Intravaginal dehydroepiandrosterone for genitourinary symptoms of the menopause: Is the evidence sufficient?

Abstract

Intravaginal dehydroepiandrosterone (DHEA) is a locally metabolised estrogen and androgen precursor, licensed in 2018 in the EU for moderate to severe vulvovaginal atrophy in postmenopausal women. A literature search revealed four original trials suitable for appraisal, three evaluating change in dyspareunia or dryness as a primary outcome, one evaluated safety as a primary outcome. In two trials of 255 and 558 women without cancer, the benefit of placebo (nightly vaginal suppositories with a lipophilic base) was a 0.9 and 1 point reduction in dyspareunia as measured on a 3 point scale, an unvalidated outcome measure. With nightly DHEA, dyspareunia was reduced by an additional 0.4 points compared to placebo. When 464 women with gynaecological cancer were randomised, those using nightly plain moisturiser gel reported a reduction of ‘most bothersome symptom’ (either dyspareunia or dryness) of 1.5 points on a 3 point scale. Those using nightly DHEA reported an additional symptom reduction of 0.3 points. This is also an unvalidated outcome measure. Data evaluating the efficacy of DHEA over placebo is unconvincing and based on unvalidated primary outcome measures that also do not reflect the complex psycho-sexual and socio-cultural components of genitourinary menopausal symptoms. The efficacy and safety data excluded women taking systemic HRT, applies to postmenopausal, not perimenopausal, women and had relatively short follow up. It is important further independent trials use sophisticated and validated assessment tools to better establish the efficacy, safety and cost effectiveness of intravaginal DHEA in clinically representative groups of women before being routinely prescribed.