Interview with a menopause researcher and specialist

In one of my many, manymanymany conversations about hormone therapy, one of my girlfriends mentioned there was a midlife clinic at the University of Virginia. I hear amazing things about it, she said and, Dr. Pinkerton [one of the doctors there] does a lot of hormone research.

That’s when it dawned on me: Why not interview an actual doctor? Talking to girlfriends is all good and well, but most of us, even the more informed ones, still aren’t clear on many of details. If I was going to write about the subject, it might be wise to get my facts straight. 

It turned out that getting an appointment with Dr. Pinkerton was complicated but, long story short, after multiple phone calls and emails, Dr. Pinkerton and I finally sat down over zoom. (And now I know how Moses felt after he’d won his one-on-one with God.) In order to chisel our 50-minute call into a consumable and concise blog post, I’ve edited and condensed, cobbling together the interview with our subsequent email correspondence, but even with all that trimming, this post is still a doozy. Pour yourself a cup of coffee and get comfortable. I hope you find this conversation as eye-opening as I did!

Note: Dr. Pinkerton and many other menopause specialists prefer “hormone therapy” over “hormone replacement therapy” because menopausal hormone treatment is not replacing the hormones. From here on, I’ll be following suit.

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Me: Hi! 
Dr. Pinkerton: I’m glad we’re finally getting to do this. You hit at a time when we were working on a clinical trial. The trial was very successful.

Does this clinical trial have to do with hormone replacement therapy? 
The study was to test the treatment of hot flushes compared to placebo in women having moderate to severe hot flushes (50 hot flushes per week). We found in both trials, Oasis 1 and 2, that the hot flushes — the frequency and severity — improved rapidly within a week with the new product, a neurokinin receptor antagonist called Elinzanetant.* There is already a similar product that went on the market in May 2023, Fezolinetant, which affects one of the receptors in the brain (neurokinin 3) while the one we were studying affects two of the receptors (neurokinin 1 and 3), so we think this new product is going to have broader applications. From the data, it not only improved hot flashes and night sweats, but it also improved sleep and menopause-related quality of life. For women who are unable to take hormone therapy (HT) due to breast cancer, blood clots, or strokes, this may be a good option for them. So stay tuned! [Update: the trial has now been published.]

Wow, that’s exciting. How did you get into women’s midlife health?
I was initially doing full spectrum OB/GYN, but when I joined the faculty here at University of Virginia, I started two clinics — a menopause clinic and a teen health clinic — and I became more and more interested in the menopause transition and the health risks that occur after menopause. It’s an area where I never get tired of learning and the clinical care is often challenging. 

Eventually, the menopause clinic led to starting the midlife multidisciplinary clinic which is ongoing. The clinic includes midlife specialists, osteoporosis experts, and other specialty areas such as fibroids, minimally invasive surgery, and even a provider for adolescents. We try to provide about 70% of women’s healthcare, linking to other areas like primary care, the breast center, the women’s heart center, urology, oncology, breast imaging, bone density testing — the areas that are connected to the changes that happen after menopause and loss of estrogen. 

The research has been really exciting. I’ve done over 30 clinical trials. I’m teaching residents and fellows. I’m teaching at a national and international level. And now I’m reaching out to primary care doctors and endocrinologists, trying to help providers understand about menopause to improve care for perimenopausal and menopausal women. 

When did you start studying menopause?
I think I started the menopause clinic in 1987. 

Considering that you’ve been practicing for so long, including over the time of the big study that caused so many women to go off hormone therapy, how has your understanding about HT evolved?
Prior to the initial release of the Women’s Health Initiative (WHI) in 2002, it was believed that HT prevented heart disease, Alzheimer’s, and osteoporosis, and that women could take it and stay on it. But when the results of the WHI came out, they showed an increased risk of breast cancer, heart disease, stroke, blood clots, and probably dementia. It was a really scary time for menopausal women. 

And yet, when we looked at that trial, we quickly realized that the average age of women in the trial was 63, and that’s not the group that we start hormones on. In 2007, the data was reanalyzed, taking into account a woman’s age and and how many years she was from menopause. For women who were under age 60, or within 10 years of menopause and who started hormone therapy during that time, there were actually fewer cardiac events and fewer deaths. That has led to confidence in hormone therapy once again. 

