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Supplementary appendixThis appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors.
Supplement to: Onasanya O, Iyer G, Lucas E, Lin D, Singh S, Alexander GC. Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews. Lancet Diabetes Endocrinol 2016; published online Sept 23. http://dx.doi.org/10.1016/S2213-8587(16)30215-7.
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Appendix 1: Inclusion and exclusion criteria
Appendix 2: List of excluded studies and rationale for exclusion
Appendix 3: Search strategy used for electronic databases
Appendix 4: Assessment of Composite MACE Outcome Among RCTs included in
Systematic Reviews
Appendix 5: Optimal Information Size (OIS) Analysis
2
APPENDIX 1. INCLUSION AND EXCLUSION CRITERIA
TYPES OF STUDIES
Include:
Systematic reviews and Meta-analysis
Exclude:
Study design with exposed and unexposed groups (RCT or observational studies)
Review articles (other than Cochrane and systematic reviews)
“Overview” in the title but no systematic searching strategy mentioned in the abstract
If the review is related to Testosterone, use the separate label so we can find it in the
future
Case reports
Case series: No unexposed group, only one exposed group
Commentary
Letter to editor
Crossover design: crossover trials and self-comparison observational studies, that is,
studies testing multiple interventions in the same participants, given in a
randomized/non-randomized order
Ex. receiving T patch, placebo, then T gel in randomized/non-randomized order between
participants
2 exposed groups with same treatment but comparing patients to healthy controls
Surveys
Cross-sectional studies
TYPES OF PARTICIPANTS
Include:
Adult males: 18 years old and older men
Exclude:
Women studies: included only females
Transsexuals
Gender identity disorder (GID)
Pediatric studies: included only adolescents and children
“Puberty/Childhood” in the title
Patients with HIV
Patients with prostate cancer or testicular cancer or other active cancer history
Patients with Schizophrenia
Effects related to antipsychotic medications
Patients with Klinefelter's syndrome
Patients with end stage renal disease (ESRD)
Patients with aplastic anemia
Patients with Prader-Willi
Patients with hypospadias
3
Patients with burns
No perisurgery
Pre- or Post-operative patients
Animal studies: Studies included only animals ->Animal study list*
Lab studies: Studies included only cells or tissues ->Basic science study list**
Studies with n < 10 (n = 10 for each group receiving T or placebo, not 10 total
participants)
If the sample size is unknown, label it as “YES”
TYPES OF INTERVENTIONS
Include:
Exogenous testosterone-> list of testosterone products***(not exclusive)
If the androgen is unknown, label it as “YES”
Compares two testosterone products by different delivery
methods/manufacturers/frequencies
T implants vs T ester injection
Studies testing different doses of same testosterone product
Studies testing exogenous testosterone alone in one group of patients while another
group of patients may receive a combination of T+GnRH, etc.
Includes studies without placebo-control (for now): Ex. T vs T+X
Testing testosterone vs. active control (another drug): Ex. T vs. X
Studies with an additional drug/compound or background therapy given to both groups
T+Y vs. X+Y or T+Y vs. Placebo+Y
Exclude:
Non testosterone studies: Testosterone/androgen is not the intervention of interest
No hormone mentioned in the title
Other kinds of hormone instead of testosterone/androgen mentioned in the title
Studies of testosterone products that are steroids: ->Anabolic Steroids and Other
Unrelated Hormone Medication List****
Androstenediol and androstenedione
Studies with co-treatment: T+X vs. X
"Natural testosterone product" or "herbal medicine"
Duration less than 3 days
TYPES OF OUTCOMES
Include if at least one of these outcomes are tested:
Safety
Disaggregated Major Cardiovascular Events
All-cause Mortality
Myocardial Infarction
Stroke
Heart Failure
Atrial Fibrillation
4
Arrhythmias
Composite Hard Cardiovascular Events
o Major Adverse Cardiovascular Events (MACE)
Risk for prostate cancer
Ex. Prostate cancer or PSA+prostate cancer (but PSA alone doesn’t count)
Exclude:
Obstructive sleep apnea
Aplastic Anemia
Tolerability
Injection pain
Diabetes-related measures
Insulin resistance
Metabolic syndrome
Blood glucose test
Efficacy
Reproductive outcomes/sexual related outcomes
Erectile Dysfunction
Contraception
Sperm count / assessment
Libido
Anabolic response: eg Body composition, lean body mass, weight gain
Muscle wasting
Bone mineral density / trabecular volume
Cognitive Function
Mood
Depressive symptoms
Fatigue symptoms
Quality of life
Reduction in hospitalizations
Studies of Testosterone on non-clinical outcomes (not “hard” clinical endpoints)
o If the outcomes of testosterone use are not specified we need to include
them to evaluate in full text
Studies testing pharmacokinetics / pharmacodynamics/ Interpersonal testosterone
transfer
Studies of pharmacogenetics
Detection methods / devices
o Chromatography
o Apparatus complex "Andro-Gin"
Studies of Different testosterone delivery systems / modes of administration
o Comparisons in safety
o Administration technique
Utilization of testosterone
o Satisfaction
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o Comfort
o Adherence / Persistance
o Interpersonal contact and transfer
Lower urinary tract symptoms
o Healing
o Wounds
o Complications
Serological measures (except cholesterol and diabetes-related)
o Hormone levels eg Growth Hormone (GH)
