CURRENT ALCOHOL USE IS ASSOCIATED WITH A REDUCED RISK OF HOT FLASHES IN MIDLIFE WOMEN

Transcription

1 Alcohol & Alcoholism Vol. 40, No. 6, pp , 2005 Advace Access publicatio 8 August 2005 doi: /alcalc/agh191 CURRENT ALCOHOL USE IS ASSOCIATED WITH A REDUCED RISK OF HOT FLASHES IN MIDLIFE WOMEN CHRISSY SCHILLING 1, LISA GALLICCHIO 2, SUSAN R. MILLER 3, JANICE K. BABUS 1, LYNN M. LEWIS 1, HOWARD ZACUR 3 ad JODI A. FLAWS 1 * 1 Departmet of Epidemiology ad Prevetive Medicie, Program i Toxicology, Uiversity of Marylad School of Medicie, 660 West Redwood Street, Howard Hall Room 133, Baltimore, MD 21201, USA, 2 Departmet of Epidemiology, Johs Hopkis Uiversity Bloomberg School of Public Health, Baltimore, MD 21205, USA ad 3 Departmet of Gyecology ad Obstetrics, Johs Hopkis Uiversity School of Medicie, Baltimore, MD 21205, USA (Received 15 Jue 2005; first review otified 1 July 2005; accepted i fial revised form 12 July 2005; advace access publicatio 8 August 2005) Abstract Aims: To examie the relatio betwee curret alcohol use, estradiol, estroe, ad testosteroe levels, ad hot flashes i midlife wome usig a case cotrol study desig. Methods: were midlife wome (45 54 years) who reported ever experiecig hot flashes. Cotrols were midlife wome (45 54 years) who reported ever experiecig hot flashes. Each participat completed a questioaire ad provided a blood sample that was used to measure estradiol, estroe, ad testosteroe levels by ezyme-liked immuosorbet assay. Results: The results idicate that curret alcohol use (at least oe day per moth) was sigificatly associated with a reduced risk of hot flashes compared to o-use of alcohol, idepedet of age ad smokig habits. The hot flashes experieced by curret alcohol users were less severe ad less frequet tha those experieced by o-users of alcohol. Further, curret alcohol users had similar levels of estradiol, estroe, ad testosteroe compared to o-users of alcohol. Coclusios: These data suggest that curret alcohol use is associated with a reduced risk of ay, severe, ad frequet hot flashes i midlife wome by a mechaism that may ot iclude chages i sex steroid hormoe levels. INTRODUCTION Hot flashes (or, i Britai, flushes ) are the most commo complait of wome trasitioig to meopause (Schwigl et al., 1994). Geerally, they are defied as a sudde feelig of heat i the face, eck, or upper part of the chest that is ofte accompaied by a reddeig or flushig of the ski ad followed by sweatig ad chills (Kroeberg ad Dowey, 1987). Hot flashes ca be mild to severe i duratio ad itesity. Some hot flashes ca be so severe or frequet that they egatively affect a woma s quality of life (e.g. sleep disturbaces, fatigue, irritability, sexual dysfuctio) (Kroeberg ad Dowey, 1987; Oldehave et al., 1993; Hollader et al., 2001). Despite the importace of hot flashes as a public health cocer, little is kow about their risk factors or precipitatig evets. Oe potetial risk factor for hot flashes may be cosumptio of alcohol, but the results from the few studies examiig the associatio betwee alcohol use ad hot flashes are equivocal. For example, i a study by Hyde Riley et al. (2004), cosumptio of 1 5 alcoholic driks per week was associated with a reduced risk of hot flashes i perimeopausal wome. Coversely, Schwigl et al. (1994) showed that ever havig cosumed alcohol was associated with a icreased risk of hot flashes i a study of postmeopausal wome, though the associatio was ot sigificat i the fial multivariate model. These differeces i study results are probably due to differeces i the sample sizes, the populatios studied, ad the meopausal status of the subjects. Therefore, oe purpose of this study was to examie the relatio betwee alcohol use ad hot flashes i more detail usig a large sample size of midlife wome who provided detailed meopausal status iformatio. Although o previous studies have examied the mechaism by which alcohol use is associated with risk of hot flashes, *Author to whom correspodece should be addressed at: Tel.: ; Fax: ; jflaws@epi.umarylad.edu it is possible that the mechaism ivolves a