Effects of androgens on haemostasis.

Maturitas. 1996 Jul;24(3):147-55.

Effects of androgens on haemostasis.

Winkler UH.

Zentrum für Frauenheilkunde, Universitätsklinikum Essen, Germany.

Androgen deficiency is associated with an increased incidence of cardiovascular
disease. There is evidence that thromboembolic disease as well as myocardial
ifarction in hypogonadic males are mediated by low baseline fibrinolytic
activity. Hypogonadism in males is associated with an enhancement of fibrinolytic
inhibition via increased synthesis of the plasminogen activator inhibitor PAI 1.
On the other hand, stanozolol and danazol reduce PAI 1 and are associated with
increased fibrinolytic activity. However, in male abusers of anabolic steroids
the net effect on the haemostatic system may change from anti- to prothrombotic;
there appears to be an individual threshold dose above which thrombogenic effects
on platelets and vasomotion may overcome the profibrinolytic effects on PAI 1.
There are numerous reports on weight-lifters dying of atherothrombotic ischemic
heart disease while abusing anabolic steroids. Androgens are known to have
profound effects on carbohydrate and lipid metabolism. In fact, much of the
individual inconsistency of the effects of androgens on fibrinolytic and
haemostatic activity appears to be based on the close interrelationship of these
metabolic systems. Androgens may have unfavourable effects on the HDL/LDL
cholesterol ratio, on triglyceride levels and on the insulin/insulin-like growth
factor 1 (IGF 1) system. Hypertriglyceridemia as well as insulin resistance are
both associated with low fibrinolytic activity and increased PAI 1 levels. On the
other hand, lipoprotein(a), a recently acknowledged independent risk factor of
CVD was shown to respond favourable to androgen treatment, in men as well as in
women. In women, agonistic as well as antagonistic effects of estrogens and
progestins need to be taken into account. In fact, estradiol may modulate
testosterone effects on haemostasis. Androgen medication in premenopausal women,
such as danazol, was found to reduce PAI 1 suggesting an improvement of the
fibrinolytic activity. Also, in hormone replacement therapy (HRT) androgenic
progestins or complex compounds with androgenic effects are associated with a
marked reduction of PAI 1 and an improvement of fibrinolytic activity. Further
improvement of fibrinolytic activity may be associated with the marked decrease
of lipoprotein (a) (Lp(a)) in women on androgenic HRT. However, little is known
on the interrelationship of estrogens, 19-nortestosterone or progesterone
derivatives and testosterone. an interrelationship that may have substantial
impact on the metabolic and particularly haemostatic net effects of a
preparation. In summary, information on the effects of androgens on haemostasis
is limited and may be particularly incomplete due to the fact that interaction
with other sex steroids appears to be an important confounder. In any case, there
are numerous effects of synthetic androgens on the synthesis and release of
haemostatic factors, namely an increase of the inhibitors of coagulation and a
decrease of the inhibitor of the fibrinolytic system. However, the use of
androgens in patients with congenital deficiencies of these coagulation factors
or previous events of cardiovascular disease has yielded disappointing results.
On the other hand, particularly the reduction of fibrinolytic inhibition (PAI 1)
and Lp(a) were considered favourable effects of androgens with regard to the risk
of cardiovascular disease. Differences between preparations with pronounced
androgenic versus antiandrogenic effects and the effect of combined preparations
need to be studied in much more detail. The profibrinolytic effects of androgens
may be of particular interest with regard to favourable effects of HRT on
cardiovascular disease.