o Sex hormone binding globulins
o CRP
o Insulin-factor
o Melatonin
o PSA alone
o Sclerostin
o Erythropoiesis
Prostate related outcomes
o Prostate volume
o Cavernous vasodilation
o Benign prostatic hyperplasia
Economic benefits
Human sociality/behavior
Prophylaxis
Vascular Reactivity
Ventricular outcomes
o Structure and function
o Ex. Repolarization
Male pattern baldness
Immune response
6
APPENDIX 2. LIST OF EXCLUDED REVIEWS
1. Mulligan T, Schmitt B. Testosterone for erectile failure. Journal of general internal medicine. 1993;8:517-21.
2. Jain P, Rademaker AW, Mcvary KT. Testosterone Supplementation For Erectile Dysfunction: Results Of A Meta-Analysis. The Journal of Urology. 2000;164:371-375.
3. Whitsel EA, Boyko EJ, Matsumoto AM, Anawalt BD, Siscovick DS. Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta-analysis. The American journal of medicine. 2001;111:261-269.
4. Price JF, Leng GC. Steroid sex hormones for lower limb atherosclerosis. Cochrane Database Syst Rev. 2002;(1):CD000188.
5. Kong A, Edmonds P. Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis. The Lancet infectious diseases. 2002;2:692-699.
6. Grimes DA, Gallo MF, Grigorieva V, Nanda K, Schulz KF. Steroid hormones for contraception in men: systematic review of randomized controlled trials. Contraception. 2005;71:89-94.
7. Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle‐aged men: a meta‐analysis. Clinical Endocrinology. 2005;63:280-293.
8. Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A, Isidori A, Fabbri A, Lenzi A. Effects of testosterone on sexual function in men: results of a meta‐analysis. Clinical endocrinology. 2005;63:381-394.
9. Ottenbacher KJ, Ottenbacher ME, Ottenbacher AJ, Acha AA, Ostir GV. Androgen Treatment and Muscle Strength in Elderly Men: A Meta‐Analysis. Journal of the American Geriatrics Society. 2006;54:1666-1673.
10. Shamlian NT, Cole MG. Androgen treatment of depressive symptoms in older men: a systematic review of feasibility and effectiveness. Canadian journal of psychiatry. 2006;51:295-299.
11. Dennis CL, Ross LE, McIntyre RS, Konarski JZ, Wilkins K, Soczynska JK, Kennedy SH, Fleury MJ, Grenier G, Lesage A, Kassam A. Androgen treatment of depressive symptoms in older men: a systematic review of feasibility and effectiveness. Can J Psychiatry. 2006;51:295-299.
12. Tracz MJ, Sideras K, Bolona ER, Haddad RM, Kennedy CC, Uraga MV, Caples SM, Erwin PJ, Montori VM. Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. The Journal of Clinical Endocrinology & Metabolism. 2006;91:2011-2016.
13. Boloña ER, Uraga MV, Haddad RM, Tracz MJ, Sideras K, Kennedy CC, Caples SM, Erwin PJ, Montori VM. Testosterone use in men with sexual dysfunction: a systematic review and
7
meta-analysis of randomized placebo-controlled trials. InMayo Clinic Proceedings. 2007;82:20-28. Elsevier.
14. Shabsigh R, Crawford ED, Nehra A, Slawin KM. Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. International journal of impotence research. 2009;21:9-23.
15. Tsertsvadze A, Fink HA, Yazdi F, MacDonal R, Bella AJ, Ansari MT et al. Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: a systematic review and meta-analysis. Annals of internal medicine. 2009;15:650-661.
16. Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. Journal of Psychiatric Practice®. 2009;15:289-305.
17. Wan ZH, Wen YB, Ding QF, Xu TY. [Effects of testosterone substitution on metabolic syndrome-related factors in hypogonadal males: a meta-analysis]. Zhonghua Nan Ke Xue= National Journal of Andrology. 2010;16:510-5.
18. Corona G, Monami M, Rastrelli G, Aversa A, Tishova Y et al. Original Research—Endocrinology. J Sex Med, 2010;8:272-283.
19. Corona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A, Forti G, Mannucci E, Maggi M. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. European Journal of Endocrinology. 2011:EJE-11..
20. Corona G, Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, Forti G, Mannucci E, Maggi M. Type 2 diabetes mellitus and testosterone: a meta‐analysis study. International journal of andrology. 2011;34:528-540.
