More Than Hot Flashes: Identifying and Addressing the Full Symptom Spectrum in Primary Care

Dr. Gloria Richard‑Davis (Morehouse School of Medicine, Atlanta): Thank you to the organizers of the conference for the opportunity to talk to you on this really important topic, Redefining Relief of Menopause, Empowering Primary Care to Navigate VMS, Sleep, and Beyond.

Menopause management is critical, yet it is oftentimes underemphasized in the aspect of primary care. As more women transition through midlife, estimates of 6,000 women per day, clinicians are increasingly called upon to address vasomotor symptoms, sleep disturbances, mood changes, and other systemic effects that impact overall health and quality of life.

[00:06:53]

Role of Primary Care in Diagnosing and Managing Menopause

Daniel has already given us the learning objectives. The role of primary care in diagnosing and managing menopause is really very important. As primary care providers, you are frequently the first point of contact and have the ability to facilitate timely diagnosis and intervention. The foundation of trust with you and your patient already exists. It lays the landscape for you to easily go into patient education and shared decision‑making.

Menopause symptoms we will talk about really impact so many different aspects of a patient's life. As you take care of patients through the lifecycle, you will see this. You will see it early, and you will see it late. Long‑term, consistent management across years to decades is needed really to optimize care and to meet goals.

[00:08:04]

Poll 3

Daniel: As a primary contact, for those of us in primary care, we have a little poll asking, which menopause‑related symptoms do you, as a primary care provider, most commonly ask patients about during office visits? In this poll, we can select all that apply, whether that is hot flashes or night sweats, sleep disturbances, cognitive symptoms, vaginal dryness or sexual discomfort, or weight gain and metabolic changes. Go ahead and answer any of those that you feel are appropriate to your own practice. We will see what everybody says here in a few seconds.

Let us see what everybody is asking about. Very good distribution of all of these symptoms. It looks like a little bit less in the cognitive symptoms. We will touch on that in the coming slides. Dr. Richard‑Davis, back to you.

[00:09:12]

Risk Factors That Amplify Symptom Burden

Dr. Richard‑Davis: Okay. We have risk factors that we know amplify the symptom burden of menopause. Factors that worsen VMS and sleep disturbances include obesity. We historically thought obesity should actually be associated with less symptoms but we know from the SWAN study that, in fact, it is the complete opposite. Obesity is associated with more severe VMS symptoms and sleep difficulties.

Smoking actually accelerates the onset because it hastens the metabolism of estrogen. Smokers oftentimes will have the onset of vasomotor symptoms earlier, more frequently, and have more severe symptoms.

Chronic pain leads to difficulty sleeping, fatigue, mood disorders. Some women, when they enter menopause, already have mood disorders, and that can heighten their perceived symptom severity and reduce ability to cope.

Then, of course, we have special populations with increased burden, like our cancer survivors. They are already carrying the burden of their disease and their treatment can oftentimes exacerbate menopausal symptoms. Patients with medically complex cases with overlapping risk factors may see intensified VMS, sleep disturbances, and general overall symptom burden.

[00:10:48]

Meet Susie

Here is Susie. She shows up in your office. She is 47 years old. Her last menstrual period was 8 months ago. She is having moderate to severe hot flashes, worse at night, and significantly impact sleep. Also, suffers from sleep disturbance.

This is a pretty typical patient that most of us see. Of course, if you look at her menstrual cycle, her last period was 8 months ago. Susie is not yet post‑menopausal. She is perimenopausal. But she says, ‘I cannot sleep, and I am always exhausted. I am so nervous. I will have hot flashes in the middle of work meetings, which is real, and my anxiety is through the roof. I really need help, Doctor. What can you do for me to lessen the burden and my concerns about these symptoms interrupting my life?’

[00:11:42]

Clinical Tools for Symptom Identification

Let us talk about that. There are clinical tools that can help you with symptom identification. On the right side, you see the tools, like Hot Flash Diary, the Greene Climacteric Scale, the MENQOL or the Menopausal Quality of Life Survey, and then the Menopause Rating Scale.

I will tell you that I am biased. My personal preference is the Menopause Rating Scale. I actually have it built into my Epic medical records, so that it is automatically there. My MA, when the patient is roomed, will actually ask the questions and include it in their note. It helps to really expedite things.