ability of alcohol to alter edogeous sex steroid hormoe levels. Alcohol cosumptio has bee associated with icreased levels of estradiol (Gavaler ad Va Thiel, 1992; Gill, 2000; Olad- Moret et al., 2005), estroe (Gill, 2000; Olad-Moret et al., 2005), ad testosteroe (Garcia-Closas et al., 2002) i wome. Similarly, altered levels of these sex steroids have bee associated with the risk of hot flashes (Erlik et al., 1982). Therefore, the secod purpose of this study was to test the hypothesis that alcohol use is associated with hot flashes through a mechaism that icludes altered sex steroid hormoe levels. MATERIALS AND METHODS Study populatio ad study desig The Mid-Life Health Study is a case cotrol study of hot flashes amog midlife wome, aged years, coducted durig amog residets of the Baltimore metropolita regio. All participats i this study gave writte iformed coset accordig to procedures approved by the Uiversity of Marylad School of Medicie ad Johs Hopkis Uiversity Istitutioal Review Boards. Names ad addresses of wome i the selected age rage residig i Marylad were obtaied from AccuData America (Fort Meyers, FL). The compay compiles ames ad addresses usig public sources, amely the Departmet of Motor Vehicles ad voter registratio lists. Recruitmet letters requestig participats for a research study o the health of wome aged years were mailed to all ames o this list. Mailigs were iitially set to zip codes located earest to the cliic ad the i cocetric circles out from the site util the target umber of erollees was reached. Wome who received the mailig ad were iterested i participatig i the study were ivited to call the cliic to obtai more iformatio. Dowloaded from at Pesylvaia State Uiversity o February 27, Ó The Author Published by Oxford Uiversity Press o behalf of the Medical Coucil o Alcohol. All rights reserved

2 564 C. SCHILLING et al. Durig the iitial call, the cliic staff determied whether the potetial participat met the eligibility criteria. Wome were eligible for study participatio if they were betwee 45 ad 54 years of age ad had itact ovaries ad uterus. To esure that wome erolled i the study were ot postmeopausal, wome were eligible oly if they reported havig at least three mestrual periods i the last 12 moths. Wome were excluded if they were pregat, were takig hormoe replacemet therapy (HRT) or hormoal cotraceptio, or had a history of cacer of the reproductive orgas. If the cliic staff determied that the potetial participat met the eligibility criteria, a cliic visit was scheduled. Data collectio Cliic visits were scheduled i the morig (8:30 10:00 a.m.) ad the wome were istructed to fast overight prior to the visit. At the cliic visit, the participat was seated i a private comfortable room ad asked to complete the study survey. The 26-page, sigle-sided survey took mi to complete ad icluded a detailed hot flash history. Specifically, iformatio was collected o the followig: whether the woma had ever experieced hot flashes, whether the woma had a hot flash i the last 30 days, the umber of hot flashes experieced withi the past 30 days, the severity ad frequecy of hot flashes, ad the legth of time each woma had experieced hot flashes. I terms of severity, each woma was asked to describe her hot flashes as: mild (sesatio of heat without sweatig), moderate (sesatio of heat with sweatig), or severe (sesatio of heat with sweatig that disrupts usual activity). I terms of frequecy of hot flashes, each woma was asked to describe her hot flashes as occurrig: every hour, every 2 5 h, every 6 11 h, every h, 1 2 days per week, 3 4 days per week, 5 6 days per week, 2 3 days per moth, 1 day per moth, <1 day per moth, or ever. Each woma was also asked to describe the duratio of her hot flashes as occurrig for: <1 moth, 1 5 moths, 6 11 moths, 1 2 years, 3 4 years, or 5 years or loger. I terms of alcohol use, each woma was asked if she had at least 12 alcoholic beverages i her etire life, at least 12 alcoholic beverages i ay 1 year, ad at least 12 alcoholic beverages i the previous 12 moths. The wome were also