21. Toma M, McAlister FA, Coglianese EE, Vidi V, Vasaiwala S, Bakal JA, Armstrong PW, Ezekowitz JA. Effect of Testosterone Supplementation on Exercise Capacity in Heart Failure Patients: A Systematic Review and Meta-Analysis. Journal of the American College of Cardiology. 2011;57:E329.
22. Yao H, Zhao CP, Kang DM. Testosterone supplementary treatment for the middle-ages and the senile with insulin resistance: a systematic review (DARE-12011002399). Chinese Journal of Evidence-Based Medicine. 2011;11:314-349.
23. Thiem A, Rolke R, Radbruch L. [Glucocorticoids and androgens for treatment of tiredness and weakness in palliative care patients: a systematic review]. Schmerz (Berlin, Germany). 2012;26:550-67.
24. Grimes DA, Lopez LM, Gallo MF, Halpern V, Nanda K, Schulz KF. Steroid hormones for contraception in men. The Cochrane Library. 2012.
25. Toma M, McAlister FA, Coglianese EE, Vidi V, Vasaiwala S, Bakal JA, Armstrong PW, Ezekowitz JA. Testosterone supplementation in heart failure a meta-analysis. Circulation: Heart Failure. 2012;5:315-321.
8
26. Carson III CC, Rosano G. Exogenous testosterone, cardiovascular events, and
cardiovascular risk factors in elderly men: a review of trial data. The journal of sexual
medicine. 2012;9:54-67.
27. Atlantis E, Fahey P, Cochrane B, Wittert G, Smith S. Endogenous testosterone level and testosterone supplementation therapy in chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis. BMJ open. 2013;3:e003127
28. Corona G, Rastrelli G, Maggi M. Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes. Best Practice & Research Clinical Endocrinology & Metabolism. 2013;27:557-579.
29. Cui Y, Zhang Y. The effect of androgen-replacement therapy on prostate growth: a systematic review and meta-analysis. European urology. 2013;64:811-822.
30. Ruige JB, Ouwens DM, Kaufman JM. Beneficial and adverse effects of testosterone on the cardiovascular system in men. The Journal of Clinical Endocrinology & Metabolism. 2013;98:4300-4310.
31. Xu L, Freeman G, Cowling B, Schooling CM. Testosterone Therapy and Cardiovascular Events Among Men: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Trials. InAmerican Journal of Epidemiology 2013;177:167. Journals Dept, 2001 Evans Rd, Cary, NC 27513 USA: Oxford Univ Press Inc.
32. Grossberg G, Amanatkar H, Chibnall J. Impact of exogenous testosterone on mood: A systematic review and meta-analysis of randomized placebo-controlled trials. InInternational Psychogeriatrics 2013;25:189. 32 Avenue of the Americas, New York, NY 10013-2473 USA: Cambridge Univ Press.
33. Amanatkar HR, Chibnall JT, Seo BW, Manepalli JN, Grossberg GT. Impact of exogenous testosterone on mood: a systematic review and meta-analysis of randomized placebo-controlled trials. Ann Clin Psychiatry. 2014;26:19-32.
34. Cai X, Tian Y, Wu T, Cao CX, Li H, Wang KJ. Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Asian journal of andrology. 2014;1:146.
35. Corona G, Maseroli E, Maggi M. Injectable testosterone undecanoate for the treatment of hypogonadism. Expert opinion on pharmacotherapy. 2014;15:1903-1926.
36. Corona G, Isidori AM, Buvat J, Aversa A, Rastrelli G, Hackett G, Rochira V, Sforza A, Lenzi A, Mannucci E, Maggi M. Testosterone Supplementation and Sexual Function: A Meta‐Analysis Study. The journal of sexual medicine. 2014;11:1577-1592.
37. Cui Y, Zong H, Yan H, Zhang Y. The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis. Prostate cancer and prostatic diseases. 2014;17:132-143.
38. Isidori AM, Buvat J, Corona G, Goldstein I, Jannini EA, Lenzi A, Porst H, Salonia A, Traish AM, Maggi M. A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment—a systematic review. European urology. 2014;65:99-112.
9
39. Kang DY, Li HJ. The Effect of Testosterone Replacement Therapy on Prostate-Specific Antigen (PSA) Levels in Men Being Treated for Hypogonadism: A Systematic Review and Meta-Analysis. Medicine. 2015;94:e410.
40. Neto WK, Gama EF, Rocha LY, Ramos CC, Taets W, Scapini KB, Ferreira JB, Rodrigues B, Caperuto É. Effects of testosterone on lean mass gain in elderly men: systematic review with meta-analysis of controlled and randomized studies. Age. 2015;37:1-10.
41. Grossmann M, Hoermann R, Wittert G, Yeap BB. Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Clinical endocrinology. 2015;83:344-51.
