33 Tombal and Berges25 noted that 1 patient in their leuprolide gel study experienced a Dorsomorphin clinical trial testosterone breakthrough. They noted that the patient was markedly obese based on BMI.25 Dosing of LHRH analogues in the obese man is deserving of increased attention as obesity is a documented adverse risk factor for prostate cancer outcomes. Optimum Testosterone Level in the Treatment of Prostate Cancer Normal Inhibitors,research,lifescience,medical serum testosterone ranges (which may vary slightly by laboratory) are 300 to 1000 ng/dL (10.4–34.7 nmol/L)

for men aged 17 years and older. Due to intra-assay variability, a deviation of about 7% should be accounted for when interpreting testosterone values. A total serum testosterone level (free + protein bound) of lower than 200 ng/dL (6.9 nmol/L) (American Association of Clinical Endocrinologists) or lower than 300 ng/dL (10 nmol/L) (FDA) is associated with Inhibitors,research,lifescience,medical hypogonadism and warrants further workup in an otherwise normal adult.34 Free testosterone (adult male range, 8.8–27 pg/mL) is sometimes Inhibitors,research,lifescience,medical used in the evaluation of hypogonadism as elevated or decreased sex hormone-binding globulin

(SHBG) changes the bioavailability of the free form (metabolically active) of testosterone. As an example, obesity is characterized by a reduced total testosterone with normal free testosterone due to reduced protein binding. Serum SHBG concentrations increase with age. With increasing age, less of the total testosterone is free or biologically active, as SHBG binds testosterone with high

affinity.35 There is clearly no defined answer to the optimum level of testosterone that should be achieved in the treatment of prostate cancer. Traditional definitions are based on the so-called castrate Inhibitors,research,lifescience,medical levels of testosterone. However, what the castrate level actually is depends on the therapeutic intervention: less than 20 ng/dL (0.69 nmol/L) has been routinely reported for surgical orchiectomy and Inhibitors,research,lifescience,medical less than 50 ng/dL (1.735 nmol/L) has been reported with LHRH therapy. An expert consensus meeting was held in 2005 in San Antonio, Texas, and a similar session took place during the Sixth International Consultation on New Developments Resminostat in Prostate Cancer and Prostate Diseases in Paris, France, in June 2005, to discuss definitions regarding optimal testosterone control in prostate cancer.36 The experts agreed that the term castration is misleading in the case of LHRH agonists, as it means surgical removal of the testes by bilateral orchiectomy. They noted that bilateral orchiectomy should be used as a benchmark for introducing the appropriate testosterone level that needs to be achieved with LHRH agonists. As most patients will achieve and maintain a serum testosterone level of lower than 20 ng/dL after bilateral orchiectomy, the experts agreed that this level should be used for defining chemical castration.