Oral lasofoxifene associated with improved vulvovaginal atrophy symptoms in menopause

Key takeaways:

• Oral lasofoxifene was associated with improvement in bothersome vaginal symptoms, vaginal pH and vaginal superficial and parabasal cells.
• The most common treatment-emergent adverse event was hot flushes.

Postmenopausal women assigned daily oral lasofoxifene had significant and clinically meaningful improvements in vulvovaginal atrophy symptoms with a favorable safety profile, researchers reported in Menopause.

“Current treatment options for genitourinary syndrome of menopause/vulvovaginal atrophy are limited to vaginal estrogens, dehydroepiandrosterone and oral ospemifene, and all with limitations for women with active breast cancer or breast cancer survivors,” Risa Kagan, MD, MSCP, clinical professor in the department of obstetrics, gynecology and reproductive sciences at the University of California, San Francisco, and the Sutter East Bay Medical Group, told Healio. “This is the first published data of a phase 3 program for oral lasofoxifene in doses of 0.25 mg and 0.5 mg per day that confirms efficacy for vaginal dryness, dyspareunia and other symptoms of genitourinary syndrome of menopause.”

Kagan and colleagues conducted two phase 3 randomized controlled trials with identical design to evaluate the safety and efficacy of investigational oral lasofoxifene (Sermonix Pharmaceuticals) to treat moderate to severe vulvovaginal atrophy for postmenopausal women aged 50 to 80 years. Study 1 enrolled 444 postmenopausal women from 48 centers in Canada and the U.S. and study 2 enrolled 445 postmenopausal women from 48 centers in Canada, the U.S., Australia, Denmark, Estonia, Lithuania, Norway and Poland. All women in study 1 and 2 were randomly assigned to receive oral lasofoxifene 0.25 mg (n = 151 and n = 150) or 0.5 mg (n = 143 and n = 146) or placebo (n = 150 and n = 149) daily for 12 weeks.

Researchers evaluated changes from baseline to 12 weeks in most bothersome symptoms, vaginal pH and percentages of vaginal parabasal and superficial cells.

Risa Kagan

At 12 weeks, in study 1, oral lasofoxifene 0.25 mg and 0.5 mg daily improved most bothersome symptoms (least square mean difference, –0.4 and –0.5, respectively), vaginal pH (–0.65 and –0.58, respectively) and vaginal superficial (5.2% and 5.4%, respectively) and parabasal (–39.9% and –34.9%, respectively) cells compared with placebo (P < .0125 for all). In study 2, results were similar for oral lasofoxifene 0.25 mg and 0.5 mg daily at week 12 for most bothersome symptoms (–0.4 and –0.5, respectively), vaginal pH (–0.57 and –0.67, respectively) and vaginal superficial (3.5% and 2.2%, respectively) and parabasal (–34.1% and –33.5%, respectively) cells compared with placebo (P < .0125 for all).

Improvements with oral lasofoxifene at both doses were observed by week 2, according to the researchers.
The most common treatment-emergent adverse event was hot flushes in study 1 and 2, reported by 23.2% and 22% of women in the 0.25 mg groups, 12.6% and 19.9% of women in the 0.5 mg groups, and 10.7% and 9.4% of women in the placebo groups. Most treatment-emergent adverse events were mild or moderate, and serious adverse events were uncommon with no deaths occurring in study 1 and 2, according to the researchers.

“Lasofoxifene in doses of 5 mg per day is currently being explored in the ELAINE phase 3 study as a treatment for advanced breast cancers that have developed mutations in the estrogen receptor,” Kagan said. “It will be interesting to see if this study confirms improvement in urogenital symptoms and sexual dysfunction based upon patient reported outcomes data in this unique population and in a higher dose formulation.”

For more information:

Risa Kagan, MD, MSCP, can be reached at risa.kagan@sutterhealth.org.