Interview: Compounded treatments, “bioidentical” hormones, and anecdotal sales pitches—what to beware of during the menopause transition
Read Doing Well’s full interview with Nanette Santoro, an expert on hormones and menopause care.
Half of the population will go through menopause—a stage in life when a woman’s ovaries stop releasing eggs and menstruation ends, making pregnancy no longer possible. The term menopause refers to the point in time when a woman has gone 12 months without a menstrual period, typically around age 51. In the years before reaching that milestone—a period known as the menopause transition or perimenopause—the body’s production of hormones including estrogen and progesterone fluctuates and declines, which can cause symptoms that range from uncomfortable to unbearable, like hot flashes and sleep problems.
There are hormonal and nonhormonal therapies that can address these symptoms. There’s also lots of misinformation about menopause—and plenty of companies and influencers marketing menopause products. If you’re a woman in her mid-40s, you’ve probably seen social media ads for pills, patches, and diets that make big promises to reduce or eliminate menopause-related woes. But it can be hard to know what to believe, and to access high-quality menopause care from a health care provider. Menopause has long been under-researched and overlooked; in one 2019 study, only around 7% of OB-GYN residents reported feeling adequately prepared to help patients manage menopause.
I spoke to Dr. Nanette Santoro—a professor at the University of Colorado School of Medicine and one of the leading experts on menopause and hormone therapy—about menopause symptoms, treatments, and myths. We discussed how to document your experience of menopause and find a health care provider who can give you appropriate care, and what you should know if you’re supporting a loved one through menopause. Our conversation has been edited for length and clarity.
Jump ahead:
Mia Armstrong-Lopez: What is the menopause transition?
Nanette Santoro: The menopause transition is a period of time that begins on average at about age 47. That's when a woman may first notice that her menstrual cycles, which were previously regular, become more irregular, or she'll skip a whole cycle. That's the beginning of the transition as we now define it.
What is going on in the background is that throughout her life, a woman’s supply of eggs is decreasing. Around mid-40s, that's when either a more than seven-day difference in your cycle length or a skipped cycle can herald entry into the transition. Once a woman goes for 60 days without a menstrual period, that places her in what we call the late menopause transition, where the typical symptoms that we associate with menopause seem to kick up.
In that late transition time, women will have the most hot flashes—that's the most common symptom and happens to about 80% of women. Other things that will bring women to seek treatment are vaginal dryness, so intercourse can be painful. Women may notice worse sleep. And both depression and anxiety can be more common. Most of those things are treatable with hormones for women who can take hormones. Don't wait until the process is over, because treatments are available.
MAL: People often also hear the term perimenopause. What is perimenopause, and how does it fit into the menopause transition?
NS: We use “menopause transition” to be a little more precise, because perimenopause just means “around menopause”—that could be just about anything. Perimenopause technically ends when you are menopausal, when you've gone one year without a period.
MAL: When someone meets the definition of menopause, once they hit a year without a menstrual period—what happens to their symptoms?
NS: They stay high for a little while, and then many of them will subside. The hot flashes go away for most women, but we know that the median duration of hot flashes is about seven years.
Vaginal dryness will not go away without treatment, the increased susceptibility to depression gets better, and anxiety in some cases gets better, but in some cases doesn't go away. Sleep is a little trickier, because some women just have worse sleep than men, and it tends to stay that way.
MAL: Imagine that someone is starting to experience the symptoms you've described. What should they do?
NS: One of the great things to do is to document when symptoms happen in relation to a menstrual period. That can help me when I see my patient in the office and I'm trying to figure out, What's the relationship here? Is it right around the time of her period? That's more suggestive that it is a menopausal thing.
Also prioritize: What is the most bothersome thing? If I could only help you with one thing today—because maybe I can't wipe out a list of seven problems with one treatment—what would that be? And then give me those in order. Sometimes people will bring in a list of 10 things, and then we'll try to get as many as we can, [and] try to address the priorities.
I have many patients come to my office, tell me what's happening, and then they leave, and they really don't want treatment—they want validation. Others come in and they say, I see these changes are beginning, where am I in this process? How much worse is it going to get, and when do I need to come back? Understand your threshold for treatment; everyone is a little bit different.
