Androgens in Health and Disease.pdf - E Library

Chapter 10/Androgens and Coronary Artery Disease 193
Table 1
Number of Studies Showing Negative (Favorable), Null, or Positive (Adverse)
Relationships Between T and DHEA
with Coronary/Cardiovascular Artery Disease in Males
Relationships
Androgen Study n Negative Null Positive
Testosterone Cross-sectional 32 16 16 0
Case control 4 0 4 0
Prospective cohort
Interventional
3 0 3 0
a
Animal
6 6 0 0
b
9 4 3 2
DHEA and DHEA-S Cross-sectional 10 6 3 1
Case control 6 1 4 1
Prospective cohort
Animal
6 1 5 0
b
5 5 0 0
a
Including studies which used direct iv or intracoronary infusion of pharmacological
doses of testosterone (15–17) but excluding 17 uncontrolled studies in the earlier
literature from before 1950.
b
Cardiovascular disease endpoints in experimental animal studies included aortic
and coronary artery plaques or fatty streak lesions, myointimal proliferation.
However, free T and androstenedione were inversely correlated with carotid artery
atherosclerosis in premenopausal and postmenopausal women (20).
POLYCYSTIC OVARIAN SYNDROME
Indirect evidence for the atherogenicity of androgens in women stems from cross-sectional
data that consistently showed a strong obesity-independent cluster of cardiovascular
risk factors, including insulin resistance, dyslipidemia, and impaired fibrinolysis in patients
with polycystic ovarian syndrom (PCOS). Based on calculated-risk profiles, women with
PCOS were predicted to have a relative risk for myocardial infarction of 7.4 : 1 (21).
In 102 consecutive women undergoing cardiac catheterization, Wild et al. (22) found
a positive correlation between angiographic evidence of coronary artery disease
and clinical evidence of hyperandrogenism. Similarly, in 143 women aged ≤60 yr
referred because of chest pain or valvular heart disease, ultrasound evidence of polycystic
ovaries (in 42% of patients) was associated with an increased number of stenosed
coronary arteries (23). The prevalence of CAD was found to be significantly higher in
28 women (45–59 yr) who had undergone ovarian wedge resection over 18 yr ago
compared to 752 aged-matched controls (24). In case-control studies using B-mode
ultrasound, significantly increased carotid artery intima–media thickness was found in
patients with PCOS compared to age-matched controls irrespective of body mass index
(BMI), fat distribution, and other risk factors (25,26). This may be regarded as evidence
in support of subclinical premature atherosclerosis in middle-aged (>45 yr) women
independently related to the increased testosterone in PCOS. An increased prevalence
of coronary artery calcification (which correlates with atherosclerosis) was found in 32
premenopausal (30–45 yr) women with PCOS compared with 52 controls using electron