Testosterone Associations with Erectile Dysfunction, Diabetes, and the Metabolic Syndrome  T. Hugh Jones  European Urology Supplements  Volume 6, Issue 16, Pages 847-857 (October 2007) DOI: 10.1016/j.eursup.2007.07.002 Copyright © 2007 European Association of Urology Terms and Conditions

Fig. 1 Prevalence of hypogonadism in men with type 2 diabetes. Incidence of positive symptom score in men with low testosterone by decades of age. (A) Total testosterone (TT). , TT < 8nmol/l; , TT < 12nmol/l. (B) Bioavailable testosterone (BT) and calculated free testosterone (cFT). , BT<2.5nmol/l; , BT<4nmol/l; , cFT<0.255nmol/l. © (2007) American Diabetes Association From Diabetes Care, Vol. 33 (2007); pages 911–917. European Urology Supplements 2007 6, 847-857DOI: (10.1016/j.eursup.2007.07.002) Copyright © 2007 European Association of Urology Terms and Conditions

Fig. 2 Correlation of total and bioavailable testosterone levels with erectile dysfunction as assessed by IIEF scores. From ref. [38]. © (2007) International Journal of Andrology, Online early articles doi:10.1111/j.1365-2605.2007.00744x. European Urology Supplements 2007 6, 847-857DOI: (10.1016/j.eursup.2007.07.002) Copyright © 2007 European Association of Urology Terms and Conditions

Fig. 3 The hypogonadal-obesity-adipocytokine cycle. Increasing abdominal obesity leads to increased activity of the enzyme aromatase, present in adipose tissue, which converts testosterone to oestrogen. The resulting low testosterone level increases lipoprotein lipase enzyme activity and triglyceride uptake leading to increased obesity and insulin resistance. This in turn causes further androgen deficiency and visceral fat deposition. Oestradiol inhibits gonadotrophin release from the pituitary. Furthermore, testosterone levels are also lowered as a result of leptin resistance at the hypothalamic-pituitary level and the inhibitory effect of leptin on the testicular axis. Proinflammatory adipocytokines such as tumour necrosis α (TNF-α) and interleukin 6 (IL-6) could also potentially inhibit the pituitary axis resulting in low testosterone levels. This represents a form of secondary hypogonadism where the hypothalamic-pituitary axis cannot respond to low circulating testosterone levels. European Urology Supplements 2007 6, 847-857DOI: (10.1016/j.eursup.2007.07.002) Copyright © 2007 European Association of Urology Terms and Conditions