Source: DGNews  |  Posted 4 years ago

By Carole Bullock

DALLAS, TX -- October 5, 2007 -- The combination of bazedoxifene and conjugated oestrogens (BZA/CE) appears to provide a new option for postmenopausal women with vaginal dryness, hot flashes and other menopausal symptoms, investigators reported here in two separate reports at the North American Menopause Society (NAMS) 18th Annual Meeting.

BZA/CE is combination of a tissue-selective oestrogen complex (TSEC) and bazedoxifene, a selective oestrogen receptor modulator (SERM).

One of the studies of BZA/CE was presented on October 5 by JoAnn V. Pinkerton, MD, Associate Professor of Obstetrics and Gynecology, Director, The Women's Place Midlife Health Center, Department of Obstetrics and Gynecology, Division of Midlife Health, University of Virginia, Charlottesville, Virginia, United States.

A follow-up to the first Selective oestrogens, Menopause and Response to Therapy (SMART) study, Dr. Pinkerton's SMART-2 study found that women who were treated with the BZA/CE had up to an 80% reduction in hot flashes compared with a 51% reduction with placebo

A 50% reduction in moderate to severe symptoms occurred by 14 to 15 days for BZA/CA versus 30 days for placebo.

"This blended combination allows you to optimize the benefit of the oestrogen and the benefits of the SERM," Dr. Pinkerton said.

"This study is the first to provide safety data on this novel complex for treatment of menopause in women with severe symptoms," she noted. "BZA/CE is a novel tissue selective oestrogen complex that can effectively and safely reduce the number and severity of hot flashes in symptomatic menopausal women, with no evidence of endometrial stimulation."

The treatment is not approved by the U.S. Food and Drug Administration, but it is in final stages of clinical testing, Dr. Pinkerton said.

In the earlier, 2-year SMART trial, both BZA/CE doses (20/0.45 mg and 20/0.625 mg) improved bone mineral density and reduced hot flashes, with no evidence of abnormal endometrial stimulation.

In the new, 12-week SMART-2 study, 332 postmenopausal women with 7 or more moderate to severe hot flashes per day or 50 or more per week were randomised to BZA/CE 20/0.45, BZA/CE 20/0.625, or placebo. The 318 women who were evaluated had a mean age of 53.4 years.

BZA/CE was highly effective and improved time to sleep compared with placebo, Dr. Pinkerton said.

The BZA/CE-treated women had fewer sleep disturbances and had improved sleep adequacy, sleep onset, and sleep duration, she said.

All treatment groups had fewer hot flashes from baseline at all time points. But BZA/CE had a significantly greater reduction in the number of moderate to severe hot flashes at weeks 4 and 12 compared with placebo (P <.001), reaching a 74% to 80% decrease from baseline at week 12.

There was a statistical difference against placebo in the daily number of moderate to severe hot flashes in the BZA/CE (20/0.45) group from week 3 onward and in the BZA/CE (20/0.625) group from week 2 onward. "That is a really big deal because it's clinical significant," Dr. Pinkerton said

At the start of the SMART-2 study, the women had an average of 10 hot flashes per day. By week 12, the 20/0.625-mg group decreased to two hot flashes per day and the 20/0.45-mg group decreased to 2.6 hot flashes per day, while the placebo group had decreased to five hot flashes per day, she said.

Transvaginal ultrasounds performed at baseline and at 12 weeks showed that adverse events and changes from baseline in endometrial thickness were the same for all groups.

Dr. Pinkerton predicted the treatment would benefit women who suffer severe symptoms and require bone protection, whereas poorer candidates would be those with clotting disorders.

In another presentation, researchers discussed the findings from the SMART-3 study, which looked at the effects of BZA/CE on vulvar/vaginal atrophy (VVA) and sexual function in postmenopausal women.

The findings were presented by Risa Kagan, MD, Clinical Professor of Obstetrics and Gynecology and Reproductive Science, University of California San Francisco Medical Center, Co-medical Director, Foundation for Osteoporosis Research and Education, and Physician, Obstetrician/Gynaecologist, East Bay Physicians Medical Group, Oakland, California, United States.

In the 12-week study, Dr. Kagan and colleagues enrolled 652 women aged 40 to 65 years with moderate-to-severe VVA, vaginal pH >5.0, and 5% or fewer superficial cells. These women were randomised to four treatment groups: BZA/CE 20 mg/0.45 mg; BZA/CE 20 mg/0.625 mg; BZA 20 mg alone; or placebo.

Vaginal superficial and parabasal cells, vaginal pH, and severity of most bothersome VVA symptom were assessed at baseline and at week 12. The women were also evaluated before treatment and at week 12 using the Arizona Sexual Experiences Scale (ASEX), which quantifies sex drive, arousal, vaginal lubrication, ability to reach orgasm, and satisfaction from orgasm; they were also given the Menopause-Specific Quality of Life Questionnaire (MenQoL) at baseline and at week 12.

Of the 652 women who were treated, 601 completed the study. After 12 weeks, the BZA/CE 20 mg/0.45 mg and BZA/CE 20 mg/0.625 mg groups had increases in the percentage of superficial cells and decreases in parabasal cells compared with placebo (P <.005).

Active treatment resulted in a greater decrease in vaginal pH compared with placebo (P <.001) and a greater improvement in the most bothersome symptom index (P <.05). ASEX lubrication score and MenQoL total and sexual function scores also improved in both treatment doses compared with the placebo group (P < 0.05 for all).

"TSECs with BZA/CE improved biologic markers of VVA and sexual function, with acceptable safety, in postmenopausal women," Dr. Kagan concluded.

"Both doses were better in improving vaginal superficial and parabasal cells, vaginal pH, and severity of most bothersome symptoms, and up to 92% [of women] continued on therapy," Kagan said.

She also noted that there were no identifiable adverse events.

[Presentation titles: SMART-2: A Phase III Study of the Efficacy and Safety of Bazedoxifene/Conjugated Oestrogens for Treatment of Menopausal Vasomotor. Abstract S-2. SMART-3: Effects of the Tissue Selective Ooestrogen Complex (TSEC) Bazedoxifene (BZA) and Conjugated Oestrogens (CE) on Vulvar/Vaginal Atrophy (VVA) and Sexual Function in Postmenopausal Women. Abstract S-4]