17 December, 2012:

Study data were drawn from the Study of Women Across the Nation (SWAN) database to address the question of whether or not weight gain preceded or followed the hormonal changes associated with the menopause transition [1]. The cohort consisted of 1528 women with a mean age of 46 years who had baseline measurements of waist circumference, body mass index (BMI), and serum follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), testosterone, and estradiol drawn at baseline and at 3, 6, and 9 years after entry. The outcome measure of weight gain or waist circumference versus hormone levels was assessed in the following manner. The dynamic sequential relationships between hormones and waist circumference were examined using structural equation modeling. Specifically, these equations examined the following three longitudinal relationships: (1) the association of current hormone values and waist circumference with their respective future values; (2) the associations of current waist circumference with future hormone values; and (3) the associations of current hormone values with future waist circumference. The results indicate that the changes in adiposity and waist circumference occur during and following the menopause transition. Current waist circumference predicted future decreases in FSH and SHBG and the increase in serum testosterone. Waist circumference predicted future estradiol levels, while current estradiol levels were associated with future weight gain. Both relationships were dependent upon the changing estradiol levels but the former result was greater than the latter [1].

Comment

The current publication uses the data from SWAN to determine whether changes in sex steroid hormones precede or follow weight gain in perimenopausal women. The SWAN investigators had previously reported that levels of estradiol, testosterone, FSH and SHBG were significantly correlated with BMI in the perimenopausal woman [2]. Ethnic differences that were found in these hormones were confounded by the differences in BMI between ethnic groups [2].

The results in the current paper indicate that the changes in adiposity and waist circumference occur during and following the menopause transition [1]. Baseline waist circumference predicted a decrease in FSH and SHBG and an increase in serum testosterone [1]. The data do not indicate that the changes in FSH, SHBG, or testosterone caused, altered or modified waist circumference. Reduced SHBG with increased testosterone has previously been observed in obese women [3]. Obesity-decreased SHBG and -increased androgenicity (increased serum testosterone) have been linked to the development of cardiovascular disease in women [3-6]. The occurrence of a lower serum FSH level in obese women has previously been reported [1], but the explanation for this finding is unknown at present. The current paper proposes that higher postmenopausal estradiol levels in obese women may be responsible for the lower FSH levels. Serum estradiol changes were not directly related to obesity but an overall weak association was found with the increase in waist circumference [1].

How often have we heard a woman state, ‘I am menopausal and have not changed what I eat but I have gained weight’? Our diet and eating behaviors probably contribute significantly to weight gain [7,8]. Marketing of food is based on studies of consumer behavior and their responses [8]. The consumption of sweetened cola has been shown to increase body weight in direct proportion to the number of genetically identified obesity factors [9]. Menopause has been associated with weight gain and changes in body fat distribution [4]. A Cochrane Review has concluded that ‘There is no evidence of an effect of unopposed estrogen or combined estrogen with progestogens on body weight and on the BMI increase normally experienced at the time of menopause. Insufficient evidence currently exists to enable examination of the effect of HRT on waist–hip ratio, fat mass or skin-fold thickness’ [10]. However, both cross-sectional and longitudinal studies have shown an increase in visceral adiposity [11]. A simple clinical method of determining visceral obesity is the waist circumference that measures both subcutaneous and visceral fat. Waist circumference and weight gain begin to increase before menopause, while lean body mass does not change during the menopause transition [1,5].

The perimenopause is associated with a rapid increase in fat mass and redistributions of fat to the abdomen [4,11]. Significant changes in visceral fat deposition have been found following the menopause in Caucasian, African American and Asian women [4]. Visceral fat is known to be metabolically active and contributes to the development of type 2 diabetes mellitus [5,11]. Estrogen has a complex interaction with adipose tissue and other metabolic changes in the body which appear to be involved in the development of cardiovascular disease in women [11].

The clinical implication is that weight gain begins during the menopausal transition and that diet and behaviors are significant contributors [1,5,12]. There appears to be an association with genetic markers of obesity and weight gain in women [9]. The contribution of weight gain and specifically visceral fat to the development of cardiovascular disease and insulin resistance (type 2 diabetes mellitus) is well known [5]. The clinical use of diet and counseling is not as effective in initiating and maintaining weight loss and we should be actively seeking better non-surgical approaches to this problem [13,14].

In conclusion, waist circumference is a valid marker for visceral adiposity. The current study provides the scientific information that weight gain precedes the changes in serum hormone levels. Other information implies that weight gain and visceral adiposity as assessed by waist circumference are a problem that requires counseling and active intervention to prevent other metabolic changes that can result in cardiovascular disease and diabetes mellitus. David F. Archer Professor of Obstetrics and Gynecology, Department of obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia, USA

References

1. 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 

2. Randolph JF Jr, Sowers M, Gold EB, et al. Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status. J Clin Endocrinol Metab 2003;88:1516-22.

http://www.ncbi.nlm.nih.gov/pubmed/12679432 

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http://www.ncbi.nlm.nih.gov/pubmed/11246820 

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http://www.ncbi.nlm.nih.gov/pubmed/22978257 

5. Lobo RA. Metabolic syndrome after menopause and the role of hormones. Maturitas 2008;60:10-18.

http://www.ncbi.nlm.nih.gov/pubmed/18407440 

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http://www.ncbi.nlm.nih.gov/pubmed/6700566 

7. Caprio S. Calories from soft drinks – do they matter? N Engl J Med 2012;367:1462-3.

http://www.ncbi.nlm.nih.gov/pubmed/22998341 

8. Cohen DA, Babey SH. Candy at the cash register – a risk factor for obesity and chronic disease. N Engl J Med 2012;367:1381-3.

http://www.ncbi.nlm.nih.gov/pubmed/23050524

9. Qi Q, Chu AY, Kang JH, et al. Sugar-sweetened beverages and genetic risk of obesity. N Engl J Med 2012;367:1387-96. http://www.ncbi.nlm.nih.gov/pubmed/22998338

10. Norman RJ, Flight IH, Rees MC. Oestrogen and progestogen hormone replacement therapy for peri-menopausal and post-menopausal women: weight and body fat distribution. Cochrane Database Syst Rev 2000:CD001018.

http://www.ncbi.nlm.nih.gov/pubmed/10796730 

11. Turgeon JL, Carr MC, Maki PM, Mendelsohn ME, Wise PM. Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: Insights from basic science and clinical studies. Endocr Rev 2006;27:575-605.

http://www.ncbi.nlm.nih.gov/pubmed/16763155 

12. Farley T, Just DR, Wansink B. Clinical decisions. Regulation of sugar-sweetened beverages. N Engl J Med 2012;367:1464-6.

http://www.ncbi.nlm.nih.gov/pubmed/22998342 

13. Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 2012;366:1577-85.

http://www.ncbi.nlm.nih.gov/pubmed/22449317 

14. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 2012;366:1567-76.

http://www.ncbi.nlm.nih.gov/pubmed/22449319 

Content updated 17 December 2012