Weight gain during the menopausal transition is a common symptom. Controversy exists as to whether perimenopausal weight gain is because of changes in energy metabolism related to aging or changes in sex hormones related to menopause. Many studies have suggested that aging is the primary driver of weight gain in perimenopausal women, rather than menopause per se 1–4. However, there is a reduction in resting energy expenditure at menopause that has been shown to be independent of changes in body composition 5. In a rodent model, this decreased energy expenditure occurs as a result of the surgical loss of ovarian function rather than aging 6. In premenopausal women, acute sex hormone suppression with GnRH antagonist therapy reduces resting energy expenditure below baseline follicular phase levels 7.
The mechanisms underlying changes in energy expenditure at menopause could include a reduction in core body temperature. Indeed, body temperature is an understudied variable linked to energy metabolism 8. It has been estimated that 40–80% of a typical mammal’s basal metabolic rate is spent in the cost of maintaining homeothermy 9. In addition, small decreases in body temperature coincide with large decreases in energy expenditure, as seen in previous studies of caloric restriction in humans 10,11. Therefore, a small decrease in core temperature with menopause could lead to significantly decreased energy expenditure and weight gain over time.
Body temperature has long been known to decline with extremes of age in men. However, recent data suggest that women may also experience a decrease in body temperature around the ages 40–60 12. The more abrupt decline in body temperature observed in women could be because of menopause. In contrast, the gradual decline in temperature that occurs in men could correlate with the more gradual sex hormone changes of andropause.
Previous studies have measured core body temperature in postmenopausal women. Using an ingested core temperature sensor (the CorTemp sensor; HQ Inc., Palmetto, Florida, USA), Freedman et al.13 found that core body temperature is significantly lower over 24 h and during sleep in postmenopausal women who experience hot flashes than in asymptomatic postmenopausal women. Freedman and Subramanian 14 assessed core temperature in premenopausal women and postmenopausal women with and without hot flashes using a rectal probe over two to four sessions lasting 5 h each. The mean rectal temperature was significantly lower in postmenopausal women with hot flashes than in asymptomatic postmenopausal and premenopausal women.
Our study is the first known study to assess 24-h core body temperature in premenopausal versus postmenopausal women using the ingested CorTemp sensor. We hypothesized that 24 h core temperature would be lower in postmenopausal women than in premenopausal women, which could have implications for energy metabolism in midlife.
Patients’ data were obtained from two separate but related studies of core temperature carried out by the same investigators using the same methods. The first study, carried out in 2009–2010, was designed to explore potential differences in core body temperature between lean (BMI: 18.5–24.9 kg/m2) and obese (BMI: 30.0–39.9 kg/m2) men and women aged 25–40 years 15. Patients were lean men (n=6), lean women (n=6), obese men (n=6), and obese women (n=6). All participants were weight stable, with no weight change of more than 2% for at least 2 months. The second study, carried out in 2011–2013, was primarily designed to examine changes in core body temperature with weight loss. This study included overweight and obese (BMI: 27–39.9 kg/m2) men (n=11) and postmenopausal women (n=13), aged 18–65 years. For this report, only baseline data were included. Participants were weight stable; they had no weight change of more than 2% in the 2 months before study enrollment and were within 3% of their maximal body weights. The sample size drawn from the combined studies was 23 men and 25 women, aged 23–64 years (Table 1). A wide range of ethnic backgrounds was represented.
Potential volunteers were excluded if they had a medical condition or took medications that might affect core temperature or the use of the CorTemp System (HQ Inc.). Premenopausal women had a history of regular menstrual cycles (25–30 days duration) and were admitted during days 1–7 of their menstrual cycle (follicular phase). Both studies were approved by Northwestern’s institutional review board.
Detailed procedures have been published previously 15. In brief, participants were admitted for a 24-h stay at the Northwestern Clinical Research Unit. Participants were asked to wear light clothing and a comfortable room-temperature (∼70°F) environment was maintained. At 9 a.m., each participant swallowed a pill-sized CorTemp sensor (HQ Inc.). The sensor passed through the participant’s gastrointestinal tract and sent a core temperature reading every minute to an external monitor worn at the waist. The monitor recorded the participants’ temperatures during standardized activities including rest, sleep, and meals. Participants also exercised on a stationary bicycle for 20 min, with a goal of achieving at least 10 consecutive minutes between a level of 5 (hard) and 7 (very hard) on the Rate of Perceived Exertion scale.
The Institute of Medicine predictive equations were utilized to estimate each participant’s total energy expenditure, which was provided in the form of three meals, each containing 15% protein, 35% fat, and 50% carbohydrate 16.
Body composition was measured using the QDR 4500 Acclaim Series Elite DEXA scan (Hologic, Bedford, Massachusetts, USA).
