Content uploaded by Taisto Sarkola
Author content
All content in this area was uploaded by Taisto Sarkola on Apr 05, 2020
Content may be subject to copyright.
Effect of Moderate Alcohol Consumption on Plasma
Dehydroepiandrosterone Sulfate, Testosterone, and
Estradiol Levels in Middle-Aged Men and
Postmenopausal Women: A Diet-Controlled
Intervention Study
Aafje Sierksma, Taisto Sarkola, C. J. Peter Eriksson, Martijn S. van der Gaag,* Diederick E. Grobbee, Henk F. J. Hendriks
Background: Moderate alcohol consumption is inversely associated with cardiovascular diseases.
Changes in hormone levels might in part help explain the positive health effect. This study was performed
to examine the effect of moderate alcohol consumption on plasma dehydroepiandrosterone sulfate
(DHEAS), testosterone, and estradiol levels.
Methods: In a randomized, diet-controlled, crossover study, 10 middle-aged men and 9 postmenopausal
women, all apparently healthy, nonsmoking, and moderate alcohol drinkers, consumed beer or no-alcohol
beer with dinner during two successive periods of 3 weeks. During the beer period, alcohol intake equaled
40 and 30 g per day for men and women, respectively. The total diet was supplied and had essentially the
same composition during these 6 weeks. Before each treatment there was a 1 week washout period, in which
the subjects were not allowed to drink alcoholic beverages. At the end of each of the two experimental
periods, fasting blood samples were collected in the morning.
Results: Moderate alcohol consumption increased plasma DHEAS level by 16.5% (95% confidence interval,
8.0–24.9), with similar changes for men and women. Plasma testosterone level decreased in men by 6.8% (95%
confidence interval, ⫺1.0 – ⫺12.5), but no effect was found in women. Plasma estradiol level was not affected.
Serum high-density lipoprotein cholesterol level increased by 11.7% (95% confidence interval, 7.3–16.0), with
similar changes for men and women. The overall alcohol-induced relative changes in DHEAS, testosterone, and
estradiol correlated positively with the relative increase in high-density lipoprotein cholesterol (adjusted for the
relative change in body weight); however, findings were only borderline significant for DHEAS and estradiol (r
⫽0.44, p⫽0.08; r⫽0.32, p⫽0.21; and r⫽0.46, p⫽0.06, respectively).
Conclusions: A protective effect of moderate alcohol consumption for cardiovascular disease risk may
in part be explained by increased plasma DHEAS level.
Key Words: Alcohol, Dehydroepiandosterone Sulfate (DHEAS), Testosterone, Estradiol, HDL Cho-
lesterol.
MODERATE ALCOHOL CONSUMPTION is in-
versely associated with cardiovascular diseases
(CVD) (Colditz et al., 1985; Grobbee et al., 1999;
Stampfer et al., 1988). Mechanisms proposed to explain
a positive health effect of moderate alcohol consumption
involve prevention of atherogenesis through changes in
lipoprotein metabolism (Hendriks et al., 1998; Van der
Gaag et al., 1999), hemostasis (Dimmitt et al., 1998;
Hendriks et al., 1994), and inflammation (Imhof et al.,
2001; Koenig et al., 1999; Sierksma et al., 2002b).
There is accumulating evidence suggesting the involve-
ment of sex hormones in atherogenesis. Studies suggest a
protective effect of high levels of dehydroepiandrosterone
sulfate (DHEAS) against atherosclerosis (Barrett-Connor
et al., 1986; Feldman et al., 2001; Leowattana, 2001). This
is further supported by an observed inverse correlation
between DHEAS levels and pulse wave velocity (Ishihara
et al., 1992) and carotid wall thickness (Bernini et al., 1999).
An independent inverse association between levels of tes-
tosterone and aortic atherosclerosis in men aged 55 years
and over has been reported (Hak et al., 2002). In addition,
studies in older men have shown an inverse association
between testosterone levels and aortic stiffness (Dockery et
From the Department of Nutritional Physiology, TNO Nutrition and Food
Research (AS, MSvdG, HFJH), Zeist, The Netherlands; Julius Center for Health
Sciences and Primary Care, University Medical Center Utrecht (AS, DEG),
Utrecht, The Netherlands; and Department of Mental Health and Alcohol Re-
search, National Public Health Institute (TS, CJPE), Helsinki, Finland.
Received for publication October 30, 2003; accepted January 7, 2004.
Supported by the Dutch Foundation for Alcohol Research (SAR).
Reprint requests: Henk F. J. Hendriks, PhD, TNO Nutrition and Food
Research, Department of Nutritional Physiology, PO Box 360, 3700 AJ Zeist,
The Netherlands; Fax: ⫹31 30 6944928; E-mail: hendriks@voeding.tno.nl.
*Deceased.
DOI: 10.1097/01.ALC.0000125356.70824.81
0145-6008/04/2805-0780$03.00/0
ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH
Vol. 28, No. 5
May 2004
780 Alcohol Clin Exp Res, Vol 28, No 5, 2004: pp 780–785
al., 2002) and intima-media thickness (Van den Beld et al.,
2003). Premenopausal women may be protected from
CVD, relative to men, due to high circulating estrogen
levels (Matthews, 1992).
