'It's Going to Be a Useful Agent': Oxybutynin for Hot Flashes

Pam Harrison

December 10, 2018

SAN ANTONIO — Oxybutynin (multiple brands), an anticholinergic widely used to treat urinary incontinence caused by an overactive bladder, is surprisingly effective in the treatment of hot flashes in breast cancer survivors, new research shows.

It was also effective in study patients who did not have breast cancer but who were bothered by frequent or severe menopausal symptoms, according to a presentation here at the San Antonio Breast Cancer Symposium (SABCS) 2018.

"Hot flashes are a big problem across the general population, but breast cancer survivors are at higher risk for experiencing either more severe or longer-lasting hot flushes, often as a consequence of our therapies," lead author Roberto Leon-Ferre, MD, assistant professor of oncology, Mayo Clinic, Rochester, Minnesota, told a press briefing here.

Hot flashes can affect breast cancer outcomes — symptoms can be so severe that patients will discontinue endocrine therapy prematurely, he added.

In the new study, oxybutynin significantly reduced the frequency and severity of hot flashes, and its use had a positive impact on several quality-of-life metrics.

"If you are dealing with a patient who does not have a lot of other comorbidities and who doesn't take a lot of other medications that could interact with the drug, this is a good option," Leon-Ferre concluded.

To qualify for the study, at baseline, women had to have been experiencing 28 or more hot flashes a week for at least 30 days.

Nearly two thirds of 150 patients enrolled in the trial took either tamoxifen (multiple brands) or an aromatase inhibitor for breast cancer for the duration of the study. The remaining women were not breast cancer patients.

Concurrent use of antidepressants, gabapentin (multiple brands), or pregabalin (Lyrica, PF Prism), which are all used to treat hot flashes, was allowed.

Almost half of the women in each group reported having 10 or more hot flashes a day, and more than three quarters of them reported that their hot flashes had persisted for 9 months or longer.

Oxybutynin was administered at a dosage of either 2.5 mg twice a day or 5 mg twice a day for 6 weeks.

"A baseline questionnaire was given to establish the degree of hot flushes women were experiencing as well as quality of life metrics," Leon-Ferre noted.

The investigators also administered the Hot Flash—Related Daily Interference Scale (HFRDIS) — a weekly "hot-flash diary" — to establish the degree to which hot flashes were interfering with various aspects of a patient's life, he added.

Approximately 50 patients were enrolled in each of the three treatment arms; 35 to 40 evaluable patients remained in each arm at study endpoint.

The investigators evaluated change in individual patient symptoms over 6 weeks from baseline.

Leon-Ferre and colleagues observed that for women who received oxybutynin 5 mg bid, hot flash scores at week 6 were reduced by nearly 80%.

The 2.5-mg bid dosage had a similar though slightly less pronounced effect on hot flash scores at study endpoint.

"Patients on both oxybutynin doses had a significantly greater reduction in their hot flash score and frequency compared with placebo (P < .01)," the investigators summarized.

For the patients who received oxybutynin at either of the two dosages, reductions in hot flash scores compared favorably to the 30% reduction experienced by patients who received placebo. This "is consistent with what we see in other placebo-controlled studies, so placebo does have an effect in controlling hot flashes," Leon-Ferre observed.

Mean frequency of hot flashes was reduced from baseline by about the same magnitude as was seen for reductions in the hot flash score in each of the three treatment arms.

Table. Mean Changes in Endpoints From baseline to Week 6

  Oxybutynin 2.5 mg bid Oxybutynin, 5 mg bid Placebo
Hot flash score -10.6 -16.9 -5.7
Hot flash frequency 4.8 fewer hot flashes per day 7.5 fewer hot flashes per day 2.6 fewer hot flashes per day

For women who received either of the two dosages of oxybutynin, most HFRDIS measures, including measures related to sleep, leisure activities, work, and relationships, were significantly better in comparison with women who received placebo.

However, neither dosage of oxybutynin offset the effect that hot flushes had on patients' ability to concentrate or on their sexuality. At the lower dosage, oxybutynin did not improve mood or enjoyment of life; at the higher dosage, improvements were seen for these measures.

Side effects were as expected with any anticholinergic and included dry mouth, abdominal pain, and difficulty urinating with both dosages.

At the higher dosage, oxybutynin also increased the risk of developing dry eyes, as well as risk for episodes of confusion, diarrhea, and headaches.

New Therapies

Leon-Ferre's home institution, the Mayo Clinic, has long been involved in the exploration of new therapies for hot flashes in women who cannot take hormone replacement therapy — the most effective treatment for menopausal symptoms — because they have either had breast cancer or are at high risk for it.

Among the agents studied in this regard have been two antidepressants, venlafaxine (multiple brands) and citalopram (multiple brands).

Results from these trials show that venlafaxine reduced hot flash scores by approximately 60%. Citalopram was slightly less effective than venlafaxine.

"We have to be cautious, as these are cross-trial comparisons, but oxybutynin shows a more significant decrease in hot flash score [than anything else so far], so with the results of this particular study, we will be more keen on using oxybutynin now," he said.

Asked to comment on the findings, Ken Osborne, MD, SABCS codirector and director of the Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, told Medscape Medical News that he personally is now going to start using oxybutynin for more patients because it is at least as effective as venlafaxine and it has some other advantages.

You have to pick the right patientT Dr Ken Osborne

For example, oxybutynin does not interfere with the metabolism of tamoxifen, an important consideration for breast cancer survivors.

In contrast, it is thought that some antidepressants used to treat hot flashes have the potential to decrease the efficacy of tamoxifen.

"You have to pick the right patient," Osborne elaborated.

"If you have a patient with a lot of anxiety or depression, then you are going to use venlafaxine; if not, you might want to use oxybutynin," he noted.

The fact that some of the patients enrolled in the current study were already taking an antidepressant or other agents presumably to treat their hot flashes suggests that these other medications were not fully working for them, Osborne also pointed out.

"When they added oxybutynin into that mix, they showed that it can help here too," he said.

"So I think it's going to be a useful agent," Osborne concluded.

Hot flashes not only affect patients who have estrogen-dependent cancer, which is treated with therapies that block estrogen production. They also affect patients with estrogen-independent cancer that is treated with chemotherapy; chemotherapy itself can induce early menopause, which will trigger hot flashes as well.

The study was supported by the Breast Cancer Research Foundation. Dr Leon-Ferre has received travel support from Immunomedics. Dr Osborne has received grant support from Puma Biotechnology and has served on the advisory board for Tolmar Pharmaceuticals and on a data monitoring committee for a clinical trial conducted by Lilly.

San Antonio Breast Cancer Symposium (SABCS) 2018. Abstract GS6-02, presented December 7, 2018.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.