Increasing numbers of women with HIV (WWH) are experiencing menopause, a pivotal phase of reproductive health that can impact physical and psychological well-being. Hot flashes are a burdensome symptom of menopause, and research suggests WWH may experience increased hot flash frequency and severity during the menopause transition, compared to women without HIV.1,2 This article provides an overview of menopausal hot flashes in WWH and potential management strategies for the care team.
Menopause: A Brief Overview
Menopause is an important stage of reproductive health for individuals assigned female at birth. Menopause is characterized by estrogen loss, changes in menstrual patterns, and increased risk for select co-morbid conditions and burdensome symptoms, including vasomotor symptoms or hot flashes.3 Natural menopause is characterized by a dramatic decline in estradiol, the prominent endogenous estrogen that helps regulate the menstrual cycle, as well as the neurologic, skeletal, and vascular systems.4 Menopause is comprised of “stages” that have been classified by the Stages of Reproductive Aging Workshop+10 (STRAW+10) criteria.5 These criteria employ a matrix of hormone levels and menstrual patterns, including the final menstrual period (FMP), to define premenopause (reproductive), perimenopause (early and late), and postmenopause (early and late).5,6 Perimenopause, particularly late perimenopause, represents a time when dramatic fluctuations in hormone levels (estradiol and follicle stimulating hormone) occur, and when more intense menopause symptoms, including hot flashes, are experienced.3 During perimenopause, changes in menstrual flow and frequency are observed, and postmenopause represents the FMP plus twelve consecutive months of no menses.6
It is essential that members of the care team understand the characteristics that distinguish each menopause stage to ensure optimal assessment and treatment of menopause and midlife health. Unfortunately, accurately determining menopause stage among WWH can be challenging due to the disproportionate rates of non-menopause-associated amenorrhea experienced by this population.7 For this reason, there are conflicting data as to whether WWH enter menopause at an earlier age than women without HIV, and the STRAW+10 indicate more research is needed to ascertain accurate menopause staging criteria for special populations of women, including WWH5.
Menopause Symptoms or HIV Symptoms?
The rapid decline in estradiol that occurs during the menopause transition results in burdensome symptoms, including hot flashes, sleep disturbance, mood and anxiety, genitourinary symptoms, cognitive decline, and musculoskeletal pain.6 Collectively menopause symptoms, coupled with estrogen loss, can result in long-term consequences, including osteopenia, osteoporosis, central abdominal fat accumulation, increased risk of cardiometabolic disease, and urogenital conditions.6 Many of the symptoms and conditions associated with menopause overlap with those associated with HIV.8 This can make it difficult for midlife WWH and their care teams to differentiate the etiology of symptoms, such as hot flashes, depressed mood, and sleep disruption. Further, if WWH are experiencing conditions such as osteopenia related to HIV before menopause, what will happen when the protective effects of estrogen are lost? Clinician understanding of menopause and associated symptoms is essential for proper assessment, diagnosis and treatment of midlife WWH.
Hot Flashes
Hot flashes are experienced by approximately 80 to 85 percent of women during menopause in the United States (U.S.).9 Hot flashes are characterized by a sudden influx of heat or a “flash” that affects the face, neck, and chest and sometimes, the whole body.9 Hot flashes can last two to four minutes and result in sweating.9 In some women, hot flashes can occur for greater than seven years during the menopause transition.10 This burdensome symptom negatively impacts sleep, mood, and cognitive function as well as overall quality of life.3 The pathophysiology of hot flashes is not entirely clear, though hot flashes stem from thermoregulatory dysfunction that may be related to estrogen deficiency and the interface of distinct neurons such as hypothalamic kisspeptin, neurokinin B, dymorphin.3,9,11
Hot Flashes in WWH
A prior study demonstrated that WWH may experience challenges differentiating symptoms of HIV and symptoms of menopause.12 An impactful article written by a WWH shared an anecdote in which she woke up sweating profusely in the middle of the night in “a panic reminiscent of the days” when her “T-cell count was 8”.13 Stories like this highlight the unique challenges WWH experience with menopausal hot flashes.
Although data are conflicting, some studies suggest that WWH experience an increased prevalence of hot flashes, and specifically perimenopausal WWH experience greater hot flash frequency and severity compared to women without HIV.1,2 Further, perimenopausal WWH demonstrated overall scores on the “Hot Flash Related Daily Interference Scale” that were six-times greater than women without HIV.2 Specifically, WWH reported that menopausal hot flashes interfere with factors including work, social activities, relationships, and quality of life to a significantly greater degree than perimenopausal women without HIV. Important studies among WWH have also shown that menopausal hot flashes are associated with reduced adherence to antiretroviral therapy (ART), HIV clinical appointments, elements of cognitive function, and depressive symptoms.14 A more recent analysis found that among WWH, hot flash frequency was associated with increased immune activation, and years since hot flash onset was related to increased intramyocardial steatosis and decreased diastolic function on Magnetic Resonance Imaging (MRI) spectroscopy.15 Thus, proper assessment of menopausal hot flashes and education provided by the care team on menopause and hot flashes is essential for optimizing care and quality of life among midlife WWH.