Changes in hormone levels may in part explain the health
benefits of moderate alcohol consumption. Two long-term
diet-controlled intervention studies in pre- and postmeno-
pausal women showed increases in DHEAS and plasma
estrogen/estrone sulfate levels after moderate alcohol in-
take (Dorgan et al., 2001; Reichman et al., 1993). Effects of
alcohol on hormone levels may depend on age and gender
(Orentreich et al., 1984; Zumoff et al., 1980). To further
investigate the effect of moderate alcohol consumption on
plasma DHEAS, testosterone, and estradiol levels and
their correlation with alcohol-induced changes in high-
density lipoprotein (HDL) cholesterol, we performed an
intervention study in both middle-aged men and postmeno-
pausal women. Diet was controlled during the study, as
nutrition might influence sex hormone variability (Tamimi
et al., 2001; Ukkola et al., 2001).
METHODS
Subjects
The study was conducted at TNO Nutrition and Food Research (Zeist,
The Netherlands). The trial was performed according to the ICH Guide-
lines for Good Clinical Practice, complied with the Declaration of Hel-
sinki, and was approved by the TNO Medical Ethics Committee. Ten
middle-aged men and 10 postmenopausal women, all nonsmoking, were
recruited from the pool of volunteers of TNO Nutrition and Food Re-
search and through an advertisement in a local newspaper. The volunteers
received all information about the study (including aim; medical, ethical,
and practical aspects; and insurance) by verbal briefing and received the
same information in writing and subsequently signed for informed con-
sent. Subjects were eligible if they fulfilled the following inclusion criteria:
consumption of ⱕ28 alcohol-containing beverages per week for men and
ⱕ21 for women, body mass index between 20 and 31 kg/m
2
, and no family
history of alcoholism. Subjects were healthy as indicated by the values of
the prestudy laboratory tests, which all were within the normal range. In
addition, they were healthy as indicated by their medical history and a
physical examination by the medical investigator. The postmenopausal
women did not have menses for at least a year, were not ovariectomized,
and did not use hormone replacement therapy. One postmenopausal
woman dropped out because of a treatment-unrelated cause. The remain-
ing 19 subjects completed the study successfully. Characteristics of the
study population are given in Table 1.
Study Design
The subjects entered an open randomized crossover trial consisting of
two periods of 3 weeks. Five men and five women were randomly allocated
to the sequence beer (Amstel Bier, Amsterdam, The Netherlands; 5 vol%
alcohol) followed by no-alcohol beer (Amstel Malt Bier, Amsterdam, The
Netherlands; ⬍0.1 vol% alcohol). The other half of the subjects consumed
no-alcohol beer first followed by beer. In this way, any bias due to the
beverage order and a possible drift of variables over time was eliminated.
There was a 1 week washout period before each treatment period in which
participants were not allowed to drink alcoholic beverages, to limit pos-
sible carryover effects.
Four glasses of each beverage for men and three glasses of each
beverage for women were consumed daily during the evening dinner.
During the beer period, alcohol intake equaled 40 and 30 g per day for
men and women, respectively. The total diet was supplied to exclude
dietary confounding. Subjects consumed all foods at home, except for
evening dinner, which was served at TNO Nutrition and Food Research,
together with the beer or no-alcohol beer. Subjects were not allowed to eat
or drink anything but the foods supplied, except for tap water and coffee
(limited amount of creamer was supplied), and they were asked to main-
tain their habitual physical activity pattern.
We considered the energy provided by alcohol to be 19.6 kJ/g, assuming
the net usable energy content of alcohol is 70% of the theoretically present
28 kJ/g (Rumpler et al., 1996; Westerterp, 1996). Taking this into account,
no-alcohol beer contained approximately 90 kJ/100 ml, and beer contained
approximately 130 kJ/100 ml. The source of energy in no-alcohol beer was
almost 100% carbohydrates; in beer approximately 40% of energy was
derived from carbohydrates and 60% of energy was derived from alcohol.
The diets, including beer or no-alcohol beer, were comparable in such a
way that the macronutrient composition and total energy were the same
during the beer and no-alcohol beer period. The macronutrient compo-
sition of the diet was based on the national Dutch food consumption
survey of 1998 (Anonymous, 1998). Diets during the beer and no-alcohol
beer period consisted of approximately 17% energy from protein, 39%
energy from fat, and 44% energy from carbohydrate, for both males and
females. Daily energy requirement was estimated for each subject accord-
ing to Schofield (1985). The diet was provided in nine different levels of
energy intake per day; 7, 8, 9, 10, 11, 12, 13, 14, and 15 MJ, depending on
the body weight of the subject. Body weight was determined every 3 or 4
days with the subjects wearing indoor clothing, without shoes, wallet, and
keys. When a subject’s body weight deviated more than 1.5 kg from his or
her weight at the first experimental day, energy supply was adjusted (⫾1
MJ), without changing the macronutrient composition, to maintain body
weight. Compliance to the protocol, physical adverse events, and medicine
use were checked by a daily questionnaire.