42. Corona G G, Rastrelli G, Maseroli E, Sforza A, Maggi M. Testosterone Replacement Therapy and Cardiovascular Risk: A Review. World Journal of Men’s Health. 2015;33:130-142.
43. Guo C, Gu W, Liu M, Peng BO, Yao X, Yang B, Zheng J. Efficacy and safety of testosterone
replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials. Experimental and Therapeutic Medicine. 2016;11:853-863.
Note: Of the 41 evidence syntheses excluded, 37 were excluded because they failed to assess cardiovascular events. The remainder were excluded because: intervention studied other than exogenous testosterone (reference #17); non-systematic review (references #26, #30 and #42); duplicate publications (#31, #32).
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APPENDIX 3. SEARCH STRATEGY USED FOR ELECTRONIC DATABASES
All databases searched from their inception date through August 28th, 2015. There were no language restrictions applied.
Medline (Ovid)
1. Testosterone/ad, ae, ct, po, tu, th, to
2. Testosterone Propionate/ad, ae, tu, to
3. Testosterone Congeners/ad, ae, ct, tu, to
4. exp Androgens/ad, ae, ct, po, tu, th, to
5. exp Hypogonadism/dt, th
6. or/1-5
7. exp Hormone Replacement Therapy/ae, ct, mo
8. ((hormone or hormonal or sex steroid*) adj3 (replacement or therapy or therapies or treatment or therapeutic
or supplement* or prescription* or prescribing or substitution or administration)).tw.
9. 7 or 8
10. Testosterone Propionate/ or Testosterone Congeners/ or exp Androgens/
11. (androgen* or testosterone).tw,nm.
12. or/10-11
13. 9 and 12
14. ("Actiser-T" or "Adrotest" or "Andro 100" or "Andro" or "Androderm" or "Androfort" or "Androgel" or "Android-10"
or "Androlan" or "Androlin" or "Andronaq" or "Andronaq-50" or "Andropatch" or "Androplex" or "Androsorb" or
"Androstenolone" or "Androtest" or "Androtop" or "Androtopic" or "Androxon" or "Andrusol" or "Aquaviron" or
"Aqueous testosterone suspension" or "Atmos" or "Axiron" or "Beta testosterone" or "Bio t gel" or "Clym-Depositum"
or "Col 1621" or "col1621" or "Cypionax" or "Depot hormon-m" or "Depotrone" or "Despamen" or "Durateston" or
"Facovit" or "First-testosterone" or "Fluoxymesterone" or "Folivirin" or "Fortesta" or "Fortigel" or "Geno cristaux" or
"Glutest Liquid" or "Halotestin" or "Histerone" or "Homosteron" or "Hydroxyandrostenone" or "Intrinsa" or "Itnogen" or
"Libigel" or "Livensa" or "Lontanyl" or "Lowtiyel" or "Malogen Aqueous" or "Malogen In Oil" or "Mertestate" or
"Metesto" or "Metharmon-F" or "Methitest" or "Methyl Testosterone" or "Methyltestosterone" or "Natesto" or "Nebid"
or "Neotestis" or "Nsc 9700" or "Nsc9700" or "Numanis" or "Nuo Shi" or "Omnadren" or "Opterone" or "Oreton f" or
"Oreton Methyl" or "Oreton" or "Orquisteron" or "Pasuma" or "Percutacrine androgenique" or "Polysteron 250" or
"Primoniat Depot" or "Primotest" or "Primoteston Depot" or "Primoteston" or "Proviron Depot" or "Reandron" or
"Restinsol" or "Rubidiosin Composto" or "Scheinpharm Testone-Cyp" or "Shotest-100" or "Shotest-50" or "Si Te Long"
or "Sostenon" or "Sten" or "Sterotate" or "Striant" or "Sustanon" or "Sustenan" or "Sustenon 250" or "Synandrol" or
"Tachynerg N" or "Tesamone" or "Teslen" or "Testamone" or "Testandro" or "Testandrone" or "Testaqua" or "Test-
Comp" or "Testerone" or "Test-Estro" or "Testim" or "Testiormina" or "Testo enant" or "Testocaps" or "Testoderm" or
11
"Testo-Enant" or "Testogel" or "Testoject-50" or "Testolent" or "Testolic" or "Testolin" or "Testoluton" or "Testomax"
or "Testopatch" or "Testopel" or "Testoprim-D" or "Testoral" or "Testosteron Aq" or "Testosterone acetate" or
"Testosterone Aq" or "Testosterone Aqueous Suspension" or "Testosterone caproate" or "Testosterone chloride" or
"Testosterone conjugate" or "Testosterone Cyclopentilate" or "Testosterone decanoate" or "Testosterone Fuel
Booster" or "Testosterone isocaproate" or "Testosterone prop" or "Testosterone Suspension" or "Testosteron" or
"Testosteronum Prolongatum" or "Testotop" or "Testoviron" or "Testovis" or "Testovital" or "Testozzard" or "Testred"
or "Testro AQ" or "Testro" or "Testrone" or "Testryl" or "Tesurene" or "Tostran" or "Tostrelle" or "Tostrex" or "T-
phenylpropionate" or "Trinestril" or "Trioestrine-Retard" or "Triolandren" or "Virilisterona" or "Virosterone" or
"Vogelxo").tw,nm.