asked to thik about a typical moth durig the previous 12 moths ad idicate o how may days they drak alcoholic beverages ad the average umber of driks cosumed o those days. The use of this set of stadard quatity-frequecy questios allows compariso of this study to other studies by ivestigators ad also to atioal surveys (Dawso, 2003; Graham et al., 2004). Based o resposes to the questios, ever drikers were defied as those wome who had ot cosumed at least 12 alcoholic beverages i their etire life. Former drikers were defied as those wome who had at least 12 alcoholic beverages i ay 1 year, but ot i the past 12 moths. Curret drikers were defied as those wome who had cosumed at least 12 alcoholic beverages i the previous 12 moths. Oly 19 cases ad 13 cotrols were categorized as ever drikers; therefore i some aalyses, the ever drikers were combied with the former drikers. Participats were also asked questios regardig demographic iformatio, reproductive history, mestrual cycle characteristics, hormoal cotraceptive use, meopausal symptoms, HRT use, medical ad family history, ad health behaviours (smokig, vitami use, ad eatig habits). Wome were cosidered premeopausal if they reported experiecig their last mestrual period i the previous 3 moths ad 11 or more periods withi the previous year. Wome were cosidered perimeopausal if they reported their last mestrual period was withi the previous year, but ot withi the previous 3 moths, or their last mestrual period was withi the previous 3 moths, but they experieced 10 or fewer periods i the previous year. After each woma completed the survey, the cliic staff reviewed the survey for completeess. Case cotrol status was assiged usig the participat s aswer to the questio Have you ever had hot flashes? Participats who aswered yes to this questio were classified as cases ad those who aswered o were classified as cotrols. Hormoe assays I additio to the participat completig the questioaire at the cliic visit, a blood sample was take ad stored at 20 C util assays were coducted to measure serum hormoe levels. Blood samples were obtaied from wome i all phases of the mestrual cycle. Iformatio from the questioaire regardig date of last mestrual period was used i the statistical aalyses to adjust for the cycle phase amog the premeopausal wome ad time sice last mestrual period amog the perimeopausal wome. Serum cocetratios of estradiol, estroe, ad testosteroe were measured usig ezymeliked immuosorbet assays (ELISA). The ELISA kits for the estradiol ad testosteroe assays were obtaied from Diagostic Systems Laboratories, Ic. (Webster, TX). The ELISA kits for the estroe assay were obtaied from America Laboratory Products Compay (Widham, NH). The assays were ru usig the maufacturers istructios ad published methods (Gallicchio et al., 2005a, b). All assays were coducted i the same laboratory by a sigle techicia. All samples were ru i duplicate ad mea values for each participat were used i the aalysis. The laboratory persoel were blid with respect to ay iformatio cocerig study subjects. For quality cotrol purposes, samples from both cases ad cotrols were ru withi the same laboratory batches. I additio, two positive cotrols cotaiig kow amouts of estradiol, estroe, or testosteroe were icluded i each batch. Further, some samples were ru i multiple assays to esure that the assay values did ot dramatically shift over time. The miimum detectio limits for the estradiol, estroe, ad testosteroe assays were 7 pg/ml, 10 pg/ml, ad 0.4 g/ml respectively. No samples were below the limit of detectio. For the assays, the average itra-assay co-efficiet of variatio was 3.3 ± 0.17% for estradiol, 4.8 ± 0.25% for estroe, ad 2.2 ± 0.56% for testosteroe. The average iter-assay coefficiet of variatio for all assays was <5%. At the completio of the study, 372 cases ad 267 cotrols were erolled. For this aalysis, 10 cases (1 missig estradiol levels, 9 missig time sice last mestrual period) ad 3 cotrols (1 missig time sice last mestrual period, 2 missig alcohol data) were excluded, leavig 362 cases ad 264 cotrols for the aalyses. Statistical aalyses Characteristics of cases ad cotrols were compared usig chi-square aalyses. Risk ratios (RR) ad 95% cofidece itervals (CI) were calculated usig methods described Dowloaded from at Pesylvaia State Uiversity o February 27, 2014