Table 1. Characteristics of the Volunteers Included in the Data Analysis
Men (n⫽10) Women (n⫽9)
Age (yr) 55 (6) 45–64 57 (4) 49–62
Body weight (kg) 79.2 (9.2) 62.7–93.7 74.0 (7.3) 66.0–85.1
BMI (kg/m
2
)24.9 (2.2) 20.1–28.6 26.8 (2.9) 22.0–30.7
Hemoglobin (mmol/liter) 9.4 (0.5) 8.7–10.7 8.5 (0.4) 7.7–9.3
Triglycerides (mmol/liter) 1.2 (0.4) 0.8–1.9 0.9 (0.4) 0.5–1.6
Total cholesterol (mmol/liter) 6.2 (1.1) 4.5–7.6 6.9 (1.3) 5.4–8.6
HDL cholesterol (mmol/liter) 1.5 (0.4) 0.9–2.3 2.0 (0.4) 1.6–2.6
LDL cholesterol (mmol/liter) 4.3 (0.9) 2.9–5.8 4.5 (1.2) 3.3–6.3
ASAT (units/liter) 25 (5) 19–34 19 (3) 15–24
ALAT (units/liter) 21 (4) 17–29 14 (3) 10–19
GGT (units/liter) 22 (7) 11–34 16 (4) 11–23
Glucose (mmol/liter) 5.4 (0.5) 4.9–6.3 5.5 (0.4) 5.0–6.1
Values are expressed as mean (SD) and range.
BMI, body mass index; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ASAT, aspartate aminotransferase; ALAT, alanine aminotransferase; GGT,
␥
-glutamyltransferase.
ALCOHOL AND SEX HORMONES 781
Blood Sampling and Analysis
Fasting blood samples were collected in the morning after the last day
of each experimental period. Blood was taken from the anticubital vein
and collected in a tube containing citrate theophylline, adenosine, and
dipyridamole and in a tube containing gel and clot activator (Becton
Dickinson, Vacutainer Systems, Plymouth, UK). To obtain plasma and
serum, the blood was centrifuged for 15 min at 2000 ⫻gand 4°C, between
15 and 30 min after collection. All aliquots were stored at ⫺80°C until
analysis.
Plasma DHEAS, testosterone, and estradiol levels were determined by
standard radioimmunoassay reagent sets (Cout-a-Count DHEA-SO4
from Diagnostic Products Corporation, Los Angeles, CA, for DHEAS;
Orion Diagnostica, Finland, for testosterone; Estradiol-2 from DiaSorin,
Italy, for estradiol). Within- and between-assay variabilities were 7.8% (n
⫽12) and 7.9% (n⫽4) at the level of 4.5
mol/liter for plasma DHEAS
(detection limit 0.05
mol/liter), 6.6% and 7.0% at the level of 0.96
nmol/liter (n⫽10) for plasma testosterone (detection limit 0.1 nmol/liter),
and 9.0% (n⫽12) and 4.7% (n⫽4) at the level of 40 pmol/liter for
plasma estradiol (detection limit about 20 pmol/liter). Serum HDL cho-
lesterol level was determined using an enzymatic method (Roche Diag-
nostics GmbH, Mannheim, Germany), with a detection limit 0.08 mmol/
liter and a between-assay variability of about 3%.
One hour after dinner on the last evening of each of the two experi-
mental periods, blood was collected in tubes containing gel and clot
activator (Becton Dickinson, Vacutainer Systems; airtight system) for
blood alcohol concentration determination. Between 15 and 30 min after
collection, blood was centrifuged for 15 min at 2000 ⫻gand 4°C, and
serum samples were stored at ⫺20°C until analysis. Blood alcohol con-
centrations were measured enzymatically (Roche Diagnostics GmbH,
Mannheim, Germany; within- and between-assay variability 0.5% and
2.3%, respectively, detection limit 2.17 mmol/liter).
All samples were analyzed in one run after the finish of the study. Staff
members who conducted the laboratory analyses were blind to the group
assignments.
Statistical Methods
Data were analyzed using the SAS statistical software package (SAS/
STAT version 6.12, SAS Institute, Cary, NC). The outcome measures were
tested for normality. Treatment effects were assessed by analysis of vari-
ance, by use of general linear modeling, using as factors gender, beverage,
and gender in combination with beverage. To test for carryover effects, the
factor treatment order was also added to this model. We calculated 95%
confidence intervals (CI) according to Mood et al. (1974) and Finney
(1964). Pearson correlation coefficients were computed to assess associa-
tions between relative alcohol-induced changes in sex hormones and HDL
cholesterol. Two-sided pvalues were considered statistically significant at
pⱕ0.05.
RESULTS
The compliance to the supplied foods and drinks was
good, and average body weight did not differ between beer
and no-alcohol beer treatment periods (data not shown).