In your observation, how did the WHI results impact women’s health? 
Many women were very frightened and stopped their hormones cold turkey. We had a big UVA symposium here in Charlottesville where we brought in a breast surgeon, a cardiovascular surgeon, a stroke expert, and myself to talk about the results and the fact that they didn’t really apply to most women going through menopause. About 25% of the women went back on the treatment. Unfortunately, a percentage of women went to non-FDA compounded therapies because they were told they were safe. In reality, they’re not safer. They’re just different. And the concern is that they’re not FDA approved or monitored. 

As we studied the new data, those of us who are menopause specialists started to feel very comfortable with hormone therapy. But our primary care colleagues, endocrine internists, and family doctors were still very frightened. The biggest difference now is that menopause in the workplace is being talked about. Unfortunately, there is now a concern about the commercialization of menopause to sell products, many of which may lack adequate testing.

How can we tell when a treatment is above board? What are the danger signs that should give us pause?
Follow the money. If someone is charging a lot for something and it doesn’t go through insurance, that’s a clue that the practitioner isn’t necessarily looking for what is best for you or providing therapies that are evidence based. I’ll give vaginal laser as an example. It definitely causes improvement in the epithelium and the vagina — 

What’s vaginal laser?
It’s a vaginal therapy for people with vaginal atrophy. The FDA devices for the therapy are approved for general use, but they are not approved for genitourinary symptoms of menopause, or vaginal atrophy. The FDA began getting complaints about pain, or the procedure’s lack of effectiveness, or the therapy’s high cost. Randomized trials have not shown that the vaginal laser is better than sham treatment. There’s no evidence that it’s better than vaginal estrogen, and women have to pay out of pocket for the vaginal laser therapy.

If you stepped back and took a bird’s-eye view, how would you describe the current views on menopause? 
When I gave my first community talk on hot flushes, people were embarrassed to be in the audience — they didn’t want people to know they were menopausal. Now we’re talking about the effects of menopause in the workplace which is a huge sign of progress. If you think about pregnancy, labor and delivery, even postpartum, the workplace is set up to help women accommodate for all those issues. Menopause has long been ignored, yet the effect of menopause on health, activity, relationships, and work productivity has been shown to be very significant. 

At the national level, Jill Biden has held listening sessions about menopause, and recently there was the executive order to increase research for women’s health. There’s a spotlight right now on menopause. The question is, are we going do what we need to do? Are we going to get better trial results than the women’s health initiative did, regarding the women who are now taking the hormones? Can we get a bioidentical low-dose patch and a progesterone in women with significant symptoms and follow them for 10 years in order to find the true risks and benefits in taking hormones? That’s what we really need, and we just don’t have that data. 

My understanding is that there isn’t good testing for hormone levels. Women have to try HT and then tweak as they go.  
The definition of menopause is 12 months without a period without any other medical reason. You don’t have to have blood work to say you’re menopausal; based on symptoms, you can tell when somebody’s going through the transition. So at any point in the process, you can have a discussion about whether or not to try hormones. You don’t have to wait until you’ve been miserable for a year without periods to try hormones. 

On the other hand, many women want to know where they are in menopause. The problem with hormone testing is that hormones are fluctuating during perimenopause. Hormones are cycling through the brain, the thyroid, the ovary, and back again — it’s a feedback loop. And so, for example, the best time to check for the FSH level for menopause and estrogen levels is 3-5 days after your last period. But that only tells you where you are for that month. It doesn’t tell you whether your ovary is fluctuating, and whether or not it will decide to kick back in, or how you’re going to feel in the next three months. The unpredictability makes interpreting the results of testing really hard. 

There are many different over-the-counter tests. Some of them are good, and some of them are not, but they can give some information. For example, if you’ve had a hysterectomy, an FSH test could tell you whether or not you’re menopausal. But most of the menopause specialists are going to listen to your story and be able to tell if you’re in early, middle, or late transition based on your periods and symptoms. (In late transition, you’re often skipping three cycles or more.) You can have symptoms throughout, but they intensify in late transition.

Interestingly enough, we’ve found four different patterns of hot flashes. Some people start early and end early. Some start late and end late. Some start late and end early. And some unfortunate women start early and go late.

