Oncologists Robert Leon-Ferre, M.D. and Charles Loprinzi, both of the Mayo Clinic, presented their findings at the 2018 San Antonio Breast Cancer Symposium.

Leon-Ferre said several factors contribute to the increased severity of hot flashes in breast cancer survivors: exposure to chemotherapy, which may bring on early menopause; the use of antiestrogen drugs, such as tamoxifen or aromatase inhibitors; and the use of medications or procedures to suppress the function of the ovaries. Hormone replacement therapy, which is sometimes used to treat hot flashes, is generally not recommended for breast cancer survivors.

“Hot flashes not only impact a patient’s quality of life, they are associated with patients prematurely discontinuing breast cancer treatment, which may increase the risk of breast cancer recurrence and mortality,” Leon-Ferre said. “It is important for physicians to have effective options to treat hot flashes.” The drug is most commonly used to treat urinary incontinence.

In this study, researchers enrolled 150 women who had experienced at least 28 hot flashes per week over more than a month, and who were bothered enough by them to want medication. Sixty-two percent of the women were on tamoxifen or an aromatase inhibitor for the duration of the study. The subjects were divided into three groups; those who had two different doses of oxybutynin and a third that got a placebo.

The study found that patients on both oxybutynin doses saw decreases in hot flashes compared to the women who took the placebo. The women in both oxybutynin doses also reported decreased interference of hot flashes in their work, social activities, leisure activities, sleep, and improvement in their overall quality of life.

The long-term effects of oxybutynin still need to be studied.

“This study, in addition to previously published work in this area, establishes that oxybutynin is an effective drug for treatment of hot flashes in patients who have relative or absolute contraindications to hormone-based therapy,” Leon-Ferre said. “We were surprised by the rapidity of the response and the magnitude of the effect, considering the relatively low dose of the drug.” He says that oxybutynin does not interfere with the metabolism of tamoxifen. That’s important for breast cancer survivors, because the efficacy of tamoxifen has been affected by some other non-hormonal treatments.  (See our story, “American Heart Association: Some Breast Cancer Treatments May Increase Heart Disease Risk.”)

Leon-Ferre said that since oxybutynin is already available for other conditions, physicians could potentially prescribe it off-label. However, he says the study did not address long-term toxicities of oxybutynin. Previous research has indicated that long-term use of this type of drug may be associated with cognitive decline. These possible side effects should be further researched and taken into consideration when physicians counsel patients.

Health outcomes have been previously reported but the earlier reports did not focus specifically on all-cause mortality and cause-specific mortality. A new study led by investigators at Brigham and Women’s Hospital, published in JAMA on September 12, 2017, is the first to examine the long-term rates of death from all-causes, and the rates of death from specific causes, including cardiovascular disease, cancer and other major illnesses over a follow-up of 18 years among 27,347 women from the two WHI hormone therapy trials.

In the overall study of women ages 50-79, researchers found no increase or decrease in total mortality or deaths from cardiovascular disease, cancer or other major illnesses in the randomized hormone therapy trials.

“All-cause mortality provides a critically important summary measure for an intervention such as hormone therapy that has a complex matrix of benefits and risks,” said JoAnn Manson, MD, DrPH, lead author and Chief, Division of Preventive Medicine at BWH. “Mortality rates are the ultimate ‘bottom line’ when assessing the net effect of a medication on serious and life-threatening health outcomes.”

Hormone therapy is known to be effective in reducing hot flashes and menopausal symptoms, and decreasing the risk of hip and other fractures, but it has been also linked to risks including venous blood clots, stroke, and certain cancers. “In this new analysis, we found that there was no association between hormone therapy and all-cause mortality during either the treatment period or the long-term follow-up of these trials,” Manson said.

Researchers used data from the two trials which included postmenopausal women with an average age of 63 at enrollment – and explored the effect of treatment over a five to seven-year period, and 18 years of cumulative follow-up, and then defined the impact of hormone therapy on mortality rates by age group. During the follow-up, 7,489 deaths occurred, more than twice as many deaths as were included in earlier reports that had shorter follow-up periods.

When examined by ten-year age groups, mortality outcomes were more favorable among younger women who received hormone therapy when compared to older women who also received the therapy. During the five to seven years of treatment, the death rates in the women aged 50-59 tended to be approximately 30 percent lower among women who received hormone therapy when compared to women of the same age who received placebo. However, among women who initiated hormone therapy in their 60s and 70s, no effect on death rate was observed.

After 18 years, which included 10-12 years of follow-up after stopping hormone therapy, the differences by age group diminished and were no longer statistically significant. Over this extended follow-up period, overall mortality rates and deaths from cardiovascular disease and cancer were neither increased nor decreased among women who received hormone therapy. The team also found that deaths from Alzheimer’s Disease and other forms of dementia were significantly lower with estrogen-alone than with placebo during 18 years of follow-up, but use of estrogen plus progestin was not associated with dementia mortality.

“We observed a trend toward reduced mortality in younger women (age 50-59) who received hormone therapy, and neutral effects in older women (in their 60s and 70s) who received hormone therapy. These findings provide support for clinical guidelines endorsing the use of hormone therapy for recently menopausal women to manage bothersome hot flashes and other menopausal symptoms. However, the findings do not provide support for the use of hormone therapy for the prevention of cardiovascular disease or other chronic diseases,” Manson said. “In clinical decision making, these considerations must be weighed against the impact of untreated menopausal symptoms that women experience, including impaired quality of life, disrupted sleep, reduced work productivity and increased health care expenditures.”

The WHI hormone therapy trials addressed the benefits and risks of the most common formulations of hormone therapy used at the start of the study. It is important to note that in current clinical practice, lower doses, different formulations and novel administration methods (such as skin patches, gels, or sprays) of hormone therapy are available and increasingly common. Additional research on the long-term benefits and risks of these newer treatments is needed, the researchers say.

An analysis to be published in the Society’s journal Menopause found that between 28% to 68% of women using hormones take the “bioidentical” substances without understanding that they are not approved by the federal Food and Drug Administration (FDA). Prescriptions for “compounded” hormones, as they’re also known aren’t tracked, unlike those for FDA-approved drugs.

According to a news release from the society, nearly 3,000 women completed surveys, and the researchers used their feedback and US Census data to estimate national use of bioidentical hormones.

The investigators estimated that from 57 million to 75 million prescriptions for hormone therapies are filled each year. Just 36 million are written for FDA-approved hormone therapy.

However, many women don’t necessarily know what they’re getting into. When asked if they thought the bioidentical hormones were FDA-approved, 76 percent weren’t sure.

The risks of bioidentical hormones aren’t known because they are not tested in clinical trials and there’s no mechanism for reporting problems. An investigation by More magazine showed that compounded hormone prescriptions didn’t always contain what they were supposed to contain. That is risky, the Society’s news release said, especially if a woman takes estrogen without enough progesterone. That puts women at increased risk of endometrial cancer.

“These results indicate a general lack of understanding about key differences between compounded and FDA-approved hormone therapy. This publication establishes the need for better education on this topic,” commented Dr. Margery Gass, executive director of The North American Menopause Society.

The analysis, “Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women,” was funded by Therapeutics MD and will be published in the September 2015 print edition of Menopause.