Androgens in Health and Disease.pdf - E Library

192 Wu and von Eckardstein
contraception, physiological aging, chronic debilitating conditions, and hormone replacement
in postmenopausal women (5), it becomes increasingly pertinent to consider
whether natural or induced changes in levels of testosterone (T) or dehydroepiandrosterone-S
(DHEA-S) will impact on the risks of coronary artery disease in men and
women. This review synthesizes data from a variety of disciplines into a global assessment
of the relationship between androgens and CAD in men and women (see ref. 6 for
more comprehensive coverage with a full bibliography).
RELATIONSHIPS BETWEEN SERUM LEVELS
OF T AND CAD: OBSERVATIONAL STUDIES
T and CAD in Men
CROSS-SECTIONAL CLINICAL STUDIES
Of the 32 cross-sectional studies on the relationships between circulating T and CAD
in men (6,7), 16 found lower levels of T in cases compared to controls, whereas 16
showed no difference. As with all cross-sectional studies, the directionality of the relationship
is indeterminate so that lower T levels may be either the consequence or a cause
of CAD or may be associated with confounding variables such as insulin, lipids, changes
in lifestyle, and medications. No study suggested that high levels of T were associated
with CAD.
PROSPECTIVE COHORT OR CASE-CONTROL STUDIES
Of the seven non-cross-sectional studies (8–14), none showed T to have any significant
relationship or predictive value for incident CAD (see Table 1). The three prospective
cohort studies followed 1009 Californian men aged 40–79 over 12 yr (8), 2512 aged
45–59 in South Wales (Caerphilly) for 5 yr (9), and 890 Baltimore men aged 53.8 ± 16
for up to 31 yr (10). There was no correlation between baseline T levels and subsequent
development of fatal or nonfatal CAD, stroke, or heart failure after adjusting for relevant
confounders. These three cohort studies go a long way toward confirming that T is not
an independent risk factor for CAD in men. In the four case-control studies, baseline T
levels in cases of CAD and matched controls from the Honolulu Heart Programme (11),
Multiple Risk Factors Inverventional Trial (12), Baltimore Longitudinal Study of Ageing
(13), and the Helsinki Heart Study (14) did not predict CAD events during observation
periods of 6–8, 19–20, 9.5, and 5 yr respectively.
In summary, the 39 studies in the literature together provide a consistent dataset that
shows the lack of a relationship between circulating T and incident or existing CAD in
men. There is a suggestion, only from cross-sectional studies, that patients with CAD
may have lower T levels; the nature of this relationship is unclear. None of the studies
showed a positive relationship between T and CAD to suggest that high levels of this
androgen may be a risk factor.
T and CAD in Women
Testosterone, bioavailable T, and androstendione did not differ significantly in 942
women with and without a history of heart disease at baseline and did not predict cardiovascular
death or death from ischaemic heart disease (18). In contrast, in a crosssectional
angiographic study of 109 postmenopausal women with chest pain, serum
levels of free T were correlated with the extent of coronary artery narrowing (19).