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An Experimental Pill Cut Hot Flashes And Improved Sleep For Women In Menopause — Without Using Hormones

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An experimental once-a-day pill that works without hormones significantly reduced the number of hot flashes experienced by women going through menopause and improved their sleep compared to a placebo, according to two new trials from drugmaker Bayer.

The drug, called elinzanetant, works by blocking the brain chemicals responsible for hot flashes and night sweats – what doctors call vasomotor symptoms – in women whose ovaries have slowed production of the hormones estrogen and progesterone. This marks a phase of life for women called menopause, which usually happens sometimes in a woman's 40s or 50s.

The US Food and Drug Administration approved a similar drug called fezolinetant, sold as Veozah, last year.

Such drugs are new options for women during a phase in their lives when their bodies are adjusting to a new hormonal normal. This transition can bring on a wide variety of symptoms including mood swings, brain fog, libido changes and insomnia.

Related article FDA greenlights a new type of drug for menopausal hot flashes

For some women, the symptoms are bothersome but don't interfere with daily functioning. For others, though, they can be debilitating, and many doctors are reluctant to offer the traditional treatment, hormone replacement therapy, for fear it could increase the risks of stroke, cancer and heart disease.

"Very few women get any sort of help," said Dr. Stephanie Faubion, who is director of the Mayo Clinic Center for Women's Health.

At the height of its use in the 1990s, some 40% of postmenopausal women were taking hormone replacement therapy, or HRT, Faubion said. But after a large government study found an increased risk of heart disease and cancer associated with the use of HRT for women, use of hormones for menopausal symptoms fell to around 4%, Faubion said in a commentary about the studies.

Newer studies, including several new analyses of the data from the government trial, have shown that HRT is not tied to increased risks to a woman's health when it's used close to the time of menopause and limited in duration, but many doctors remain skeptical.

In addition, survivors of hormone-sensitive cancers, such as some breast cancers, can't take hormones for menopausal relief. For them, the new non-hormonal drugs are great options, said Faubion, who was not involved in the new studies. Veozah, the drug already approved, is expensive, however. Veozah has a list price of $550 a month, and many insurers are reluctant to pay for it. Bayer, the company that makes elinzanetent, has not said what it would charge for its drug.

Faubion says she's tried to prescribe Veozah for a few patients but their insurance companies required that they try at least two different, less expensive medications before covering the drug.

"They have to jump through hoops. And I have prescribed it before," Faubion said. She's not sure her patients actually took the Veozah. "I don't know if they actually received the prescription or if they gave up before they got it."

Both fezolinetant and elinzanetant are among the first drugs to take advantage of a newly understood pathway in the brain that appears to control hot flashes.

Related article What to know about menopause, according to a doctor

As estrogen decreases in menopause, nerves in the hypothalamus — a tiny almond-sized region deep inside the brain that among other functions helps to regulate the body's thermostat — become hyperactive and produce an overabundance of chemical signals called neurokinins. Both new drugs block the doorways on cells where certain neurokinins dock, which turns down their ability to stimulate the brain to cause hot flashes.

"These neurons are super interesting because they are also tied to mood, sleep and appetite. And we know this is a big conglomeration of what happens with women in midlife. They're hot flashing, their mood is terrible, they're not sleeping and they gain weight," Faubion said. It's not yet clear if targeting those neurons might help with problems beyond hot flashes.

Hot flashes are exactly what they sound like — a sudden feeling of being very hot that's usually centered around the face, chest and head. It can also cause intense sweating and flushing that can last several minutes. When this happens at night, it's called a night sweat. Women in menopause may get these occasionally or many times a day, which can be extremely disruptive.

The roughly 400 women enrolled in each of two related studies published Thursday in JAMA, had moderate to severe symptoms, which the researchers defined as having more than 50 hot flashes a week, and an average of 14 to 16 per day.

In each trial, researchers gave half the women the experimental drug, while the other half took a placebo, which does nothing. Neither the researchers nor the women knew who was taking the drug or the placebo. The women kept daily diaries to track their symptoms. After 12 weeks, the women given the placebo were switched to the study drug, and they continued to take the medication for another 14 weeks.

