The relation between testosterone (T) production and action is complex, involving protein binding in the circulation affecting clearance and tissue availability, T production from precursors in peripheral tissues, deactivating and activating (to dihydrotestosterone and estradiol) metabolism within target tissues, besides factors affecting androgen responsiveness (receptor concentrations, cofactors, genetics,…). Yet, in absence of a useful independent marker of androgen action, serum T remains the main, albeit imperfect tool for assessment of androgen exposure. As many factors affect SHBG levels and thus total T(TT), free T(FT) more closely reflects androgen exposure. There are analytical issues deserving attention. Increased FT is the most reliable marker of hyper-androgenism in women, most frequently part of a PCO syndrome, often with overweight and insulin resistance, and with alopecia, hirsutism and/or acne as clinical expression. Evidence for a female hypoandrogenic syndrome is limited. After menopause, decreasing production of adrenal androgens become the only source of sex steroids. At all ages between men variability in T levels is substantial. (F)T levels follow pubertal development, remain stable until the 6th decade. Thereafter population means decline mildly for TT and sharper for FT due to SHBG increase. Symptoms of severe primary or secondary hypogonadism include sexual dysfunction, muscle waist, increased adipositas, osteoporosis and decreased well-being. Low (F)T in older men is associated with increased mortality, but may be marker rather than cause of poor health. Adiposity is a negative determinant of SHBG and TT. Obesity, diabetes and cardiovascular disease are associated with lower (F)T; although low (F)T may be the consequence of these situations, there is also evidence for bidirectional relationship.
Biographical details: Jean-Marc Kaufman obtained his MD and PhD degrees at the Ghent University, Belgium. He was a senior postdoctoral research fellow (19821984) in reproductive physiology with Ernst Knobil at the University of Texas Medical School at Houston. He is board certified in Endocrinology and in Nuclear Medicine. In 1985 he joined the staff of the Ghent University Hospital; he headed the department of Endocrinology from 2003 to 2014 and the Laboratory for Hormonology from 1995 to 2014. He was appointed in 1993 professor of medicine at the Ghent University (1993) and is past chair of the university department of Internal Medicine (20102014). From October 1st 2014 he is professor emeritus at the Ghent University. Main research interests are in the assessment, regulation and action of sex steroids with focus on their role in health, disease and aging in men. He is (co)author of 290 publications in international peer reviewed journals; >13000 SSCI citations