Extended-release oxybutynin therapy for vasomotor symptoms in women: a randomized clinical trial.

OBJECTIVE: Assess effects of once-daily, extended-release oxybutynin chloride on frequency and severity of vasomotor symptoms in healthy, postmenopausal symptomatic women. METHODS: A 12-week, multicenter, double-blind, placebo-controlled, phase 2 clinical trial randomized naturally postmenopausal women experiencing at least seven moderate-to-severe vasomotor symptoms daily to oxybutynin 15 mg once daily (n = 73) or placebo (n = 75). Co-primary outcomes were the change from baseline to week 12 in the frequency and severity of moderate-to-severe vasomotor symptoms. RESULTS: Significant reductions in both frequency and severity of moderate-to-severe vasomotor symptoms in women who received oxybutynin compared with placebo were observed at all weeks of treatment (P ≤ 0.007, all time points) through week 12. Mean changes in frequency in the oxybutynin and placebo groups were -9.48 and -4.69 episodes/d, respectively, at week 12. Mean changes in severity (scale 0-3) in the oxybutynin and placebo groups were -1.27 and -0.30, respectively, at week 12. At the end of treatment, 73% of women in the oxybutynin group and 26.1% in the placebo group rated symptom improvement "much better" (P ≤ 0.001). Women treated with oxybutynin showed significant improvement in sleep quality, sleep disturbance, and the global sleep index on the Pittsburgh Sleep Quality Index (P ≤ 0.023). Dry mouth was reported by 52.1% of participants given oxybutynin and 5.3% of participants given placebo, leading to discontinuation of oxybutynin in 6.8% of participants. CONCLUSIONS: Oxybutynin is an effective, nonhormonal therapy for moderate-to-severe vasomotor symptoms in postmenopausal women.

The breast cancer "plunge" after initial publication of the WHI results: an alternative explanation.

From 2002 to 2003, the breast cancer incidence in the United States, as reported by the National Cancer Institute's Surveillance Epidemiology and End Results (SEER 9) database, appeared to decrease by 6.7%. This phenomenon has been attributed to a reduction in the use of menopausal hormone therapies after the initial publication of the Women's Health Initiative (WHI) study results in July of 2002. However, attempts to draw a causal association between the use of menopausal hormone therapies and the incidence of breast cancer have not accounted for the facts that prescriptions of estrogen-plus-progestin menopausal therapies, which are associated with increased rates of breast cancer, fell by 53% from 2002 to 2003, while prescriptions of estrogen-only therapies fell by only 27%. To address this issue, we analyzed the effects of the higher rate of discontinuation of estrogen-plus-progestin menopausal therapies relative to estrogen-only treatments during the 2002-2003 time period, based upon the effects of different types of menopausal hormone therapies on breast cancer incidence as determined by the WHI interventional hormone trials. This approach demonstrates that the relative persistence with menopausal estrogen-only therapies - as compared to estrogen-plus-progestin therapies - can explain the reduction in breast cancer incidence from 2002 to 2003. In addition, we point out the incompatibility of the breast cancer incidence rates found in the two WHI interventional hormone trials and the rates reported in the SEER 9 database. Based on these findings, we conclude - as previously demonstrated in the estrogen-only arm of the WHI interventional hormone trials - that menopausal estrogen-only use is not responsible for increasing the risk of breast cancer in menopausal women and may, in fact, be protective. Additional studies are still needed to better define the relationship between different types of menopausal hormone therapies and the incidence of breast cancer.