Low Dehydroepiandrosterone Sulfate and Heart Disease in
Middle-Aged Men: Cross-Sectional Results from the Massachusetts
Male Aging Study
HENRY A. FELDMAN,
, CATHERINE B. JOHANNES,
, JOHN B. M
AND CHRISTOPHER LONGCOPE,
PURPOSE: Serum concentrations of the adrenal androgen dehydroepiandrosterone (DHEA) and its
sulfate ester (DHEAS), both of which decline with age more markedly than other sex hormone levels,
have been alternately credited and discredited as “protective” correlates of heart disease. Baseline data
from the Massachusetts Male Aging Study (MMAS), collected in 1987–89, provided a large population-
based random sample (n ϭ 1709) in which to examine cross-sectionally the relation of DHEA and
DHEAS levels to heart disease, while controlling for a comprehensive set of potential confounders
including serum lipid and hormone levels as well as smoking, alcohol intake, obesity, hypertension,
diabetes, diet, medication, physical activity, and psychological measures.
METHODS: The subjects were men aged 40–70 years, randomly sampled from the Massachusetts state
census listing, measured and interviewed at home. Nonfasting blood samples were assayed for hormones
RESULTS: In all strata of age, smoking, and alcohol intake, the age-adjusted odds ratio for self-
reported heart disease was between 0.55 and 0.85 per standard deviation (SD) of log DHEA and DHEAS
concentration. Multiple logistic regression analysis indicated a strong independent role for DHEAS as
a predictor of self-reported heart disease, controlling for age and the potential confounders listed above.
The multiply-adjusted odds ratio for heart disease was 0.64 per SD log DHEAS concentration, with
95% conﬁdence interval (CI) 0.50–0.83 (P ϭ 0.0002). The DHEAS effect was not diminished by
controlling for use of cardiac, vasodilator, antihypertensive, or lipid-lowering medication.
CONCLUSIONS: These ﬁndings suggest that serum DHEAS levels bear an inverse relationship to
heart disease, independently of a large set of established cardiovascular risk factors. The cross-sectional
nature of this study requires that the ﬁndings be interpreted with caution.
Ann Epidemiol 1998;8:217–228. 1998 Elsevier Science Inc.
Aging, Androgens, Cardiovascular Diseases, Coronary Heart Disease,
Dehydroepiandrosterone, Ischemic Heart Disease, Risk Factors.
numerous provocative ﬁndings in animal models and in vitro
demonstrating actions of DHEA related to vascular disease,
Dehydroepiandrosterone (DHEA), a circulating ketoste-
cancer, diabetes, cognition, memory, and immune re-
roid, and its conjugated form dehydroepiandrosterone sul-
fate (DHEAS) are commonly considered secondary or
DHEAS, secreted largely by the adrenals rather than the
“weak” androgens, mere precursors to testosterone, estrogen,
gonads, is the most plentiful circulating steroid in adults (6,
and other important steroids. A speciﬁc physiological func-
10, 18). The bulk of serum DHEA arises by conversion from
tion for DHEA or DHEAS has indeed proved difﬁcult to
DHEAS in peripheral tissues (10). Serum levels of DHEA
pinpoint, despite the abundance of DHEAS in serum and
and DHEAS peak in young adulthood, at a somewhat higher
level in men than in women, and proceed to decline with
age more markedly than any other hormone, corroborating
the experimental evidence of their involvement in age-
From the New England Research Institutes, Watertown, MA (H.A.F.,
related health problems (22–25). DHEA shows anti-clotting
C.B.J., J.B.M.); and the Department of Obstetrics and Gynecology, Univer-
sity of Massachusetts Medical Center, Worcester, MA (C.L.).
and anti-proliferative properties in vitro (16, 26–28) and
Address reprint requests to: Dr. Henry Feldman, New England Research
anti-atherosclerotic properties in animals (29, 30). More
Institutes, 9 Galen St., Watertown, MA 02172.
generally, DHEA has been painted as a marker of good
Received December 26, 1996; revised July 24, 1997; accepted October
health (31–33) and is touted by some—many others say
1998 Elsevier Science Inc. All rights reserved. 1047-2797/98/$19.00
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