Summary
We studied thirteen male-to-female (M→F) and ten female-to-male (F→M) transsexuals
who, for four months, received cross-sex treatment with, respectively, ethinylestradiol
and cyproterone acetate, and with testosterone esters. We assessed the effects of
treatment on plasma levels of tissue-type plasminogen activator (tPA), von Willebrand
factor (vWF), vWF-propeptide (vWF:AgII) and bigendothelin-1 (big-ET-1), four proteins
that are markers of endothelial cell functioning. We also measured urokinase-type
PA (uPA) and plasminogen activator inhibitor-type 1 (PAI-1), which may not be endothelium-derived
but share major clearance pathways with tPA.
In M→F transsexuals, mean plasma levels of tPA (minus 4.4 ng/ml), big-ET-1 (minus
0.8 pg/ml), uPA (minus 0.5 ng/ml) and PAI-1 (minus 26 ng/ml) decreased (all Ps ≤0.02).
The level of vWF increased (plus 24%; P = 0.005), while vWF:AgII did not change (P
= 0.49).
In F→M transsexuals, levels of big-ET-1 increased (plus 0.4 pg/ml; P = 0.02), while
tPA, uPA and PAI-1 did not change (all Ps >0.25). In this group vWF decreased (minus
14%; P = 0.06), but vWF:AgII did not change (P = 0.38).
Estrogens and androgens have clear effects on plasma levels of endothelial marker
proteins. The mechanisms behind these effects are complex and appear to involve both
altered secretion (big-ET-1) and processing and/or clearance (vWF and possibly tPA).
Therefore, effects of hormones on the levels of endothelial marker proteins do not
necessarily reflect changes in endothelial cell functioning, at least with regard
to changes in vWF level associated with the oral administration of high doses of ethinylestradiol
and cyproterone acetate to healthy men and the parenteral administration of testosterone
to healthy women.
