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For people going through menopause, symptoms like hot flashes and insomnia can be debilitating. While hormone replacement therapy (HRT) is one of the most direct treatments available right now, it’s not for everyone.
Sarah, a 59-year-old woman living in Concord, Massachusetts who asked to remain anonymous, said insomnia kept her up at night during perimenopause. When she entered menopause at 52, she had hot flashes up to five times every night.
“I would wake up at 1 a.m. and couldn’t get back to sleep,” she told Verywell. “It wreaks havoc on your energy level and so many other things.”
After having an adverse reaction to a progestin-only birth control earlier in life, Sarah was reluctant to try HRT. She said the possibility of cancer-causing agents also played a big role in her decision to forgo HRT. Working with her doctor, she tried a number of different treatment options, including other types of hormonal birth control, which were not that effective.
A few years later, a healthcare provider recommended taking a half dose of the antidepressant Effexor (venlafaxine) to treat hot flashes. The drug was nothing short of life-changing, Sarah said. Now, her daily half dose is essential—if she misses a day, she starts to feel the symptoms again.
Sarah is one of the many women who had to navigate the labyrinth of menopause treatment options. Although HRT is considered the gold standard treatment for menopause, people who are at higher risk of breast cancer or concerned about hormonal treatments are seeking alternatives.
How Well Does Hormone Replacement Therapy Work?
For decades, HRT has been the go-to treatment for menopause. Since menopause symptoms are caused by decreased estrogen and progesterone levels, HRT simply replaces the lost hormones, leveling out the body’s function. This can help reduce hot flashes, eliminate vaginal dryness, and prevent bone loss.
Robin Noble, MD, chief medical advisor of the nonprofit Let’s Talk Menopause, told Verywell that HRT is the only treatment that addresses multiple symptoms of menopause, while many other options focus primarily on hot flashes or insomnia.
HRT works really well for some people, but it’s not completely without risk. A large-scale trial that began in 1991, sponsored by the National Heart, Lung, and Blood Institute, indicated a slightly increased risk of breast cancer with the use of HRT in women who didn’t have a hysterectomy.1 Subsequent studies showed that estrogen-only therapy might slightly increase the risk of endometrial cancer.2
However, Noble said that these increased odds of cancer are comparable to and sometimes lower than other risk factors, such as obesity and smoking. The benefits of HRT still outweigh the risk for women who are struggling with multiple severe symptoms, Noble added, and some HRT can actually reduce the risk of cancers.
“If someone has had a hysterectomy, estrogen alone decreases the risk of breast cancer, colon cancer, osteoporosis, and possibly even lung cancer,” she said. “Estrogen alone absolutely does not increase the risk of breast cancer, and it likely reduces that risk.”
Noble said that the exception to this would be someone who’s currently in treatment for breast cancer or who has survived breast cancer. Patients who use HRT for a fairly extended period of time, more than five to seven years, may face slightly elevated risks for some cancers, so additional considerations should be made.
Can You Treat Menopause With Antidepressants?
A 2014 study showed that the antidepressant venlafaxine could be as effective as HRT for hot flashes.3 It’s not FDA-approved for treating menopausal symptoms, but physicians could prescribe this drug off-label.
Research shows that common antidepressant medications, including SSRIs and SNRIs, can reduce the frequency and severity of hot flashes. Researchers found that the most effective SSRIs were Paxil, Celexa, and Lexapro, and Effexor was the most impactful SNRI for treating hot flashes.4
Since most antidepressants prescribed for hot flashes are in very low doses, Noble explained, side effects from SSRIs and SNRIs are typically minimal, making these drugs a convenient treatment option.
One of Noble’s patients saw particular success with Brisdelle (paroxetine), an SSRI that’s been FDA-approved to treat hot flashes and night sweats associated with menopause.
“My patient said, ‘this is like a magic pill. I don’t have any more hot flashes. My mood is better,’” Noble said. “She was thrilled.”
Are There New Treatments on the Horizon?
Astellas Pharma, a Japanese pharmaceutical company, recently published the results of its phase 3 trial on a new oral, non-hormonal compound called fezolinetant.5 The results showed that hot flashes were reduced within the first week of regular usage. Side effects from the drug were also minimal.
Genevieve Neal-Perry, MD, PhD, department chair of obstetrics and gynecology at the University of North Carolina at Chapel Hill, said fezolinetant is a blocker for the incoming chemicals that cause hot flashes.
“This drug is like a ball and glove. The receptor is like a glove and it’s waiting for the hormone to connect with it,” Neal-Perry told Verywell. “The drug connects with the receptor and alleviates the hot flash.”
Alleviating hot flashes is more than just cooling down the body—it can also improve sleep quality and anxiety when there’s less disruption in the night, she added.
Astellas is currently conducting post-approval trials and the drug might receive FDA approval sometime in May.
Elinzanetant, a new non-hormonal compound developed by Bayer Pharmaceuticals recently completed phase 2 clinical trials that showed promise.6
Yesmean H. Wahdan, MD, vice president of U.S. medical affairs and women’s healthcare at Bayer, said the compound—an NK-1 and NK3 antagonist—targets signals that would trigger menopause-related symptoms.
“It’s non-hormonal, so instead of tricking the body into thinking the ovaries are making that estrogen and progesterone… this is working in a completely novel way. This is working to target those receptors that are actually the source of the symptoms that women are experiencing,” Wahdan told Verywell.
The phase 2B trial was focused on finding appropriate dosing ranges while also looking for potential side effects. The reported side effects were mild or moderate. Phase 3 trials are in progress, with results expected early next year. Wahdan said that she hopes the new drug can clear FDA approval sometime in 2025.
A recent survey published in the journal Menopause showed that 78.7% of people who use medical cannabis think that it helps manage menopause symptoms such as low sex drive, hot flashes, sleep disturbance, and anxiety.7 However, there hasn’t been enough research to prove the effectiveness of cannabis in treating menopause.
Menopausal Hot Flashes
Among all the menopause symptoms, hot flashes in particular last much longer than many people realize—from five to seven years—and can affect women of color more acutely, according to Neal-Perry.8
Neal-Perry and Wahdan both said that talking about menopause is another powerful tool in the arsenal against severe symptoms. Having more open conversations teach people what to expect prior to and during menopause.
Noble said that more than anything, people need to understand that they have options. It’s important to evaluate available treatment options with a healthcare provider based, she added.
“Everybody is different in terms of their individual risk factors, their goals, and their philosophy as well,” Noble said.
What This Means For You
Severe menopause symptoms are fairly common, and treatment methods are available, but they are not one size fits all. In the next few years, new pharmaceuticals may offer non-hormonal forms of relief, but none have been FDA-approved as of right now. Talk to your doctor if you’re experiencing symptoms about the right treatment for you.
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