Evaluation and Management of Testosterone Deficiency: AUA ...

1 Evaluation and Management of Testosterone Deficiency: AUA GuidelineJohn P. Mulhall, Landon W. Trost, Robert E. Brannigan, Emily G. Kurtz, J. Bruce Redmon,Kelly A. Chiles, Deborah J. Lightner, Martin M. Miner, M. Hassan Murad,Christian J. Nelson, Elizabeth A. Platz, Lakshmi V. Ramanathan and Ronald W. LewisFrom the American Urological Association Education and Research, Inc., Linthicum, MarylandPurpose:There has been a marked increase in Testosterone prescriptions in thepast decade resulting in a growing need to give practicing clinicians properguidance on the Evaluation and Management of the Testosterone and Methods:A systematic review utilized research from the MayoClinic Evidence Based Practice Center and additional supplementation by theauthors. Evidence-based statements were based on body of evidence strengthGrade A, B, or C and were designated as Strong, Moderate, and ConditionalRecommendations with additional statements presented in the form of ClinicalPrinciples or Expert Opinions (table 1 in supplementary unabridged guideline, ).

2 Results:This guideline was developed by a multi-disciplinary panel to informclinicians on the proper assessment of patients with Testosterone deficiency andthe safe and effective Management of men on Testosterone therapy. Additionalstatements were developed to guide the clinician on the appropriate care of pa-tients who are at risk for or have cardiovascular disease or prostate cancer aswell as patients who are interested in preserving :The care of Testosterone deficient patients should focus on accurateassessment of total Testosterone levels, symptoms, and signs as well as proper on-treatment monitoring to ensure therapeutic Testosterone levels are reached andsymptoms are ameliorated. Future longitudinal observational studies and clin-ical trials of significant duration in this space will improve diagnostic techniquesand treatment of men with Testosterone deficiency as well as provide more dataon the adverse events that may be associated with Testosterone Words: Testosterone , hypogonadism, men s health, androgensBACKGROUNDT estosterone testing and pre-scriptions have nearly tripled inrecent years; however, it is clear fromclinical practice that there are manymen using Testosterone without aclear studiesestimate that up to 25% of men whoreceive Testosterone therapy do nothave their Testosterone tested prior toinitiation of treatment.

3 Of men whoare treated with Testosterone , nearlyhalf do not have their testosteronelevels checked after therapy ,3 While up to a third of menwho are placed on Testosterone ther-apy do not meet the criteria to bediagnosed as Testosterone deficient,2,3 Abbreviations andAcronymsASCVD atherosclerotic cardio-vascular diseaseAUA American UrologicalAssociationFDA Food and DrugAdministrationHct hematocrithCG human chorionicgonadotropinLH luteinizing hormoneMACE major adverse cardiaceventRCTs randomized controlledtrialsRT radiation therapyVTE venous thromboembolismAccepted for publication March 22, complete unabridged version of theguideline is available at document is being printed as submittedindependent of editorial or peer review by theeditors ofTheJournalofUrology.

4 0022-5347/18/2002-0423/0 THE JOURNAL OF UROLOGY 2018 by AMERICANUROLOGICALASSOCIATIONEDUCATION ANDRESEARCH, 200, 423-432, August 2018 Printed in are a large percentage of men in need oftestosterone therapy who fail to receive it due toclinician concerns, mainly surrounding prostatecancer development and cardiovascular events,although current evidence fails to definitely supportthese STATEMENTSD iagnosis of Testosterone should use a total testosteronelevel below 300 ng/dL as a reasonable cut-offin support of the diagnosis of low testos-terone. (Moderate Recommendation; EvidenceLevel: Grade B) diagnosis of low Testosterone should bemade only after two total Testosterone mea-surements are taken on separate occasions withboth conducted in an early morning fashion.

5 (Strong Recommendation; Evidence Level:Grade A) clinical diagnosis of Testosterone defi-ciency is only made when patients have lowtotal Testosterone levels combined with symp-toms and/or signs. (Moderate Recommendation;Evidence Level: Grade B) should consider measuring totaltestosterone in patients with a history of unex-plained anemia, bone density loss, diabetes,exposure to chemotherapy, exposure to testic-ular radiation, HIV/AIDS, chronic narcotic use,male infertility, pituitary dysfunction, andchronic corticosteroid use even in the absenceof symptoms or signs associated with testos-terone deficiency. (Moderate Recommendation;Evidence Level: Grade B) use of validated questionnaires is notcurrently recommended to either definewhich patients are candidates for testos-terone therapy or monitor symptom responsein patients on Testosterone therapy.

