Body mass, estrogen levels, and hot flashes in midlife women

doi:10.1016/j.ajog.2005.04.001

American Journal of Obstetrics and Gynecology

Volume 193, Issue 4, October 2005, Pages 1353-1360

https://doi.org/10.1016/j.ajog.2005.04.001 Get rights and content

Objective

This study was undertaken to determine whether body mass index (BMI) is associated with hot flashes and whether the mechanism by which BMI increases the risk of hot flashes is by lowering estrogen levels.

Study design

A case-control study was conducted among midlife women to examine risk factors for hot flashes. Cases were women who reported experiencing hot flashes (n = 353). Controls were women who reported never experiencing hot flashes (n = 258). Each participant completed a questionnaire and provided a blood sample for estrogen measurement.

Results

Compared with normal weight women, very obese women had significantly higher odds of hot flashes. The odds ratios remained elevated although attenuated when the hormone variables were added to the model.

Conclusion

These results indicate that very obese women are at increased risk for hot flashes compared with normal weight women. Estrogen levels may partly explain this relationship; however, other mechanisms appear to be involved as well.

Section snippets

Materials and methods

A case-control study of hot flashes among midlife women (45-54 years) was conducted during 2000 through 2004 among residents of the Baltimore metropolitan region who reported their history of hot flashes and other information through a survey and donated a blood sample for measurement of hormone levels. All women gave written informed consent according to procedures approved by the University of Maryland School of Medicine and Johns Hopkins University Institutional Review Boards.

Names and

Variable definitions

A detailed hot flash history was obtained through a series of questions on the enrollment questionnaire that asked for information on the following: whether the woman had experienced hot flashes within the last 30 days; the number of hot flashes experienced within the last 30 days; the age when hot flashes first occurred; and the severity and frequency of the hot flashes. Outcomes examined were the experiencing of any hot flashes, moderate to severe hot flashes, and daily hot flashes. Severity

Measurement of hormone levels

Samples were stored at −20°C until the hormone assays were conducted. Plasma concentrations of estradiol and estrone were measured using enzyme-linked immunosorbent assays (ELISA). ELISA kits and reagents for the estradiol assay were obtained from Diagnostic Systems Laboratories, Inc (Webster, TX). ELISA kits and reagents for the estrone assay were obtained from American Laboratory Products Company (Windham, NH). The assays were run according to the manufacturers' instructions and published

Statistical analyses

For this analysis, women were excluded if they did not have data on BMI (n [case] = 1) or days since last menstrual period (n [case] = 9; n [control] = 1). Characteristics of cases and controls were compared by using χ² analyses. Unadjusted associations between BMI and the experiencing of any hot flashes, severe/moderate hot flashes, and daily hot flashes were examined by using logistic regression. Multivariable logistic regression models were created to examine the association between BMI and the

Results

Characteristics of the cases and controls are presented in Table I. Cases were significantly older than controls and were significantly more likely to be perimenopausal, to smoke at the time of enrollment, and to report prior use of hormone replacement therapy. In addition, cases were less likely to be of white race and to report current alcohol use than the controls. The mean plasma concentrations of both estradiol and estrone were significantly lower among the cases compared with the controls.

Comment

The results of this case-control study confirm previous cross-sectional reports that high BMI increases a woman's likelihood of experiencing any and more severe hot flashes during the menopausal transition.3, 4, 5, 7, 15, 16, 17 Importantly, we found that the significant increase in risk of any or more severe hot flashes was present among women who were very obese (≥35.0 kg/m²), a group not examined in the previous literature. Similar to previous reports, we observed an elevated risk of any and

