Intravaginal ring shows preliminary efficacy in treating vasomotor symptoms

Key takeaways:

• Intravaginal ring that contains estradiol and progesterone reduced vaginal pH and percentage of parabasal cells.
• The ring also increased vaginal maturation index and percentage of superficial cells.

An intravaginal ring with combination estradiol and progesterone was safe and effective in treating vasomotor symptoms in postmenopausal women, according to phase 1/2 study results published in Menopause.

According to the researchers, low systemic estradiol concentrations during menopause are linked with increases in vaginal pH and decreases in glycogen, which can lead to heightened mucosal susceptibility to infection in the vaginal cytology. In addition, women with moderate to severe genitourinary syndrome of menopause experience vaginal dryness, vaginal and/or vulvar itching and pain associated with sexual intercourse.

“DARE-HRT1 is an ethylene vinyl acetate copolymer intravaginal ring containing 17-beta estradiol and progesterone. It is being developed for the treatment of moderate to severe vasomotor symptoms associated with menopause in women with an intact uterus,” Andrea Thurman, MD, medical director for Daré Bioscience, and colleagues wrote. “This would be the first vaginally delivered combination vasomotor symptom product.”

Thurman and colleagues conducted a randomized, open-label, parallel-group study with 21 healthy postmenopausal women who reported vasomotor symptoms associated with menopause to assess the efficacy and usability of the DARE-HRT1 intravaginal ring, which contains estradiol plus progesterone. Participants were randomly assigned to DARE-HRT1 intravaginal ring 1, which contains estradiol 80 µg per day plus progesterone 4 mg per day (n = 11), or DARE-HRT intravaginal ring 2, which contains 160 µg per day plus progesterone 8 mg per day (n = 10). All participants used their assigned intervention for three 28-day cycles, with new intravaginal rings inserted monthly.

Researchers estimated treatment efficacy of preliminary genitourinary syndrome of menopause through changes from baseline in vaginal pH, vaginal maturation index and changes in severity of symptoms. Researchers also measured preliminary systemic vasomotor symptoms efficacy through changes in Menopause-Specific Quality of Life questionnaire responses.

The most bothersome genitourinary symptom at baseline for women in the DARE-HRT1 intravaginal ring 1 and 2 groups were vaginal dryness among 14 women, vaginal and/or vulvar itching among two women and dyspareunia among three women.

Vaginal dryness significantly decreased from a median of 2 in severity score to a median of 0 at the end of treatment in both intravaginal ring groups (P< .01 for both). When self-reported subjective severity scores for all genitourinary syndromes of menopause symptoms were compared from baseline to the end of treatment as continuous variables, women in the intravaginal ring 1 group had significant improvement in vaginal dryness and dyspareunia (P < .01). However, women in the intravaginal ring 2 group had a nonsignificant trend in improvement for vaginal dryness and dyspareunia.

Preliminary local genitourinary syndrome of menopause treatment efficacy was observed with significant reductions in previously increased vaginal pH and percentage of parabasal cells (P < .01 for all). In addition, researchers observed significant increases in overall vaginal maturation index and percentage of superficial cells for both intravaginal ring groups (P < .01 for all).

Preliminary vasomotor symptom efficacy was observed with significant reductions that indicated improvement in overall Menopause-Specific Quality of Life score and in all questionnaire domains from baseline for both intravaginal ring groups (P < .01 for all).

“By delivering estradiol and progesterone by a nonoral route, this product meets recommended guidance from NAMS and other international organizations on the safe and effective treatment of vasomotor symptoms,” the researchers wrote. “We will use these data to move forward with the development of DARE-HRT1.”