MAL: What are the major available treatments?
NS: In the menopause world we have a problem, because there's a lot of things that are not evidence based. Supplements are not regulated by the FDA. The FDA requires you to prove efficacy and safety, and that is not required for supplements. So it's really buyer beware.
There are evidence-based treatments out there. I very much encourage people to use FDA-approved products because they have gone through the process required to prove efficacy, safety, and proof of claim—if you say it's going to do this, it's going to do it.
For hot flashes and for women that have multiple menopausal symptoms at the same time, the preferred treatment is hormone therapy, because it is the most effective overall, and it will address multiple symptoms. If I have a patient who does not have any contraindications and is willing to try it, and she's got hot flashes, poor sleep, and her mood is not great, that would be my first choice. Hot flashes are important because they're the thing that drives most women to see a doctor about their menopause. If it's just hot flashes and nothing else is really a problem, there's a number of nonhormone treatments. There's now an FDA approved nonhormone treatment that targets a specific receptor in the brain where the brain's thermostat is located. Blocking that receptor works well in blocking hot flashes.
The other nonhormone treatments were found by serendipity, because the patients who were taking them went back to their doctors—they were all people with bad hot flashes who couldn't take hormones, and said, Whatever you gave me made my hot flashes better. Then their care team got together and said, Hey, why don't we test this? So things that have been tested in clinical trials but not FDA approved include a number of SSRI and SNRI drugs. One of them, paroxetine mesylate, is approved in the form of Brisdelle as a treatment for hot flashes. Gabapentin is another medication that's used for pain, and oxybutynin, used for overactive bladder, has also been looked at. In some older studies, clonidine, a blood pressure medication, has shown some activity against hot flashes. Those are all non-hormone options, but a lot of them have what we call off-target side effects. So if you're not a depressed person, and I give you an antidepressant, it may put your mood a little bit off in a way that you don't like. Gabapentin can make people drowsy, so it's best used at night, and oxybutynin and clonidine can give you a dry mouth. A lot of these things will have annoying side effects that make them a little harder for patients to stick with.
MAL: What is a compounded hormone?
NS: A compounded hormone is measured by the pharmacist. This is a pharmacist, this is a professional—he or she can measure the proper amount of a hormone based on dose. But everything that's given in a compounded form for menopause is put with something called an excipient, or a set of excipients. So if it's cream, there's a cream base that you're putting it in. There's no systematic study of how that cream base works with that amount of hormone. Same thing for those lozenges that people use. It's very difficult to know for sure exactly how much hormone you are getting in a compounded preparation.
MAL: People may also come across terms like “bioidentical hormones” or “natural hormones.” What do those terms mean?
NS: “Bioidentical” was a completely made-up term. I try to make this clear when I'm interacting with patients that want something that's chemically identical to the naturally occurring substance in their body—if you're a woman, that's estradiol and the corresponding progestin type. Both of those hormones are available in FDA-approved forms, which also renders the whole concept of compounded bioidentical hormones obsolete, because we have these, so there's no reason to take something that's compounded. The only reason I ever prescribe compounded hormones for patients is because there's no preparation that's available, either in the dose or in a form that they can tolerate—some people are allergic to every kind of tablet, they can't use a patch.
MAL: We’ve been talking about the hormones estrogen and progesterone. What are those hormones? What do they do?
NS: Estrogen in general turns on processes associated with growth in certain tissues, growth in the breast, growth in the lining of the uterus. It helps maintain bone density. Progesterone prevents the uterine lining from overgrowing and sets the stage for pregnancy.
Estrogen is involved with many, many processes, which is why menopause is pretty frustrating, and on the other end, why puberty can be pretty intense, because all your organ systems are being tweaked by this hormone.
MAL: The menopausal transition can cause a loss in bone density. What should people do to combat that?
If you are a high-risk person, you should push for a bone density measurement, and if your insurance won't pay for it, find out where you can get it done in your community. If anyone in your family has had what we call a fragility fracture (a spine fracture and a hip fracture are the common ones), if you are white, if you are a smoker, if you weigh less than 127 pounds, and if you have taken steroids like cortisol or cortisone for a condition like an autoimmune condition, you are at higher risk—those are all reasons to think about and request a bone density measurement.
