How has menopause treatment changed in the last 20 years?

Dr. Sally Greenwald: In the early 2000s, the Women’s Health Initiative (WHI) came out. It was a big trial that stopped early because researchers saw that giving hormones to post-menopausal women was actually so dangerous that the benefit did not outweigh the risk. At the time, not only were doctors not prescribing hormone replacement therapy, but subsequently, there was this whole generation of OBGYNs who were not adequately trained on hormone replacement therapy because of the results of that trial.

Even though in the years to follow, more and more trials were done in a more appropriate setting, targeting the appropriate-aged women (those trials even started to show a lot more benefit), there was still this dearth of training that resulted in many patients seeing a provider who didn’t have adequate menopausal training. But in the last five years, patients are now more interested in hormone therapy as we become a society that thinks about women in all stages of their life.

Dr. Sarah Isquick: Because of the initial concern around the WHI findings, women have really been encouraged to “tough it out,” and to try lifestyle modifications to manage very bothersome and disruptive menopausal symptoms. Subsequent analyses of the initial WHI findings and many newer studies have demonstrated that hormone replacement therapy is safe for most women who are less than 10 years out from the start of menopause. In light of these newer studies, health care providers are regaining comfort and experience prescribing hormone replacement therapy. There is also increasing recognition that menopause is not just hot flashes and vaginal dryness, and providers are beginning to ask patients about many more symptoms associated with the menopausal transition.

Dr. Amy Levin: In the 20 years that I’ve been in practice, working with women to address needs around menopause has completely shifted. From a primary care standpoint, it was nearly taboo to consider hormone therapy. It was absolutely a last resort because of the WHI and its concerns about heightened risk of breast cancer and stroke in particular. And so we tried everything else with women: lifestyle changes, but also often multiple prescriptions to target specific symptoms, including insomnia, hot flashes, night sweats, or mood changes. A woman back in the day might have ended up on three or four different prescriptions to try to manage this potpourri of symptoms. Now we understand that hormone therapy is a lot safer than we had thought. It’s not for everyone, but it is less risky than had been understood. I find myself asking not what is the rare case that someone should be on one of these medications, but in fact, what is the compelling argument for not considering it?

Dr. Isquick: I think we are truly in a “menopause renaissance,” where medical providers are trying to understand how best to holistically treat and support women going through a major life change that affects so many aspects of their health and well-being.

“We are truly in a ‘menopause renaissance,’ where medical providers are trying to understand how best to holistically treat and support women going through a major life change that affects so many aspects of their health and well-being.”

Dr. Leila Alpers: There are more professional women who are in the perimenopausal stage and beyond, and those people are advocating for a different perspective on it – I just saw an article about how menopause needs to be brought into the boardroom!

I do talk about the symptoms with the people at work, because what if you’re in the middle of a meeting and suddenly you’re having these symptoms, it helps for them to know what’s going on and why. It’s not a coincidence that there are more women in the workplace in these transitions and that the conversation is different now.

How did our scientific understanding of hormone replacement therapy evolve?

Dr. Isquick: After the initial outcry around the findings of the Women’s Health Initiative Study, researchers re-analyzed the original trial and we now understand that the initial study design was very flawed. The average age of menopause for women is 51, yet in the original study, no women under 50 were included and only 10 percent of women in the study were between the ages of 50 and 55. When we looked at the data for women in the 50-59 year age group, we saw that the risk of heart disease for women taking estrogen actually decreased, as did the risks of diabetes, fractures due to osteoporosis, colon cancer, and death from any cause.

Dr. Greenwald: What the newer trials have alluded to is that the closer to menopause or the hormonal transition that you start hormone replacement therapy, the safer it is. If you catch women as their hormone levels are dropping, the body is more used to that higher level.

The cardiovascular hypothesis for postmenopausal women in hormone replacement therapy is that it actually can be protective and it can be healthy for the heart when you start it close to menopause.

The second thing that’s changed very recently is our knowledge around the risk of breast cancer. Most of the breast cancer studies were done on a progesterone called Medroxyprogesterone. These days we use a progesterone more commonly called micronized progesterone or Prometrium. The North American Menopause Society has had some papers talking about how potentially with micronized progesterone, we don’t have to think too much about the link to breast cancer (with some studies saying there may be no link at all).

