ORIGINAL ARTICLE Body fat distribution in relation to smoking and exogenous hormones in British women See Kwok*, Dexter Canoy† , ‡, Handrean Soran§, David W. Ashton–, Gordon D. O. Lowe**, David Wood–, Stephen E. Humphries†† and Paul N. Durrington* *School of Biomedicine, Core Technology Facility, †School of Community-Based Medicine, University of Manchester, Manchester, ‡Cancer Epidemiology Unit, University of Oxford, Oxford, §Manchester Royal Infirmary, Manchester, –National Heart & Lung Institute Faculty of Medicine, Imperial College of Science Technology & Medicine, Charing Cross Hospital Cardiology Department, London, **University of Glasgow, Department of Medicine, Glasgow Infirmary, Glasgow and ††Centre for Cardiovascular Genetics, Royal Free & University College Medical School, London, UK Summary Objective Both cigarette smoking and use of exogenous hor- mones are associated with changes in regional distribution of body fat, but their combined effects are less investigated. We examined the interrelation between smoking, exogenous hormones and fat distribution in premenopausal and postmenopausal women. Method We used data from 20 962 women without known car- diovascular disease (CVD) who were employees of a major depart- ment store in Britain. They completed a health questionnaire and attended a clinical examination that included waist and hip circumference measurements. The cross-sectional analyses were conducted using linear regression models. Results Cigarette smoking, particularly smoking ‡20 cigarettes/ day, was associated with larger waist circumference and higher waist/hip ratio (WHR) in pre- and postmenopausal women after adjusting for potential confounding factors (all P <0Æ001). Pre- menopausal women using combined oral contraceptive (COC) and postmenopausal women using oestrogen-only hormone replacement therapy (HRT) had lower WHR than non-hormone users in both smokers and nonsmokers. However, smokers had higher WHR than nonsmokers in both groups of hormone users and nonusers. There was no significant interaction between smok- ing and hormone use in premenopausal and postmenopausal women (P >0Æ05). Conclusion Although exogenous hormones use was related to a more favourable fat distribution in women, smoking was associ- ated with greater abdominal fat accumulation. (Received 21 Nov 2011; returned for revision 5 December 2011; finally revised 21 December 2011; accepted 21 December 2011) Introduction Fat stored in the viscera has been considered to be more metaboli- cally active than those stored subcutaneously. 1 Excess visceral fat is closely associated with dyslipidaemia and insulin resistance and is a major determinant of metabolic syndrome, 2 which could increase the risk for cardiovascular disease. 3 Thus, body fat distribution could be an important indicator of metabolic health. However, fac- tors that influence body fat distribution require greater clarifica- tion. Genetic influences are likely to play a role, 4 but sex hormones may also play a role as fat distribution is known to differ between the sexes. 5 Men tend to accumulate fat centrally (android obesity), whereas premenopausal women more often accumulate fat in the gluteofemoral region (gynaecoid obesity), which is mainly stored subcutaneously. Postmenopausal women tend to follow the male android pattern of fat distribution, even without significant change in body weight, 6 presumably because of reduction in oestrogen and increase in androgen levels. 7 Indeed, there has been some evidence that menopause-related phenotype of android fat distribution may be prevented with hormone replacement therapy (HRT). 8 Body fat distribution could be an important determinant of cardiovascular health in women. Cardiovascular disease rates are low in premeno- pausal women, but this apparent advantage in women may be partly negated by excess abdominal adiposity and its associated metabolic risks after the menopause. 9,10 Cigarette smoking has been associated with increased abdominal (or central) fat distribu- tion in men and women. 11–14 Although the exact mechanism is unclear, the effect of smoking on body fat patterns could be medi- ated by sex hormones and smoking could have an androgenic effect in women. 15–18 Although various studies have investigated associa- tions between smoking and body fat distribution, these studies have not taken into account menopausal status or use of exogenous hormones among women. 11–14 Moreover, little is known about the influence of smoking on body fat distribution among premenopau- sal women. Exogenous oestrogen and progestogen are likely to have different relationship with fat distribution, but their effects have not been considered separately before; neither has possible different interaction of these hormones with smoking been studied Correspondence: Dr See Kwok, School of Biomedicine, Core Technology Facility, 3rd Floor, 46, Grafton Street, Manchester M13 9NT, UK. Tel.: +44 161 276 4682; Fax: +44 161 276 4684; E-mail: see.kwok@manchester.ac.uk Clinical Endocrinology (2012) 77, 828–833 doi: 10.1111/j.1365-2265.2012.04331.x 828 Ó 2011 Blackwell Publishing Ltd