We know from SWAN that VMS prevalence and duration vary by race, ethnicity, BMI, and socioeconomic status. We will intermittently talk about this because it is really a significant concern and point that oftentimes is overlooked as we are providing care for patients across different ethnic groups. The highest burden is really among black women. From SWAN, we know that. We talked about the increased BMI and lower socioeconomic status, increasing the burden, but also the severity and frequency of VMS for our black patients.

[00:13:19]

Symptoms of Menopause

The cascades of symptoms that women experience during menopause are many. We have estrogen receptors in almost every organ system in our body. It makes sense when you know that and you think about all of the different areas that are impacted by estrogen depletion.

Hot flashes, night sweats. That is usually the tip of the iceberg. That is the most common complaint that women come into the office with. But sleep disturbances are also very common. Combined, they are very burdensome symptoms.

If you look at the changes in the menstrual cycle we talked about, that is when the symptoms are often noticed. The symptoms may, in fact, be worse before post‑menopause, during the perimenopausal phase, because of the erratic distribution of hormones. Hot flashes, sleep problems, mood changes, irritability, and depression.

What I usually say to our students and residents is, if you have been on call night after night, you most likely will be quite irritable and have some degree of depression. It is understandable that, as hot flashes or night sweats disrupt a woman's sleep night after night, those things are an issue. The same thing is true with memory issues. She does not enter REM sleep, so she does not have restorative sleep. Cognitive impairment is oftentimes seen when we have those sleep disruptions.

Typically, later in menopause, women will experience vaginal dryness, pain with intercourse, lack of interest in sex, so low libido. Bladder control. The bladder trigone and the vaginal mucosa are very estrogen‑sensitive. Those symptoms show up in terms of genitourinary syndrome of menopause, or what we used to call vaginal atrophy.

The other thing that is commonly complained about is weight gain. We know that we lose muscle mass as we age. Postmenopausal, we lose even more muscle mass. It does stabilize, thank goodness. But as we lose muscle mass, we really burn our calories less efficiently.

Joint pain. Estrogen is anti‑inflammatory. Oftentimes, women will complain about joint pain and headaches.

If we look at the left side, sleep problems affect 40 to 60% of women. It is not asked about often enough in primary care. If anything, we want to make sure that we underscore that for you.

We talked about the most frequent symptom being vasomotor symptoms. It peaks at about a year after the final menstrual cycle.

I do want to draw your attention to the fact that, when I first was in residency training, we thought menopause symptoms were short‑lived. In fact, after the SWAN study publications, we now know that the median duration is 7.4 years. That is a long time to have your life disrupted, to have your sleep disrupted. It is incumbent upon us to recognize that. As we have conversations with patients talking about treatment, that will come up.

Then, of course, 10 to 20% of patients will find VMS just almost unbearable. I have patients who take a leave of absence from their job, who will not accept promotions because they feel like they really cannot function optimally. For some ‘lucky’ patients, 10 to 15%, the symptoms persist for over 15 years. Again, very extended periods of time.

[00:17:17]

Menopausal Symptoms and Burden of VMS

When we look at menopause symptoms and the burden of VMS, at the bottom are the symptoms that most patients complain about. You see again, the most common characteristics like hot flashes, sleep problems, vaginal dryness, down to thinning of hair, dryness. Everything from our CNS to our skin is impacted by loss of estrogen.

The areas that women say are mostly affected by this are sleep, self‑care, and then you see work. We are seeing more and more publications actually addressing the disruption of work, the loss of productivity with either absenteeism or even presenteeism. The cost of menopause in the workforce is pretty significant. Also, thinking about the fact that women who are menopausal are usually at the pinnacle of their careers, it really impacts their ability to function and to look at career advancement.

Moods, relationships, just every aspect. Social activities. Patients will oftentimes retract from social activities because of embarrassment.

[00:18:43]

Physiologic Changes and Clinical Timeline

Let us drill down into some of the physiological changes in the clinical timelines that we see. Perimenopause is the 10 years or so that precede menopause. What we see happening is, in the early perimenopause, oftentimes your estrogen level is relatively unchanged, but as a reproductive endocrinologist, what we start to see is a slow eking up of the FSH level, indicating that the number of oocytes that are remaining is dwindling. From a cardiovascular risk perspective, we see an increase in carotid intima‑medial thickness, vascular remodeling, and a decrease in endothelial function.

As we enter into the late perimenopause, we then begin to see the drop in estrogen and anti‑mullerian hormone assay.

While I am telling you these changes are occurring hormonally, we really do not have to have those levels to know where the patient is. It is not part of your diagnosis. Your diagnosis is really clinical. It is based on her symptomatology.