The overall mean blood alcohol concentration at 1 hr after
dinner with beer was 10.5 mmol/liter (range 6.0–15.9 mmol/
liter), and the mean blood alcohol concentrations for men
and women separately did not differ (11.2 [SD 3.0] and 9.7
[SD 1.6] mmol/liter, p⫽0.20; ttest). No carryover effects
in outcome measures were seen.
Plasma DHEAS level
Plasma DHEAS level increased by 16.5% (95% CI,
8.0–24.9) after beer consumption compared with no-
alcohol beer consumption. No gender differences were
observed (Table 2).
Plasma Testosterone Level
Three weeks of beer consumption decreased plasma tes-
tosterone level by 6.8% in men (95% CI, ⫺1.0 –⫺12.5)
compared with no-alcohol beer consumption. In women no
effect on plasma testosterone level was observed (Table 2).
Plasma Estradiol Level
Plasma estradiol level was not affected after 3 weeks of
beer consumption compared with no-alcohol beer con-
sumption (Table 2).
Serum HDL Cholesterol Level
After 3 weeks of daily beer consumption, serum HDL
cholesterol level significantly increased by 11.7% (95% CI,
7.3–16.0) compared with no-alcohol beer consumption. Sim-
ilar changes in men and women were observed (Table 2).
Correlations Between Relative Alcohol-Induced HDL
Cholesterol and Sex Hormone Changes
The overall alcohol-induced relative changes in DHEAS,
testosterone, and estradiol correlated positively with the
relative increase in HDL cholesterol (adjusted for the rel-
ative change in body weight); however, these changes were
only borderline significant for DHEAS and estradiol (r⫽
0.44, p⫽0.08; r⫽0.32, p⫽0.21; and r⫽0.46, p⫽0.06,
respectively).
DISCUSSION
To our knowledge, this is the first diet-controlled study to
examine the effects of moderate alcohol consumption on
Table 2. Mean (SD) serum HDL cholesterol and plasma DHEAS, testosterone, and estradiol levels in 10 middle-aged men and 9 postmenopausal women after 3
weeks consumption of beer and no-alcohol beer
Men (n⫽10) Women (n⫽9)
Beer No-alcohol beer Beer No-alcohol beer
HDL cholesterol (mmol/liter) 1.34 (0.24)* 1.18 (0.16) 1.70 (0.33)* 1.55 (0.32)
DHEAS (micromol/liter) 4.0 (1.8)# 3.5 (1.7) 3.9 (2.7) 3.3 (2.2)
Testosterone (nmol/liter) 15.3 (3.6)* 16.4 (2.9) 1.1 (0.6) 1.1 (0.6)
Estradiol (pmol/liter) 66.6 (11.7) 65.2 (8.9) 28.2 (16.3) 28.0 (13.0)
*p⬍0.05; # p⬍0.001; significantly different from the no-alcohol beer period.
782 SIERKSMA ET AL.
sex hormone levels in middle-aged men and postmeno-
pausal women. A moderate daily dose of alcohol consumed
with evening dinner increased plasma DHEAS level.
Plasma testosterone level was decreased in men, and there
was no effect on plasma estradiol level in both men and
women. The volunteers were maintained on adequate nu-
tritional regimen, and average body weight did not differ
between beer and no-alcohol beer treatment periods. Con-
sequently, the findings are unlikely to have been con-
founded by concomitant nutritional changes.
The increased plasma DHEAS level after moderate al-
cohol consumption agrees with observational data (Field et
al., 1994; Kiechl et al., 2000; Ravaglia et al., 2002) and the
two intervention studies in women (Dorgan et al., 2001;
Reichman et al., 1993). With our study design, we cannot
differentiate a chronic effect of moderate alcohol consump-
tion from a possible acute effect of last evening drink. The
increase in plasma DHEAS level in part could be a conse-
quence of increased adrenal secretion and in part could be
derived by ethanol-mediated inhibition of the isomerase-
dehydrogenase reaction of dehydroepiandrosterone
(DHEA) to androstenedione (Frias et al., 2002). We could
previously not disclose similar effects of moderate alcohol
intake in a study in middle-aged men (Sierksma et al.,
2002a). The reason for this discrepancy could be the
shorter treatment period (17 days) and the more liberal
dietary control (only evening dinner) compared with the
current study. The increase in plasma DHEAS level in the
current study would be compatible with an approximate
10% decrease in mortality from CVD (Barrett-Connor et
al., 1986). However, doubts have been raised regarding the
proposed inverse association between DHEAS and athero-
sclerosis risk (Kiechl et al., 2000). Some could not confirm
this relationship (Barrett-Connor and Goodman-Gruen,
1995), whereas others found a positive rather than an in-
verse relationship (Johannes et al., 1999). Ravaglia et al.
(2002) have suggested that low DHEAS levels are probably
a nonspecific indicator of aging and health status. DHEAS
is measured, because it is the stable form of DHEA. De-
spite the high correlation between DHEA and DHEAS
levels (Nafziger et al., 1991) and their biological linkage, it
cannot be ruled out that an association exists between
DHEA and atherosclerosis risk, which could be missed by
measuring its sulfated form. In addition, DHEA(S) may
beneficially affect certain age-related disorders, such as
cognitive impairment and dementia (Kalmijn et al., 1998;
Watson et al., 1996). This would explain data suggesting
that moderate alcohol consumption may protect against
dementia (Mukamal et al., 2003; Ruitenberg et al., 2002).