15. testosterone ester*.tw,nm.
16. ("Testosterone Cipionate" or "andro cyp" or "andronaq la" or ciclosterone or depandro or "depo testosterone" or
depotest or "Depo-Test" or depotestosterone or depovirin or depoviron or duratest or "malogen cyp 200" or
pertestis or "testa c" or "testodrin prolongatum" or "testosterone 17beta cyclopentanepropionate" or "testosterone
17beta cypionate" or "testosterone beta cyclopentylpropionate" or "testosterone cyclopentylpropionate" or
"testosterone cypionate" or "testred cypionate" or "Andro-Cyp 100" or "Andro-Cyp 200" or "Andronate 100" or
"Andronate 200" or "Deposteron" or "Shotest-La" or "T-Cypionate" or "Testa-C" or "Testoject-La" or "Testra-C" or "T-
Ionate P.A." or "Testex" or "Virilon").tw,nm.
17. ("Testosterone Enantate" or "andro la 200" or "androstenolone enanthate" or androtardyl or delatestryl or
durathate or everone or jenasteron or "malogen la 200" or malogex or "testosterone 1 hexanecarboxylate" or
"testosterone enanthane" or "testosterone enanthate" or "T-enanthate" or "testosterone ethanate" or "testosterone
heptanoate" or "testosterone heptonate" or "testosterone heptylate" or "testosterone oenanthate" or "testosterone
oenanthic acid derivative" or "testosviron depot" or "testoviron depot" or "testro-l.a." or "virormone depot" or
"Andropository" or "Andryl 200" or "Everone" or "Testone L.A." or "Testostroval P.A." or "Testra-E" or "Testrin Pa" or
"Ablacton").tw,nm.
18. ("testosterone propionate" or akroteston or anderone or andronate or "andronex amp" or "androsan amp" or
"androtest p" or androteston or androxid or androxil or "andrusol p" or anertar or "bio testiculina" or "bio teston" or
"cosex tp 50" or "delta4 androstene 17beta propionate 3 one" or enarmon or entestil or gonadrone or "homandren
amp" or hormandren or hormoteston or masenate or napionate or nasdol or "neo hombreol" or neohombreol or "nsc
9166" or nsc9166 or "okasa mascul" or orchiol or orchiormon or orchisterone or orchistin or oreton or oretone or
"orquisteron p" or "orquisterone p" or pantestin or penandren or perandren or perandrone or primoniat or
propiokan or recthormone or sterandryl or sterotest or "suprasteron amp" or suprasterone or synerone or testaform
or testex or testodet or testodrin or testogen or testonique or testormol or testormon or testosid or "testosteron
propionate" or "Testosteron propionat" or testosteronepropionate or "testoviron amp" or testoxyl or testrex or
tostrin or uniteston or "virormone x" or "Agovirin" or "Virormone").tw,nm.
19. ("Testosterone undecanoate" or andriol or aveed or nebido or pantestone or restandol or "tosterone 17
undecylate" or "testosterone undecylate" or "Undestor" or "Understor" or "Virigen").tw,nm.
12
20. ("testosterone phenylpropionate" or androject or retandrol).tw,nm.
21. (Exogenous testosterone or "exogenous T" or T trial* or T therap* or "T Supplementation" or "T Treatment" or "T
Treated" or "T Administration" or "Transdermal T" or "testosterone product" or "testosterone products").tw.
22. ((Testosterone or androgen*) adj1 (intramuscular or intravenous or long-acting or oral or parenteral or gel* or
patch* or topical or transdermal or transscrotal or implant* or injectable* or synthetic or cream or subcutaneous or
transdermal or pellet* or sublingual or use* or abuse* or misuse*)).tw.
23. ((Testosterone or androgen*) adj3 (replacement or therapy or therapies or treatment or therapeutic or
supplement* or prescription* or prescribing or substitution or administration)).tw.
24. (Hypogonadism adj3 (replacement or therapy or therapies or treatment or therapeutic or supplement* or
prescription* or prescribing or substitution or administration)).tw.
25. 6 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24
26. exp animals/ not exp humans/
27. 25 not 26
28. female/ not male/
29. 27 not 28
30. exp Androgen Antagonists/
31. 29 not 30
32. (androgen depriv* or androgen suppress* or androgen block* or androgen ablation or anti-androgen* or
antiandrogen* or androgen antagonist* or testosterone depriv* or testosterone suppress* or testosterone block* or
testosterone ablation).ti.
