Oxybutynin, a medicine commonly used to treat bladder incontinence, reduced the number and severity of hot flashes in women treated for breast cancer, according to a study.
The research was presented on Dec. 7, 2018, at the San Antonio Breast Cancer Symposium. Read the abstract of “A randomized, double-blind, placebo-controlled trial of oxybutynin (Oxy) for hot flashes (HF): ACCRU study SC-1603.”
The ACCRU study
Oxybutynin is an anticholinergic agent, which means it blocks certain substances in the brain that regulate a number of functions, including involuntary muscle activity. It’s used to treat urinary incontinence because it controls bladder spasms.
In other studies on oxybutynin to control muscle spasms, researchers noticed that a side effect was decreased sweating. So researchers thought it might help control night sweats and hot flashes, especially since oxybutynin doesn’t interfere with the effectiveness of tamoxifen. Other research has shown that certain medicines used to control hot flashes, including some antidepressants, can reduce the effectiveness of tamoxifen.
This study, called the ACCRU study, included 113 women who were having 28 or more hot flashes per week for more than 30 days:
- average age was 58
- about half the women were having 10 or more hot flashes per day
- 62% of the women were taking hormonal therapy: either tamoxifen or an aromatase inhibitor
- all the women had asked for medicine to treat hot flashes
Hormonal therapy medicines work in two ways:
- by lowering the amount of estrogen in the body
- by blocking the action of estrogen on breast cancer cells
There are several types of hormonal therapy medicines. Tamoxifen, a selective estrogen receptor modulator (SERM), is one of the most well-known. Tamoxifen can be used to treat both premenopausal and postmenopausal women. In the early 2000s, the aromatase inhibitors:
- Arimidex (chemical name: anastrozole)
- Aromasin (chemical name: exemestane)
- Femara (chemical name: letrozole)
were shown to be more effective at reducing the risk of breast cancer recurrence (the cancer coming back) in postmenopausal women and are now used more often than tamoxifen to treat women who’ve gone through menopause. Aromatase inhibitors aren’t commonly used to reduce recurrence risk in premenopausal women.
Most women take hormonal therapy for 5 to 10 years after breast cancer surgery.
Both tamoxifen and the aromatase inhibitors can cause hot flashes.
The women in the study were randomly assigned to one of three treatments for hot flashes:
- 2.5 mg of oxybutynin twice per day for 6 weeks
- 2.5 mg of oxybutynin twice per day for 1 week, then 5 mg twice per day for 5 weeks
- a placebo pill that looked just like oxybutynin but contained no medicine twice per day for 6 weeks
The women completed questionnaires on the number and severity of their hot flashes before the study started and again when the study was completed. During the study, they kept a hot flash diary and tracked how the hot flashes affected their daily routines.
Oxybutynin helped ease hot flashes
The results showed that women taking either dose of oxybutynin saw a decrease in the number and severity of hot flashes compared to women taking the placebo. Women taking the higher dose of oxybutynin had a slightly greater decrease in the number and severity of hot flashes compared to women taking the lower dose.
- Women taking 5 mg of oxybutynin for the last 5 weeks of the study had 7.5 fewer hot flashes per day.
- Women taking 2.5 mg of oxybutynin for 6 weeks had 4.8 fewer hot flashes per day.
- Women taking the placebo had 2.6 fewer hot flashes per day.
“What we saw was that oxybutynin indeed was more effective than placebo in both doses,” Roberto Leon-Ferre, M.D., assistant professor of oncology at the Mayo Clinic in Rochester, Minnesota, who presented the research, told Breastcancer.org. “The study was not designed to compare the two doses against each other but to compare each dose to placebo, and both of those doses were effective. They significantly decreased hot flashes. The oxybutynin 5 mg twice daily decreased hot flashes by about 80%, the hot flash severity and frequency; the lower dose decreased them by about 65%; and then placebo by about 20–30%, which is consistent with what we’ve seen in other studies.
“More important than just reducing the frequency and severity of hot flashes, what we saw in our study as well is that patients rated a significant improvement in the hot flash interference with daily activities,” he continued. “So we measured, for example, how did the hot flashes interfere with work, how did the hot flashes interfere with leisure activities, social activities, concentration, sexuality, and overall quality of life, and patients on oxybutynin reported an improvement in nearly all of those quality metrics with the exception of concentration and sexuality. All the others were improved.”
Oxybutynin side effects
Both doses of oxybutynin caused more side effects than the placebo, but none of the side effects were considered serious.
Compared to women taking placebo, women taking the 2.5-mg dose of oxybutynin had more:
- stomach pain
- episodes of confusion
- dry mouth
- dry eyes
Compared to women taking placebo, women taking the 5-mg dose of oxybutynin had more:
- dry mouth
- difficulty urinating
There were no differences in the number of women who stopped taking either dose of oxybutynin or placebo because of side effects (6 women in the 2.5-mg group, 7 women in the 5-mg group, and 5 women in the placebo group).
“It was also very pleasing to see that the side effects that [the women] experienced were very tolerable, did not lead to discontinuation of the drug more frequently than placebo, and that most patients had mild degree of side effects,” Leon-Ferre said.
Long-term use linked to cognitive decline
While these results are promising, it’s unclear whether oxybutynin can be a long-term solution for hot flashes. In other studies looking at oxybutynin to treat overactive bladder, long-term use has been linked to some cognitive decline.
“This is not something that we can necessarily answer with our study,” Leon-Ferre said. “What I can say is that the common use of oxybutynin for many years has been linked to potential cognitive decline in the long term. In the short term there can also be episodes of confusion, particularly in the elderly patients or in patients that are taking other medications that are also anticholinergic, and there are a variety of medicines that can have that effect. So, it’s more of a problem when you mix medications of that nature, and we did not allow the use of those potential medications in our study, so that’s why we didn’t see a lot of that. But it is a precaution that clinicians and patients need to be aware of if they choose to try this medication.
“In terms of how long is too long, I don’t think that we fully understand that,” he continued. “But we’re talking about, you know, years of taking the medicine. In the setting of urinary incontinence, patients usually take it long-term for years because… it’s not a reversible problem unless they have a procedure done.”
In the ACCRU study, oxybutynin was effective at easing hot flashes when taken for only 6 weeks. The researchers didn’t track whether the women’s hot flashes returned at the same frequency and severity when the study ended and the women stopped taking oxybutynin or placebo.
Still, in most studies looking at hot flashes as a results of breast cancer treatment, the hot flashes tend to fade over time.
“Our hope would be that you can use this medication in the initial period when the hot flashes are more severe, more frequent, and then as the patient starts to adjust to their menopausal state, hopefully they won’t need as much of the medication and eventually, hopefully stop,” Leon-Ferre said.
What this means for you
If you’ve been diagnosed with breast cancer and are having troubling hot flashes, talk to your doctor about all your options to ease them. While this study suggests oxybutynin may be a good option for some women, other women, including older women and women taking other anticholinergic medicines, likely aren’t good candidates for oxybutynin.
Still, there are a number of other options to help ease hot flashes, including:
- regular exercise
- limiting or avoiding alcohol
For more information, visit the Breastcancer.org Menopause Symptoms: Hot Flashes pages.
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, M.D., medical adviser