Treatments that act on the thermoregulatory region
Dr. Neal-Perry: I have described what happens in the brain around the time of menopause, and what triggers those hot flashes.
Estrogen. The reason that estrogen worked to treat the hot flashes is because estrogen inhibits and calms the neurons that become hyperactive during the menopause.
Fezolinetant. Fezolinetant is unique because it specifically targets the hormone receptor that triggers hot flashes, the neurokinin receptor. Fezolinetant is a nonhormone therapy that not only reduces the activity of KNDy neurons but also blocks the effects of neurons in the thermoregulatory zone, thereby reducing the sensation of the hot flashes. We are in such a special time in medical history for individuals who experience hot flashes because now we understand the basic biology of hot flashes, and we can generate targeted therapy to manage hot flashes—that is for both individuals who identify as women and individuals who identify as men, because both experience hot flashes.
OBG Management: Is there a particular threshold of hot flash symptoms that is considered important to treat, or is treatment based on essentially the bother to patients?
Dr. Neal-Perry: Treatment is solely based on if it bothers the patient. But we do know that people who have lots of bothersome hot flashes have a higher risk for heart disease and may have sleep disruption, reduced cognitive function, and poorer quality of life. Sleep dysfunction can impact the ability to think and function and can put those affected at increased risk for accidents.
For people who are having these symptoms that are disruptive to their life, you do want to treat them. You might say, “Well, we’ve had estrogen, why not use estrogen,” right? Well estrogen works very well, but there are lots of people who can’t use estrogen—individuals who have breast cancer, blood clotting disorders, significant heart disease, or diabetes. Then there are just some people who don’t feel comfortable using estrogen.
We have had a huge gap in care for individuals who experience hot flashes and who are ineligible for menopausal HT. While there are other nonhormonal options, they often have side effects like sexual dysfunction, hypersomnolence, or insomnia. Some people choose not to use these nonhormonal treatments because the side effects are worse for them than to trying to manage the hot flashes. The introduction to a nonhormonal therapy that is effective and does not have lots of side effects is exciting and will be welcomed by many who have not found relief.
OBG Management: Is fezolinetant available now for patients?
Dr. Neal-Perry: It is not available yet. Hopefully, it will be approved within the next year. Astellas recently completed a double blind randomized cross over design phase 3 study that found fezolinetant is highly effective for the management of hot flashes and that it has a low side effect profile.10 Fezolinetant’s most common side effect was COVID-19, a reflection of the fact that the trial was done during the COVID pandemic. The other most common side effect was headache. Everything else was minimal.
Other drugs in the same class as fezolinetant have been under development for the management of hot flashes; however, they encountered liver function challenges, and studies were stopped. Fezolinetant did not cause liver dysfunction.
Hot flash modifiers
OBG Management: Referring to that neuropathway, are there physiologic differences among women who do and do not experience hot flashes, and are there particular mechanisms that may protect patients against being bothered by hot flashes?
Dr. Neal-Perry: Well, there are some things that we can control, and there are things that we cannot control (like our genetic background). Some of the processes that are important for estrogen receptor function and estrogen metabolism, as well as some other receptor systems, can work differently. When estrogen metabolism is slightly different, it could result in reduced estrogen receptor activity and more hot flashes. Then there are some receptor polymorphisms that can increase or reduce the risk for hot flashes—the genetic piece.11
There are things that can modify your risk for hot flashes and the duration of hot flashes. Individuals who are obese or smoke may experience more hot flashes. Women of color, especially African American women, tend to have hot flashes occur earlier in their reproductive life and last for a longer duration; hot flashes may occur up to 2 years before menopause, last for more than 10 years, and be more disruptive. By contrast, Asian women tend to report fewer and less disruptive hot flashes.8
OBG Management: If fezolinetant were to be FDA approved, will there be particular patients that it will most appropriate for, since it is an estrogen alternative?
