13 May 2013

Menopause is associated with dramatic changes in a woman's hormonal and metabolic profile. Whereas menopause per se does not seem to affect body weight, the estrogen decline around menopause is associated with a body fat redistribution favoring an android pattern [1]. Furthermore, although incapable of producing estrogens, the postmenopausal ovary remains an active endocrine organ, contributing substantially to the circulating androgen pool [2]. Cao and colleagues [3] in their recent paper conducted a cross-sectional study in early (≤ 5 years) and late (≥ 10 years) postmenopausal women to investigate the association of these two parameters, namely body fat distribution and circulating serum androgens. Late postmenopausal women had a higher percentage of body fat, compared to their younger counterparts, although body mass index (BMI) did not differ between groups. Both early and late obese postmenopausal women had higher androgen levels and more abdominal fat compared to women with normal weight. Serum androgens (free testosterone in early and DHEAS in late postmenopausal women) showed an independent and significant positive association with abdominal adiposity.

Comment

The first important message of this paper is that body adiposity is not reflected by BMI as age increases. Although BMI was not different, the percentage of body fat was higher in older compared to younger postmenopausal women. This may imply that postmenopausal aging is associated either with an increase in fat mass or with a decrease in lean mass. The latter phenomenon, described as sarcopenia, is particularly prevalent in the elderly and is associated with considerable morbidity and mortality. Sarcopenia is the pathophysiological mechanism explaining the 'obesity paradox': elderly people with 'normal' BMI show higher mortality rates compared to overweight individuals of the same age, a finding that probably reflects the effect of low lean mass [4]. When assessing anthropometric parameters in aging postmenopausal women, therefore, BMI is not a reliable indicator of adiposity and body composition parameters should be used in taking intervention decisions.

The second crucial message of the study by Cao and colleagues [3] is that obesity in the postmenopausal woman is hormonally and metabolically more harmful, compared to the woman of reproductive age. Postmenopausal women, either younger or older, store excess fat in the abdominal region. Abdominal fat is a cardinal feature of the metabolic syndrome, a major contributor to cardiovascular mortality in postmenopausal women. Insulin resistance is the principal pathogenetic pathway, mediating the endocrine impact of abdominal obesity: the efflux of free fatty acids to the liver and the resulting high triglyceride levels decrease liver insulin sensitivity and muscle glucose uptake [5]. Elevated insulin levels, on the other hand, have a stimulating effect on postmenopausal ovarian androgen production, both directly and indirectly, by increasing luteinizing hormone (LH) receptors in the ovarian stroma, an effect amplified by the postmenopausal high levels of LH [2]. In a recent prospective analysis of 1500 perimenopausal women who were followed up for 9 years, it became evident that higher trunk fat resulted in future higher testosterone levels, indicating that the abdominal adiposity precedes the alterations in postmenopausal androgens [6].

High androgen levels in women may confer an independent cardiovascular risk, as indicated by experimental studies on the effect of testosterone on the vasculature and by clinical studies in women with androgen excess conditions like polycystic ovarian syndrome [6].

In conclusion, menopause has major cardiometabolic consequences, one of the principal being central fat accumulation. The accompanying insulin resistance, along with lean mass decrease due to inactivity and sex hormone decline, accelerates the aging process and increases cardiovascular risk. Intervention measures should primarily aim to preserve body lean mass, as this is the main way to increase insulin sensitivity and to ensure fitness in older age. As regular physical exercise predicts physical performance in later life [7], women should be encouraged to incorporate exercise in their daily routine as a natural and effective way to counterbalance the metabolic impact of menopause.

Irene Lambrinoudaki
Associate Professor of Gynecological Endocrinology, Medical School, University of Athens, Greece and Vice President of the European Menopause and Andropause Society

References

1. Davis SR, Castelo-Branco C, Chedraui P, et al. Understanding weight gain at menopause. Climacteric 2012;15:419-29.
http://www.ncbi.nlm.nih.gov/pubmed/22978257 
2. Androgen production and therapy in women, UpToDate
http://www.uptodate.com/contents/androgen-production-and-therapy-in-women?source=search_result&search=postmenopausal+androgens&selectedTitle=1~150 
3. Cao Y, Zhang S, Zou S, Xia X. The relationship between endogenous androgens and body fat distribution in early and late postmenopausal women. PLoS One 2013;8:e58448.
http://www.ncbi.nlm.nih.gov/pubmed/23484029 
4. Chang SH, Beason TS, Hunleth JM, et al. A systematic review of body fat distribution and mortality in older people. Maturitas 2012;72:175-91.
http://www.ncbi.nlm.nih.gov/pubmed/22595204 
5. Insulin action. UpToDate
http://www.uptodate.com/contents/insulin-action?source=search_result&search=abdominal+fat+metabolism&selectedTitle=27~150 
6. Wildman RP, Tepper PG, Crawford S, et al. Do changes in sex steroid hormones precede or follow increases in body weight during the menopause transition? Results from the Study of Women's Health Across the Nation. J Clin Endocrinol Metab 2012;97:E1695-704
http://www.ncbi.nlm.nih.gov/pubmed/22723312