Outlier temperature data points because of incorrect signals from CorTemp monitors were excluded if they were greater than two SDs from the mean. Mean temperature and SD were calculated for each participant during four time intervals: exercise (20 min), during dinner (30 min), sleep (excluding the first and last half hour), and 24 h (excluding the first 4 h after the pill was swallowed to ensure passage into the small intestine). Data analyses were carried out using SPSS, version 22 (IBM Corp., Armonk, New York, USA). Means and SEM were calculated for participant characteristics (Table 1). Independent-samples t-tests were performed to assess for significant differences between study groups. Pearson’s correlations were utilized to explore relationships between continuous variables. Significance was considered at a P-value of less than 0.05.
The mean (±SEM) 24-h core body temperature was 0.25±0.06°C lower in postmenopausal women than in premenopausal women (P=0.001) (Fig. 1). The mean core temperature during sleep was 0.28±0.08°C lower in postmenopausal women than premenopausal women (P=0.002), and similar differences were found during dinner and exercise (both Ps<0.05) (Fig. 1). Similarly, the mean core body temperature was significantly lower at all timepoints (all Ps<0.05) among our postmenopausal women (mean BMI 34.8±1.1) than among the subset of obese premenopausal women (mean BMI 33.9±0.2). The mean 24 h core temperature was 0.34±0.05°C lower in men than premenopausal women (P<0.001), with similar differences found during sleep, dinner, and exercise (all Ps<0.01) (Fig. 1). The mean core temperature was not significantly different between postmenopausal women and men (Fig. 1). There was a significant correlation between age and 24-h core body temperature for women (r=0.615, P=0.001) (Fig. 2), but not men in our cohort of individuals younger than 65 years of age.
In this post-hoc analysis, we observed that postmenopausal women, like men, have lower core body temperatures than premenopausal women. Postmenopausal women were on average 0.25°C cooler, which is equivalent to a 3.25% reduction in energy expenditure, or 65 fewer kilocalories burned per day. For a typical postmenopausal woman, 50 years old, 150 lbs (68 kg) and 5 ft 4″ (162.5 cm) tall, this would lead to 6.7 lbs (3.04 kg) of weight gain in 1 year, assuming no metabolic adaptation to weight gain. However, it is well known that energy expenditure increases in response to weight gain; thus, the amount of weight accumulated over time may be more modest 17. If confirmed in future studies, however, our findings are likely to have important implications for cardiometabolic health. Relatively small weight gains of 5 kg or less in adulthood have been associated with an increased risk of type 2 diabetes, cardiovascular disease, and stroke in women as well as men 18–21.
Importantly, the differences in core temperature in this study cannot be attributed to differences in body composition nor size. The regulation of core body temperature is a function of the hypothalamic set-point and, as such, it is considered to be independent of body surface area, fat mass, and lean mass 22.
Our findings add to what has already been reported by Freedman and Subramanian 14, who found that postmenopausal women with hot flashes had significantly lower core temperatures than asymptomatic postmenopausal and premenopausal women. Notably, we did not assess for the presence of hot flashes in our participants.
Our study had several other limitations. We may not have observed a decline in core temperature with increasing age in men because our cohort included few men older than 50 years of age and none older than 65 years of age, when we would expect to see the greatest decreases in core temperature in men. Another limitation is that all the female participants aged 41 years and older were postmenopausal; thus, we could not differentiate the effects of age and menopausal status on core temperature. Finally, the season was not standardized in this study; all volunteers were studied in a research unit under thermoneutral conditions, however, to minimize any potential environmental effect on core body temperature.
Although exploratory in nature, our post-hoc analyses of two of our previous studies suggest that postmenopausal women have lower core body temperatures than premenopausal women and their temperatures are more similar to the temperatures of men. These preliminary observations may have implications for energy metabolism, perimenopausal weight gain, and cardiometabolic risk and thus merit further study.
The Joseph and Bessie Feinberg Foundation and David Kabiller, the project described was supported, in part, by the Northwestern University Clinical and Translational Science Institute, Grant Number UL1TR000150 from the National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, and by the National Center for Research Resources, Grant Number UL1RR025741. The content is solely the responsibility of the authors (LMN, MEH, LL) and does not necessarily represent the official views of the NIH. The Clinical and Translational Science Award (CTSA) is a registered trademark of the U.S. Department of Health and Human Services (DHHS).
Conflicts of interest
Dr Neff received unrelated research funding from GI Dynamics, performed unrelated consulting work for Eisai Inc. and received an honorarium for speaking on an unrelated topic for Pfizer India. For the remaining authors there are no conflicts of interest.
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Keywords:Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
menopause; metabolism; obesity; temperature; weight; women