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Vasomotor symptom trajectory varies by patient characteristics
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In menopausal women, hormone level, race, BMI, lifestyle and psychosocial factors predict distinct patterns regarding the timing and severity of vasomotor symptoms, according to findings.
“This work challenges the long-held assumption that most women experience [vasomotor symptoms] for the few years around the [final menstrual period] and then cease thereafter,” Ping G. Tepper, PhD, of the department of epidemiology at the Graduate School of Public Health at University of Pittsburgh, Pennsylvania, and colleagues wrote. “Conversely, it shows that [vasomotor symptom] patterns are not heterogeneous and, consistent with prior work, [vasomotor symptoms] typically last for a decade or longer.”
Tepper and colleagues analyzed data from 1,455 women participating in the Study of Women’s Health Across the Nation (SWAN), a multisite, longitudinal study of women from five racial groups transitioning through menopause. Women were aged 42 to 52 years, had their uterus and at least one ovary and were premenopausal or perimenopausal at baseline; women in this study had an observable final menstrual period during a median of 15.4 years’ follow-up (mean age, 52 years; 47.3% white; 25.8% black; 11.5% Japanese; 9.8% Chinese; 5.6% Hispanic). Women self-reported vasomotor symptom presence and frequency during the 2 weeks before follow-up visits and provided fasting blood samples during the early follicular phase at each visit; women who ceased menstruating provided a random fasting blood sample within 90 days of recruitment anniversary date. Researchers analyzed temporal patterns of vasomotor symptoms and associations with serum estradiol and follicle-stimulating hormone (FSH), race, BMI and demographic and psychosocial factors using group-based trajectory modeling.
Researchers identified four distinct trajectories of vasomotor symptoms. Within the cohort, 27% of women had a low probability of symptoms with a slight increase around the time of the final menstrual period (low); 25.6% had a persistently high probability of vasomotor symptoms through menopause transition (high); 18.4% of women experienced “early onset,” defined as symptoms occurring well before the final menstrual period but decreasing immediately after the final menstrual period; 29% of women experienced “late onset,” defined as the probability of vasomotor symptoms increasing sharply after the final menstrual period and decreasing later.
When compared with women in the persistently low frequency group, women in the persistently high vasomotor symptom group tended to have less education, greater alcohol use, higher depressive and anxiety symptoms and higher symptom sensitivity and were more likely to be black, as well as having a trend of low levels of estradiol before the final menstrual period with a gradual and slow decline.
Black women were overrepresented in the late-onset and high vasomotor symptom subgroups relative to white women. Women with obesity were underrepresented in the late-onset subgroup. In multivariable models, the pattern of estradiol over menopause was associated with the vasomotor symptom trajectory.
Researchers did not observe a relationship between symptom trajectory and hormone use before the final menstrual period, physical activity level or financial strain.
“Hormones, race/ethnicity, BMI, education, smoking, drinking alcohol, general health status, anxiety and depression ... seem to have a strong relation to both the timing and the persistence of [vasomotor symptoms] in a diverse population of mid-aged women,” the researchers wrote. “Interventions to reduce [vasomotor symptoms] can both be tailored to address those specific factors contributing to her [vasomotor symptoms] and be targeted to women who are most affected by persistent and burdensome [vasomotor symptoms] across the [menopause transition].”
The researchers noted that information about a woman’s race, hormonal status, overall health status and psychosocial profile can help a woman predict what course her [vasomotor symptoms] may follow. – by Regina Schaffer
Disclosure: Tepper reports receiving grant support from Pfizer. Please see the full study for the other authors’ relevant financial disclosures.
Perspective
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Richard Santen
The series of reports from the Study of Women’s Health Across the Nation (SWAN) over the past decade has provided substantial information about vasomotor symptoms (VMS) in perimenopausal and menopausal women. The current report newly describes four specific trajectories that define patterns of VMS in a large and diverse group of women. This report has multiple strengths, including the number of women studied (3,302 from seven different sites), the diversity of racial/ethnic groups (five in all), the duration of follow up (13 years before the final menstrual period and 17 years after) and the careful assessment of covariates.
What have we learned from this elegant study? Most importantly, the trajectories of VMS are highly variable in individual patients, with subgroups experiencing early and late onset of VMS and a low and high probability of symptoms. The study confirms several previously held concepts: VMS may last as long as 17 years; symptomatology is increased in women in poor health and with increased alcohol use, anxiety and depression and lower education levels. These data provide credence to the reports of experienced clinicians that recrudescence of VMS can occur in older women in association with onset of acute illness, exacerbation of chronic conditions, or increased anxiety. Unfortunately, the data from this study do not translate into methods to predict the trajectory of VMS in individual patients.
This study highlights how little we know regarding the biological mechanisms underlying the variability of VMS among women. Clearly, a reduction in estrogens enhances the likelihood of VMS, but the absolute levels of estrogen and the rapidity of decline are not linearly correlated with symptoms. Regarding this issue, the authors conclude, “Changes in other reproductive hormone and/or intracellular and central nervous system processes that may be variably triggered by the hormone dynamics warrant further investigation to elucidate the biologic basis for VMS.”
A key finding from this study deserves special emphasis: the presence of anxiety and depression are related to a higher incidence of VMS. This is interesting because other studies have found that the subgroup of women experiencing fewer hot flashes while receiving a placebo in clinical trials are characterized by having high levels of anxiety. Taken together, these findings suggest that similar neuroregulatory pathways may mechanistically link anxiety and VMS.
A final comment is based on my clinical experience in managing VMS in menopausal women. Health care providers need to differentiate nocturnal from daytime hot flashes. Nighttime hot flashes, night sweats and associated nocturnal awakenings are usually more bothersome to women than daytime VMS, mainly because of the associated fatigue and mild depression often resulting from poor sleep. In addition, nocturnal VMS are associated with sleep stages, enhanced during deep sleep and ameliorated during REM sleep. For clinicians, the treatment of nocturnal and daytime hot flashes can differ in women in whom estrogen is contraindicated or not chosen. As an example, gabapentin taken at night induces sleep, retards hot flashes and usually is metabolized by the next morning, an effect that reduces side effects. While this agent also reduces VMS during the daytime, its associated drowsiness reduces its practical efficacy compared with the SSRI/SNRI class of drugs. Based on these clinical and neurophysiologic observations, it is surprising that the series of SWAN studies has not routinely reported information comparing daytime with nocturnal VMS symptoms.
Disclosure: Santen reports serving on advisory boards of Pfizer and Sermonix and consulting for Tolmar.
Cynthia A. Stuenkel
We have landed men on the moon and broken the genetic code, but as of yet, we have fully elucidated neither the mechanism nor the clinical significance of the menopausal hot flash. In spite of recent research findings, this cardinal manifestation of declining ovarian estrogen production and harbinger of menopause — for all women who live long enough — remains a mystery. In the past year, reports from SWAN have moved this science considerably forward dispelling some myths regarding this (almost) universal experience. New evidence from SWAN that VMS typically last longer than a decade is consistent with clinical experience and challenges us to counsel women accordingly, including routine discussion of treatment options. Furthermore, correlations of patterns of VMS over the menopause transition with clinical characteristics ranging among race, psychological symptoms, weight and patterns of endogenous estrogen provide additional directions for future research. Clinical interventions to reduce VMS might eventually be tailored to address not only a woman’s desires and baseline risks for cardiovascular disease and breast cancer, but also specific individual contributing factors, including her anticipated trajectory of symptom duration. Finally, SWAN investigators are poised to explore the link between VMS and CV health, another significant contribution in the making.
Disclosure: Stuenkel reports no relevant financial to disclosures.
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