3 ALCOHOL USE AND HOT FLASHES 565 by Greelad (2004) to assess the associatio betwee alcohol itake ad the occurrece, severity, ad frequecy of hot flashes, cotrollig for cofouders. Factors were cosidered potetial cofouders if they were associated (P < 0.1) with alcohol ad/or hot flash status. To determie whether each potetial cofouder would remai i the fial models, the uadjusted RR for curret alcohol itake ad experiecig ay hot flashes was compared to the RR for curret alcohol itake ad experiecig ay hot flashes adjusted for the potetial cofouder. If the RR for curret alcohol use ad experiecig of ay hot flashes chaged by >5% with the iclusio of the potetial cofouder, the potetial cofouder was retaied i the fial models. Variables tested as potetial cofouders were: race, body mass idex (BMI), prior HRT use, ad smokig status. Oly the smokig status variable remaied i the fial cofouder-adjusted models. All regressio aalyses were also adjusted for participat age. The associatios betwee curret alcohol use ad plasma hormoe levels adjusted for age, race, smokig status, BMI, ad mestrual cycle phase (for premeopausal wome oly) were assessed usig geeralized liear models (PROC GLM i SAS). For these ad all of the aalyses, the estradiol, estroe, ad testosteroe variables were log-trasformed because oe were ormally distributed. All aalyses were stratified by meopausal status; however, the regressio results for wome categorized as pre- ad perimeopausal did ot materially differ whe compared to each other ad to the results for the etire sample. Therefore, oly the aalyses for the etire sample are show. All aalyses were performed usig SAS Versio 8.2 (Cary, NC). A P-value of <0.05 was cosidered to be statistically sigificat. RESULTS Table 1 presets the characteristics of cases ad cotrols i the study populatio. were sigificatly older ad more likely to be of black race tha cotrols. were also more likely to smoke at the time of erollmet ad to be overweight (BMI > 30.0 kg/m 2 ) compared to cotrols. The associatio betwee curret alcohol use ad the occurrece of ay hot flashes is show i Table 2. I the cofouder-adjusted aalyses, curret alcohol use was associated with a statistically sigificat reduced risk of experiecig ay hot flashes (RR: 0.80, 95% CI: ) compared to o-use of alcohol. Moreover, alcohol cosumptio o 1 3 days per moth was associated with a statistically sigificat reduced risk of ay hot flashes compared to ouse of alcohol (RR: 0.77, 95% CI: ), as was cosumig alcohol 4 or more days per moth (RR: 0.83, 95% CI: ). The RR for experiecig ay hot flashes amog wome who cosumed 1 2 driks per sittig i the past moth was 0.81 (95% CI: ), while the RR for wome cosumig 3 or more driks per sittig i the past moth was 0.76 (95% CI: ). The associatio betwee curret alcohol use ad severity of hot flashes is depicted i Table 3. The cofouder-adjusted aalyses of alcohol cosumptio o 1 3 days per moth was associated with a statistically sigificat reduced risk of moderate or severe hot flashes compared to o-use of alcohol Table 1. Characteristics of cases ad cotrols, Baltimore, MD, Cotrols Variable (%) (%) P-value a Sample size Participat characteristics Age (years) Race White Black Other Marital status Sigle Married Widowed Divorced/separated Educatio <College Some college College graduate Graduate school Aual household icome <$ $ $ $ $ >$ Parity Nulliparous Multiparous Prior HRT use Yes No Smokig status Curret Former Never Body Mass Idex (kg/m 2 ) < > Due to missig iformatio, some colum percetages do ot add up to 100. a P-values reflect chi-square comparisos for categorical variables. Table 2. Associatio of curret alcohol use ad hot flashes ( = 362) Cotrols ( = 264) Uadjusted Ay hot flashes Adjusted a Curret alcohol user No Referece 1.00 Referece Yes ( ) 0.80 ( ) Number of days cosumed alcohol i past moth Noe Referece 1.00 Referece ( ) 0.77 ( ) > ( ) 0.83 ( ) Number of driks per sittig Noe Referece 1.00 Referece ( ) 0.81 ( ) > ( ) 0.76 ( ) a Adjusted for age ad smokig status. Dowloaded from at Pesylvaia State Uiversity o February 27, 2014