33. 31 not 32
34. ((Fish not "fish oil") or (snake not "snake oil") or chicken or chickens or chick or chicks or goat or goats or rat or
rats or rat's or mice or murine or murinae or pig or pigs or goose or geese or stallion or stallions or bovine or rabbit
or rabbits or duck or ducks or quail or eggs or bird or canine or gecko or Rhea or Ratite or passerine or muskrat or
baboon or baboons or bat or sheep or bulls or monkey or monkeys or cats or junco or cow or cows or heifer or
heifers or cattle or livestock or horse or hamster or hamsters or mouse or turtles or lamb or lambs or scallop or
voles or coyotes or grouse or blackbirds or crane or Ibis or Stork or sparrow or sparrows or albatross or albatrosses
or albatrosses' or muntjac or cervids or gerbil or gerbils or songbird or songbirds or rams or dog or dogs or jays or
starling or starlings or avian or whale or whales or mollusc or molluscs or caecilians or rodent or rodents or
swallows or gull or gulls or budgerigar or budgerigars or finch or finches or rhino or rhinos or rhinoceros or toad or
toads or hen or hens or degus or gilt or gilts or boar or boars or lizard or lizards or anuran or anurans or treefrog or
treefrogs or frog or frogs or crocodile or crocodiles or Colt or Colts or chimpanzee or chimpanzees or salamander
or salamanders or insect or insects or wasp or wasps or snakes or rattlesnake or rattlesnakes or treesnake or
treesnakes or maggot or maggots or urchin or urchins or alligator or Alligators or shrimp or shrimps or corals or
newt or newts or Pleurodeles or rotifer or rotifers or moth or moths or marmoset or marmosets or elephant or
elephants or trout or flycatcher or flycatchers or iguana or iguanas or worm or worms or marten or martens or hare
13
or hares or deer or ferret or ferrets or ewe or ewes or tuatara or tuataras or pintail or pintails or partridge or
partridges or jerboa or jerboas or bucks or squirrel or squirrels or cock or cocks or capon or capons or reptile or
reptiles or minnow or minnows or salmon or beetle or beetles or zebrafish or mallard or mallards or catfish or
macaque or macaques or tadpole or tadpoles or porcine or porcines or guppy or guppies or buffalo or buffaloe or
buffaloes or buffalos or parasite or parasites or teleost or teleosts or carp or tilapia or snail or snails or grouper or
medaka or greyhounds or eel or mudsnail or mudsnails or canary or canaries or bullfrogs or swine or parrot or
shrews or "non human" or nonhuman).ti.
35. 33 not 34
36. (menstrual* or premenstrual* or vagina* or uterus or uterine* or ovarian* or ovary* or endometrial*).ti.
37. 35 not 36
38. ((child* or adolescent* or adolescenc*) not (adult* or men)).ti.
39. 37 not 38
40. ("in vitro" or "in vivo").ti.
41. 39 not 40
42. limit 41 to yr="1990 -Current"
PubMed
1. ((hormone[tw] OR hormonal[tw] OR sex steroid*[tw]) AND (replacement[tw] OR therapy[tw] OR therapies[tw]
OR treatment[tw] OR therapeutic[tw] OR supplement*[tw] OR prescription*[tw] OR prescribing[tw] OR
substitution[tw] OR administration[tw]))
2. (androgen*[tw] OR testosterone[tw])
3. #1 AND #2
4. ("Actiser-T"[tw] OR "Adrotest"[tw] OR "Andro 100"[tw] OR "Andro"[tw] OR "Androderm"[tw] OR
"Androfort"[tw] OR "Androgel"[tw] OR "Android-10"[tw] OR "Androlan"[tw] OR "Androlin"[tw] OR "Andronaq"[tw]
OR "Andronaq-50"[tw] OR "Andropatch"[tw] OR "Androplex"[tw] OR "Androsorb"[tw] OR "Androstenolone"[tw]