Then body composition. We see an increase in fat distribution, mostly abdominal fat. Again, I mentioned that previously, the loss of muscle mass which adds to the fat distribution. Our energy levels, our energy expenditure is reduced.

And then our cardiovascular risk starts to go up. Estrogen actually creates a favorable lipid profile. As we lose estrogen, what we see is an increase in our LDL, a decrease in HDL. Some dyslipidemia occurs mostly within the first year of the final menstrual period. Again, those cardiovascular changes that we mentioned earlier continue. In addition to that, what we see is an increase in insulin resistance. The sleep disruption and the cortisol level actually add to the insulin resistance and to actual cardiovascular risk as well.

In the postmenopausal phase, we see that estrogen level really drop off the cliff for the first 2 years post the final menstrual cycle, then it evens out. The same thing is true about the FSH level increasing. Body mass composition, increased abdominal fat, the lean loss, all of those things continue to worsen, but even out about 2 years post.

The other thing that I would mention under cardiovascular risk, we have already talked about dyslipidemia and insulin resistance, but women are at an increased risk for glucose intolerance and diabetes.

[00:21:58]

How Menopause Affects Sleep

We mentioned sleep. The diagram on the left really illustrates the close interrelationship between vasomotor symptoms, sleep disturbances, and mood changes, which are all occurring because of the hormonal changes that we see. The decline in estrogen and progesterone, which impacts sleep quality. The symptoms affecting sleep, hot flashes, night sweats. Restless leg syndrome is another.

Again, I want to just underscore the elevated cortisol level, which, when you do not go into deep sleep or REM sleep, you have a chronic, tonic, elevated cortisol level, which contributes to the sleep disruption and the accumulation of abdominal fat. It makes it much more difficult to lose weight.

[00:22:56]

Ovarian Hormones in the Pathophysiology of Sleep

This is a very complex diagram on the left, but it is really just to show you that in the hypothalamic area, the lateral hypothalamic area is where the suprachiasmatic nucleus resides. That is where our circadian rhythm is managed or moderated.

On the right side, it really illustrates the direct and indirect action of estrogen on the central nervous system, and in addition at the periphery. Estrogen plays a role in so many of our CNS symptoms, like our serotonergic and dopaminergic. The neurotransmitters are impacted by estrogen. Neurokinin B signaling, which we will talk about later, because now the recognition that the KNDy neuron, or the kisspeptin, neurokinin, and dynorphin neuron, plays a very critical role in the regulation of the thermoregulatory zone and vasomotor symptoms. Estrogen is very important in regulating that signaling.

From a peripheral perspective, progesterone is a muscle relaxant, so you may see some airway relaxation, obstructive sleep apnea, esophageal sphincter muscle tone with some reflux. A cascade of things that might be impacted by the loss of estrogen and progesterone.

[00:25:07]

From Hormones to Hypothalamus: Practical Treatment Pathways for the Primary Care Setting

Let us go on and talk about hormones and practical treatment pathways in primary care setting.

[00:25:11]

Discussing Treatment Options With Susie

Here is Susie. We want to begin to discuss with her treatment options. Again, she is 47. Moderate to severe hot flashes, which are worse at night. It is really impacting her sleep and waking after she falls asleep. Her past medical history is notable for just mild anxiety, occasional migraines, but she is up to date on all her preventive health and maintenance screens. She had a C‑section. The rest of her social history is pretty unremarkable. Her labs, which I am going to assume are the preventive health screens that we would do, were all normal.

Daniel: We have a poll question here. Again, asking a fairly open‑ended question.

[00:25:58]

Poll 4

How comfortable are you with selecting and prescribing hormone and nonhormone therapies for patients like Susie, who have menopause‑associated VMS and sleep disturbance symptoms? You can answer from A to E, ranging from not at all comfortable through very comfortable. We will give you a few seconds to answer that open‑ended practice question.

Let us close the poll there. Even distribution from not at all comfortable through comfortable. A rare few who say very comfortable. Hopefully, we can sway that more to the comfortable and very comfortable part of the spectrum there. Back to Dr. Richard‑Davis.

[00:26:58]

Current VMS Treatment Use

Dr. Richard‑Davis: This study, Barb DePree’s study, really looks at the current use of VMS treatment across our practice landscape. What we see is in terms of prescriptive therapy, hormone therapy is the predominant option that is prescribed, followed by compounded hormone therapy, which we will talk about, SSRIs, SNRIs, clonidine, and gabapentin, some SERMs, and a small portion of others.

