Testosterone therapy (TTh) is on the rise in theUnited States as more and more men seek to managethe age-related symptoms of hypogonadism [1]. Lowtestosterone levels have been associated with a mul-titude of symptoms and clinical conditions thathave wide-reaching effects on a man’s overall healthand quality-of-life (QoL). An increasingly strongevidence base suggests that TTh may safely improvepsychological health and a sense of well being in anumber of clinical domains.Male hypogonadism refers to a clinical syn-drome resulting from failure of the testes to producephysiological levels of testosterone as a result of adisruption in the hypothalamic–pituitary axis ordamage to the testis itself [2]. The clinical presenta-tion of hypogonadism is highly variable rangingfrom asymptomatic to a constellation of signs andsymptoms, many of which can have significanteffects on a patient’s QoL [3–6].Whereas a serum testosterone level of less than300ng/dl is often used to define biochemical hypo-gonadism, evidence suggests that a number of menwill develop clinically significant symptoms beforereaching this threshold [7–10]. In a survey of menaged 40–90, an increased prevalence of hypogona-dal symptoms was observed with serum testosteronevalues of 320–375ng/dl [10]. Similar results wereseen in a retrospective review of younger men withhypogonadism (less than 40 years)
EFFECTS ON CARDIOVASCULAR DISEASEAND MORTALITY
Large clinical trials have linked low testosteronelevels with increased overall mortality [18,56,57].Although fraught with controversy (detailed in[56]), the conclusion of these trials results in thediscovery that TTh should be used with caution inelderly males of more than 65 years of age. The causeof this association has traditionally been felt to besecondary to the effects of testosterone on cardio-vascular disease. A number of critical cardiovascularrisk factors have been associated with testosterone
TESTOSTERONE THERAPY MODALITIES
Patients treated with TTh have been found to havehigh rates of satisfaction with their therapy, regard-less of formulation (i.e., gels, injections, pellets).Satisfaction with TTh correlates with notableimprovements in well being and QoL outcomes[68]. As such, individual preferences should be takeninto account to limit treatment dissatisfaction. Tes-tosterone pellets, for example, are favored for theirease of use and convenience whereas injectable for-mulations are more affordable [68]. For patientsexperiencing erythrocytosis as a result of their treat-ment, formulations other than injectable testoster-one (gels, pellets) may be more appropriate due totheir lower rates of polycythemic occurrence [69].Patient comorbidities and primary symptomsshould also be considered. A meta-analysis of TThin hypogonadal men with depression found testos-terone gel formulations to be much more effective insymptom improvement compared with injectables.The authors of this study proposed that the intra-muscular route of administration may exacerbatepreexisting low mood and feelings of helplessness inthis population [25]. Strolloet al.[39] found thattransmucosal and transdermal delivery of testoster-one was much more effective in elderly hypogona-dal, hyperglycemic men compared with oralpreparations (not available in the United States).Newer formulations, such as intra-nasal testos-terone, offer another noninvasive delivery methodwhich may be appealing to some patients. In earlyclinical trials, Lipshultzet al.examined the effects of4.5% nasal testosterone on erectile dysfunction andmood. The formulation produced significantimprovements in all erectile and mood domainsstudied as early as 30 days following initiation. Easeof use, avoidance of potential transference, and therapid effect of this delivery method, may proveparticularly appealing to men who value conve-nience [
Due to its broad clinical presentation, symptomatichypogonadism can have a significant influence on aman’s general well being and psychological health.An increasingly strong body of evidence has shownsubstantial improvements following TTh in depres-sion, general QoL, body composition, diabetes andmetabolic syndrome, and cardiovascular mortality
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ayton JB, Li D, Meier CR,etal.Testosterone lab testing and initiation in theUnited Kingdom and the United States, 2000 to 2011. J Clin EndocrinolMetab 2014; 99:835 – 842.2.Bhasin S, Cunningham GR, Hayes FJ,etal.Testosterone therapy in men withandrogen deficiency syndromes: an Endocrine Society clinical practice guide-line. J Clin Endocrinol Metab 2010; 95:2536 – 2559.3.Araujo AB, Esche GR, Kupelian V,etal.Prevalence of symptomatic androgendeficiency in men. J Clin Endocrinol Metab 2007; 92:4241 – 4247.4.Zitzmann M, Faber S, Nieschlag E. Association of specific symptoms andmetabolic risks with serum testosterone in older men. J Clin Endocrinol Metab2006; 91:4335 – 4343.5.Basaria S. Male hypogonadism. Lancet 2014; 383:1250 – 1263.6.Hall SA, Esche GR, Araujo AB,etal.Correlates of low testosterone andsymptomatic androgen deficiency in a population-based sample. J ClinEndocrinol Metab 2008; 93:3870 – 3877.7.Rosner W, Auchus RJ, Azziz R,etal.Position statement: utility, limitations, andpitfalls in measuring testosterone: an Endocrine Society position statement.J Clin Endocrinol Metab 2007; 92:405 – 413.8.Rosen RC, Araujo AB, Connor MK,etal.The NERI Hypogonadism Screener:psychometric validation in male patients and controls. Clin Endocrinol (Oxf)2011; 74:248 – 256.9.Scovell JM, Ramasamy R, Wilken N,etal.Hypogonadal symptoms in youngmen are associated with a serum total testosterone threshold of 400 ng/dL.BJU Int 2015; 116:142 – 146.10.Ramasamy R, Wilken N, Scovell JM,etal.Hypogonadal symptoms areassociated with different serum testosterone thresholds in middle-agedand elderly men. Urology 2014; 84:1378 – 1382.11.Feldman HA, Longcope C, Derby CA,etal.Age trends in the level of serumtestosterone and other hormones in middle-aged men: longitudinal resultsfrom the Massachusetts male aging study. J Clin Endocrinol Metab 2002;87:589 – 598.12.Harman SM, Metter EJ, Tobin JD,etal.Baltimore Longitudinal Study of Aging.Longitudinal effects of aging on serum total and free testosterone levels inhealthy men. J Clin Endocrinol Metab 2001; 86:724– 731.13.Zmuda JM, Cauley JA, Kriska A,etal.Longitudinal relation between endo-genous testosterone and cardiovascular disease risk factors in middle-agedmen. A 13-year follow-up of former Multiple Risk Factor Intervention Trialparticipants. Am J Epidemiol 1997; 146:609 – 617.14.Mulligan T, Frick MF, Zuraw QC,etal.Prevalence of hypogonadism in malesaged at least 45 years: the HIM study. Int J Clin Pract 2006; 60:762 – 769.15.Araujo AB, O’Donnell AB, Brambilla DJ,etal.Prevalence and incidence ofandrogen deficiency in middle-aged and older men: estimates from theMassachusetts Male Aging Study. J Clin Endocrinol Metab 2004;89:5920 – 5926.16.Wu FC, Tajar A, Pye SR,etal.Hypothalamic-pituitary-testicular axis disrup-tions in older men are differentially linked to age and modifiable risk factors:the European Male Aging Study. J Clin Endocrinol Metab 2008; 93:2737 – 2745.17.Basaria S, Travison TG, Alford D,etal.Effects of testosterone replacement inmen with opioid-induced androgen deficiency: a randomized controlled tri
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