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Urinary phthalate metabolite concentrations and hot flash outcomes: Longitudinal associations in the Midlife Women's Health Study
2023, Environmental Research
Midlife in women is an understudied time for environmental chemical exposures and menopausal outcomes. Recent cross-sectional research links phthalates with hot flashes, but little is known regarding such associations over time. Our objective was to estimate longitudinal associations between repeated measures of urinary phthalate metabolite concentrations and hot flash outcomes in midlife women. Using data from the Midlife Women's Health Study (MWHS), a prospective longitudinal study, we fit generalized linear mixed-effects models (GLMMs) and Cox proportional hazards regression models to repeated measures over a 4-year period. Recruitment occurred in Baltimore and surrounding counties, Maryland, USA between 2006 and 2015. Participants were premenopausal/perimenopausal women (n = 744) aged 45–54 years, who were not pregnant, not taking menopausal symptom medication or oral contraceptives, did not have hysterectomy/oophorectomy, and irrespective of hot flash experience. Baseline mean (SD) age was 48.4 (2.45), and 65% were premenopausal. Main outcome measures included adjusted odds ratios (ORs) for 4 self-reported hot flash outcomes (ever experienced, past 30 days experience, weekly/daily, and moderate/severe), and hazard ratios (HRs) for incident hot flashes. We observed mostly increased odds of certain hot flash outcomes with higher concentrations of metabolites of di (2-ethylhexyl) phthalate (DEHP), monoisobutyl phthalate (MiBP), and a molar summary measure of plasticizer phthalate metabolites (DEHP metabolites, mono-(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP)). Some associations between exposures and outcomes indicated decreased odds. In conclusion, phthalate metabolites were associated with certain hot flash outcomes in midlife women. Midlife may be a sensitive period for higher phthalate metabolite concentrations with respect to menopausal symptoms.
Urinary phthalate metabolite concentrations and hot flashes in women from an urban convenience sample of midlife women
2021, Environmental Research
Phthalate exposure is associated with altered reproductive function, but little is known about associations of phthalate exposure with risk of hot flashes.
To investigate associations of urinary phthalate metabolite levels with four hot flash outcomes in midlife women.
A cross-sectional study of the first year of a prospective cohort of midlife women, the Midlife Women's Health Study (2006–2015), a convenience sample from an urban setting.
728 multi-racial/ethnic pre- and perimenopausal women aged 45–54 years.
Women completed questionnaires about hot flash experience and provided 1–4 urine samples over four consecutive weeks that were pooled for analysis. Phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates: ƩPhthalates; DEHP: ƩDEHP), exposure sources (plastics: ƩPlastic; personal care products: ƩPCP), and modes of action (anti-androgenic: ƩAA). Covariate-adjusted logistic regression models were used to assess associations of continuous natural log-transformed phthalate metabolite concentrations with hot flash outcomes. Analyses were conducted to explore whether associations differed by menopause status, body mass index (BMI), race/ethnicity, and depressive symptoms.
Overall, 45% of women reported a history of hot flashes. Compared to women who never experienced hot flashes, every two-fold increase in ƩPlastic was associated with 18% (OR: 1.18; 95%CI: 0.98, 1.43) and 38% (OR: 1.38; 95%CI: 1.11, 1.70) higher odds of experiencing hot flashes in the past 30 days and experiencing daily/weekly hot flashes, respectively. Some associations of phthalates with certain hot flash outcomes differed by menopause status, BMI, race/ethnicity, and depressive symptoms.
This study suggests that phthalates are associated with hot flash experience and may impact hot flash risk in women who are susceptible to experiencing hot flashes.
Association between body mass index and surgical menopausal symptoms in patients with early stage endometrial cancer
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Citation Excerpt :
Previously reported data is limited to patients undergoing natural menopause and those women without an underlying malignancy, but have suggested patients with a high BMI have significantly more vasomotor symptoms than women with a lower BMI [13]. An Australian study identified patients with BMI >35 have lower estradiol and estrone than those with BMI <25 [14]. Our study cohort is unique as compared to the women included in prior studies for three reasons.
