (local) therapy or menopausal hormone therapy (systemic) before BC diagnosis, 1957 usef local and 133 used systemic therapy after diagnosis. Median follow-up was 9.8 years for recurrence and 15.2 years for mortality. The adjusted relative risk of recurrence was 1.08 (95% CI 0.89 to 1.32) for local (1.39. 95% CI 1.04 to 1.85 in the subgroup receivingof adjuvant aromatase inhibitors) and 1.05 (95% CI 0.62 to 1.78) for systemic therapy. The adjusted hazard ratios for overall mortality were 0.78 (95% CI 0.71 to 0.87) for local and 0.94 (95% CI 0.70 to 1.26) for systemic therapy.
The following decision support rules contain links to this evidence summary:
Primary/Secondary Keywords