In the non‑prescriptive therapy realm, what we see are herbs, vitamins, supplements, the over‑the‑counter things that patients oftentimes will try on their own. Complementary or alternative therapy.

Behavioral and lifestyle intervention. We oftentimes talk about some of the lifestyle changes. Certainly, we want patients to really practice a healthy lifestyle, but there are certainly improvements when you look at stress reduction, especially for women who have mild vasomotor symptoms, not necessarily the moderate to severe.

[00:28:12]

The Menopause Society 2022 Hormone Therapy Position Statement

If you are not familiar with the Menopause Society, historically, it is the North American Menopause Society, or NAMS. It is an amazing professional society that is a blend of researchers and clinicians who are keenly focused on improving the quality of life for midlife women based on evidence‑based information that is within our research domain.

Every 5 years or so, we review all of the literature and do an update on statements. The previous hormone therapy statement was in 2017. This is the most recent one, 2022. Again, it is underscoring that hormone therapy remains the most effective treatment for vasomotor symptoms and genitourinary syndrome of menopause or GSM. It has been shown to also prevent bone loss and fractures.

The risk of hormone therapy differs depending on the type, dose, duration of use, route of administration, time of initiation, and whether a progestin is used. A lot of this we also learned post WHI in terms of the timing of initiation. We will talk about that.

Treatment should be individualized. We want to use the best available evidence to maximize benefits and minimize risk with periodic reevaluation of that risk‑benefit balance or ratio as we continue therapy.

[00:29:50]

Indications for Hormone Therapy

The indication for hormone therapy is very clear. The FDA approved hormone therapy for the treatment of moderate to severe vasomotor symptoms. We are talking about vasomotor symptoms that are disruptive to a woman’s life. It also is approved for prevention of bone loss, premature estrogen loss, like our premature ovarian insufficiency patients, or even patients who have surgical menopause early on. Also, for GSM, you want to use preferably local estrogen. You do not need systemic treatment for GSM. In fact, it is better served with local estrogen.

For women with a uterus in place, we know that what we have to do is add a progestin in order to protect the endometrium from that unopposed estrogen and risk of endometrial hyperplasia and cancer. We can also use bazedoxifene, which is a SERM combined with conjugated equine estrogen. Bazedoxifene protects the endometrium, as well as does any progestin.

[00:31:07]

Hormone Therapy Options

There is no paucity of therapy options when it comes to hormone treatment from the route perspective, from the dosing, and the different regimens that can be used. For estrogen, we have oral preparations, vaginal, transdermal, and then of course the tissue‑selective estrogen complex that we talked about before with conjugated equine estrogen and bazedoxifene. But look at all the options that we have. Certainly, we can find something that works for our patients.

Then, when we have patients with a uterus in place and we have to offer an estrogen plus progestin, we have combination treatments which already have the estrogen and progestin built into them. Different oral options. We also have some transdermal options that are combined. We can do oral intermittent combined when you separate the 2 preparations.

I am going to come back to compounding hormone therapy because, as I said before, it is not FDA‑approved or monitored. The potential safety and efficacy concerns do exist. Really, compounded hormones should be reserved for treatment of conditions that we do not have an FDA‑approved therapy for, or for whatever reason you cannot use the FDA‑approved treatment options.

[00:32:45]

Starting Hormone Therapy

There are a number of different factors that we take into consideration. The age at menopause, whether the patient has a uterus or has she had a hysterectomy. First is her age.

For patients who are less than 40 to 45, they are fairly young. Oftentimes, they are still perimenopausal. They will have those menopausal symptoms, but they might also still have some irregular vaginal bleeding. In these patients, I will tell you that my preference of choice is a low dose continuous OC, assuming that she has no contraindication to using oral contraceptive. You can also use hormone therapy with estrogen with a patch or oral preparation, whether it is cyclic or continuous. But you have to make sure that you use adequate progestin to counter the estrogen influence on the endometrium. What you will see in terms of the dosing is, we start higher in our younger patients. For patients who are hysterectomized, then of course, you do not have to have the progestin. But again, the dosing of estradiol is usually a little bit higher in order to alleviate their symptomatology.