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After four weeks, women taking elinzanetant where having about eight fewer hot flashes each day — about half the number they reported before the study started, while women taking the placebo were reporting about four fewer hot flashes a day, a drop of about one-third. The difference was statistically significant, meaning it was unlikely to be due to chance.  After 12 weeks, women taking elinzanetant were reporting having about 10 fewer hot flashes each day on average compared with an average change of about seven hot flashes each day in the placebo group. Women taking the drug also reported their hot flashes were less intense and that they were sleeping better.

By the end of the study, which ran for 26 weeks, more than 80% of the women in the study taking elinzanetant had seen at least a 50% reduction in their hot flashes. Results from both studies were very similar, giving researchers confidence in their results.

The most common side effects in women taking the drug were headaches and fatigue.

In a recent news release, Bayer said it had already submitted its study data to the FDA for approval.

Faubion said it looks like a very promising medication. How accessible it will be remains to be seen.

"More options for women are a good thing," Faubion said.

Dutch Researchers Suggest Women Consider Waiting A Bit After Stopping The Pill Before Getting Pregnant

A woman holding a packet of birth control pills.

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In a study published last month, Dutch researchers suggest that the use of birth control pills close to the time of conception may increase certain pregnancy risks.

Specifically, the use of oral contraceptives is associated with a modest increase in risk of preeclampsia, premature birth, and low birth weight. However, it's suggested that the risks differ depending on the timing of discontinuation, and the amount of estrogen and progestin content in the birth control pill.

There's a lack of systematic and comprehensive data on the peri-conceptional use of oral contraceptives and pregnancy complications and birth outcomes. Dutch researchers have partially filled that void. In a large prospective study, researchers in the Netherlands, at the Radboud University Medical Center in Nijmegen, examined data from nearly 7,000 pregnant women. About 1050 of them, or 15%, became pregnant within three months of stopping the pill. This group was compared with pregnant women who had not used the pill for a longer period of time. What the researchers observed was that in the first group preeclampsia and preterm birth (as well as low birth weight) occurred more than one and a half times as often as in the second group. High blood pressure and protein in the urine are key features of preeclampsia, while preterm birth indicates a birth that occurs before the 37th week of pregnancy.

The researchers emphasize that in absolute terms the complications were relatively rare, even in women who became pregnant shortly after stopping the pill. Specifically, about three percent of women experienced preeclampsia and six percent premature birth.

Nonetheless, the researchers recommend that women who have just stopped taking the pill to wait three months before becoming pregnant.

The study also shows that different variants of the pill are associated with complications. In particular, preeclampsia was more common when using the pill from the first and second generations, while preterm births were more common in the third generation. There wasn't enough data to derive reliable conclusions from the fourth-generation pill.

Combined oral contraceptives contain two hormones, an estrogen, such as ethinylestradiol, and a progestin. Progesterone is the naturally occurring hormone in the body, while progestin is a synthetic hormone that mimics progesterone. The first generation progestin includes norethindrone and norethisterone; the second generation, levonorgestrel and norgestrel; the third generation, desogestrel, gestodene, and norgestodene; and the fourth generation progestin, drospirenone and dienogest.

Lead researcher Marleen van Gelder explains: "Different generations contain a different type of progestin. This may play a role in the development of the complications." To illustrate, high estrogen doses were associated with enhanced pre-eclampsia risk, whereas low to moderate estrogen doses were associated with increased risk of adverse birth outcomes.

The newer generation combination pills are associated with far fewer side effects - nausea, bloating, weight gain - than the first generation oral contraceptive. Moreover, the pill has been used to prevent pregnancy relatively safely and effectively for many decades. Further, its usage doesn't affect the ability to get pregnant. In other words, the body doesn't need to time to "clear" birth control hormones. Once a woman stops taking the pill, the hormones will be out of the system in a matter of days and she can start ovulating and conceive almost immediately.

However, the new Dutch study does indicate a possible correlation between the use of birth control pills at or near the time of conception and certain pregnancy complications.

Previous studies looked separately at preeclampsia or preterm birth risks. For instance, a study from more than 40 years ago suggested that women who discontinued oral contraceptives as recently as two months before conception did not differ significantly with respect to incidence of preeclampsia at delivery than women last exposed three to 12 months before. And, a Norwegian study from 2015 showed a positive association between use of a combination oral contraceptive and preterm birth and low birth weight.