4 566 C. SCHILLING et al. Table 3. Associatio of curret alcohol use ad severity of hot flashes ( = 228) Table 4. Associatio of curret alcohol use ad frequecy of hot flashes ( = 81) Cotrols ( = 264) Cotrols ( = 264) Uadjusted Daily hot flashes Adjusted a Curret alcohol user No Referece 1.00 Referece Yes (0.49, 1.05) 0.66 (0.47, 0.92) Number of days cosumed alcohol i past moth Noe Referece 1.00 Referece (0.50, 1.25) 0.75 (0.51, 1.13) > (0.41, 1.03) 0.58 (0.38, 0.88) Number of driks per sittig Noe Referece 1.00 Referece (0.50, 1.10) 0.68 (0.49, 0.96) > (0.28, 1.32) 0.51 (0.23, 1.14) a Adjusted for age ad smokig status. Moderate/severe hot flashes Uadjusted Adjusted a Curret alcohol user No Referece 1.00 Referece Yes ( ) 0.80 ( ) Number of days cosumed alcohol i past moth Noe Referece 1.00 Referece ( ) 0.77 ( ) > ( ) 0.82 ( ) Number of driks per sittig Noe Referece 1.00 Referece ( ) 0.80 ( ) > ( ) 0.80 ( ) a Adjusted for age ad smokig status. (RR: 0.77, 95% CI: ), while the reduced risk of moderate or severe hot flashes associated with cosumig alcohol o 4 or more days per moth was of borderlie sigificace (RR: 0.82, 95% CI: ). Also, cosumig 1 2 driks per sittig was associated with a statistically sigificat reduced risk of moderate or severe hot flashes (RR: 0.80, 95% CI: ). Similarly, cofouder-adjusted aalyses showed that curret alcohol use was associated with a statistically sigificat reduced risk of frequet hot flashes (RR: 0.66, 95% CI: ) compared to o-use of alcohol (Table 4). Most otably, cosumig alcohol o 4 or more days per moth was associated with a sigificat reductio i the risk of frequet hot flashes (RR: 0.58, 95% CI: ). I additio, cosumptio of 1 2 driks per sittig was associated with a statistically sigificat reduced risk of daily hot flashes compared to o-use of alcohol (RR: 0.68, 95% CI: ). Results of the sex hormoe aalysis are show i Table 5. Curret alcohol use was ot associated with altered estradiol, estroe, or testosteroe levels. Similarly, curret alcohol use was ot associated with the ratios of estroe to estradiol or estradiol to testosteroe. Table 5. Associatio of curret alcohol use ad steroid hormoes Geometric mea a 95% LL 95% UL P-value Estradiol (pg/ml) Alcohol use 0.9 Curret Former Never Estroe (pg/ml) Alcohol use 0.4 Curret Former Never Testosteroe (g/ml) Alcohol use 0.5 Curret Former Never Estradiol/Estroe Alcohol use 0.6 Curret Former Never Estradiol/Testosteroe Alcohol use 0.8 Curret Former Never a Adjusted for age, smokig status, race, BMI, ad time sice last mestrual period. DISCUSSION I this study, alcohol use was associated with a reduced risk of hot flashes i midlife wome. Specifically, wome who cosumed alcohol 4 or more days per moth, or cosumed 1 2 alcoholic beverages per sittig, experieced a reduced risk of ay, moderate or severe, ad daily hot flashes. These data are cosistet with a study by Hyde Riley et al. (2004), which showed reduced odds of hot flashes i perimeopausal wome who cosumed 1 5 alcoholic driks per week, compared to perimeopausal wome who did ot cosume alcohol. These data, however, are ot cosistet with studies by Freema et al. (2003) ad Schwigl et al. (1994) which foud a icreased risk of hot flashes i premeopausal (Freema et al., 2001) or postmeopausal (Schwigl et al., 1994) wome who reported ever havig cosumed alcohol compared to wome who reported that they had ever cosumed alcohol. The discrepacy betwee our fidigs ad those of Freema et al. (2001) may be due to their study havig a smaller sample size ad youger wome who were cyclig o a regular basis. Our fidigs may differ from those obtaied by Schwigl et al. (1994), as their study had a smaller sample size, the wome were older tha those i our study, ad alcohol cosumptio was ot broke dow ito categories, wome were oly defied as ever or ever drikers. Results from our study also idicate that curret alcohol use is ot associated with sex hormoe levels or their ratios. This fidig is cosistet with a few studies showig o associatio betwee alcohol itake ad estradiol levels, testosteroe levels (Gill, 2000; Olad-Moret et al., 2005), or the ratio of estradiol to testosteroe i postmeopausal wome (Olad- Moret et al., 2005). Our fidigs, however, differ from a few Dowloaded from at Pesylvaia State Uiversity o February 27, 2014

