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- Testosterone (T) and estradiol (E2) have important metabolic actions which are gender-specific (sex-dimorphic).
- Most T and E2 circulate bound to sex hormone-binding globulin (SHBG), a glycoprotein that regulates the amount of sex steroids available for biological action.
- Of total T, 54% weakly bound to albumin and other proteins, 44% bound to SHBG, 2% unbound (free T) .
- In reproductive age women, one third of T is secreted by the ovary, whereas two thirds arise from the peripheral conversion of androstenedione to T.
- Androstenedione is directly produced by the ovary but also from peripheral conversion of adrenal dehydroepiandrosterone sulfate (DHEA-S).
- Male Hypogonadism (for example, with androgen deprivation therapy for prostate cancer) is linked to the metabolic syndrome, type 2 diabetes and an increased risk for cardiovascular disease .
- Hyperandrogenism in women (for example, with polycystic ovarian syndrome) is linked to the metabolic syndrome, type 2 diabetes and cardiovascular disease . High T in postmenopausal women is also linked to an increased risk of type 2 diabetes  .
- High endogenous E2 is associated with an increased risk for type 2 diabetes in males and postmenopausal women  .
- Low SHBG is a risk factor for type 2 diabetes in both males and females .
- A recent study suggested that women under the age of 45 years who have type 2 diabetes have three times the risk of early menopause compared to women without diabetes .
- Low total T may be associated with more advanced atherosclerotic disease markers in middle-aged men with type 2 diabetes .