Sex Steroids, Insulin, and Arterial Stiffness in Women and Men

Abstract

Abstract-Arterial stiffness may be influenced by sex steroids and insulin; the association with fasting insulin level may be stronger in women than in men. Therefore, we analyzed the effects of sex steroid administration on (1) arterial stiffness and (2) the relationship between fasting insulin level and arterial stiffness. Twelve male-to-female transsexuals were treated with ethinyl estradiol and cyproterone acetate, and 18 female-to-male transsexuals were treated with testosterone esters, with assessments made at baseline and after 4 and 12 months. Changes in distensibility and compliance coefficients (DC and CC, respectively) of the common carotid artery, femoral artery (FA), and brachial artery (BA) were analyzed in relation to changes in fasting plasma levels of glucose, insulin, HDL-cholesterol, and triglycerides. After 4 months of estrogens and antiandrogens in men, significant reductions in the CC and DC of the FA (Pϭ0.006 and Pϭ0.04, respectively) and BA (Pϭ0.04 and Pϭ0.04, respectively) were observed. In women, testosterone, on average, did not affect DC or CC, but the changes in fasting insulin level were strongly negatively associated with changes in the CC and DC, especially in the FA and BA. These associations were significantly less strong in genetic men and were independent of age, mean arterial pressure, and glucose and lipid levels. This experimental study shows (1) that short-term administration of estrogens and antiandrogens increases FA and BA stiffness in men and (2) that the fasting insulin level is a stronger determinant of arterial stiffness in women than in men.(Hypertension. 1999;34:590-597.)M en are at a higher risk of developing cardiovascular disease (CVD) than women, but in non-insulindependent diabetes mellitus, this gender difference is much less pronounced. 1-4 A core element of non-insulin-dependent diabetes mellitus is insulin resistance, and the question arises of whether insulin resistance or other elements clustered in the insulin resistance syndrome, 5 such as hyperinsulinemia, glucose intolerance, dyslipidemia, abdominal obesity, and hypertension, partially negate the normal gender difference in cardiovascular risk.Large-artery stiffening, a major determinant of cardiac workload and systolic blood pressure, 6 may contribute to the development of CVD. Data on a possible gender difference in arterial stiffness are contradictory. Measurement of pulsewave velocity, an estimate of regional arterial stiffness, indicates that arteries in men are stiffer than those in premenopausal women. [7][8][9] In contrast, local arterial stiffness of the common carotid artery (CCA), measured by ultrasound, 10 -12 and global vascular stiffness, derived from pulsepressure waveform analysis, 13 occur less in men than in women. Conflicting data on the modulating effects of endogenous 14 and exogenous 15-20 estrogens on regional 17-20 and local arterial stiffness 14 -16 in women have also been published. Currently, there is no prospective information on the effects of estrogen or testosterone ad...

A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones

“…The favorable serum lipid changes associated with ethinyl estradiol (7) -an increase in highdensity lipoprotein cholesterol (C20%) and a decrease in low-density lipoprotein cholesterol (K12%) -did apparently not translate into a reduced risk of cardiovascular death. Recently, raised levels of circulatory inflammatory markers in transsexuals treated with high dose of oral estrogens have been reported, which could further contribute to the increased cardiovascular risk (10). An increased risk of cardiovascular disease was also reported in women using oral contraceptives (OC), in particular if they used OC pills with a higher ethinyl estradiol content (50 mg), even more so when they were smokers (21)(22)(23).…”

“…Several studies have looked at the effects of cross-sex hormone administration on laboratory variables related to cardiovascular risk in transsexuals, finding partially favorable and partially unfavorable effects (7)(8)(9)(10). The skewed sex ratio in cardiovascular disease favoring women at all ages and the increasing incidence of cardiovascular disease after menopause were previously interpreted to indicate that estrogens are cardioprotective.…”

Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern

“…As ethinyl estradiol stood out as a risk factor in MtoF in the study on mortality (14), we have reviewed our earlier studies of the effects of cross-sex hormone administration on surrogate cardiovascular risks (28,39,40,41,42,43,44,45) included in Tables 2 and 3. The estrogen used in our own studies was ethinyl estradiol.…”

The effects of the aromatase inhibitor anastrozole on bone metabolism and cardiovascular risk indices in ovariectomized, androgen-treated female-to-male transsexuals

“…The distensibility coefficient (DC), reflecting intrinsic vascular wall elasticity, and the compliance coefficient (CC), reflecting buffering capacity of the vessel wall, were calculated from the arterial diameter (D) and changes in arterial diameter during the heart cycle (DD or distension) and pulse pressure (DP) as follows: DC ¼ (2 * DD)/(D * DP) and CC ¼ (D * DD * D)/(2 * DP) (17). All hemodynamic measurements were performed with a non-invasive ultrasound system as previously described (17).…”