Heavy alcohol intake decreases testosterone in men
(Van Thiel and Lester, 1979; Ylikahri et al., 1974). This
could reflect decreased plasma binding capacity and in-
creased hepatic testosterone A-ring reductase activity
(rate-limiting enzyme for the metabolism of testosterone in
the liver) (Gordon et al., 1976) and/or an inhibited testos-
terone synthesis in the testis (Van Thiel and Lester, 1979).
Possibly these changes already occur with moderate alcohol
consumption, explaining the decrease in plasma testoster-
one levels in the middle-aged men in our study. The clinical
relevance of this change is unclear, as reproductive distur-
bances such as decreased libido, impotence, and infertility
are found in long-term heavy alcohol drinkers (Van Thiel
and Lester, 1979). In postmenopausal women, no effect of
moderate alcohol intake on plasma testosterone level was
found, which is in agreement with earlier increases in tes-
tosterone only in long-term female heavy drinkers (Cigolini
et al., 1996; Pettersson et al., 1990; Välimäki et al., 1990,
1995). The testosterone reduction in men and the absence
of an effect in women might well be a consequence of the
last evening drink instead of a chronic effect of moderate
alcohol consumption. Studies in women have shown that
testosterone was elevated acutely by a low dose of alcohol
(Eriksson et al., 1994; Sarkola et al., 2001).
The lack of effect of moderate alcohol consumption on
plasma estradiol level is consistent with other studies (Cau-
ley et al., 1989; Ginsburg et al., 1996; Hankinson et al.,
1995; Newcomb et al., 1995). There are indications that the
hops and barm in beer contain substances with estrogenic
activity (Lapcík et al., 1998). Because both beer and no-
alcohol beer contain these substances, we assume that this
will not have influenced the alcohol effect on plasma es-
tradiol level. In women, substantial evidence exists for a
protective role of endogenous sex hormones (Matthews,
1992). It has been discussed whether in postmenopausal
women estrogen therapy may prevent the development of
atherosclerosis (Grady et al., 2002; Hodis et al., 2003;
Manson et al., 2003). Estradiol levels have been positively
associated with breast cancer risk (Thomas et al., 1997).
The lack of an alcohol-induced effect on plasma estradiol
level in our study would suggest that moderate alcohol
consumption does not operate through this pathway.
The alcohol-induced increase in serum HDL cholesterol
level of about 12% in the present study is similar to that
observed in other diet-controlled studies of our group (Van
der Gaag et al., 1999, 2000). A 2% increase in HDL cho-
lesterol has been estimated to translate to a 2% to 4%
decrease in coronary heart disease risk (Kinosian et al.,
1995).
The correlations between the alcohol-induced relative
changes in HDL cholesterol and sex hormones suggest that
sex hormones may affect CVD risk indirectly via an effect
on lipoproteins (Kiel et al., 1989; Okamoto, 1998; Zmuda
et al., 1997).
CONCLUSIONS
Alcohol intake seems to decrease testosterone in men
already at a moderate consumption level. In addition, the
results of this randomized trial in healthy middle-aged men
and postmenopausal women support the view that moder-
ate intake of alcohol may increase plasma DHEAS level.
This small endocrine effect of alcohol is consistent with a
ALCOHOL AND SEX HORMONES 783
protective effect of moderate alcohol consumption with
respect to CVD risk and possibly also the risk for dementia.
ACKNOWLEDGMENTS
We acknowledge all those involved in the conduct of the study
and thank the volunteers for their enthusiastic participation.
REFERENCES
Anonymous (1998) Zo eet Nederland, 1998, Resultaten van de voedsel-
consumptiepeiling 1997–1998. Voedingscentrum, Den Haag.
Barrett-Connor E, Khaw KT, Yen SS (1986) A prospective study of
dehydroepiandrosterone sulfate, mortality, and cardiovascular disease.
N Engl J Med 315:1519–1524.
Barrett-Connor E, Goodman-Gruen D (1995) Dehydroepiandosterone
sulfate does not predict cardiovascular death in postmenopausal
women. The Rancho Bernardo Study Circulation 91:1757–1760.
Bernini GP, Sgro’M, Moretti A, Argenio GF, Barlascini CO, Cristofani R,
Salvetti A (1999) Endogenous androgens and carotid intimal-medial
thickness in women. J Clin Endocrinol Metab 84:2008–2012.
Cauley JA, Gutai JP, Kuller LH, LeDonne D, Powell JG (1989) The
epidemiology of serum sex hormones in postmenopausal women. Am J
Epidemiol 129:1120–1131.
Cigolini M, Targher G, Bergamo Andreis IA, Tonoli M, Filippi F, Muggeo
M, De Sandre G (1996) Moderate alcohol consumption and its relation
to visceral fat and plasma androgens in healthy women. Int J Obes Relat
Metab Disord 20:206–212.