Premenopausal women may undergo surgical menopause after staging for their endometrial cancer. Our aim was to determine the association between body mass index (BMI) and surgical menopausal symptoms.
We report a retrospective review of endometrial cancer patients whom underwent menopause secondary to their surgical staging procedure. Symptoms were classified as severe if treatment was prescribed, or mild if treatment was offered, but declined. Univariate analysis was performed with ANOVA and Chi-square tests as appropriate. Relative risks (RR) were generated from Poisson regression models.
We identified 166 patients in whom the BMI (kg/m²) distribution was as follows: 33 (19.9%) had BMI <30, 49 (29.5%) had BMI 30–39.9, 50 (30.1%) had BMI 40–49.9, and 34 (20.5%) had BMI ≥50. There were no differences in race, age, or adjuvant treatment among the groups. Overall, 65 (39.2%) women reported symptoms of surgical menopause, including 19 (11.4%) mild and 46 (27.7%) severe. Symptom type did not differ by BMI; however, the prevalence of severe menopausal symptoms decreased with increasing BMI: <30 (45.5%), 30–39.9 (30.6%), 40–49.9 (22%), and ≥ 50 (14.7%); P = 0.002. Multivariate analysis confirmed that symptom prevalence decreased with increasing BMI. Compared to women with a BMI of <30, those with a BMI 40–49.9 (RR = 0.39, 95% CI: 0.17–0.87) or ≥ 50 (RR = 0.24, 95% CI: 0.08–0.70) were significantly less likely to experience menopausal symptoms.
Women younger than 50 with BMI >40 and stage I endometrial cancer are significantly less likely than women with BMI <30 to experience menopausal symptoms after oophorectomy. This information may assist in peri-operative counseling.
Hormone variability and hot flash experience: Results from the midlife women's health study
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Hot flashes are believed to be related to hormonal changes. However, the relationship between hormonal fluctuations and hot flashes has not been studied. The objective of this study is to determine hormone measurement summaries that best explain the incidence of hot flashes in midlife women.
In a cohort study of 798 midlife women over 1–7 years, women provided 4 weekly blood samples annually and completed a survey detailing life history, ongoing behaviors, and menopausal symptoms. Estradiol, progesterone, and testosterone were measured in all serum samples. Annual summary variables of each hormone were median, mean, maximum, minimum, variance, and range. The association of these values with hot flashes was assessed using multivariable logistic regression and Bayesian network analysis, controlling for smoking history and menopausal status. Main outcome measures: Hot flash incidence, severity, and frequency.
For most outcomes, the best-fit model included progesterone variability; increased progesterone variance or range was correlated with decreased hot flash frequency (OR = 0.82, 95% CI = 0.74–0.91) and severity (OR = 0.82, 95% CI = 0.77-0.88). In the Bayesian network model, the maximum estradiol value was negatively correlated with many outcomes (OR for hot flashes = 0.68). Relationships between progesterone variability, maximum estradiol level, maximum progesterone level, and hot flashes indicate that the effects of progesterone variance on hot flash outcomes are likely mediated through progesterone’s relationship with maximum estradiol level.
Variability of progesterone, as opposed to mean values, should be used as an indicator of risk of hot flashes in midlife women.
Factors associated with poor sleep during menopause: results from the Midlife Women's Health Study
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Poor sleep is one of the most common problems reported during menopause, and is known to vary throughout the menopause transition. The objective of this study was to describe the dynamics of poor sleep among participants of the Midlife Women's Health Study and to identify risk factors associated with poor sleep during the menopausal transition.
Annual responses to surveys that included questions about the frequency of sleep disturbances and insomnia were analyzed to determine the likelihood of persistent poor sleep throughout the menopausal transition and the correlation of responses to the different sleep-related questions, including frequency of restless sleep during the first year of the study. Responses to questions about a large number of potential risk factors were used to identify risk factors for poor sleep.
