Bibf iothèque nationale ffi@ffi Ï¡3ä".:u0.'.' du Canada Canadian Theses Service Service des thèses canadiennes Ottawa. C¿n¿da Kl A ON¿ The author has granted an ¡nevocable non- L'auteur a accordé une licence irrévocable et exclusive licence allowing the National Ubrary non exclusive permettant à la B¡bf@thèque of Canada to reproduce, loan, disbibute or sell nationale du Canada.de reproduire, prêter, cop¡es of his/her thesis by any means and in distribuer ou vendre des any form or copies de sa thèse format, making this thesis ava¡lable de quelque manière to interested persons. et sous quelque forme que ce soit pour mettre des exemdaires de cette thèse à la disposition des personnes intéressées. The author retains ownership of the copyright L auteur conserve la propriété du in his/her thesis. Neither the thesis droit d'auteur nor quiprotège sa thèse. Nila thèse nides extraits substantial extracts from it may be printed or substantiels otherwise reproduced de celte-ci ne doivent être without his/her per- imprimés ou autrement mission- reproduits sans son autorisation. I SBN rr-315-718Ø5*É Canadä SEX HORMONE LEVELS AND REGIONAL ADIPOSITY IN FEMALE SMOKERS by MARKDANIEL B.Sc., Simon Fraser University, 1989 A Thesis Submitted to The Faculty of Graduate Studies In Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE Sport & Exercise Sciences Resea¡ch Institute University of Manitoba Winnipeg, Manitoba @ by Mark Daniel 1990. Str HORMONE LEVELS .AND REGTONAT, A-D]POSTTY IN FTXVfAIE SMOKERS BY MA-RK DAN]EL A thesis subnrined to tlrc Faculty of Craduate Studies of the University of Marritoba in part¡al fulfìltment of the requirenrents of the degree of MASTER OF SC]ENCE @ 1990 Permission has been granred ro the LIBRARY OF THE UNIVER- S¡TY OF MANITOBA to lend or selt copies of rhjs thesis. to the NATIONAL LIBRARY OF CANADA ro ¡nicrofitm this thesis and to lend or sell copies oi the film, and UNIVERSITY MICROFILMS to publish an absrract of rhis thesis. The author reserves other publication rights, and neither thc thesis nor extensive extracts from it may be pnnteC or other- wise reproduced without the author's written permission. lil AtsST'R,&CT The distribution of the adipose tissue mass is a better predictor of heatth risk than overall adiposity. Sex steroids are involved in determining and regulating the distribution of adipose tissue. Androgenic profiles relate to android (aMominat) adiposity, esn'ogenic profiles to gynoid (gluæal-femorat) adiposity. Women of repnrductive viability tend to be gynoid, while men tend to be android; android adiposity represenrs much greater health risk than gynoid adiposity. Limited evidence suggests increased androgenic relative to estrogenic activity in female cigarette smokers, and smokers of either sex are characænzed, by greater degrees of android adiposity than nonsmokers. There is, however, no known mechanism for an effect of smoking on the distribution of body fat. It was hypothesized that cigarette smoking might interact with androgeny'esrogen levels and adipose tissue distribution in reproductively capable women, thus providing some rationale for an association with and¡oid adiposity. Relationships benveen indices of regional adiposity -- waist-to-hip grrth ratio (WHR), waist-to-thigh girth ratio (WTR) and waist girth-to-hip breadth ratio (lMHbR) -- and serum concenÍations of testosterone, estradiol and sex hormone-binding globulin (SHBG) were studied n27 premenopausal smokers and,29 premenopausa-l nonsmokers. All va¡iables were adjusted for overall fatness. Smokers were characteizrd,by significantly greater degrees of android adiposiry (elevated 'WHR, WTR and WHbR) and greater serum concentrations of SHBG than nonsmokers. There were no significant differences betrveen groups for testosterone or esradiol levels, although testosterone w¿ìs relatively greater in the snrokers, and estradiol relatively lower. There were significant interactions benveen smoking, testosterone levels and both WHR and V/TR; the relative effect of testosterone on android adiposity was greater in smokers. The data conf,rm (a) the association of smoking with aMominally localized body fat and (b) an ea¡lier observation of elevated serum SHBG in premenopausal smokers (which has not been adequately studied), contrary to directional differences in testosterone and estradiol. The data demonstrate, for the first time, an interactive effect of cigarette smoking with serum testosterone levels and regional adiposity. Such a frnding is of biologicat significance in that smoking appears to predispose premenopausal women toward a more masculine distribution of bdy fat, one which is clearly linked to health risk, via effects on sex steroids. iv ÐEDNC^AT'TON This work is dedicated to Donna for her love, patience