OR "Androtest"[tw] OR "Androtop"[tw] OR "Androtopic"[tw] OR "Androxon"[tw] OR "Andrusol"[tw] OR
"Aquaviron"[tw] OR "Aqueous testosterone suspension"[tw] OR "Atmos"[tw] OR "Axiron"[tw] OR "Beta
testosterone"[tw] OR "Bio t gel"[tw] OR "Clym-Depositum"[tw] OR "Col 1621"[tw] OR "col1621"[tw] OR
"Cypionax"[tw] OR "Depot hormon-m"[tw] OR "Depotrone"[tw] OR "Despamen"[tw] OR "Durateston"[tw] OR
"Facovit"[tw] OR "First-testosterone"[tw] OR "Fluoxymesterone"[tw] OR "Folivirin"[tw] OR "Fortesta"[tw] OR
"Fortigel"[tw] OR "Geno cristaux"[tw] OR "Glutest Liquid"[tw] OR "Halotestin"[tw] OR "Histerone"[tw] OR
"Homosteron"[tw] OR "Hydroxyandrostenone"[tw] OR "Intrinsa"[tw] OR "Itnogen"[tw] OR "Libigel"[tw] OR
"Livensa"[tw] OR "Lontanyl"[tw] OR "Lowtiyel"[tw] OR "Malogen Aqueous"[tw] OR "Malogen In Oil"[tw] OR
"Mertestate"[tw] OR "Metesto"[tw] OR "Metharmon-F"[tw] OR "Methitest"[tw] OR "Methyl Testosterone"[tw] OR
14
"Methyltestosterone"[tw] OR "Natesto"[tw] OR "Nebid"[tw] OR "Neotestis"[tw] OR "Nsc 9700"[tw] OR
"Nsc9700"[tw] OR "Numanis"[tw] OR "Nuo Shi"[tw] OR "Omnadren"[tw] OR "Opterone"[tw] OR "Oreton f"[tw] OR
"Oreton Methyl"[tw] OR "Oreton"[tw] OR "Orquisteron"[tw] OR "Pasuma"[tw] OR "Percutacrine
androgenique"[tw] OR "Polysteron 250"[tw] OR "Primoniat Depot"[tw] OR "Primotest"[tw] OR "Primoteston
Depot"[tw] OR "Primoteston"[tw] OR "Proviron Depot"[tw] OR "Reandron"[tw] OR "Restinsol"[tw] OR "Rubidiosin
Composto"[tw] OR "Scheinpharm Testone-Cyp"[tw] OR "Shotest-100"[tw] OR "Shotest-50"[tw] OR "Si Te Long"[tw]
OR "Sostenon"[tw] OR "Sten"[tw] OR "Sterotate"[tw] OR "Striant"[tw] OR "Sustanon"[tw] OR "Sustenan"[tw] OR
"Sustenon 250"[tw] OR "Synandrol"[tw] OR "Tachynerg N"[tw] OR "Tesamone"[tw] OR "Teslen"[tw] OR
"Testamone"[tw] OR "Testandro"[tw] OR "Testandrone"[tw] OR "Testaqua"[tw] OR "Test-Comp"[tw] OR
"Testerone"[tw] OR "Test-Estro"[tw] OR "Testim"[tw] OR "Testiormina"[tw] OR "Testo enant"[tw] OR
"Testocaps"[tw] OR "Testoderm"[tw] OR "Testo-Enant"[tw] OR "Testogel"[tw] OR "Testoject-50"[tw] OR
"Testolent"[tw] OR "Testolic"[tw] OR "Testolin"[tw] OR "Testoluton"[tw] OR "Testomax"[tw] OR "Testopatch"[tw]
OR "Testopel"[tw] OR "Testoprim-D"[tw] OR "Testoral"[tw] OR "Testosteron Aq"[tw] OR "Testosterone
acetate"[tw] OR "Testosterone Aq"[tw] OR "Testosterone Aqueous Suspension"[tw] OR "Testosterone
caproate"[tw] OR "Testosterone chloride"[tw] OR "Testosterone conjugate"[tw] OR "Testosterone
Cyclopentilate"[tw] OR "Testosterone decanoate"[tw] OR "Testosterone Fuel Booster"[tw] OR "Testosterone
isocaproate"[tw] OR "Testosterone prop"[tw] OR "Testosterone Suspension"[tw] OR "Testosteron"[tw] OR
"Testosteronum Prolongatum"[tw] OR "Testotop"[tw] OR "Testoviron"[tw] OR "Testovis"[tw] OR "Testovital"[tw]
OR "Testozzard"[tw] OR "Testred"[tw] OR "Testro AQ"[tw] OR "Testro"[tw] OR "Testrone"[tw] OR "Testryl"[tw] OR
"Tesurene"[tw] OR "Tostran"[tw] OR "Tostrelle"[tw] OR "Tostrex"[tw] OR "T-phenylpropionate"[tw] OR
"Trinestril"[tw] OR "Trioestrine-Retard"[tw] OR "Triolandren"[tw] OR "Virilisterona"[tw] OR "Virosterone"[tw] OR
"Vogelxo"[tw])
5. testosterone ester*[tw]
6. ("Testosterone Cipionate"[tw] OR "andro cyp"[tw] OR "andronaq la"[tw] OR ciclosterone[tw] OR depandro[tw]
OR "depo testosterone"[tw] OR depotest[tw] OR "Depo-Test"[tw] OR depotestosterone[tw] OR depovirin[tw] OR