Colditz GA, Branch ALG, Lipnick RJ, Willett WC, Rosner B, Posner B,
Hennekens CH (1985) Moderate alcohol and decreased cardiovascular
mortality in an elderly cohort. Am Heart J 109:886–889.
Dimmitt SB, Rakic V, Puddey IB, Baker R, Oostryck R, Adams MJ,
Chesterman CN, Burke V, Beilin LJ (1998) The effects of alcohol on
coagulation and fibrinolytic factors: a controlled trial. Blood Coag
Fibrinol 76:39–45.
Dockery F, Bulpitt CJ, Agarwal S, Rajkumar C (2002) Testosterone
suppression in men with prostate cancer is associated with increased
arterial stiffness. Aging Male 5:217–222.
Dorgan JF, Baer DJ, Albert PS, Judd JT, Brown ED, Corle DK, Campbell
WS, Hartman TJ, Tejpar AA, Clevidence BA, Giffen CA, Chandler
DW, Stanczyk FZ, Taylor PR (2001) Serum hormones and the alcohol-
breast cancer association in postmenopausal women. J Natl Cancer Inst
93:710–715.
Eriksson CJP, Fukunaga T, Lindman R (1994) Sex hormone response to
alcohol. Nature (Lond.) 369:711.
Feldman HA, Johannes CB, Araujo AB, Mohr BA, Longcope C, McKin-
lay JB (2001) Low dehydroepiandrosterone and ischemic heart disease
in middle-aged men: prospective results from the Massachusetts male
aging study. Am J Epidemiol 153:79–89.
Field AE, Colditz GA, Willet WC, Longcope C, McKinlay B (1994) The
relation of smoking, age, relative weight, and dietary intake to serum
adrenal steroids, sex hormones, and sex hormone-binding globulin in
middle-aged men. J Clin Endocrinol Metab 79:1310–1316.
Finney DJ (1964) Statistical Method in Biological Assay. 2nd ed. Charles
Griffin, London.
Frias J, Torres JM, Miranda MT, Ruiz E, Ortega E (2002) Effects of acute
alcohol intoxication on pituitary-gonadal axis hormones, pituitary-
adrenal axis hormones, beta-endorphin and prolactin in human adults
of both sexes. Alcohol Alcohol 37:169–173.
Ginsburg ES, Mello NK, Mendelson JH, Barbieri RL, Teoh SK, Rothman
M, Gao X, Sholar JW (1996) Effects of alcohol ingestion on estrogens
in postmenopausal women. JAMA 276:1747–1751.
Gordon GG, Altman K, Southren L, Rubin E, Lieber CS (1976) Effect of
alcohol (ethanol) administration on sex-hormone metabolism in normal
men. N Engl J Med 295:793–797.
Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M,
Hsia J, Hulley S, Herd A, Khan S, Newby LK, Waters D, Vittinghoff E,
Wenger N, HERS Research Group (2002) Cardiovascular disease out-
comes during 6.8 years of hormone therapy: Heart and Estrogen/
Progestin Replacement Study follow-up (HERS III). JAMA 288:49–57.
Grobbee DE, Rimm EB, Keil U, Renaud S (1999) Alcohol and cardio-
vascular system, in Health Issues Related to Alcohol Consumption (Mac-
Donald EI ed), pp 125–179. ILSI Europe, Blackwell Science, Philadel-
phia.
Hak AE, Witteman JC, de Jong FH, Geerlings MI, Hofman A, Pols HA
(2002) Low levels of endogenous androgens increase the risk of athero-
sclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab
87:3632–3639.
Hankinson SE, Willett WC, Manson JE, Hunter DJ, Colditz GA,
Stampfer MJ, Longcope C, Speizer FE (1995) Alcohol, height, and
adiposity in relation to estrogen and prolactin levels in postmenopausal
women. J Natl Cancer Inst 87:1297–1302.
Hendriks HFJ, Veenstra J, Van Tol A, Groener JEM, Schaafsma G (1998)
Moderate doses of alcoholic beverages with dinner and postprandial
high density lipoprotein composition. Alcohol Alcohol 33:403–410.
Hendriks HFJ, Veenstra J, Velthuis-te Wierik EJM, Schaafsma G, Kluft C
(1994) Effect of moderate dose of alcohol with evening meal on fibrino-
lytic factors. BMJ 308:1003–1006.
Hodis HN, Mack WJ, Azen SP, Lobo RA, Shoupe D, Mahrer PR, Faxon
DP, Cashin-Hemphill L, Sanmarco ME, French WJ, Shook TL,
Gaarder TD, Mehra AO, Rabbani R, Sevanian A, Shil AB, Torres M,
Vogelbach KH, Selzer RH: Women’s Estrogen-Progestin Lipid-
Lowering Hormone Atherosclerosis Regression Trial Research Group
(2003) Hormone therapy and the progression of coronary-artery ath-
erosclerosis in postmenopausal women. N Engl J Med 349:535–545.
