Secondary Logo

Journal Logo


Is a reduction in brown adipose thermogenesis responsible for the change in core body temperature at menopause?

Aldiss, Peter; Budge, Helen; Symonds, Michael E.

Author Information
doi: 10.1097/XCE.0000000000000089
  • Free

Following menopause, women are at a greater risk of becoming obese and suffering from associated cardiometabolic diseases 1,2. The transition towards greater visceral adiposity and metabolic dysregulation after menopause is likely to be a consequence of changes in energy metabolism, primarily mediated by a reduction in circulating sex hormones such as estrogen or progesterone 1,2. In the current issue of cardiovascular endocrinology, Neff et al.3 describe that core body temperature is lower in women who have reached menopause, reaching temperatures similar to that of men. Their observation that the lower core body temperatures in those women who had reached menopause raises the possibility that this little studied factor could itself play a role in the increase in disease risk after this time 1,2, although whether the associated higher BMI and adiposity is an effect of age or the menopause per se cannot be determined from their study. Although the researchers acknowledge that the study was an exploratory post-hoc analysis of data synthesized from temporally distinct studies, it is worth further consideration, given current interest in brown adipose tissue (BAT) as a therapeutic target to combat cardiometabolic diseases 4. BAT is a thermogenic organ located mainly in the supraclavicular regions and in much smaller amounts 5 in other locations such as surrounding the kidneys and heart. Most abundant at birth 6, BAT is responsible for nonshivering thermogenesis and the maintenance of thermal homeostasis. This is achieved through the uncoupling of oxidative metabolism from ATP production through mitochondrial uncoupling protein 1, which dissipates chemical energy as heat 7. We now know that a majority of adults retain metabolically active BAT into adulthood 8, in declining amounts with age, and that sex hormones such as estrogen are likely to play a key role in the development of brown adipocytes and their function 9,10. Preclinical research has long demonstrated that exogenous sex hormones play a key role in the metabolic activity of BAT, and more recently it has been shown that cerebroventricular estradiol administration stimulates BAT function, increasing core body and BAT temperatures 11–13.

Another feature of the study by Neff and colleagues is the large variation in body temperatures within women irrespective of age, and this appears to be most marked in the group described as postmenopausal. Although the authors do not define how many of the so-called postmenopausal women in the study were still experiencing hot flushes, a stage already known to be associated with lower body temperature, 14,15 and a truly age-matched group of men is omitted, their observations fit with studies showing that women are more sensitive to cold compared with men 8,16. This is likely to be a primary factor contributing to their higher incidence of BAT 17. Moreover, a recent small study in premenopausal women demonstrated a potentially important relationship between salivary cortisol and basal temperature of BAT within the neck 18. A combination of differences in the hypothalamic–pituitary–adrenal axis, BAT abundance, stress and thermal sensitivity could explain the large variation in body temperatures of healthy women. These relationships may shift after menopause as BAT activity declines.

However, whether a decline in BAT after menopause occurs in humans and, therefore, contributes to greater BMI and fat mass remains to be determined. Given the role of BAT in metabolic homeostasis 19,20 and the recent associations between BAT activity and cardiovascular events 21, investigation of changes in BAT around the menopause and any effects of hormone replacement therapy are warranted. Maintenance of active BAT after the menopause has potential to attenuate the development of adiposity. Future investigations would require well-matched groups as differences in age, body mass and seasonality can all have a significant impact on BAT functionality as highlighted by the authors. Future studies should use additional methods as core body temperature measurements to determine thermal homeostasis and should include supraclavicular skin temperature 22–25 and thermal imaging 22,25 to assess BAT function (Fig. 1).

Fig. 1
Fig. 1:
Overview of phenotypic differences between premenopausal/postmenopausal women and possible mechanisms involved. Histological image adapted from Ravussin and Galgani 26.


Conflicts of interest

There are no conflicts of interest.