Going upstream to patients who are now late 40s, early 50s with symptoms, we want to reassess yearly. But again, the options are very similar, with a slightly lower dose of estrogen. Still the same dose in terms of progestin, whether it is continuous or intermittent. Then the patch or oral. When patients reach late 50s or 60s with symptoms, again, we are reassessing yearly to make sure that they have not developed any contraindication. The dosing that we usually start with is a little bit lower, being 0.025 to 0.035 in terms of the patch, and 0.1 to 1. For conjugated equine estrogen, we would use very comparable doses.

[00:35:10]

Warning and Contradictions for Hormone Therapy

Let us then talk about the contraindication. It is very clear what the contraindications are for hormone therapy. Anyone with estrogen‑dependent cancers, if they have active VTE or thrombophilia, unexplained vaginal bleeding, severe active liver disease, and untreated or uncontrolled cardiovascular or cerebrovascular disease: contraindications.

You should exercise caution in the case that patient's personal preference is to avoid HT, if they have a history of VTE, established cardiovascular disease, hyperlipidemia, diabetes, or migraine. It is not an absolute contraindication, but you should exercise your clinical decision there.

For women who are over 60 or the onset of menopause is greater than 10 years, again, exercise caution. It is not to say that you cannot prescribe it, but to make sure that you are adequately counseling the patient with regard to the risk‑benefit profile.

[00:36:28]

WHI: Benefits and Risks of HT in Patients Aged 50‑49 Yr

Speaking of risk‑benefit profile, the WHI, the Women's Health Initiative, that most of us are quite familiar with, this is a re‑analysis of that data but really specifically focusing on younger women aged 50 to 59. We know that in the total group for WHI, the women were a lot older. The average age was 67. The risk‑benefit profile is very different for older patients, hence the recommendation now for initiation of hormone therapy for younger menopausal women, less than 60.

What you see here is the absolute risk of events per 10,000 women per year. The dotted line shows the rare events which occur. It is less than 10 per 10,000 per year. What you see is deep vein thrombosis and pulmonary embolism, which are usually the adverse events that we focus on. It is still relatively low.

There is the benefit of decreased coronary heart disease, which is consistent with our observational data, like the Nurses’ Health Study, that showed, again, the benefit of the favorable lipid profile with atherosclerosis disease. There is also a decreased risk of stroke, breast cancer, colorectal cancer, all cancers, and all fractures. Also, death from any cause. Then, you see here I mentioned diabetes earlier, that there is a decrease in diabetes in women who were on the estrogen‑only arm.

We compare that to the combined arm with CEE and MPA, and you see that the risk‑benefit profile is a little bit different, where there is a slightly increased risk for deep vein thrombosis, pulmonary embolism, coronary heart disease, stroke, and breast cancer. But again, it does not cross that dotted line of rare events. And still we see improvement in fractures and a decrease in all‑cause mortality.

[00:39:08]

Tissue‑Selective Estrogen Compounds

The tissue‑selective estrogen compound, or bazedoxifene, is in a combined preparation with CEE. There is diminished risk because it does offer endometrial protection. It does not increase bleeding, which is always a concern in our perimenopause or early menopause patients. There is a decrease in breast tenderness and breast cancer with the TSEC or the tissue‑selective compound.

It maximizes benefits by decreasing vasomotor symptoms. It does increase bone mineral density, as does hormone therapy, prevention of vulvovaginal atrophy. There is some added benefit that it is shown to decrease breast density because it is a SERM.

[00:39:59]

Heart Disease and Mortality Risks of Using HT for VMS by Age and Duration of Menopause

Let us take a look at heart disease and mortality risk for patients who are using HRT by age and duration of menopause. Again, this information is a subanalysis of the Women's Health Initiative.

What we see here with coronary heart disease is that, one, there is no impact at all. When we initiate treatment in women who are less than 60 and less than 10 years since menopause, there is actually a protective effect. You have a relative risk of 0.68 as compared to women who are over 60 or greater than 10 years, and all ages, where you do not see that benefit. Timing is really critical in terms of delivering the benefits of hormone therapy to our patients.

Then our total mortality. Again, what we see is, when we initiate therapy younger, less than 60, the mean age here was 54, again there were benefits as it relates to a decrease in mortality. Relative risk of 0.6. As we begin therapy later than we lose that benefit.

[00:41:31]

The Menopause Society 2023 Nonhormone Therapy Position Statement

Changing gears, we are going into the Menopause Society non‑hormonal position statement, which was released in 2023. What this says is for women who are not a good candidate for hormone therapy because of contraindications or personal preferences, it is important that you know and understand what some of the options are for non‑hormonal treatment to reduce vasomotor symptoms. We do not want these patients to go untreated.