There are ethnic variations, too. Black women in menopause have longer and more intense hot flushes compared to those of either white women or the group that has the fewest, which is Japanese and Asian women. We don’t understand the reasons for these ethnic differences. We just recognize that they are different.

Are you saying flushes or flashes?
It’s flashes in this country and flushes in Europe.

You refer to hot flashes a lot. Is that your catch-all word for the huge variety of symptoms?
The most common symptom is hot flashes and night sweats, followed by sleep and mood issues. Hot flashes are often the most noticeable. However, many women have worsening anxiety, central weight gain with central adiposity (belly fat), worsening mood swings, irritability, or difficulty with concentration (brain fog). With the sleep disruptions and worsening mood, there is a risk of depression. Menstrual cycles can be lighter, heavier, longer, more frequent, or less frequent. Some people get worsening migraine headaches, while for some, migrane headaches lessen.

So practitioners need to take a good history, listen to what the women’s cycles are doing and what symptoms they are having, figure out how the symptoms are affecting their ability to work and their relationships, and then we decide whether to intervene with lifestyle adaptations, supplements, or medications. 

Some women just go right along with regular periods and then boom! The periods stop. These women are in menopause, with no long transition and no symptoms. These women are harder to treat for their diminishing estrogen because of their lack of symptoms, but they still have declining levels of hormones. The women suffering from bothersome hot flashes and night sweats present a clearer decision-making process about hormone therapy.

Does having a lot of symptoms mean that a women is at greater risk for bone and heart issues later on? 
There is some evidence that people with more bothersome vasomotor symptoms (VMS, also known as hot flashes) have a higher risk of cardiac disease, white-matter changes in the brain, and bone loss. So yes, we do think that having significant vasomotor symptoms indicates that those issues need to be addressed.

Is there a test to determine a proper hormone dosage, or does it just depend on the person? 
With menopause, we don’t necessarily go by levels. One caveat: if you have early menopause (under age 40), then we want to make sure you’re getting adequate amounts of estrogen. That’s the one time we may test.

Primarily, I will do blood tests for people who don’t seem to be responding to a dose. If the symptoms aren’t being controlled, the person might not be absorbing the patch. But if we start someone on a low-dose hormone therapy and progesterone, and they tolerate it well, I don’t have to have a blood levels to tell me that the woman is on the best dose.

On the other hand, if someone is taking increasingly higher doses because they’re not getting control of their symptoms, I want to know whether it’s because they’re not absorbing the patch. Do we need to try something different, or do they just require higher levels? Will those higher levels put them at risk of breast or uterine cancer? Because with longer-term use and higher doses, we are concerned about increased breast cancer risk. If a woman doesn’t have adequate uterine protection against the estrogen being given, it might increase her risk for uterine cancer. That’s why we primarily add the progestogens — either the natural micronized progesterone or the synthetic progestins. They protect the uterus against cancer. 

Is there a progesterone baseline — a specific amount you need to take if you’re taking estrogen — or does the amount fluctuate? 
Women who don’t have a uterus don’t need progestogen, a natural progesterone or a synthetic progestin. Women who have a uterus and use a progestin intrauterine system (IUD), which contains a synthetic progestin and delivers small amounts at the uterus, only need to take estrogen by itself because the uterus is protected by the progestin from the IUD. But anyone who has a uterus needs to take a progesterone, a synthetic progestin, or a small niche product that’s an estrogen combined with a designer product called bazedoxifene, which is for women who can’t tolerate progestins. There are many FDA-approved options, both oral and transdermal (absorbed through the skin).

We understand that certain doses of estrogen require certain doses of progesterone. Some women come in who are on these expensive pellets that give them super physiological levels. If they are taking progesterone creams, we become concerned because the molecule is large and doesn’t absorb well through the skin; with the pellets’ high dose of estrogen, women need adequate protection of the uterus against the estrogen.

Pellets — what are they?
There’s a very common procedure where providers insert pellets under the skin. They provide really high levels of hormones. Women feel good on them — it’s a money maker. However, the risks of these high levels are not well established. I prefer FDA-approved therapies and use the lowest dose that works because it is safer, particularly if women end up staying on HT long term. 