The Dutch study appears to confirm the Norwegian finding, in addition to suggesting a modestly enhanced risk of preeclampsia. In brief, the Dutch research demonstrated that any peri-conceptional use of oral contraceptives was associated with increased risks of pre-eclampsia, pre-term birth and low birth weight. Additionally, such associations were strongest when the pill was discontinued between zero and three months before conception.

Should Creatine Be Part Of A Menopause Supplement Stack?

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Talking about bone density loss is not sexy. Hot flashes and brain fog aren't super empowering either, but at least they're getting some airtime in menopause media. Bone density, muscle mass, and the complications that can follow are more silent. They're slow-burning menopause symptoms, if you will. They don't quite smack you in the face so much as they sneak up on you when you're trying to pick up a loaded armful of groceries and realize, "Wow, that feels different."

Supplementation is one of the many ways women (and the clinicians who treat them) help reduce menopause symptoms. Whether it's supplements or hormone replacement therapy, finding the right methods to support your body during this drastic change is important. So it got Hone Health wondering: Is there anything out there for maintaining muscle and mitigating age-related bone issues?

We looked around the gym for inspiration—specifically at the age-old body-builder's favorite supplement, creatine.

How Does Menopause Impact Muscle And Bone Health?

Menopause hormone shifts bring about a lot of symptoms and changes. Think: joint pain, fatigue, and even nausea. The main culprit? Estrogen. As women's ovaries phase out of operation, levels of the hormone drop significantly.

Estrogen plays a crucial role in maintaining bone density. It helps balance bone formation at a cellular level. When estrogen levels decline during perimenopause, bone resorption (or breakdown) increases, leading to a decrease in bone density. Estrogen also has an indirect role in maintaining muscle mass. A decrease in estrogen levels during menopause often leads to a gradual loss of muscle mass and strength, which can lead to skeletal muscle conditions like sarcopenia or dynapenia—or muscle loss and strength loss.

What Is Creatine?

Creatine is a compound naturally produced in the body composed of three amino acids: arginine, glycine, and methionine. Its main role is to help our muscles efficiently produce energy during intense exercise or strenuous activity by producing a compound called ATP (adenosine triphosphate). ATP is the fuel our muscles need for short bursts of activity, explains Brittany Werner, a registered dietitian.

That's why athletes of all levels often take creatine before a workout to enhance their performance in activities that involve high-intensity effort, such as weightlifting, sprinting, jumping, resistance training, and other explosive movements.

Another reason athletes and bodybuilders take creatine is to help build muscle mass. Studies show that creatine aids in muscle growth by increasing water content in muscle cells and promoting protein synthesis.

Women have between 70–80 percent less creatine stores than men and tend to consume less through their diets, too, explains Kristin Kirkpatrick, a registered dietitian. So it is even more important for them to supplement, especially during periods of hormonal fluctuations, like during menses, pregnancy, postpartum, perimenopause, and post-menopause.

Can Creatine Help Women Prevent Menopause-Related Muscle and Bone Loss?

Yes. Women over 40 can benefit the most from creatine's well-documented benefits, including increased lean mass, faster muscle growth, improved bone density, and overall improved wellness, says Werner. Many experts advocate for creatine as an essential supplement for aging women because it addresses some of the key physiological challenges faced by women in this age group.

In a comprehensive overview study, creatine supplementation in older women was shown to counteract menopause-related decreases in muscle, bone, and strength. Results showed the supplement was effective in reducing inflammation, oxidative stress, and serum markers of bone resorption while also resulting in an increase in bone formation.

That said, dosage is important, and more long-term studies with larger groups of people are needed to determine if creatine, with or without resistance training, can truly improve muscle and bone health in postmenopausal women.

"It's not easy to get all the creatine your body needs from your diet—and this is especially true if you follow a vegetarian (or primarily vegetarian) or plant-based diet," says Kirkpatrick. "While the human body can synthesize about half of its daily creatine needs, the rest must come from dietary sources (often found in meat, fish, and other protein-rich foods) and/or supplementation."