Treatment of Hot Flashes
Most of the research and treatment guidelines on the treatment of hot flashes is based on data from women without HIV. In general, the treatment of hot flashes is determined by an individual’s tolerance of symptoms, health history, risk factors, and preferences.3 It is important for members of the care team to stay current with research and treatment guidelines to ensure the delivery of evidenced-based care. A credible and reliable resource for clinicians providing midlife and menopause care is The Menopause Society (www.menopause.org). Presently in the U.S., guidelines for the treatment of hot flashes have not been established distinctly for WWH. Thus, while research on the use of menopausal hormone therapy and clinician education on menopause in WWH is underway (National Institutes of Health grants: 1R01AG081155-01A1; 1R25LM014348-01A1), clinicians can refer to research and recommendations for women without HIV and consider individual risk factors for WWH.
Common non-hormone therapy treatments for hot flashes include cognitive behavioral therapy, maintaining a cool environment, and dressing in layers.16 Other non-hormone therapy strategies for the management of hot flashes include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentinoids, and neurokinin 3 (NK3) receptor antagonists.16 Specific medications within the SSRI and SNRI categories have been shown to be effective at reducing hot flash frequency, severity, and bother compared to placebo in randomized clinical trials (RCT).17,18 Further, the first NK3 receptor antagonist medication was recently approved by the Food and Drug Administration (FDA), and in an RCT, this medication compared to placebo significantly reduced hot flash frequency and severity within one month of treatment with sustained benefit over twelve-weeks.19 Clinical trials for the SSRIs, SNRIs, and the NK3 receptor antagonist did not include WWH, to my knowledge.
Menopausal hormonal therapy (MHT, formally ‘hormone replacement therapy’ or HRT), consists of estrogen and concurrent progestogen in women with a uterus and is the most effective treatment for hot flashes. However, MHT is largely underutilized in WWH, owing to the lack of safety and efficacy data of its use in this population, lack of formal clinical guidelines for MHT in WWH and, importantly, lack of care team and consumer education and comfort on the use of MHT.20
MHT is approved by the FDA for individuals with moderate to severe hot flashes [and or genitourinary symptoms, prevention of bone loss, and premature hypoestrogenism] who are below the age of 60 years and within ten years of menopause and healthy.3,21 The decision to use MHT is individualized and based on evidence-based guidelines. Importantly, the use of transdermal estrogen administered as a gel or patch bypasses the liver metabolism and is associated with lower cardiovascular disease (CVD) risk and risk for blood clots.21 This method of delivery is likely preferred for WWH given the potential traditional and non-traditional risk factors for CVD observed in this population. More pharmacokinetic data are needed to explore the relationship between MHT and ART. Specific ART may lower or increase MHT concentrations and doses of MHT may need to be adjusted based on ART type. Among WWH, initiating treatment with MHT should be individualized, include a comprehensive medical history, and attention to timing of initiation (within 10 years of menopause and under the age of 60) is essential to maximize benefit and reduce risk for CVD.3,21
Menopause Education for Clinicians and WWH
WWH experience menopause symptoms and associated conditions that differ from women without HIV. HIV care team members may consider asking WWH what they know about menopause, and menopausal hot flashes. Providing resources and education on menopause to WWH, including education on symptoms such as hot flashes, that may have deleterious effects on HIV treatment and appointment adherence, in addition to mood and cognitive function, may help improve overall health and quality of life in this population.8 In the context of hot flashes, clinicians may ask WWH to keep a diary – either paper or on a smartphone – to record the number of hot flashes they experience over a 24-hour period, over the course of a month, including the severity of their hot flashes, and whether they occur during the day or night.22 This information is useful for assessment and for establishing a treatment plan. Lastly, given that most individuals with HIV receive primary care and women’s health care from their HIV clinician, it is important for clinicians from all professions and specialty areas to stay current on menopause education and care for midlife WWH. This includes attending webinars and conferences, and reading research publications, and importantly, listening to WWH share their experiences with menopause and associated symptoms and conditions.
Teamwork Among Interprofessional Clinicians
Interprofessional collaboration among clinicians from diverse clinical backgrounds is essential for optimizing treatment outcomes and quality of life for menopausal hot flash management among WWH. As discussed in the previous section, effective treatment with MHT requires both clinician and patient education on the use and potential side effects of each treatment, including MHT, and consideration of the unique assessment and treatment priorities for WWH. For example, prescribing clinicians can work mutually with WWH to tailor MHT (or other treatment strategies) to carefully align with an individual’s medical history, comorbid conditions, medication regimen and distinct social circumstances. Nurses can provide both general and tailored patient education for WWH and establish effective communication strategies such as follow-up check-in calls set to a specific schedule, to identify and help resolve any patient concerns, symptoms, and treatment-related questions. Pharmacists should consider potential ART interactions when dispensing MHT and offer WWH additional education support so that women feel safe and confident with using MHT. Menopause and midlife are complex. All clinicians and healthcare team members caring for WWH during this time should routinely assess for mental health and wellbeing, social service and support needs, and encourage participation in lifestyle and stress reduction strategies that promote wellness.
