A vaginal softgel capsule of solubilized estradiol may be effective for treating vulvovaginal atrophy with less systemic exposure to estradiol, as compared with a currently approved vaginal estradiol tablet (Vagifem), new study results suggest.

These data were presented at the North American Menopause Society (NAMS) 2014 Annual Meeting.

Researchers compared the bioavailability of the novel solubilized vaginal estradiol gelcap, containing bioidentical 17 beta-estradiol (TX-004HR), with the Vagifem tablet in two randomized, single-dose, two-way crossover pharmacokinetic trials.

In both studies, they administered a single dose of TX-004HR or the estradiol tablet to 36 healthy postmenopausal women aged 40 to 65 years. After a 14-day washout period, the participants received a single dose of the alternate drug.

A 10-mcg dose of TX-004HR was examined in one trial while a 25-mcg dose was examined in the other.

After adjustment for baseline levels, area under the curve values were 63% for the 10-mcg dose and by 69% for the 25-mcg dose less for estradiol. For estrone, they were 50% less with the 10-mcg dose and 70% less with the 25-mcg dose, as compared with the tablet.

Moreover, results showed that peak serum concentrations were 29% and 46% less for estradiol with the 10-mcg and 25-mcg doses, respectively, and 26% and 55% less for estrone with the 10-mcg and 25-mcg doses, respectively.

Systemic exposure was also significantly lower with both doses of the capsule vs. the tablet, and no adverse events were reported in either trial.

The researchers also assessed the estradiol capsule’s safety and efficacy in a pilot study involving 50 healthy postmenopausal women aged 40 to 75 years. The participants were randomly assigned to the 10-mcg dose of the capsule or placebo.

All women had at least one moderate to severe vulvovaginal atrophy symptom, superficial cells 5% or less and a vaginal pH greater than 5.

Compared with placebo, the capsule yielded significantly higher mean percent increases from baseline for superficial cells (35% vs. 4%; P=.0002) and intermediate cells (13% vs. 4%; P=.0002) after 2 weeks, the researchers reported.

Mean percent decrease in parabasal cells from baseline was significantly greater with the capsule vs. placebo (54% vs. 5%; P=.0001), and mean decrease in vaginal pH from baseline was also significantly greater in the treatment arm (0.97 vs. 0.34; P=.0002).

Results also indicated greater improvements in vaginal epithelial integrity and secretions with the capsule vs. placebo.

Although vaginal symptom improvement was similar between groups, the researchers noted that the small sample size and short duration may be responsible.

Twenty-eight percent of women had 17 treatment-emergent adverse events, though not all were related to treatment. Eye contusion; nephrolithiasis; increase in blood pressure’ vaginal discharge, dysplasia or pruritis; vulvovaginal pain or burning; hot flush; and cervical dysplasia were among those that occurred in the treatment group, while paresthesia, vaginal hemorrhage and vulvovaginal discomfort were reported in the placebo group.

None were deemed serious, according to the study results.

The researchers concluded that their study suggests the novel estradiol softgel capsule could be a treatment option for women with vulvovaginal atrophy.

Reference

  1. Pickar JH et al. Abstract S-6. Presented at: North American Menopause Society (NAMS) 2014 Annual Meeting; Oct. 15-18, 2014; Washington, D.C.