HOT FLASHES: MENOPAUSAL MISERY
I’m not a woman so I’ve never experienced the misery that comes with “the change of life,” but I have seen lots of women patients who have, or were at the time. Plus, I’m married to a woman. The biggest complaint reported by women going through menopause is Hot Flashes, or as some more accurately call it, Hot Flushes. Whatever you call it, it often drives women to the doctor’s office seeking relief.
Menopause occurs in most women between ages 45 to 55. It is termed “the change of life,” or “the change,” because it just that—a huge change in a woman’s life where she stops having menstrual periods. The definition of menopause is the absence of menstrual periods for 12 consecutive months as a result of the gradual reduction in the production of estrogen and progesterone. It is these two hormones that make women feel like women, and when they are gone, there is no longer a stimulus to ovulate (produce eggs for reproduction) or cause menstrual blood flow.
The absence of estrogen and progesterone is also involved in mood swings, depression, and our subject of interest today, hot flashes. They are technically known as Vasomotor Symptoms, VMS. They are characterized by a hot sensation coming in waves, or flashes, that range in severity from mild, annoying, but tolerable to overwhelming forcing the patient to stop what she’s doing, take some type of remedy, and lie down in a cool, comfortable place. They occur 4-5 times a day on average, but can occur up the 15-20 times a day. They last 1-5 minutes. The skin can actually feel hot internally and externally. Sweating of the upper body is common.
It is estimated that 80 percent of menopausal women have hot flashes. They occur when estrogen and progesterone, produced by the ovaries for ovulation, are no longer available to block the thermoregulatory center in the hypothalamus of the brain. It is this center that controls the mechanism that maintains our core body temperature and protects us against extremes of temperature exposure as well as infectious and non-infectious processes (inflammation, malignancy, autoimmune disorders) that attack our bodies.
Hormonal variability is one of the natural “changes” women experience as they age. The thermoregulatory center responds to stimulation by neurokinin receptors. Estrogen and progesterone block the function of these receptors and thus suppress the thermoregulatory center. When there is no longer enough (or no) circulating estrogen, in particular, the neurokinin receptors run amok and allow the thermoregulatory center free rein to produce hot flashes and all the attendant miseries!
The absence of menstrual flow in menopausal women is a welcome occurrence, but the development of hot flashes as a result is a very unfair trade-off. For decades, the standard of care for hot flashes et al. was HRT, hormone replacement therapy. Women were prescribed estrogen to counteract all the unpleasantness of “the change.” It worked great because it mimicked the natural processes.
Then came the Women’s Health Initiative Study. Started in 1991 by the National Heart, Lung, and Blood Institute (NHLBI), the purpose of the study was to research cardiovascular disease, cancers, and osteoporosis in women. In 2002, eleven years into the study, researchers realized that women on post menopausal estrogen therapy had a statistically significant increase in coronary artery disease, stroke, pulmonary embolism, and breast cancer. BREAST CANCER! Panic ensued. The study was halted and women in the estrogen-only group were taken off estrogen. Through a media blitz, women not in the study were also warned to stop estrogen! That spawned an epidemic of misery—hot flashes not experienced by women for years suddenly reappeared to everyone’s dismay. Doctors and patients were both struggling to find treatments for this consequence.
Patients were prescribed vitamins B (B6, B12) and E, antidepressants (Prozac, Lexapro, Effexor), tranquilizers (Xanax, Ativan, Valium), progesterone-only or combined estrogen-progesterone drugs (Provera, Premphase, Prometrium), and anticonvulsants (Neurontin, Lyrica) for relief of symptoms. Although, it was later discovered that combining progesterone with estrogen had a protective benefit over estrogen alone, there remained the concern about estrogen causing breast cancer. Women with breast cancer should not be on estrogen in any form, and most women without breast cancer fear it enough to refuse to take it.
So an effective, non-hormonal treatment was the desired endpoint for treating hot flashes, and last year the FDA approved such a product. It is called Veozah (fezolinetant) and just like estrogen, it blocks the brain receptors that trigger the thermoregulatory center. In clinical trials comparing Veozah to placebo, episodes of hot flashes were reduced by an average of five per day beginning the first day of therapy and continued working through 4 and 12 weeks of therapy. Severity of episodes was measured by a Vasomotor Symptom Score and corroborated by a Quality of Life Score. These scores “significantly improved” immediately and at 4 and 12 weeks, also. So both frequency and severity of hot flashes episodes were reduced significantly by a once-daily 45 mg pill to be taken the same time every day.
No drug achieves perfection and Veozah is no exception. The most common adverse event was uncomplicated benign headache (5-10%). It is not to be taken by patients with cirrhosis of the liver, severe kidney damage or end-stage kidney disease. Abdominal pain, diarrhea, insomnia and elevated liver enzyme tests were seen, also. Baseline liver enzymes should be tested, and if ok, retested every three months to maintain surveillance.
Now the 80% of postmenopausal women who suffer with hot flashes have a “safe,” effective, non-hormonal treatment that has demonstrated “an improvement in quality of life.” It is called Veozah (fezolinetant) and is a “viable alternative to hormonal therapy for managing vasomotor menopausal symptoms.” It was developed by a Japanese drugmaker, Astellas Pharma Inc. and approved by the U.S. Food and Drug Administration in March 2023. Nothing matches the efficacy of estrogen (HRT) for hot flashes, but Veozah is a close and safe alternative.
References: https://www.fda.gov/news-events/press-announcements/fda-approves-novel-drug-treat-moderate-severe-hot-flashes-caused-menopause.
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