Creatine Dose for Postmenopausal Bone and Muscle Health

Studies that focused on low doses of creatine (3g) taken over a long period of time (think two years) showed little effect on bone density or muscle gain in older women. Research that worked with larger doses of creatine based on individual body mass over shorter periods of time (around one week) showed significant increases in women's ability to perform strength-training exercises and bone strength. This is known as a loading phase and can come with some temporary adverse side effects, like cramping.

Creatine supplement plus resistance training yielded the best results. Not only does resistance training help strengthen bone and muscle mass, but it also aids in creatine absorption. Safe, consistent resistance training plus a short-term high-dose loading period supplementation followed by maintenance dosing is the sweet spot for reaping the benefits of creatine.

Individual dosage is based on unique health risks, other medications or supplements you're taking, as well as other lifestyle interventions. "In fact, creatine dosage may change throughout the course of working with someone," Kirkpatrick says.

Are There Any Side Effects?

There are two popular forms of creatine: Creatine HCL and creatine monohydrate, explains Kirkpatrick. "Creatine HCL is what I typically recommend since it is more soluble with higher absorption and fewer side effects."

Potential side effects when loading creatine include water retention, GI distress (such as bloating and diarrhea), and increased stress on the kidneys, explains Werner. While studies point to higher doses, or a loading period, being more effective, more research is needed to support the benefits of loading (or large doses) of creatine without side effects. One note: if you have kidney issues, be sure to ask your doctor before supplementing.

Loading creatine is often seen as a beneficial way to jump-start the benefits of adding creatine to your routine but should not be seen as a long-term solution. To avoid potential side effects, experts recommend taking 5g of creatine daily long-term. This maintenance dose has been shown in practice to provide benefits without the side effects of a large dose.

Are There Any Other Benefits of Creatine?

Creatine's health-promoting effects beyond fitness and muscle-building are the subject of the supplement's most recent research and are still very much in the early stages of understanding. That said, there is some promise.

Studies link creatine to enhancement in energy levels (through the production of ATP, which is a primary action of creatine), maintenance and growth of muscle mass, and enhancement to brain health. It may even strengthen the immune system and promote heart health—though these areas of research are very new, and shouldn't be taken as fact. "Think of creatine as a turbocharger for your cells," says Kirkpatrick.

Stabilize and increase mood

The increased prevalence of depression among women has been directly linked with hormonal milestones in some cases. Mood swings are a common symptom of perimenopause. Since creatine is a molecule that helps supply energy to cells, including brain cells, studies found that sufficient levels of creatine in the fluid surrounding the brain and spinal cord are related to increased levels of dopamine and serotonin (neurotransmitters involved in mood regulation). Basically, creatine helps in the transmission of neurotransmitters that affect mood, meaning that a well-functioning and supplied creatine system might be helpful for mood stability. This assertion, though, is still very much the subject of research to further prove the connection.

Ward off brain fog

Females are known multitaskers and systematically process stress differently than males. They're also susceptible to sleep deprivation due to hormonal fluctuations, like those during menopause (hello, hot flashes and cold flashes). Poor sleep often leads to a decrease in mental alertness. Overall, creatine supplementation has been shown to improve cognitive performance and brain function, as well as reduce mental fatigue, especially under conditions of stress, sleep deprivation, or during aging.

Other Natural Ways to Reduce Bone Loss During Menopause

It turns out there are a few things you can do to help prevent muscle and bone loss during and after menopause. Werner has had great results implementing weight-bearing activities such as lifting weights, running, and even walking to help rebuild and replenish bone density with her menopausal clients. A diet rich in protein and nutrients can be beneficial too.

The Bottom Line

No one supplement can solve the health risks associated with women after the age of 45, but there is strong clinical and experiential evidence to support the effectiveness and safety of including low- to moderate-doses of creatine—3g to 5g—in your menopausal supplement stack to improve bone density and muscle mass (and maybe more benefits that are still being studied). Adding resistance training, getting in adequate protein and other nutrients, and quality sleep, is the best way to maintain strength and bypass issues with age-related bone health.

This story was produced by Hone Health and reviewed and distributed by Stacker Media.

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