Dr. Neal-Perry: Yes, there may be different patients who might benefit from fezolinetant. This will depend on what the situation is—patients who have breast cancer, poorly controlled diabetes, or heart disease, and those patients who prefer not to use estrogen will benefit from fezolinetant, as we are going to look for other treatment options for those individuals. It will be important for medical providers to listen to their patients and understand the medical background of that individual to really define what is the best next step for the management of their hot flashes.
This is an exciting time for individuals affected by menopausal hot flashes; to understand the biology of hot flashes gives us real opportunities to bridge gaps around how to manage them. Individuals who experience hot flashes will know that they don’t have to suffer, that there are other options that are safe, that can help meet their needs and put them in a better place. ●
Multiethnic differences in the menopause experience
Excerpted from the presentation, “Do you see me? Culturally responsive care in menopause,” by Makeba Williams, MD, NCMP, at The North American Menopause Society meeting in Atlanta, Georgia, October 12-15, 2022.
Dr. Williams is Vice Chair of Professional Development and Wellness, Associate Professor, Washington University School of Medicine
The Study of Women’s Health Across the Nation (SWAN) challenged the notion that there is a universal menopausal experience.1 Up until that time, we had been using this universal experience that is based largely on the experiences of White women and applying that data to the experiences of women of color. Other research has shown that African American women have poorer quality of life and health status, and that they receive less treatment for a number of conditions.2,3
In a recent review of more than 20 years of literature, we found only 17 articles that met the inclusion criteria, reflecting the invisibility of African American women and other ethnic and racial minorities in the menopause literature and research. Key findings included that African American women1,4:
- experience an earlier age of onset of menopause
- have higher rates of premature menopause and early menopause, which is a risk factor for cardiovascular disease
- experience a longer time of the menopausal transition, with variability in the average age of menopause onset
- overall report lower rates of vaginal symptoms
- are less likely to report sleep disturbances than White women or Hispanic women, but more likely to report these symptoms than Asian women
- experience a higher prevalence, frequency, and severity of vasomotor symptoms (VMS), and were more bothered by those symptoms
− 48.4 years in the Healthy Women’s Study
− 50.9 years in the Penn Ovarian Aging Study
− 51.4 years in SWAN
- reported lower educational attainment, experiencing more socioeconomic disadvantage and exposure to more adverse life effects
- receive less treatment for VMS, hypertension, and depression, and are less likely to be prescribed statin drugs
- experience more discrimination
- use cigarettes and tobacco more, but are less likely to use alcohol and less likely to have physical activity.
Cultural influences on menopause
Im and colleagues have published many studies looking at cultural influences on African American, Hispanic, and Asian American women, and comparing them to White women.5 Notable differences were found regarding education level, family income, employment, number of children, and greater perceived health (which is associated with fewer menopausal symptoms). They identified 5 qualitative ideas:
- Positive acceptance. Minority women, or racial and ethnic women, perceived the transition to menopause more positively, and generally took on a posture of acceptance, reporting feeling liberated from many of the challenges associated with the reproductive period. In addition, many associated a greater sense of maturity and respect within their communities with the natural aging process.
- Optimism. Ethnic women tended to embrace menopause, using humor and laughter to express emotions during stressful life changes. This runs counter to many of the perspectives reported by White women, who often viewed the menopausal transition and aging negatively, as we equate aging with the loss of youthfulness in the United States.
- Unique, not universal. Most of the ethnic minority women thought that there was something unique about their menopausal experiences, and that they were influenced by immigration transition, financial situations, etc. Many White woman perceived that the menopausal experience was shared among all women.
- Closed, not open. There were differences in how we talk about symptoms, or whether or not we talk about them at all. Ethnic women tended to be silent about their symptoms. By contrast, White women tended to be more open and talkative and communicative about their symptoms.
- Minimizing, not controlling. No symptom management was the strategy of choice for most women. Minority women tended to manage their symptoms by tolerating and normalizing them. Only those women with the most serious symptoms sought out medication for temporary relief. Some expressed a tendency to downplay their symptoms because many of them had more important things that they were dealing with in their lives.
What is an individual social identity?
