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Evidence summaries

Local Oestrogen for Genitourinary Syndrome of Postmenopause

Local oestrogen is effective and safe for symptoms of vaginal atrophy. Creams, tablets and the estradiol vaginal ring are equally effective. Level of evidence: "A"

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.

Oestrogen tablets/cream compared to placebo for vaginal atrophy in postmenopausal women

OutcomeRelative effect(95% CI)Assumed risk - PlaceboCorresponding risk -Intervention (95% CI)No of participants (trials)
Improvement in symptoms (participant-assessed),oestrogen tabletsOR 12.47 (9.81 to 15.84)294 / 1000839 / 1000(803 to 868)1638(2)
Improvement in symptoms (clinician-assessed), oestrogen tabletsOR 1.03 (0.70 to 1.52)697 / 1000699 / 1000(612 to 774)528(3)
Improvement in symptoms (participant-assessed), oestrogen creamOR 4.10 (1.88 to 8.93)685 / 1000899 / 1000(803 to 951)198(2)
Improvement in symptoms (clinician-assessed), oestrogen creamOR 3.29 (1.47 to 7.36)646 / 1000857 / 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).

The following decision support rules contain links to this evidence summary:

References

  • Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2016;(8):CD001500. [PubMed]
  • Biehl C, Plotsker O, Mirkin S. A systematic review of the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause. Menopause 2019;26(4):431-453. [PubMed]
  • Constantine GD, Graham S, Lapane K et al. Endometrial safety of low-dose vaginal estrogens in menopausal women: a systematic evidence review. Menopause 2019;26(7):800-807. [PubMed]

Primary/Secondary Keywords