The recommendation for a non‑pharmacologic strategy for cognitive behavioral therapy has been shown to be very effective. Then, clinical hypnosis, weight loss, and stellate ganglion do have some benefit.

Not recommended – not that you do not want your patients to use these strategies, but know that if they have moderate to severe vasomotor symptoms, they are not likely to work. They will not alleviate their symptoms. They will improve mild symptoms. Certainly, we want them to follow a healthy lifestyle.

[00:42:52]

Nonhormonal Therapies for VMS

Non‑hormonal therapies for VMS fall into different classes. We have SSRIs and SNRIs. Really, the benefit of venlafaxine came from the breast cancer prevention trials, where we noted that the patients were having less hot flashes. Since then, many of the SSRIs and SNRIs have been used for vasomotor symptoms but the only one that is actually approved is paroxetine. You see the asterisk saying FDA‑approved. That is a 7.5mg dose.

The newer options on the market, the NK3 receptor antagonist, and the NK1 and 3 receptor antagonist, fezolinetant, is very effective in terms of decreasing or eliminating vasomotor symptoms. What is important to note, though, is that we do have to check liver function tests before starting this option for patients, and we have to monitor liver function tests monthly for the first 3 months for fezolinetant, and then 6 months and 9 months. If there are any symptoms in between that, suggestive of any abnormal liver function studies, then you may have to actually order labs at that point.

For elinzanetant, now FDA approved as of October 4th, very promising data to improve VMS and sleep disturbances, including among women who have HR‑positive breast cancer. Gabapentin is another option, and then oxybutynin.

There are a number of different agents in the non‑hormonal realm that can be used to alleviate vasomotor symptoms, so there is really no reason for us to not treat patients who are very symptomatic. The agents not recommended due to a lack of efficacy are clonidine, fluoxetine, pregabalin, and sertraline.  

[00:45:27]

Low‑Dose Paroxetine for VMS

Let us look briefly at some of the data from the clinical trials. This is the low‑dose paroxetine trial, 7.5mg. What you see is placebo versus treatment arm at 4 weeks, 12 weeks. We usually see about a 40% improvement, even on placebo. You see that drop here. But it is very clear that paroxetine improved vasomotor symptoms above and beyond placebo. It started dropping at 4 weeks, and then continued at 12 weeks, and then leveled off.

[00:46:19]

Novel and Emerging Nonhormone Therapies

Moving into the novel and emerging non‑hormonal therapies. Fezolinetant was approved 5/2023, and it was approved at the 45 milligram dose. Some of the data you will see actually has the 30 milligram dose. I will really focus on 45mg because that is what is on the market. But it is an NK3 antagonist. When estrogen depletion occurs, you actually have an increased stimulation of the KNDy neuron or activation of the NK3 receptor. This medication blunts that response so that the thermoregulatory zone does not initiate vasomotor symptoms. It blocks the NK3 receptors in the KNDy neuron, modulating that thermoregulatory center. Elinzanetant works very similarly but in addition to NK3, it is actually working on the NK1 receptor as well, and impacting substance B. It is a 120mg dose orally.

SKYLIGHT 1: Efficacy of Fezolinetant for VMS

In the fezolinetant clinical trial, Skylight 1, looking at frequency of moderate to severe VMS and then the actual severity. Frequency, as I mentioned – the green is the 45 milligram dose, which is approved – what you see is that compared to placebo, there is a dramatic drop in the frequency of moderate to severe VMS. Patients who were recruited for the clinical trial had to have at least 7 to 8, moderate to severe, or greater than 50 to 60 per week. You see a drop of 6 or more. Then, by 12 weeks, that drop was 6 or 7.

In terms of severity, the severity 1 to 3 in terms of the vasomotor symptoms, 3 being you really have to stop what you are doing because of the disruption that you feel during vasomotor symptoms. What we see here is that the average was about 2.3, 2.4 in terms of the severity of vasomotor symptoms. We see a drop in placebo of maybe 0.2 for the 45 milligram dose arm. That drops to about 0.5 at 4 weeks. Then by 12 weeks, it drops further to about 0.6. Patients who had severe probably dropped into the moderate category, those that were moderate dropped into the mild category. VMS frequency is also improved as it relates to fezolinetant.