5 ALCOHOL USE AND HOT FLASHES 567 studies idicatig that alcohol use is associated with altered levels of sex steroid hormoes. I oe study by Olad- Moret et al. (2005), cosumptio of >25 g (2.5 driks) of alcohol per day by postmeopausal wome was associated with a icrease i estradiol ad estroe levels, ad i the ratio of estradiol to estroe. The differece with our fidigs ad those of Olad-Moret et al. (2005) may be due to their study beig much larger ad therefore havig a greater statistical power to detect small differeces i hormoe levels. I other studies, alcohol use was associated with a icrease i estradiol levels, as well as a icrease i the ratio of estradiol to testosteroe i postmeopausal wome (Gavaler ad Va Thiel, 1992; Gill, 2000). Gavaler ad Va Thiel (1992) collected alcohol itake by two methods, self-reported quatity/frequecy iformatio ad a 3-day food record. If the results o alcohol itake differed by method, the 3-day food record was used for the calculatio of alcohol cosumptio. Our fidigs may differ from those of Gavaler ad Va Thiel (1992) due to differeces i collectio of the alcohol itake data. Sex hormoe results from this study are ot cosistet with studies i premeopausal wome that have show a icrease i estradiol ad testosteroe levels (Garcia-Closas et al., 2002), ad estradiol ad estroe levels (Gill, 2000), with alcohol use. These studies had small sample sizes, the wome were youger tha those i our study, ad the wome were regularly cyclig. These poits may accout for the differece with our fidigs. Collectively, the data from this study suggest that curret alcohol use is associated with a reduced risk of hot flashes i midlife wome ad that this associatio is ot mediated by sex steroid hormoes. This raises the possibility that curret alcohol use may be associated with hot flashes through aother pathway. It is possible that alcohol use may be associated with hot flashes by directly affectig the euros that cotrol the thermoregulatory cetre located withi the hypothalamus pituitary adreal axis (Olad-Moret et al., 2005). Alcohol ihibits the euros that cotrol core body temperature, stimulatig the hypothalamus ad causig fluctuatios i body temperature. Therefore, a icrease i body heat while cosumig alcohol may lead a woma to associate the trasiet rise i body temperature with alcohol use, causig uderreportig of hot flashes. Although this study shows curret alcohol use may be associated with a decreased risk of hot flashes, these fidigs must be cosidered with respect to their limitatios. Oe of the limitatios of this study is that alcohol use was obtaied by self-report, ad previous studies have show that alcohol use teds to be uderreported by wome (Olad-Moret et al., 2005). Uderreport of alcohol use would drive the results towards the ull hypothesis. Our study, however, still showed a sigificat associatio betwee curret alcohol use ad hot flashes, suggestig that the observed reductio i risk may be eve greater if alcohol use was reported accurately. Aother limitatio is that wome were ot asked questios about the type of alcohol (beer, wie, spirits) they cosumed. Therefore, aalyses could ot be performed to determie which types of alcohol were associated with hot flashes or hormoe levels. The desig of this study does ot eable us to determie the temporality of the associatio betwee alcohol use, sex hormoe levels, ad the occurrece of hot flashes, or the prevalece of hot flashes i the populatio. Although we had adequate sample size to examie the mai effects, a larger sample size would have allowed us to explore all iteractios. Despite