Androgens in Health and Disease.pdf - E Library

194 Wu and von Eckardstein
beam computed tomography (27). However, in 18 healthy obese young women (32.7 ±
1.9 yr) with PCOS, endothelium-dependent and endothelium-independent vascular responses
were normal compared to age-matched controls (28).
Mortality and morbidity in over 786 women (over 45 yr of age) diagnosed to have
PCOS on histopathological and hospital inpatient diagnostic records were compared
retrospectively with 1060 age-matched controls. Despite significantly increased diabetes,
hypertension, cholesterol and nonfatal cerebrovascular disease, standardized mortality
ratio of 1.4 (95% confidence interval [CI]: 0.75–2.40) and the odds ratio of 1.5
(95% CI: 0.7–2.9) were not significantly increased (29,30). In another cohort of 346
nonobese patients aged 30.3–55.7 yr diagnosed to have PCOS in a specialized clinic, the
prevalence of cardiac complaints (serious heart disease or cardiac arrest) ascertained by
telephone questionnaire was not significantly different from that in 8950 age-matched
females in the general population (31). However, both of these studies suffer from
methological drawbacks such as underascertainment of PCOS (29,30) and the relative
young age of the small cohort (31).
In summary, although PCOS patients have an adverse-risk profile for CAD, whether
this will lead to an increased and premature disease morbidity and mortality and, if so,
whether this is causally related to chronic hyperandrogenemia per se as opposed to the
associated risk factors remain unclear. Nevertheless, given the high prevalence of
PCOS in the female population, this issue should remain a high priority target for
future research.
RELATIONSHIPS BETWEEN SERUM LEVELS OF T
AND CAD: INTERVENTIONAL CLINICAL STUDIES
Endogenous Androgen Deprivation
A frequently cited but misquoted study (32) compared the life expectancy of 297
castrated inmates with 735 intact inmates (white males) in a single state institution for
the mentally retarded. Castrated males lived an average of 13.6 yr longer than intact
controls. However, the excess mortality in intact inmates was the result of infections with
no difference in cardiovascular disease mortality between the two groups. The authors
concluded that postpubertal castration did not decrease the frequency of deaths because
of cardiovascular disease. In a historical review (33), the life-span of 50 castrati singers
(prepubertal castrates) born between 1581 and 1858 in Europe was 65.5 ± 13.8 yr compared
to 64.3 ± 14.1 yr in 50 noncastrated singers. Prepubertal castration has no effect
on longevity in men. The abolition of testicular androgens by prepubertal or postpubertal
castration does not decrease cardiovascular mortality in men. This is supported by findings
from cross-gender sex hormone treatment in 816 male-to-female transexuals aged
18–86 yr (34). Administration of ethinylestradiol 100 µg/d and cyproterone acetate 100
mg/d for 7734 patient-years was not associated with any significant difference in cardiovascular
mortality or morbidity compared to the general male population despite a 20fold
increase in venous thromboembolic complications.
Androgen Excess from Anabolic Steroid Abuse
Excessive androgen exposure in men is uncommon in clinical practice. However,
anabolic–androgenic steroid (AAS) abuse in the general population is said to have
reached epidemic proportion, with over 1 million current and former users in the United