So when people say they’re getting compounded therapies under the skin, these pellets are what they’re talking about?
Right. Compounded hormone therapy is where a pharmacist takes a prescription and mixes it. Pellets are made by companies. Compounded therapies are not FDA monitored unless sold interstate, nor have they gone through the rigorous FDA approval process. FDA-approved products get a bad name because pharma companies are making them, but they’ve actually spent a huge amount of time and funding to provide the rigorous testing to allow FDA approval.

Why does progesterone make me sleepy? A few nights ago I took it a couple hours before going to bed and I felt almost drunk. 
Progesterone works through a GABA receptor in the brain, so it may make you drowsy. Some people can take it anytime during the day, but we don’t generally recommend that. 

For women who are going through the menopause transition but feel okay, how do they know that they’re still getting sufficient estrogen?
We don’t really know what level women need as they age to protect their bones, heart, or brain. (As women age, they need less estrogen.) So for most symptomatic menopausal women, we identify a dose that relieves symptom, prescribe it for 3-5 years, and then start weaning down to see if symptoms still need to be managed. At the same time, we’re checking to see about their risk for cardiac disease and osteoporosis by following lipid panels and bone density when indicated. If women have vaginal or bladder symptoms only, we may add nonsystemic estrogen for the vaginal tissues.

So if you take estrogen while going through menopause, and then wean off it when you reach age 60 or thereabouts, are you suddenly going to crash and be back where you were at age 50?
After the results of the WHI came out, researchers couldn’t find a difference between how women felt tapering off the hormones versus stopping abruptly. But most menopause specialists slowly wean women off the hormones. We might make a change at six months, or a year. When we get down to a half patch, if some women notice that they’re starting to have symptoms again, we may increase the dose or consider non hormonal options.

How long should a woman stay on HT?
Nobody knows the answer for that — it’s a gray zone. We don’t have good data on long-term use. For some women who continue to have symptoms, we will continue HT longer, but then we’re concerned about potentially increasing the risk of breast cancer, as well as needing to monitor bone loss and changes in cholesterol.

There’s no hard and fast rule that says you have to stop after five years. But health risks increase with age, so ongoing evaluation is needed to assess for risk versus benefit and determine the safest methods if using HT for longer term.

Keep in mind, menopausal hormone therapy provides the low levels of the hormones a woman had before menopause. It provides about one-fifth the hormones your ovaries made. (Oral contraceptives are five times the HT dosage.)

So when women go off HT, how do they deal with the vaginal dryness? I gather HT does not include topical estrogen?
For most women who are postmenopausal and not on a high-enough dose of systemic estrogen, we add a vaginal hormone therapy. Very little of these vaginal estrogen products is absorbed into the blood system, so even though the packaging warns against breast cancer, heart disease, stroke, blood clots, and probably dementia, these products are actually not causing those risks if used in low doses. We have good studies that show that vaginal creams, tablets, suppositories, low-dose rings — there’s also dehydroepiandrosterone (DHEA) — are all good options for treating vaginal and bladder symptoms. We think it is safe to continue vaginal hormones as long as a woman needs them.

Are you saying that if women take HT until their symptoms are gone, the amount of estrogen they receive during the treatment will be enough to benefit and sustain their bodies for the rest of their lives?
You’re asking a question that science has not answered. What I can tell you is that most of the bone loss, for example, is in the first five years of menopause. After menopause, many women can maintain bone density with exercise, calcium, vitamin D, and strength training.

Supplemental estrogen at menopause decreases your risk for heart disease, and appears to be neutral or positive on your brain, and definitely helps your bone, but what happens if you start HT when you’re 65? The WHI found that it could exacerbate or accelerate the changes of heart disease and changes in the brain, so it’s hard to know when estrogen goes from being something good for you to being harmful for you.

Generally speaking, do you think relatively healthy women without a history of breast cancer ought to take HT during menopause?
We do a risk benefit assessment for each woman. For many healthy women with menopausal symptoms, the benefits of hormone therapy outweigh the risks. But it requires individual assessment and shared decision making about whether to take it and how to minimize the risks.

And yet there is still so much negativity about HT within the medical community!
I think it’s a result of the WHI study. Even though we have much better safety data now, it’s only beginning to trickle down to non menopause specialists, and to women. 