An individual social identity reflects the many groups to which one belongs. It is how one shows up, and yet it is much more than how they physically show up. When you pass your eye on patients, you are only seeing the tip of the iceberg. The full social identity of a patient resides below the surface. Social identity is complex, on a continuum, and can change depending on time and place. How we prioritize our social identities may change, depending on the context and the situation.
Our intersecting social identities give rise to our cultural identity, and it is through the prism of intersectionality that we can understand the ways in which our social identities converge to give rise to disparities in health care in midlife and menopausal women. Holding space for cultural identity, we can impact how our patients are perceiving their menopause, how they are moving through decision making about taking care of themselves in menopause. And we can provide more responsive care to their cultural identities, and hopefully at the end of the day we reduce some of these disparities that we are seeing in our menopausal patients and also are reducing our unconscious bias in our patient interactions.
Culturally responsive care
There are several components to home in on when we are trying to provide culturally responsive care to patients.
- A commitment to being culturally curious. We have to accept what the literature is sharing with us, that there is not a universal menopausal experience. We have for far too long applied this universal experience of menopause that has largely been based on White women to different racial and ethnic populations.
- Recognizing. I appreciate that my identity as a Black woman may be very different from other Black women in the room, or whatever their social identity. I am not expected to understand all of the others’ experiences, and I don’t expect that for you either.
- Acknowledge unconscious implicit biases. Acknowledge the groups to which you have a strong implicit bias, and allow it to drive you to reduce barriers to engaging with patients.
- Connecting with the individual patient. It is through a process of individuating that we learn from our patients’ unique characteristics, rather than relying on assumptions and stereotypes. We have a window of opportunity to see our patient and move beyond thinking of them in terms of racial and ethnic stereotypes or particular social groups. It is through this process of individualizing that we can seek answers to key questions.
The ultimate goal is to understand our individual patients’ perceptions, outlook on menopause, and contextual factors in their lives that influence the menopause journey.
CASE ENCOUNTER
I quickly look at the patient-filled form before I knock on the exam door, and I see that the patient has checked off that she has hot flashes, night sweats, and I make a mental note, she’s menopausal. I already have a preliminary plan to give this patient hormone therapy. I open the door, and I see that she’s Black. I know, based upon the data from SWAN and others, that her menopause means longer duration, more severe vasomotor symptoms. I have already teed up a prescription to go to the pharmacy.
The problem is, I have not even talked to her. She may actually nod her head, saying that she is going to go to the pharmacy, but she may never pick up that prescription. She likely leaves my office feeling unheard; her needs are unmet. I move onto the next patient. I feel good, but in actuality, I didn’t hear her. I have provided her bias and stereotyped care. I missed an opportunity to truly engage this patient and her care, and my good intentions of following the literature about her experience in menopause have contributed quite likely to her increased morbidity and mortality, her increased cardiovascular disease risk, all because I have not held space for her cultural identity.
References
- Harlow SD, Burnett-Bowie SM, Greendale GA, et al. Disparities in reproductive aging and midlife health between Black and White women: the Study of Women’s Health Across the Nation (SWAN). Women’s Midlife Health. 2022;8:3. doi: 10.1186/s40695-022-00073-y.
- Chlebowski RT, Aragaki AK, Anderson GL, et al. Forty-year trends in menopausal hormone therapy use and breast cancer incidence among postmenopausal black and white women. Cancer. 2020;126:2956-2964. doi: 10.1002/ cncr.32846.
- Weng HH, McBride CM, Bosworth HB, et al. Racial differences in physician recommendation of hormone replacement therapy. Prev Med. 2001;33:668673. doi: 10.1006/pmed.2001.0943.
- Williams M, Richard-Davis G, Williams PL, et al. A review of African American women’s experiences in menopause. Menopause. 2022;29:1331-1337. doi: 10.1097/GME.0000000000002060.
- Im EO. Ethnic differences in symptoms experienced during the menopausal transition. Health Care Women Int. 2009;30:339-355. doi: 10.1080/07399330802695002.