Poor sleep in premenopause was not predictive of poor sleep in perimenopause, and poor sleep in perimenopause was not predictive of poor sleep in postmenopause. Frequencies of each of the measures of poor sleep were highly correlated. For all sleep outcomes, high frequency of depression was related to a high frequency of poor sleep. Vasomotor symptoms were also significantly related with a higher frequency of all poor sleep outcomes. A history of smoking was also associated with higher frequencies of insomnia and sleep disturbances.
The risk factors identified for poor sleep, depression and vasomotor symptoms, were consistently associated with poor sleep throughout the menopausal transition. The likelihood of these risk factors changed from premenopause, through perimenopause, and into postmenopause, however, which could explain changes in sleep difficulties across the menopausal transition. Treatment of these risk factors should be considered when addressing sleep difficulties in menopausal women.
Evaluating the prevalence and predictive factors of vasomotor and psychological symptoms in prostate cancer patients receiving hormonal therapy: Results from a single institution experience
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Citation Excerpt :
The greater peripheral conversion of androgens to oestrogen in adipose tissue [27], which can have protective effects on thermoregulation through modulation of the serotonin receptor suggest that those who are overweight should experience less flushes and is at odds to what was observed in this study. However, there may be several other explanations for a high BMI and hot flushes including a greater degree of insulation with adiposity which increases core body temperature [28,29] and recognition that other hormones produced by adipose tissue such as IL-8 may also be influencing thermoregulation [30]. This may in part account for the BMI not being predictive of hot flushes or sweating in our logistic regression analysis, although heavier patients were more likely to have grade 4 toxicity than experience no toxicity
The impact of vasomotor symptoms (VMS) occurring in prostate cancer (PC) patients whilst on androgen deprivation therapy (ADT) has not been extensively researched. This longitudinal study sought to assess the VMS and identify any predictive factors.
Data from 250 PC patients on ADT were prospectively evaluated between January 10 and August 13 using a physician-directed questionnaire, to assess the impact of VMS. Parameters including height, weight, body surface area (BSA), body mass index (BMI), duration/type of ADT, co-morbidities and ethnicity were recorded.
Fifty (20%) men reported no toxicity, whilst 171 (68.4%), and 29 (11.6%) reported mild to moderate and severe symptoms, respectively. Drenching sweats and hot flashes were common, and coexisted with sleep disturbances and fatigue. Patients with severe toxicity were younger (73 vs. 77 yrs; p = 0.04), had higher BMI (28 vs. 26; p = 0.02), and higher BSA (1.99 vs. 1.90; p = 0.04), when compared with those experiencing no toxicity. On multivariate analysis, younger age was predictive of sweats and hot flushes, whilst Afro-Caribbean men were twice as likely to experience sweats (OR 2.03, p = 0.05).
The short-term side-effect profile of ADT for prostate cancer was favourable, though debilitating VMS can occur in a significant minority of cases. Younger age and higher BMI predicted for severe toxicity but not the duration of ADT.

View all citing articles on Scopus

: This study was supported by NIH grant AG18400.

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General Obstetrics and Gynecology: GynecologyBody mass, estrogen levels, and hot flashes in midlife women

Objective

Study design

Results

Conclusion

Section snippets

Materials and methods

Variable definitions

Measurement of hormone levels

Statistical analyses

Results

Comment

Obstet Gynecol

Maturitas

Maturitas

Lancet

Am J Obstet Gynecol

Public Health

Eur J Obstet Gynecol Reprod Biol

Thermoregulatory physiology of menopausal hot flashes: a review

Can J Physiol Pharmacol

Risk factors for hot flashes in midlife women

J Womens Health

Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40-55 years of age

Am J Epidemiol

Differential association of modifiable health behaviors with hot flashes in perimenopausal and postmenopausal women

J Gen Intern Med

Hot flashes in the late reproductive years: risk factors for African American and Caucasian women

J Womens Health Gend Based Med

Psychosocial, behavioral, and health factors related to menopause symptomatology

Womens Health

General Obstetrics and Gynecology: Gynecology
Body mass, estrogen levels, and hot flashes in midlife women