Do you get frustrated by the misinformation? 
What drives me crazy is when there is a 51-year-old woman with moderate to severe hot flushes and no contraindications to hormone therapy, and yet her internist gives her an antidepressant. Data on antidepressant use is only based on 1-2 years of data. We have longer data about the risks and benefits of HT.

The other thing that bothers me is when a woman hasn’t been sexually active for years because sex is so painful, and even though she’s been routinely going to her doctor, nobody has asked, “Are you having painful sex?” or evaluated the vagina for genitourinary syndrome of menopause, which is where diminished estrogen leads to a decrease in elasticity in the vagina, vulva, bladder, urethra — women can get spasms in the muscles and sex hurts. It’s mostly reversible for most women. With time and treatment, most women can be successful at having sex, if they want. But they are the ones who need to take the therapies: work with the dilators, if needed, or work with pelvic-floor therapists, if needed. 

We are really trying to get this information out to all of the primary care doctors — family practice, internal medicine, OB/GYNS, endocrine — so they will understand, not only about hot flushes and menopause therapies, but also know to check bone densities, cholesterols, risk for heart disease, and vaginal issues.

How we take care of ourselves during menopause is going to affect the rest of our lives. It’s a really important time for women to take stock of their health and try to decide what’s best for them, and then reevaluate every year. Ask: what’s going on? What are my risks? How am I doing? What have I learned in the past year? HT is not a one-time decision. 

Do you recommend that peri/menopausal women request tests such as bone density?
Current recommendations are that women should get a bone density by 65 and then treat for osteoporosis, if they have it. But I’m a believer in preventative health. Why would I wait to find out I have osteoporosis? If a woman doesn’t have a family history of osteoporosis and is taking HT, I’m not going to hurry to get a bone density. But if she’s had an eating disorder, or if she’s over-exercised when she was younger to the point that she lost her periods, or if she’s had a gastric bypass, or if she’s run hyperthyroid, she’s going to have a higher risk of bone loss. So a bone density gives me a baseline. If it’s on the low side, I can encourage adequate amounts of calcium, vitamin D, and strength training. We’re all victims of being busy. Sometimes we just need a test to help us focus on how to take better care of ourselves. 

Are there particular resources that you like to point women to?
I’m a believer in the Menopause Society. It has free, targeted information, including videos about the decision to take HT, vaginal dryness, and menopause and depression. They also have a “look for a provider” section: women across the country can enter their zip code and find credentialed menopause practitioners in their area. The Menopause Society, the Endocrine Society, Healthy Women, and the Society for Women’s Health Research: they all have vetted information. We’re not trying to sell products or make decisions for women. We’re just trying to give them the information.

Thank you for taking the time to talk with me — this has been wonderful. Do you have anything you’d like to add?
Women deserve to be listened to. Menopause is misunderstood, underdiagnosed, and undertreated. If your provider is not listening to you, seek a different provider. Be careful: not all the people who say they are menopause specialists are actually credentialed, or giving evidence-based information. If something sounds too good to be true, it probably is. Buyer beware if you’re doing compounded therapies or pellets.

We think hormone therapy is safe and effective for healthy women at menopause, and that the benefits exceed the risks for those women.

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Thank you so much, Dr. Pinkerton, not only for the time you spent with me, but for your many years of work and research around women’s healthcare. It’s an enormous gift to all of us.

^{*For those who want to know more about the clinical trial of the new nonhormone Elinzanetant, you can read about it here, but Dr. Pinkerton also shared this brief summary: 
The pivotal OASIS1 and 2 Phase 3 studies of the investigational compound Elinzanetant achieved a statistically significant reduction in frequency and severity of vasomotor symptoms over 12 weeks compared to placebo. In addition, Elinzanentant met its key secondary endpoints, showing a statistically significant reduction in the frequency of VMS from baseline to week 1 (rapid response) and improved sleep disturbances and menopause-related quality of life compared to placebo. The safety profile of Elinzanetant was favorable. Headache and fatigue were the most frequent treatment-related adverse events (TEAEs), which improved over time.}

This same time, years previous: the quotidian (9.11.23), the cheesemaking saga continues, the quotidian (9.10.18), lemony mashed potato salad, what writing a book is like, the good things that happen, ketchup, two ways, hot chocolate.