these limitatios, this study had several stregths. A major stregth is that the study was desiged to examie hot flashes i midlife wome. By presetig the study as research ito factors related to midlife ad ot specifically as a study o hot flashes, wome who participated i the study may have bee less likely to over report hot flashes. Aother stregth is that, to our kowledge, this is the first study to examie the associatio betwee alcohol use, sex hormoe levels, ad hot flashes i the same study. A additioal stregth ivolves the miimizatio of misclassificatio of case cotrol status by assigig case cotrol status after the cliic visit based o the questioaire iformatio provided by each participat. I coclusio, the results of this study suggest that limited alcohol itake may have some beefits to midlife wome experiecig ay, moderate or severe, or daily hot flashes. Future studies should be coducted to cofirm our fidigs ad to examie the mechaism by which curret alcohol use decreases the risk of hot flashes i midlife wome. Ackowledgemets This study was supported by NIH grat AG18400 ad a grat from the Wome s Health Research Group at the Uiversity of Marylad. REFERENCES Dawso, D. A. (2003) Methodological issues i measurig alcohol use. Alcohol Research ad Health 27, Erlik, Y., Meldrum, D. R. ad Judd, H. L. (1982) Estroge levels i postmeopausal wome with hot flashes. Obstetrics ad Gyecology 59, Freema, E. W., Sammel, M. D., Grisso, J. A. et al. (2001) Hot flashes i the late reproductive years: risk factors for Africa America ad Caucasia wome. Joural of Womes Health ad Geder Based Medicie 10, Gallicchio, L., Miller, S. R., Visvaatha, K. et al. (2005a) Cigarette smokig, estroge levels, ad hot flashes i midlife wome. Maturitas, i press. Gallicchio, L., Visvaatha, K., Miller, S. R. et al. (2005b) Body mass, estroge levels, ad hot flashes i midlife wome. Am J Obstetrics ad Gyecology, i press. Garcia-Closas, M., Herbstma, J., Schiffma, M. et al. (2002) Relatioship betwee serum hormoe cocetratios, reproductive history, alcohol cosumptio ad geetic polymorphisms i pre-meopausal wome. Iteratioal Joural of Cacer 102, Gavaler, J. S. ad Va Thiel, D. H. (1992) The associatio betwee moderate alcoholic beverage cosumptio ad serum estradiol ad testosteroe levels i ormal postmeopausal wome: relatioship to the literature. Alcoholism, Cliical ad Experimetal Research 16, Gill, J. (2000) The effects of moderate alcohol cosumptio o female hormoe levels ad reproductive fuctio. Alcohol ad Alcoholism 35, Graham, K., Demers, A., Rehm, J. et al. (2004) Problems with the graduated frequecy approach to measurig alcohol cosumptio: results from a pilot study i Toroto, Caada. Alcohol ad Alcoholism 39, Greelad, S. (2004) Model-based estimatio of relative risks ad other epidemiologic measures i studies of commo outcomes ad i case-cotrol studies. America Joural of Epidemiology 160, Dowloaded from at Pesylvaia State Uiversity o February 27, 2014

6 568 C. SCHILLING et al. Hollader, L. E., Freema, E. W., Sammel, M. D. et al. (2001) Sleep quality, estradiol levels, ad behavioral factors i late reproductive age wome. Obstetrics ad Gyecology 98, Hyde Riley, E., Iui, T. S., Kleima, K. et al. (2004) Differetial associatio of modifiable health behaviors with hot flashes i perimeopausal ad postmeopausal wome. Joural of Geeral Iteral Medicie 19, Kroeberg, F. ad Dowey, J. A. (1987) Thermoregulatory physiology of meopausal hot flashes: a review. Caadia Joural of Physiology ad Pharmacology 65, Oldehave, A., Jaszma, L. J., Haspels, A. A. et al. (1993) Impact of climacteric o well-beig. A survey based o 5213 wome 39 to 60 years old. America Joural of Obstetrics ad Gyecology 168, Olad-Moret, N. C., Peeters, P. H., va der Schouw, Y. T. et al. (2005) Alcohol ad edogeous sex steroid levels i postmeopausal wome: a cross-sectioal study. Joural of Cliical Edocriology ad Metabolism 90, Schwigl, P. J., Hulka, B. S. ad Harlow, S. D. (1994) Risk factors for meopausal hot flashes. Obstetrics ad Gyecology 84, Dowloaded from at Pesylvaia State Uiversity o February 27, 2014