Menopause with Breast Cancer
Milly is a lovely 52-year-old female with a recent history of breast cancer treated with lumpectomy, radiation and tamoxifen therapy. She has an unusually “happy-go-lucky” attitude for a New Yorker and rarely complains. However, on our most recent visit she appears defeated not by her breast cancer diagnosis but instead by severe menopausal symptoms. Her eyes are ringed by dark circles and her skin glistens with beads of sweat. She recites the usual litany of complaints: vaginal dryness, hot flashes/insomnia, weight gain, and mood changes. She is quick to reassure me that she realizes she can’t be treated given her history of breast cancer – which of course begs the question, how do we treat women for menopausal symptoms when estrogen is simply not an option?
Vaginal dryness
The first line agents are vaginal moisturizers which should be used 2-3 times per week (not just during sexual activity). The active ingredient is typically hyaluronic acid. Examples include Replens, Vagisil moisturizer, Feminease, Moist Again, K-Y Liquibeads, Hyalo GYN, and Revaree suppositories. Low dose vaginal estrogen in the form of creams, tablets and rings may be an option for patients with a history of breast cancer who fail non-hormonal therapies. There are no long-term randomized controlled trials evaluating the use of vaginal estrogen. However, long-term observational trials have NOT shown an increased risk of breast cancer.[1]-[2] Of course, this requires an in-depth discussion of the risks and benefits with the breast oncologist.
Hot flashes/insomnia
In the old days, we relied on antidepressants in the SSRI and SNRI class for management of hot flashes when estrogen was contraindicated. While these medications take weeks to work for depression and anxiety, they typically work within days to improve hot flashes. They are equally effective for women with breast cancer (with or without tamoxifen). The only FDA approved agent for hot flashes is paroxetine (Paxil), but this drug should be avoided in patients taking tamoxifen since paroxetine interferes with the activation of tamoxifen. In patients on tamoxifen, venlafaxine (Effexor) is the preferred agent since it has minimal effect on tamoxifen metabolism.
If hot flashes are primary nocturnal, gabapentin is an option. Nocturnal hot flashes occur during the first 4 hours of sleep. REM sleep in the subsequent 4 hours typically suppresses additional hot flashes. A single dose of gapapentin at bedtime might help suppress early nighttime hot flashes through a reduction in vasomotor symptoms and an increase in sedation.
My newest go-to agent (on my short list of miracle drugs) is called fezolinetant (Veozah). In studies, it resulted in a 64% reduction in hot flashes and a significant improvement in sleep disturbances after 12 weeks.[3] While it has yet to be approved for use in women with a history of breast cancer, I have been using it successfully in this population since it hit the market in May 2023.
Other sleeping aids include magnesium, melatonin, trazodone or even low doses of benzodiazepines (used with restraint).
Weight gain
During the menopausal transition, women typically gain up to 1 pound per year. Unfortunately, this weight typically doesn’t disappear when menopause ends. As circulating estrogen levels drop, the body often becomes less responsive to insulin, the hormone that lowers blood sugars. The body produces excess insulin to overcome the systemic resistance. Insulin is an example of an anabolic hormone which means that higher levels of insulin translate to weight gain. The key to weight loss during menopause, beyond healthy eating and regular exercise, likely involves incretin therapy to overcome systemic insulin and incretin resistance. Medications like semaglutide and tirzepatide help restore insulin sensitivity, allowing for weight loss and a simultaneous reduction cardiovascular risk. Since obesity is a risk factor for hot flashes, weight loss may also reduce hot flashes.[4]
Mood changes
Estrogen affects the production of serotonin, a neurotransmitter in the brain involved in boosting happiness. When estrogen levels drop, this can trigger anxiety and depression.
In one eight-year study, a diagnosis of depression was 2.5 times more likely during the perimenopausal transition vs the premenopausal years.[5] A little SSRI or SNRI (see above) goes a long way towards improving mood when estrogen is not an option. I am quick to remind patients that there should be no stigma here. This is a physiological condition that deserves prompt and proper treatment like any other medical issue.
Milly and I discussed all of these options at length. Ultimately, I started her on Reveree inserts for her vaginal dryness, fezolinetant for her hot flashes, and a small dose of citalopram for her rising anxiety. Two months later, she reports a significant improvement in vaginal lubrication (with a decrease in urinary tract infections), complete resolution of hot flashes, and noticeably decreased anxiety. She is no longer walking around with an iPhone-powered hand-held mini fan. Her face is back to its beautiful self and most importantly, her glass-half-full attitude has returned in full force.
[1] Bhupathiraju SN et al. Vaginal estrogen use and chronic disease risk in the Nurses' Health Study. Menopause. 2018;26(6):603.
[2] Crandall CJ et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study. Menopause. 2018;25(1):11.
[3] Johnson KA et al. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT.
J Clin Endocrinol Metab. 2023;108(8):1981.
[4] Huang AJ et al. An intensive behavioral weight loss intervention and hot flushes in women. Arch Intern Med. 2010;170(13):1161.