That being said, I still don’t recommend or prescribe it to patients who have had a personal history of breast cancer. But who’s to say that that will continue to be the case. It’s a hard study to write, but the data is definitely trending towards more and more patients being candidates for hormone replacement therapy – and not just candidates, but recommending that it could overall benefit their all-cause mortality.

“The data is definitely trending towards more and more patients being candidates for hormone replacement therapy – and not just candidates, but recommending that it could overall benefit their all-cause mortality.”

Dr. Isquick: We’ve also learned more about the best way to prescribe these medications. In the WHI study, women taking estrogen had an increased risk of blood clots in their legs or their lungs, but all of the women in the study were taking oral estrogen. Follow-up studies have shown that when estrogen is administered transdermally (through a patch, a gel, or a vaginal ring), that this risk is significantly decreased, likely back to a person’s baseline risk based on their other health issues.

What are the health and lifestyle risks of untreated menopause?

Dr. Colleen Ryan: There is some association of severe vasomotor symptoms (hot flashes and night sweats) with cardiovascular risk factor, more so than your risk with obesity or high cholesterol. Certainly the reduction of sleep quality itself can be very bad for your health. We know that sleep is important and we know that menopause, even without hot flashes, can be disruptive for certain people’s sleep.

Dr. Levin: A lot of disease states are expedited in women around this time. For example, peak bone loss occurs during the years right around menopause. I tend to work with women to try to understand their personal risk around those things – what is their bone profile, what is their vascular health profile – so that we understand before they enter this phase of life where they’re starting.

Studies also support that women’s performance is absolutely impacted by menopause in the workplace and there are higher rates of attrition during this transition in life due to menopausal symptoms. So it absolutely is critical to address.

Dr. Isquick: In addition to the risks of heart disease and sleep disruption, there are a number of newer studies showing that untreated menopause, and particularly severe hot flashes, is associated with an increased risk of osteoporosis, memory difficulties, poor cognition, and potentially increased risk for dementia.

We also don’t often speak about other risks of untreated menopause symptoms. For example, for women with significant vaginal dryness, this can often lead to an increase in urinary symptoms, nighttime waking to use the restroom, and an increased risk of urinary tract infections. For older women, increased nighttime waking to use the restroom can be a risk for falls, and urinary tract infections can progress to more serious infections in the kidneys or bloodstreams if symptoms are not identified and treated.

What are the symptoms women should be looking out for?

Dr. Levin: People are increasingly informed, but there’s still a lot of uncertainty of which symptoms to attribute to menopause. We know that up to 80 percent of people will experience some degree of vasomotor symptoms. We know that a lot of women can have changes in their sleep cycle, memory, mood changes, vaginal dryness, urinary leakage, and decreased libido. And then there are other symptoms that are second-tier that can include joint pain, changes in hair and skin quality. That’s when I ask the questions: Do you want to be medicating for these symptoms? How impactful are they in your life? It’s not to say that any of this is necessarily fixed by hormones, but many women can respond to hormones for at least some of these symptoms.

“People don’t necessarily identify these symptoms as being menopausal, and they won’t all respond to hormones, but we need to normalize them.”

Dr. Alpers: There are many non-gynecologic symptoms that I see. Changes in nails and hair, new acne in your forties, reflux is very common because of the increase in progesterone. I also see breast symptoms, rashes and allergies, migraines changing or becoming worse, and changes in metabolism. Periods can actually get much heavier before they stop, and a lot of people don’t expect that. People don’t necessarily identify these symptoms as being menopausal, and they won’t all respond to hormones, but we need to normalize them.

How do you pinpoint the right time to prescribe hormone replacement therapy?

Dr. Greenwald: The most up-to-date guidelines say to start hormone replacement therapy less than 10 years out from menopause and under 60. I want these symptoms to be on people’s radar because it’s absolutely best to start hormone therapy as soon as you experience any of these symptoms as close to the transition as we can. So I say, “I’m going to recruit you, the patient, to be on the lookout and when you have these symptoms then we can really start to talk about treatment early on.”

I think we should find teaching opportunities before women enter this time period so that they don’t put all these symptoms under the rug. They really associate them with that condition so they seek help accordingly.

What exactly does hormone replacement therapy entail?