6 (Condi-tional Recommendation; Evidence Level:Grade C)The diagnosis of Testosterone deficiency requiresboth a low Testosterone measurement as well as thepresence of select symptoms and/or signs. The Paneldefines the threshold for low Testosterone as beingconsistently<300 ng/dL onatleasttwoserum totaltestosterone measurements obtained in an earlymorning fashion, preferably using the same labo-ratory with the same method/instrumentation formeasurement (fig. 1).2,4 Clinicians should make note of any patient-reported symptoms associated with low testos-terone, such as reduced energy, reduced endurance,diminished work and/or physical performance, fa-tigue, visual field changes (bitemporal hemianopsia),anosmia, depression, reduced motivation, poor con-centration, impaired memory, irritability, infertility,reduced sex drive, and changes in ,6 Clinicians should also conduct a targeted phys-ical exam to examine patients for signs that areassociated with low Testosterone .

7 This assessmentshould include Evaluation of general body habitus;virilization status (examination of body hair pat-terns and amounts in androgen dependent areas);body mass index or waist circumference; gyneco-mastia; testicular Evaluation including presence,size, consistency and masses; varicocele presence;and prostate size and ,6A meta-analysis of the literature suggests thatmen who have a history of unexplained anemia,7bone density loss,8diabetes,9exposure to chemo-therapy,10direct or scatter radiation therapy to thetestes,11 HIV,12a history of chronic narcotic use,13infertility,14pituitary disorders,15and chronic corti-costeroid use16are at risk for low Testosterone . ThePanel recommends measuring Testosterone in all pa-tients who have a history of these conditions, even inthe absence of symptoms or signs listed questionnaires are not an appropriatetool to identify candidates for Testosterone therapyand should not be used at the expense of a full patientevaluation and laboratory Testosterone measure-ment.

8 Specificities and sensitivities vary greatlyamongst available questionnaires making them ill-suited for screening or for use as a surrogate fortestosterone laboratory patients with low Testosterone , cliniciansshould measure serum luteinizing hormonelevels. (Strong Recommendation; EvidenceLevel: Grade A)Measuring luteinizing hormone levels may help toestablish the etiology of Testosterone deficiency andmay be an important factor in determining if adjunc-tive tests should be ordered (Appendix C in supple-mentary unabridged guideline, ).17 Testosterone deficient patients with low or low/normalLH levels are also candidates for selective estrogenreceptor modulator use as a treatment for testosteronedeficiency, particularly those wishing to preserve prolactin levels should bemeasured in patients with low testosteronelevels combined with low or low/normalluteinizing hormone levels.

9 (Strong Recom-mendation; Evidence Level: Grade A) with persistently high prolactinlevels of unknown etiology should undergoevaluation for endocrine disorders. (StrongRecommendation; Evidence Level: Grade A)424 AUA GUIDELINE ON Testosterone DEFICIENCYS erum prolactin should be measured in patientswho have low total Testosterone and low or low/normalLH levels to screen for hyperprolactinemia. If patientshave elevated prolactin levels, prolactin measurementshould be repeated to ensure that the initial elevationwas not spurious. Persistently elevated prolactinlevels can indicate the presence of pituitary tumors,such as prolactinomas,19and the Panel recommendsthat such patients should be referred to an endocri-nologist for further Evaluation . Men with totaltestosterone levels of<150 ng/dL in combination witha low or low/normal LH should undergo a pituitaryMRI regardless of prolactin levels, as non-secretingadenomas may be estradiol should be measured intestosterone deficient patients who presentwith breast symptoms or gynecomastia priorto the commencement of Testosterone therapy.

10 (Expert Opinion)Men who have elevated baseline estradiol mea-surements should be referred to an it is not uncommon for estradiol levels to in-crease while patients are on Testosterone therapy astotal Testosterone increases, clinicians should beaware that symptomatic gynecomastia or otherbreast symptoms are uncommon. For men whodevelop gynecomastia/breast symptoms on treat-ment ( , breast pain, breast tenderness, nippletenderness), a period of monitoring based on clinicaljudgment should be considered as breast symptomssometimes with Testosterone deficiency whoare interested in fertility should have areproductive health Evaluation performedprior to treatment. (Moderate Recommenda-tion; Evidence Level: Grade B)Men diagnosed with Testosterone deficiency whoare interested in preserving their current fertilityshould undergo testicular exam to evaluate testic-ular size, consistency, and descent and have theirserum follicle-stimulating hormone measured toassess their underlying reproductive health algorithmAUA GUIDELINE ON Testosterone DEFICIENCY425 Elevated follicle-stimulating hormone levels in thesetting of Testosterone deficiency (hypergonadatropichypogonadism) is typically indicative of impairedspermatogenesis;6therefore, clinicians shouldconsider adjunctive fertility testing , such as a semenanalysis, in such patients.