1. Rosano GM, Vitale C, Marazzi G, Volterrani M. Menopause and cardiovascular disease: the evidence. Climacteric 2007; 10 (Suppl 1):19–24.
2. Carr MC. The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab 2003; 88:2404–2411.
3. Neff LM, Hoffmann ME, Zeiss DM, Lowry K, Edwards M, Rodriguez SM, et al. Core body temperature is lower in postmenopausal women than premenopausal women: potential implications for energy metabolism and midlife weight gain. Cardiovasc Endocrinol 2016; 5:154–157.
4. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med 2013; 19:1252–1263.
5. Sacks H, Symonds ME. Anatomical locations of human brown adipose tissue: functional relevance and implications in obesity and type 2 diabetes. Diabetes 2013; 62:1783–1790.
6. Symonds ME, Pope M, Budge H. The ontogeny of brown adipose tissue. Annu Rev Nutr 2015; 35:295–320.
7. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84:277–359.
8. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009; 360:1509–1517.
9. Velickovic K, Cvoro A, Srdic B, Stokic E, Markelic M, Golic I, et al. Expression and subcellular localization of estrogen receptors α and β in human fetal brown adipose tissue. J Clin Endocrinol Metab 2014; 99:151–159.
10. Bloor ID, Symonds ME. Sexual dimorphism in white and brown adipose tissue with obesity and inflammation. Horm Behav 2014; 66:95–103.
11. Kemnitz JW, Glick Z, Bray GA. Ovarian hormones influence brown adipose tissue. Pharmacol Biochem Behav 1983; 18:563–566.
12. Yoshioka K, Yoshida T, Wakabayashi Y, Nishioka H, Kondo M. Reduced brown adipose tissue thermogenesis of obese rats after ovariectomy. Endocrinol Jpn 1988; 35:537–543.
13. Martínez de Morentin PB, González-García I, Martins L, Lage R, Fernández-Mallo D, Martínez-Sánchez N, et al. Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metab 2014; 20:41–53.
14. Freedman RR, Subramanian M. Effects of symptomatic status and the menstrual cycle on hot flash-related thermoregulatory parameters. Menopause 2005; 12:156–159.
15. Freedman RR, Norton D, Woodward S, Cornélissen G. Core body temperature and circadian rhythm of hot flashes in menopausal women. J Clin Endocrinol Metab 1995; 80:2354–2358.
16. Au-Yong IT, Thorn N, Ganatra R, Perkins AC, Symonds ME. Brown adipose tissue and seasonal variation in humans. Diabetes 2009; 58:2583–2587.
17. Nedergaard J, Bengtsson T, Cannon B. Three years with adult human brown adipose tissue. Ann N Y Acad Sci 2010; 1212:E20–E36.
18. Robinson LJ, Law JM, Symonds ME, Budge H. Brown adipose tissue activation as measured by infrared thermography by mild anticipatory psychological stress in lean healthy females. Exp Physiol 2016; 101:549–557.
19. Hanssen MJ, Hoeks J, Brans B, van der Lans AA, Schaart G, van den Driessche JJ, et al. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nat Med 2015; 21:863–865.
20. Van der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vosselman MJ, et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest 2013; 123:3395–3403.
21. Takx R, Ishai A, Truong QA, MacNabb MH, Scherrer-Crosbie M, Tawakol A. Supraclavicular brown adipose tissue FDG uptake and cardiovascular disease. J Nucl Med 2016. [Epub ahead of print].
22. Robinson L, Ojha S, Symonds ME, Budge H. Body mass index as a determinant of brown adipose tissue function in healthy children. J Pediatr 2014; 164:318.
23. Van der Lans AA, Vosselman MJ, Hanssen MJ, Brans B, van Marken Lichtenbelt WD. Supraclavicular skin temperature and BAT activity in lean healthy adults. J Physiol Sci 2016; 66:77–83.
24. Boon MR, Bakker LE, van der Linden RA, Pereira Arias-Bouda L, Smit F, Verberne HJ, et al. Supraclavicular skin temperature as a measure of 18F-FDG uptake by BAT in human subjects. PLoS One 2014; 9:e98822.
25. Symonds ME, Henderson K, Elvidge L, Bosman C, Sharkey D, Perkins AC, Budge H. Thermal imaging to assess age-related changes of skin temperature within the supraclavicular region co-locating with brown adipose tissue in healthy children. J Pediatr 2012; 161:892–898.
26. Ravussin E, Galgani JE. The implication of brown adipose tissue for humans. Annu Rev Nutr 2011; 31:33–47.
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.