ABSTRACT
BACKGROUND: Animal experiments suggest that exposure to elevated levels of androgens during development by means of so-called hormonal programming causes metabolic aberrations at adulthood. An indirect strategy to address the possible importance of such an influence also in humans would be to study female dizygotic twins, presuming that those with a twin brother--due to diffusion of testosterone--have been exposed to higher androgen levels prenatally. DESIGN: We have compared 8409 women with a male twin with 9166 women with a dizygotic female twin with respect to self-reported indices of anthropometry and metabolic aberrations at age 42 or older. RESULTS: Body mass index (BMI), body weight and rate of dyslipidemia were moderately, but significantly, higher in women from opposite-sexed (OS) twin pairs; splitting for age revealed this difference to be present in those ≥ 60 years of age only. CONCLUSION: The results (i) support the notion that comparisons of women with a twin brother with women from same-sexed twin pairs may be used to shed light on possible long-term effects of interindividual variations in early androgen exposure, and (ii) suggest that the effects of early androgen exposure on metabolism previously observed in animal experiments are of relevance also for humans.
Subject(s)
Androgens/genetics , Body Mass Index , Dyslipidemias/genetics , Receptors, Androgen/metabolism , Twins, Dizygotic , Adult , Aged , Androgens/metabolism , Body Weight , Cohort Studies , Dyslipidemias/epidemiology , Dyslipidemias/etiology , Dyslipidemias/metabolism , Female , Humans , Male , Middle Aged , Risk Assessment , Sex Characteristics , Sex Distribution , Sweden/epidemiologyABSTRACT
Previous studies on the cardiovascular effects of androgens in females, most of them using testosterone treatment, have yielded conflicting results. Testosterone is metabolized into oestradiol (E2) and dihydrotestosterone (DHT) within cardiovascular tissues. The aim of the present study was to explore the cardiovascular effects exerted by E2 and the non-aromatizable androgen DHT and to study possible interactions between these in female rats. Ovariectomized rats were treated with DHT, E2, or DHT+E2 for 6 weeks. DHT increased left-ventricular posterior wall thickness, assessed by echocardiography, whereas left-ventricular dimension, as well as total heart weight and calculated left-ventricular mass, were unchanged. DHT also increased the levels of insulin-like growth factor-I mRNA in the left ventricle. E2 abolished the effect of DHT on left-ventricular remodelling and insulin-like growth factor-I mRNA when the two treatments were given in combination. E2 also reduced androgen receptor mRNA levels in the heart. Neither E2 nor DHT changed blood pressure measured by telemetry. In conclusion, treatment with the endogenous non-aromatizable androgen DHT causes cardiac concentric remodelling in ovariectomized rats, possibly mediated by increased local levels of insulin-like growth factor-I. The effect of DHT on cardiac wall thickness was antagonized by E2, possibly through downregulation of cardiac androgen receptors. These mechanisms may be of importance for the concentric left-ventricular geometric pattern developing in women after menopause.