Imhof A, Froehlich M, Brenner H, Boeing H, Pepys MB, Koenig W (2001)
Effect of alcohol consumption on systemic markers of inflammation.
Lancet 357:763–767.
Ishihara F, Hiramatsu K, Shigematsu S, Aizawa T, Niwa A, Takasu N,
Yamada T, Matsuo K (1992) Role of adrenal androgens in the devel-
opment of arteriosclerosis as judged by pulse wave velocity and calcifi-
cation of the aorta. Cardiology 80:332–338.
Johannes CB, Stellato RK, Feldman HA, Longcope C, McKinlay JB
(1999) Relation of dehydroepidandrosterone and dehydroepiandros-
terone sulfate with cardiovascular disease risk factors in women: longi-
tudinal results from the Massachusetts Women’s Health Study. J Clin
Epidemiol 52:95–103.
Kalmijn S, Launer LJ, Stolk RP, de Jong FH, Pols HA, Hofman A,
Breteler MM, Lamberts SW (1998) A prospective study on cortisol,
dehydroepiandrosterone sulfate, and cognitive function in the elderly.
J Clin Endocrinol Metab 83:3487–3492.
Kiechl S, Willeit J, Bonora E, Schwarz S, Xu Q (2000) No association
between dehydroepiandrosterone sulfate and development of athero-
sclerosis in a prospective population study (Bruneck Study). Arterio-
scler Thromb Vasc Biol 20:1094–1100.
Kiel DP, Baron JA, Plymate SR, Chute CG (1989) Sex hormones and
lipoproteins in men. Am J Med 87:35–39.
Kinosian B, Glick H, Preiss L, Puder KL (1995) Cholesterol and coronary
heart disease: predicting risks in men by changes in levels and ratios.
J Invest Med 43:443–450.
Koenig W, Sund M, Fröhlich M, Fisher HG, Lowel H, Doring A, Hutchin-
son WL, Pepys MB (1999) C-Reactive protein, a sensitive marker of
inflammation, predicts future risk of coronary heart disease in initially
healthy middle-aged men. Circulation 99:237–242.
Lapcík O, Hill M, Hampl R, Wahala K, Adlercreutz H (1998) Identifica-
tion of isoflavonoids in beer. Steroids 63:14–20.
Leowattana W (2001) DHEA(S): the fountain of youth. J Med Assoc Thai
84:S605–S612.
Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL,
Trevisan M, Black HR, Heckbert SR, Detrano R, Strickland OL, Wo
ND, Crouse JR, Stein E, Cushman M, Women’s Health Initiative
784 SIERKSMA ET AL.
Investigators (2003) Estrogen plus progestin and the risk of coronary
heart disease. N Engl J Med 349:523–534.
Matthews KA (1992) Myths and realities of the menopause. Psychosom
Med 54:1–9.
Mood AM, Graybill FA, Boes DC (1974) Introduction to the Theory of
Statistics. 3rd ed. McGraw-Hill, New York.
Mukamal KJ, Kuller LH, Fitzpatrick AL, Longstreth WT, Mittleman MA,
Siscovick DS (2003) Prospective study of alcohol consumption and risk
of dementia in older adults. JAMA 289:1405–1413.
Nafziger AN, Herrington DM, Bush TL (1991) Dehydroepiandrosterone
and dehydroepiandrosterone sulfate: their relation to cardiovascular
disease. Epidemiol Rev 13:267–293.
Newcomb PA, Klein R, Klein BE, Haffner S, Mares-Perlman J, Cruicks-
hanks KJ, Marcus PM (1995) Association of dietary and life-style
factors with sex hormones in postmenopausal women. Epidemiology
6:318–321.
Okamoto K (1998) Distribution of dehydroepiandrosterone sulfate and
relationships between its level and serum levels in a rural Japanese
population. J Epidemiol 8:285–291.
Orentreich N, Brind JL, Rizer RL, Vogelman JH (1984) Age changes and
sex differences in serum dehydroandrosterone sulfate concentrations
throughout adulthood. J Clin Endocrinol Metab 59:551–555.
Pettersson P, Ellsinger BM, Sjoberg C, Bjorntorp P (1990) Fat distribution
and steroid hormones in women with alcohol abuse. J Intern Med
228:311–316.
Ravaglia G, Forti P, Maioli F, Sacchetti L, Nativio V, Scali CR, Mariani
E, Zanardi V, Stefanini A, Macini PL (2002) Dehydroepiandrosterone-
sulfate serum levels and common age-related diseases: results from a
cross-sectional Italian study of a general elderly population. Exp Ger-
ontol 37:701–712.
Reichman ME, Judd JT, Longcope C, Schatzkin A, Clevidence BA, Nair
PP, Campbell WS, Taylor PR (1993) Effects of alcohol consumption on
plasma and urinary hormone concentrations in premenopausal women.
J Natl Cancer Inst 85:722–727.
Ruitenberg A, van Swieten JC, Witteman JC, Mehta KM, van Duijn CM,
Hofman A, Breteler MM (2002) Alcohol consumption and risk of
dementia: the Rotterdam Study. Lancet 359:281–286.