[00:49:33]

SKYLIGHT 2: VMS Frequency With Fezolinetant vs Placebo at 12 Wk, Followed by 40 Wk Active Treatment Extension

This is just SKYLIGHT 2. It is a crossover study. Placebo dropped. Then, when you change from placebo to active, you can see that further drops and continue to be suppressed.

[00:49:52]

Fezolinetant FDA Restrictions

We talked about risk with fezolinetant. FDA restrictions require that we check liver function tests and that we repeat them. Contraindication: known cirrhosis, severe renal impairment, or concomitant use of CYP1A2 inhibitors.

[00:50:08]

OASIS 1 and 2: Elinzanetant Efficacy in VMS Frequency

Elinzanetant OASIS trial, very, very similar profile of patients who were recruited for the trial. You see placebo at 4 to 12 weeks. The active arm clearly shows an improvement. Then what we see is when you cross over and you have the placebo arm changed to fezolinetant, you see that drop.

[00:50:41]

OASIS 1 and 2: Elinzanetant Efficacy in VMS Severity

We see the same thing in frequency and severity. Again, severity looks very similar.

[00:50:53]

Key Takeaways to Share With Susie About Treating VMS

The takeaway is, we want to share with Susan about treatment. Hormone therapy is highly effective. For women who are not good candidates, we do have lots of options that we can offer. That would be when you would offer the non‑hormonal options, especially for women who have moderate to severe vasomotor symptoms. It is the NK blocking agents.

[00:51:21]

Empathy and Engagement: Delivering Culturally Attuned Menopause Care in Primary Practice

How do we counsel patients? We certainly want to be empathetic, engaging, and deliver culturally attuned care.

[00:51:30]

Practical Tools for Primary Care Toolkit

We talked about the validated screeners that you can use. Oftentimes, I will use that as a starter for my visit, because I look at the menopause rating scale and see what the patients have checked off as their most bothersome symptoms. But conversation prompts might be, how is your sleeping pattern? Are you concerned about intimacy or vaginal comfort? All of those things that we know are impacted by the drop in estrogen. Your decision support is the position statement. It should be a shared decision. Use risk stratification tools for those patients that you see that are at risk of cardiovascular disease.

[00:52:18]

Designing a Treatment Plan With Susie

Susie says, ‘Okay. Doctor, do you think I should wait it out? This is just part of life, I guess. I have heard that taking hormones can be unsafe and is not recommended. Is that true?’ She is concerned about the non‑hormonal medication being covered. Her friends are taking herbal preparations. What do you think about that? How would you approach Susie when she is asking all of these questions about what treatment options she should use?

[00:52:50]

Shared Decision‑making

I would say, first and foremost, we want to make sure that Susie’s quality of life is improved. It should be a collaborative process between the patient and the healthcare provider. What bothers her the most?

[00:53:02]

Engaging and Empowering Patients in Their Care

Engage and empower her in decision‑making. Provide information about alternatives and all treatments. Do not make that decision for her, but educate her and incorporate patient preferences and values into the plan.

We want to make sure we are discussing menopause. It is a normal part of life. Most women will go through menopause, and most of them will have symptoms. We would like to prepare them earlier because that is one of the things that patients say, that they really do not know what to expect. If we start that conversation earlier, they will be better prepared.

Explore all therapies from a holistic and individual care perspective, and really recognize and address those health disparities that we do know exist in women's health care. We will talk about that in a minute. Collaborate with a multidisciplinary team. You may need to bring in physical therapy or counseling. Make sure that we use our ancillary team members.

[00:54:09]

Employing Motivational Interviewing

Motivational interviewing you are probably very familiar with. Open‑ended questions, making sure that you are listening to the patients and planning collaboratively.

[00:54:21]

Culturally Sensitive Care

The SWAN data has made us very aware of the cultural differences, that Black and Hispanic patients have longer duration and greater severity of symptoms compared to our White and Asian patients. Really, being culturally sensitive in the approach. Some of our recent data show that many of our Black patients who show up, even when they are complaining about moderate to severe vasomotor symptoms, only 13% of them leave the office with treatment.

[00:54:53]

Race‑ and Ethnicity‑Specific Prevalence of Menopause Symptoms: SWAN and FMEG Studies

I am going to skip this.

[00:54:56]

The Lived Menopause Experience Among Diverse Populations

But when we looked at the lived experience of a diverse population, Black women experienced more frequent, severe, and long‑lasting VMS. Asian women, less frequent. There is a cultural stigma associated with reporting sexual or mood symptoms, so we need to make sure that we are asking about it. Lower hormone therapy use among women of color. That tends to be the perception, that they are not receptive to it, but I think a lot of that is education.