Dr. Greenwald: Anybody who has a uterus has to be on estrogen and progesterone. If you don’t have a uterus, you can just be on estrogen. In terms of what is FDA-approved, there’s one standard type of estrogen and a few types of progesterone. Estrogen can be administered in three common ways for systemic treatment: pill, patch, ring, and a gel, which is less common. Progesterone can be administered as a pill, patch, or IUD. You can find both estrogen and progesterone compounded in many other forms but because they are not FDA-approved we have a hard time knowing their exact doses and therefore they are not first-line treatment.

Dr. Levin: I find that one of the most common misconceptions is that women will feel dramatically better right when they start hormone therapy. That has not been my experience. Beginning the treatment is a process. More often than not, I find that some women can even feel a little worse – at first, some women experience breast tenderness, nausea, or more irritability. It may be because we’re tuned into our bodies and our symptoms more. That tends to dissipate. It may be three to six months before you see the full benefit.

How long should someone be using hormone therapy?

Dr. Ryan: Right now the understanding is five to 10 years of hormone replacement, depending when you started. If you start younger, around 45 or less, then we really want to make sure you at least take the hormones until the time that you should have gone through menopause, which is 52 on average. When you are 55, hitting 60, and you feel great on hormone replacement, all of your symptoms are controlled, the question is: Do you need to stop it? With these patients, I work with them to see how they feel without the hormones. The great thing about hormone replacement therapy is there’s no problem stopping and starting again. There’s no withdrawal. You can really try that on for size. But as you get older, there might be increased risk of blood clots, stroke, or a cardiovascular event. If you feel terrible off of it, then we have this risk-benefit discussion.

Dr. Isquick: The most recent guidelines from The Menopause Society say that long-term use of hormone replacement therapy can be considered in women older than 60 who are at low-risk for breast cancer and cardiac disease and who continue to have persistent menopause symptoms. These guidelines also note that hormone therapy does not need to be routinely discontinued at age 60 or 65, and that this should be an individualized discussion that a woman has with her provider. We also know that in 50 percent of women who discontinue their hormone therapy, hot flashes may recur, so some women may choose to stay on hormone therapy for a longer period of time.

Are there other therapies you’d recommend besides, or in addition to, hormone replacement therapy?

Dr. Ryan: You can be in your mid- to late thirties and start having perimenopausal symptoms. That’s what happened to me and I had no idea why I was suddenly getting these crazy periods and having night sweats. There is a conundrum between it being better to start hormones early versus waiting for the symptoms to be disabling enough to warrant a medication. We really need more research to understand that. But certainly if you are younger, there are some alternatives. There’s low-dose birth control or a hormonal IUD that can help regulate the cycle. I think it’s important to talk to your doctor earlier to understand what’s coming and that what you’re experiencing right now might be early signs.

Dr. Isquick: For women in their 40s and early 50s who are otherwise healthy, low-dose birth control can be a nice option to help ease the transition into menopause. Once you reach age 51 (the average age of menopause), typically I’ll transition that person onto hormone replacement therapy dosing.

One exciting new development is the approval of the drug, Veozah. Veozah is a new type of non-hormonal medication for people who either can’t take hormone replacement therapy because of other medical conditions (like a history of breast cancer, or a history of a blood clot), or can’t tolerate hormone replacement therapy. It has been shown to be very effective at reducing hot flashes and sleep disturbances.

While it’s great to have these medication options, for women who are candidates for estrogen and progesterone, hormone replacement therapy is still the most effective treatment for hot flashes, and has a number of other health benefits as well.

Dr. Alpers: We use other medications for menopausal symptoms that I call two-fers. We use medications that are used for anxiety and depression like SSRIs, which treat both hot flashes and mood. If someone can’t sleep or they have chronic pain, gabapentin can check off those boxes and can be used alone or alongside lower dose hormone replacement therapy.

It’s equally important to keep up a healthy lifestyle. There’s a clear association between alcohol and the worsening of vasomotor symptoms. So I tell everyone, even if they drink just a tiny bit, try one month with zero alcohol and see how your hot flashes and sleep change. A lot of times, even for people who only occasionally drink, they see that those symptoms are vastly improved. Regular exercise is another one – it cannot be overstated how much it helps during the menopausal transition.

“Our understanding of menopause is in evolution.”

Our understanding of menopause is in evolution. I’m very grateful to the women 10 to 20 years ahead of us who have brought this conversation to the fore. And I do think in another 10 to 20 years, we’re going to know so much more.