Prasterone is a plant-derived version of endogenous dehydroepiandrosterone (DHEA). It is an inactive precursor that is converted into oestrogens and androgens in the body.
Efficacy of the once-daily prasterone pessary was established in two 12-week randomised, double-blind placebo-controlled clinical trials in postmenopausal women with VVA. In both trials, the four co-primary efficacy endpoints were moderate to severe dyspareunia, percentages of vaginal parabasal cells and superficial cells and vaginal pH.
At baseline, women had ≤5.0% superficial cells in the vaginal smear, a vaginal pH >5.0 and they had identified dyspareunia (moderate to severe) as their most bothersome VVA symptom.
In the first trial (n=255), women were randomised to receive prasterone 3.25mg or 6.5mg or placebo daily. At week 12, the prasterone 6.5mg group showed a reduction of 0.40 units (46%) compared with the placebo group in the mean severity score of most bothersome dyspareunia (p=0.013). Compared with placebo, the percentage of parabasal cells in the prasterone 6.5mg group decreased by 45.8% (p<0.0001), the percentage of superficial cells increased by 4.7% (p<0.0001), and vaginal pH decreased by 0.83 pH units (p<0.0001).
The 3.25mg dose failed to achieve statistical significance versus placebo for dyspareunia at week 12, thus confirming 6.5mg as the lowest effective dose.
In the second trial (n=558), patients were randomised to either prasterone 6.5mg or placebo. After 12 weeks of daily treatment, the prasterone group demonstrated significant improvements in all four co-primary endpoints compared with placebo (p=0.0002 for the dyspareunia comparison; p< 0.0001 for the other three comparisons).
The most common adverse reactions to prasterone were vaginal discharge, abnormal Pap smear and weight fluctuation.