and understanding. Read not to contradict and confute, nor to believe and take for granted, nor to find talk and discourse, but to weígh and constder. - Francis Bacon ACKNTWI,EÐGEMENT'S Many people contributed toward this study. First and foremost, I wish to thank my advisor, Dr. Alan D. Martin, for his enthusiasn¡ faith and support throughout the entire project. He inspired nre to grcÀter levels of achievenrcnt and taught rne more than words can convey. Special thanks are due also to the other members of my supervisory committee: Dr. Donald T. Drinkwater and Dr. Charles Faiman; their guidance and unique contributions ¿ìre much appreciated. Benefits of my exposure to such combined wisdom (and wit) will hopefully last a lifetime. The technical assistance of Registered Technologists of Nuclear Medicine Gina Devos and Karen Taraschuk is gratefully acknowledged along with the cooperation of the Departrnent of Nuclear Medicine at St. Boniface General Hospital. Appreciation is also expressed to the St. Boniface General Hospital Research Interest Group for their support and cooperation. I am indebted to Mr. Derek Grant of the Endocrinology and Metabolism l-aboratory at the Health Sciences Centre for technical help and advice regarding hormone assays, and the contributions of l,aboratory Technicians Wayne Atkinson and Beatrice Bourgeois are acknowledged with gratitude. Permission to reproduce certain figures is gratefully acknowledged from the following authors and publishers: George A. Bray, M.D.; I-eif Lapidus, M.D.; Hans Th. 'Waaler, M.D.; Acta Medica Scandinavica (Journal of Internal Medicine), British Medical Journal and Yeil Book Medical Publishers. Last, but not least, I wish to express my appreciation to all panicipants of this study for their interest, enthusiasm and cooperation. vl T'AtsN,E TF'' CONTENT'S Page Abstract.. ......... üi Dedication ........ iv Acknowledgerrì€nts ........... v List of Figures ....... .... ...... x List of Tables .... .... .. xi List of Abbreviations......... .................xü Chapter 1. INTRODUCTION . .... 1 Obesity, Adipose Tissue Distribution and Associated Healrh Risks. .... .. I Health Implications of Obesity.... ....... 1 He¿lth Implications of Regional Adiposity .......4 Pathogenesis of Complications Associated with Regional Adiposity ..........5 Assessment of Regional Adiposity .....1 Methods ........ ... 7 Considerations... .. ..... 8 Weight Change ..... 9 Physical Activiry. ..........9 Parity. .... ...... 9 Oral Contraceptives ........10 Alcohol Consumption.......... ..................10 The Premenopausal Woman: A Speciat Case. ....1 I Assessment of Relative AndrogenicÆstrogenic Activity . ...12 Methds .......I2 Considerations.... ...........12 Physical Activity... ................12 Parity. ......14 Oral Contraceptives .. ......14 Alcohol Consumption.......... ..................14 Effects of Smoking.. ........"...."....15 Summary and Conclusion.. .......16 StatementoftheProblem. .....16 vii Importance and Relevance ...........16 Delimitations and Limitations . .. .. 18 Hypothesis ........19 Definition of Terms ....19 Assumptions ... ..... .....2L 2. REVIEW OF LITERATURE .....23 Section I: Sex Horrnones and Adipose Tissue Distribution ... .. ......24 Sex- and Age- Dependent Differences in Regional Adiposity .......24 Infancy and Childhod .. ..........24 Puberty .......26 Menopause .. ... .. ..28 Female Sex Hormones ......29 Physiology ......29 Chitdhood and Puberry .....32 Menopause ......33 Sex Hormone-Binding Globulin ........37 Sex Hormones in Relation to Regional Adiposity. ..38 Menarche ... ...38 Adipogenesis... .....40 RelativeAndrogenicÆstrogenicBalance .......43 Obesity. ......45 Regional Characteristics of Adipocytes. ... ..47 Regional Differences in Adipocyte Metabolism..............49 Lipolysis .....49 Lipogenesis..... ....51 Reprductive Status and Metabolism .. .... ... ..53 Summary .......55 Section II: Smoking, Sex Hormones and Regionat Adþsity...............56 Relationship of Smoking to Sex Hormone Balance. .... .. ....56 Women .......56 AntiestrogenicEffectMechanisms...... ........58 Men. ......59 Relationship of Smoking to Regional Adiposity......................60 Other Hormonal Effects of Smoking: Implications for Fat Distribution........... .....61 vt11 Endogenous Opiates and Prolactin .. ....62 Cortisol ... .....63 Summary ........65 Conclusion . .....65 J. METHODS AND PROCEDURES......... ............67 S ubj ects.. ...........67 Recruiûnent....... .....67 Selection. .......67 Exprirnental Design . .... .. ..69 Procedures ... .....70 Sex Hormone Profiles . ... ..70 Blood Samples.. ...............70 AnatyticalMethdology.... ........71 lnstrumentation... .........73 Anthropometric Measurernents ......73 Ginhs and Hip Breadth.. Skinfolds