Giovanni Caffagni

Human models of aromatase deficiency.

Estrogens exert a wide range of biological effects in both sexes also on non-reproductive systems and organs. Human congenital estrogen deficiency, due to an inactivating mutation of the aromatase gene, leads to the lack of the estrogen synthesis, with gonadotropins and circulating testosterone ranging from normal to elevated. The aromatese-deficient females show hyperandrogenism and virilization at birth with ambiguous genitalia. During childhood there are a dysfunction in the LHRH-LH/FSH axis and a progressive delay in bone age. At puberty they show primary amenorrhea, no breast development, worsening of the virilization and the absence of growth spurt. The clinical phenotype in the male affected subjects comprises tall stature, persistent linear growth and delayed bone age, osteopenia/osteoporosis, eunuchoid body proportion, different degrees of glucose-insulin and of fertility impairment. These phenotypes suggest the physiological role of estrogens on the skeleton, on pituitary function, on the reproductive system, on glucose metabolism, being the precise mechanism on each of these functions not yet known in detail. The estradiol replacement treatment leads to a complete epiphyseal closure and to the skeletal maturation. Moreover, the increasing knowledge on the role of estrogen in several metabolic pathways could be important for a better management of several metabolic diseases.

Sex steroids and sexual desire in a man with a novel mutation of aromatase gene and hypogonadism

Sexual behavior was investigated by a sexological interview in a man with aromatase deficiency and hypogonadism. The study was performed at the end of a long testosterone treatment, during transdermal estradiol treatment and during estradiol and testosterone associated treatment. Sexual behavior did not show abnormalities. As assessed by a sexological interview and by a sexological questionnaire gender-identity was male, sexual orientation was heterosexual and libido was normal. Sexual function was limited to masturbation and was seemingly unaffected by testosterone or estradiol alone; only the associated treatment induced a great increase in libido and in frequency of masturbation and sexual fantasies when both testosterone and estradiol reached the range of normality. Sexual behavior is mainly under the control of cognitive functions in men, but sex steroids may modulate some aspects of male sexuality. Our findings suggest that in men estrogens could play a role in sexual activity.

Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in men

Aims  The role of sex steroids in glucose and insulin metabolism in men remains unclear. To investigate the effects of sex steroids and oestrogen on insulin sensitivity in men, we studied two male adults with aromatase deficiency (subject 1 and subject 2).

Endocrine NAFLD: a hormonocentric perspective of Non-Alcoholic Liver Disease (NAFLD) pathogenesis in HIV-infected patients

We included endocrine variables (but not sex hormones) and known independent predicting variables (sex, waist circumference, ALT/AST, NRTI cumulative exposure) in a backward stepwise multivariate logistic regression analysis. Independent variables associated with NAFLD were NRTI cumulative exposure (OR = 1.11 per year; CI 1.01– 1.20), ALT/AST (OR = 3.97; CI 1.78–8.87), waist circumference (OR = 1.06; CI 1.03–1.11). When including sex hormones in different gender groups insulin increased predictive value in female only (OR = 1.18; CI 1.03, 1.34). Conclusion Homeostasis of glucose appears the only endocrine system associated with NAFLD. from Ninth International Congress on Drug Therapy in HIV Infection Glasgow, UK. 9–13 November 2008