I think it's helpful for women to keep track of how much calcium they take in. The International Osteoporosis Foundation website has a chart where you can enter in what you eat, because it is preferable to get your calcium through diet.
MAL: What recommendations would you make for people trying to find the correct provider to help them manage their symptoms?
NS: The Menopause Society provides specific training. It has a guidebook, and you have to read it and pass the test to become a menopause-certified practitioner. A menopause-certified practitioner is a good place to start for a patient who feels she has menopausal symptoms, because they'll know that they're seeing someone who's knowledgeable in the area.
There are some internists who specialize in women's care. The Endocrine Society and the American College of OB-GYNs have websites and information for patients.
MAL: How can people sort through the information about menopause symptoms and treatments, especially online?
NS: Beware if all that you're seeing are anecdotes, like I tried this stuff, and oh, my goodness, it was the greatest thing ever! Look for the data. It's worthwhile to actually click on links, because I have been to websites that have fraudulent links—they link to nothing, or to something that is not what it was stated to be.
The things that you're looking for in a reliable study is: Is it an adequate number of people? For most menopause studies, 100 to 200 people is a reasonable sample to show that something improved. Is there a placebo control? You need to control the treatment against a dummy treatment, especially in menopause medicine, and especially when we're talking about situations where the symptoms are subjective—there can be a very profound placebo effect.
The next thing you need to see is, How robust are the findings? One study doesn't always mean much. Most of science has to be confirmed—that is the nature of science, it has to evolve as the data come in. Independent confirmation is one of the keystones of science.
MAL: I like that suggestion, because people might not be able to read through a whole academic research article, but you can usually find how many people participated in the study and whether there was a placebo in the abstract (or the summary paragraph) at the beginning of a research article.
NS: You often don't have to read beyond that. Another thing to look for: There's a website called clinicaltrials.gov. If you are performing a clinical trial you must register it with clinicaltrials.gov in order to publish it in a reputable journal. If you register your trial on clinicaltrials.gov, it's a matter of public record that the study was done, and people will look for the results.
MAL: What are the most common myths about menopause?
NS: Hormones will cure all problems, all the time, for everyone is one myth. Hormones are the worst thing in the world is the second myth.
One of the other things that is troublesome is that many women feel we tolerate suffering in women that we probably shouldn't tolerate. So my advice to most patients is, if you're not getting an appropriate response to your symptoms, then you need to either ask for a referral or find someone else.
People who look like they have all the answers, those are the ones I'm the most afraid of.
MAL: What recommendations do you have for supporting someone through the menopause transition?
NS: We know that if you have worse hot flashes during your menopause transition, 20 to 25 years later, you have a higher risk of heart disease. That may be because a person who has hot flashes is more prone to heart disease. But it might also be that if you treat them, you can avoid some of that risk later in life. If you have a loved one who's struggling, pointing out that there may be long-term benefits to not just treating the symptoms, but recognizing how she's at risk is important.
Then, you may want to prod them, because you can get a little bit like a boiled frog through menopause symptoms—you just tolerate them. They're getting worse and worse, the water is getting hotter and hotter, and you don't realize it until you really feel bad. Depressive symptoms can become quite serious. If your loved one is showing signs of major depression, you may need to be more active about getting them to help.
MAL: When we talk about menopause, there's often this feeling of dread, because so many women suffer unpleasant to debilitating symptoms and haven't gotten the care they need. Is a different version of menopause possible?
NS: The menopause transition is a physiologic stress, it can break a woman's stride. So that is when treatment becomes important, because the annoying stuff is treatable: 75 to 80% of women will have hot flashes, but a smaller proportion have the most severe ones. There are some women who sail through it. There are some women who can step up their exercise, can cope in different non-pharmacologic ways. But if that's not working, move on. If you need relief, get the relief.
Women can talk to their mothers: What was your experience like? What kinds of symptoms did you have? That's probably a decent sneak preview for many of us for what our own transition will be like.
Read more from Dr. Nanette Santoro on identifying menopause misinformation.
Do you have a question or topic you’d like us to tackle? Would you like to share your experience? Reach out at any time—we’d love to hear from you.