Again, they are less likely to seek medical care but when they do come in, we need to make sure that we are listening. Removing those structural barriers and mistrust, because we know this impacts the woman's well‑being. The sleep disruption, an adverse impact on productivity and daily function. All of these things can be improved when we appropriately treat their vasomotor symptoms, night sweats, and the sleep disruption that comes with it.

[00:56:04]

Bridging the Gap Between Evidence and Personalized Care

Treatment. We have talked about this before. You want to make sure you are doing a baseline health assessment, you are stratifying care based on whether the patient is less than 60, less than 10 years without contraindication. If they have a contraindication, then we are really kicking them over to considering non‑hormonal therapy. If they are over 60 or greater than 10 years since the onset of menopause, non‑hormonal. We always want to weigh the risks and benefits, no matter what option we are offering the patients.

[00:56:44]

Key Takeaways: Sustaining Symptom Relief and Patient Engagement Over Time

Takeaway. Vasomotor treatment adjustment. Dose adjustments. Therapy based on efficacy and tolerability. You always want to look at the comorbid conditions and health status to determine how often risks and benefits should be reassessed. Navigating withdrawal of VMS therapy can be tricky. We do not have any set regimen that is recommended. Making sure that we are doing the annual, which I know you are all doing, annual exam, preventive health screenings.

Daniel: Okay. Thank you.

[00:57:21]

Posttest Questions

We will move on to these posttest questions, similar to our pretest ones.

[00:57:27]

Posttest 1

A 52‑year‑old female comes for her annual visit, reports occasional hot flashes and decreased energy, but no other concerns. How do you identify menopause‑related concerns that may otherwise go unrecognized? Which next step would best demonstrate comprehensive, patient‑centered care? You can go ahead and answer that question.

1. Ask about joint musculoskeletal pain
2. Ask about mood changes
3. Sleep problems
4. Sexual health concerns

Let us see what everybody has answered there. Good. A lot of people are asking about sleep problems in the posttest. We see that it is probably the more appropriate question to ask as part of that intake process. Moving on to the second question.

[00:58:23]

Posttest 2

We have a 57‑year‑old female who is 8 years postmenopausal with severe hot flashes and sleep disturbances. She wants to be treated, but she has a history of breast cancer with adjuvant endocrine therapy. Which one of these would be the best treatment? You can go ahead and answer either:

1. Lifestyle modification
2. NK3 receptor antagonists
3. An SSRI
4. Or oral estrogen therapy

Let us see what everybody has answered. We still have a good mix between the NK3 antagonists and SSRIs, similar to our pretest. You would probably want to discuss an NK3 receptor antagonist here, which is probably more effective overall than the SSRI would be.

[00:59:17]

Posttest 3

Our final post‑test. Again, just open‑ended. After this education, how confident are you in the use of culturally responsive, patient‑centered communication strategies to encourage symptom disclosure?

1. Not at all
2. Not very
3. Somewhat confident
4. Very confident after this program

Let us see what everybody said here. More of that shift towards the somewhat confident and confident discussion. Good.

We are running low on time here. Unfortunately, we do not have time for the question and answer session. That said, Dr. Richard‑Davis is going to be answering some of those questions that have come through the Q&A. Those answers will be posted to the website after our program today, so keep an eye on that.

[01:00:16]

Question and Answer Session

It looks like we have time for maybe 1 or 2 questions. One that came through fairly often is screening. If a patient comes to you with concerns of perimenopause or menopausal symptoms, are you doing any hormonal labs or any other lab testing for them?

Dr. Richard‑Davis: I mentioned earlier, that you do not need hormonal therapy to initiate treatment. Sometimes they want to be reassured, but it is not necessary at all.

Daniel: Got you. As far as non‑pharmacologic therapy, there have been some questions coming through about diets or other over‑the‑counter supplements. Where does that play a role in your treatment regimen?

Dr. Richard‑Davis: As I mentioned earlier, I think we need to counsel all of our patients in terms of a healthy lifestyle, healthy weight, because we noted that obesity actually worsens vasomotor symptoms. But if you are talking about truly treating moderate to severe symptoms, those lifestyle changes are not going to handle it. We really need to be looking at how we treat them with either hormone therapy or non‑hormonal options.