January 4, 2023
Menopause Therapies to Watch in 2023
New drugs and hormonal therapies promise to make menopause better for all.
By Selene Yeager
If hot flashes and night sweats are wreaking havoc on your quality of life, you’re part of a large percentage of women that are negatively impacted by the hormonal changes that happen during menopause. And that’s something researchers are working hard to change.
For far too long, these vasomotor symptoms (VMS) were written off as par for the course for women. Wear layers. Buy some fans. Keep dry PJs by the bedside. It’ll “only” be a couple of years (which, let’s not even get started on the fact that it was considered okey-doke to suffer so long as it was “just” two or three years of your life).
Now we know that’s not true. Though some women do indeed have relatively mild, short-lived symptoms. Others can suffer with more severe symptoms for years. In one meta-analysis, nearly half the women reported having hot flashes 4 years after their final menstrual period, and 10 percent were still having hot flashes up to 12 years later. Moderate and/or severe hot flashes continue on average for nearly five years following menopause and more than one-third of women experience them for a decade or longer, according to research.
Research is also increasingly linking severe vasomotor symptoms with health risks such as cardiovascular disease, depression, and maybe even cognitive decline.
Evidence shows that hormone therapy can reduce weekly symptom frequency by about 75 percent and symptom severity by 87 percent. It is also largely safe. As we’ve reported here many times, the NAMS Position Statement is clear that the benefits of VMS relief outweigh the risks for women younger than 60 years or who are within 10 years of menopause onset and have no contraindications (i.e., breast cancer, heart disease, or blood clot risk).
All that said, many women are reluctant to use it. A 2022 study of women in five European countries and the U.S. published in Maturitas found that most women with vasomotor symptoms were eligible for hormone therapy (57.3 %) but averse to using it, likely because of the long lingering impact of the negative press following the Women’s Health Initiative, which has since been reexamined and revised.
Recognizing the reluctance and hoping to provide relief for those who cannot use hormone therapy, menopause researchers and practitioners are working on improving the messaging around hormone therapy and coming up with effective alternative treatment options. Those were hot topics at this year’s NAMS Annual Meeting. Here’s what to watch.
Bioidentical hormones have been the subject of controversy for years. The term indicates hormones that have chemical structures that are identical to that of hormones produced naturally by a woman’s body. Though it’s often considered a marketing term, research is showing meaningful differences in breast cancer risks with different progestogens used along with estrogen in combined hormone therapies. As one meta-analysis reported, progesterone was associated with a lower breast cancer risk compared to synthetic progestins in combination with estrogen.
Historically, the issue has been quality control. Bioidentical hormone therapies are frequently custom compounded, which NAMS doesn’t recommend because they don’t have FDA approval, and research presented at the Annual Meeting showed that up to 34% of these products failed FDA quality tests in early testing. NAMS has been pressing for awareness that there are FDA-approved bioidentical estrogen and progesterone products like Prometrium (micronized progesterone) and Bijuva (a combination product that contains E2/estradiol and P4/progesterone) that check all the boxes. Women in the UK and Australia can also get regulated bioidentical hormones. As research continues, there will be more options available.
A “New” Estrogen
There was a buzz at the NAMS meeting over estetrol (E4) as a potential new hormonal treatment for menopausal symptoms. Estetrol is a natural human estrogen, which was discovered in 1965 in the urine of pregnant women. During the past several years it’s been undergoing testing for the treatment of menopausal symptoms and the results are looking promising.
Data is demonstrating that E4 has no effects on breast cell stimulation, which means less breast tenderness and “low carcinogenic impact,” according to researcher Wulf H. Utian, MD, in Ob.Gyn News, who has been presenting his E4 research at the NAMS meeting for the past several years. That’s promising news for women who aren’t candidates for hormone therapy because of breast health concerns.
E4 is currently approved for use in hormonal birth control, and is in Phase 3 clinical trials for menopausal therapy. It’s expected to receive FDA approval by 2024.
KNDy (pronounced “candy”) Neuron Modulators
Stay tuned for the first new drug to treat hot flashes in 80 years (the first was the conjugated estrogen tablet Premarin). Fezolinetant is a new non-hormonal drug that’s working its way through the regulatory system and is anticipated to receive FDA approval this February. Fezolinetant works by manipulating a special type of brain cell called KNDy neurons, which are located in the hypothalamus, the region of the brain that acts as the switchboard between your hormonal signals and your central nervous system. These neurons play key roles in numerous functions, including temperature regulation, and as research indicates — hot flashes.
Through your reproductive years, estrogen helps regulate KNDy neurons (Dr. Jen Gunter does a brilliant job of explaining all the mechanisms here). When it declines, so does our temperature regulation and hot flashes and night sweats can occur. That’s why estrogen is an effective therapy. Fezolinetant works by moderating activity of these estrogen-sensitive KNDy neurons, which research shows can reduce the frequency and severity of hot flashes.
Keep an eye out for other KNDy modulators in the pipeline, including elinzanetant from Bayer, which is in Phase 3 trials with results anticipated in late 2023, or early 2024, according to Susan Reed, MD, MPH, at the 2022 NAMS annual meeting.