Rumpler WV, Rhodes DG, Baer DJ, Conway JM, Seale JL (1996) Energy
value of moderate alcohol consumption by humans. Am J Clin Nutr
64:108–114.
Sarkola T, Adlercreutz H, Heinonen S, Eriksson CJP (2001) Alcohol
intake, androgen and glucocorticoid steroids in premenopausal women
using oral contraceptives: an interventional study. J Steroid Biochem
Mol Biol 78:157–165.
Schofield WN (1985) Predicting basal metabolic rate, new standards and
review of previous work. Hum Nutr Clin Nutr 39:S5–S41.
Sierksma A, Sarkola T, Eriksson CJP, Hendriks HFJ (2002a) Effects of
moderate alcohol consumption on plasma hormone levels in healthy
middle-aged men. Alcohol Research 7:235–238.
Sierksma A, Van der Gaag MS, Kluft C, Hendriks HFJ (2002b) Moderate
alcohol consumption reduces plasma C-reactive protein and fibrinogen
levels: a randomized, diet-controlled intervention study. Eur J Clin Nutr
56:1130–1136.
Stampfer MJ, Colditz GA, Willett WC, Speizer FE, Hennekens CH (1988)
A prospective study of moderate alcohol consumption and the risk of
coronary disease and stroke in women. N Engl J Med 319:267–273.
Tamimi R, Mucci LA, Spanos E, Lagiou A, Benetou V, Trichopoulos D
(2001) Testosterone and oestradiol in relation to tobacco smoking, body
mass index, energy consumption and nutrient intake among adult men.
Eur J Cancer Prev 10:275–280.
Thomas HV, Reeves GK, Key TJ (1997) Endogenous estrogen and post-
menopausal breast cancer: a quantitative review. Cancer Causes Con-
trol 8:922–928.
Ukkola O, Gagnon J, Rankinen T, Thompson PA, Hong Y, Leon AS, Rao
DC, Skinner JS, Wilmore JH, Bouchard C (2001) Age, body mass index,
race and other determinants of steroid hormone variability The HER-
ITAGE Family Study. Eur J Endocrinol 145:1–9.
Välimäki MJ, Laitinen K, Tiitinen A, Steman UH, Ylöstalo P (1995)
Gonadal function and morphology in non-cirrhotic female alcoholics: a
controlled study with hormone measurements and ultrasonography.
Acta Obstet Gynecol Scand 74:462–466.
Välimäki M, Pelkonen R, Härkönen M, Tuomala P, Koistinen P, Roine R,
Ylikahri R (1990) Pituitary-gonadal hormones and adrenal androgens
in non-cirrhotic female alcoholics after cessation of alcohol intake. Eur
J Clin Invest 20:177–181.
Van den Beld AW, Bots ML, Janssen JAMLL, Pols HAP, Lamberts SWJ,
Grobbee DE (2003) Endogenous hormones and carotid atherosclerosis
in elderly men. Am J Epidemiol 157:25–31.
Van der Gaag MS, Sierksma A, Schaafsma G, Van Tol A, Geelhoed-
Mieras T, Bakker M, Hendriks HFJ (2000) Moderate alcohol consump-
tion and changes in postprandial lipoproteins of premenopausal and
postmenopausal women: a diet-controlled, randomized intervention
study. J Womens Health Gend Based Med 9:607–616.
Van der Gaag MS, Van Tol A, Scheek LM, James RW, Urgert R,
Schaafsma G, Hendriks HFJ (1999) Daily moderate alcohol consump-
tion increases serum paraoxonase activity; a diet-controlled, random-
ised intervention study in middle-aged men. Atherosclerosis 147:405–
410.
Van Thiel DH, Lester R (1979) The effect of chronic alcohol abuse on
sexual function. Clin Endocrinol Metab 8:499–510.
Watson RR, Huls A, Araghinikuam M, Chung S (1996) Dehydroepi-
androsterone and diseases of aging. Drugs Aging 9:274–291.
Westerterp KR (1996) Effect of moderate alcohol consumption on energy
expenditure. Alcohol Research 1:187–189.
Ylikahri R, Huttunen M, Härkönen M, Seuderling U, Onikki S, Karonen
SL, Adlercreutz H (1974) Low plasma testosterone values in men
during hangover. J Steroid Biochem 5:655–658.
Zmuda JM, Cauley JA, Kriska A, Glynn NW, Gutai JP, Kuller LH (1997)
Longitudinal relation between endogenous testosterone and cardiovas-
cular disease risk factors in middle-aged men. A 13-year follow-up of
former Multiple Risk Factor Intervention Trial participants. Am J
Epidemiol 146:609–617.
Zumoff B, Rosenfeld RS, Strain GW, Levin J, Fukushima DK (1980) Sex
differences in the twenty-four-hour mean plasma concentrations of
dehydroisoandrosterone (DHA) and dehydroisoandrosterone (DHAS)
and DHA to DHAS ratio in normal adults. J Clin Endocrinol Metab
51:330–333.
ALCOHOL AND SEX HORMONES 785