depoviron[tw] OR duratest[tw] OR "malogen cyp 200"[tw] OR pertestis[tw] OR "testa c"[tw] OR "testodrin
prolongatum"[tw] OR "testosterone 17beta cyclopentanepropionate"[tw] OR "testosterone 17beta cypionate"[tw]
OR "testosterone beta cyclopentylpropionate"[tw] OR "testosterone cyclopentylpropionate"[tw] OR "testosterone
cypionate"[tw] OR "testred cypionate"[tw] OR "Andro-Cyp 100"[tw] OR "Andro-Cyp 200"[tw] OR "Andronate
100"[tw] OR "Andronate 200"[tw] OR "Deposteron"[tw] OR "Shotest-La"[tw] OR "T-Cypionate"[tw] OR "Testa-
C"[tw] OR "Testoject-La"[tw] OR "Testra-C"[tw] OR "T-Ionate P.A." [tw] OR "Testex"[tw] OR "Virilon"[tw])
7. ("Testosterone Enantate"[tw] OR "andro la 200"[tw] OR "androstenolone enanthate"[tw] OR androtardyl[tw] OR
delatestryl[tw] OR durathate[tw] OR everone[tw] OR jenasteron[tw] OR "malogen la 200"[tw] OR malogex[tw] OR
"testosterone 1 hexanecarboxylate"[tw] OR "testosterone enanthane"[tw] OR "testosterone enanthate"[tw] OR
"T-enanthate"[tw] OR "testosterone ethanate"[tw] OR "testosterone heptanoate"[tw] OR "testosterone
heptonate"[tw] OR "testosterone heptylate"[tw] OR "testosterone oenanthate"[tw] OR "testosterone oenanthic
15
acid derivative"[tw] OR "testosviron depot"[tw] OR "testoviron depot"[tw] OR "testro-l.a." [tw] OR "virormone
depot"[tw] OR "Andropository"[tw] OR "Andryl 200"[tw] OR "Everone"[tw] OR "Testone L.A." [tw] OR
"Testostroval P.A." [tw] OR "Testra-E"[tw] OR "Testrin Pa"[tw] OR "Ablacton"[tw])
8. ("testosterone propionate"[tw] OR akroteston[tw] OR "anderone"[tw] OR "andronate"[tw] OR "andronex
amp"[tw] OR "androsan amp"[tw] OR "androtest p"[tw] OR "androteston"[tw] OR "androxid"[tw] OR
"androxil"[tw] OR "andrusol p"[tw] OR "anertar"[tw] OR "bio testiculina"[tw] OR "bio teston"[tw] OR "cosex tp
50"[tw] OR "delta4 androstene 17beta propionate 3 one"[tw] OR "enarmon"[tw] OR "entestil"[tw] OR
"gonadrone"[tw] OR "homandren amp"[tw] OR "hormandren"[tw] OR "hormoteston"[tw] OR "masenate"[tw] OR
"napionate"[tw] OR "nasdol"[tw] OR "neo hombreol"[tw] OR "neohombreol"[tw] OR "nsc 9166"[tw] OR
"nsc9166"[tw] OR "okasa mascul"[tw] OR "orchiol"[tw] OR "orchiormon"[tw] OR "orchisterone"[tw] OR
"orchistin"[tw] OR "oreton"[tw] OR "oretone"[tw] OR "orquisteron p"[tw] OR "orquisterone p"[tw] OR
"pantestin"[tw] OR "penandren"[tw] OR "perandren"[tw] OR "perandrone"[tw] OR "primoniat"[tw] OR
"propiokan"[tw] OR "recthormone"[tw] OR "sterandryl"[tw] OR "sterotest"[tw] OR "suprasteron amp"[tw] OR
"suprasterone"[tw] OR "synerone"[tw] OR "testaform"[tw] OR "testex"[tw] OR "testodet"[tw] OR "testodrin"[tw]
OR "testogen"[tw] OR "testonique"[tw] OR "testormol"[tw] OR "testormon"[tw] OR "testosid"[tw] OR "testosteron
propionate"[tw] OR "Testosteron propionat"[tw] OR "testosteronepropionate"[tw] OR "testoviron amp"[tw] OR
"testoxyl"[tw] OR "testrex"[tw] OR "tostrin"[tw] OR "uniteston"[tw] OR "virormone x"[tw] OR "Agovirin"[tw] OR
"Virormone"[tw])
9. ("Testosterone undecanoate"[tw] OR "andriol"[tw] OR "aveed"[tw] OR "nebido"[tw] OR "pantestone"[tw] OR
"restandol"[tw] OR "tosterone 17 undecylate"[tw] OR "testosterone undecylate"[tw] OR "Undestor"[tw] OR
"Understor"[tw] OR "Virigen"[tw])
10. ("testosterone phenylpropionate"[tw] OR "androject"[tw] OR "retandrol"[tw])
11. ("Exogenous testosterone"[tw] OR "exogenous T"[tw] OR T trial*[tw] OR T therap*[tw] OR "T
Supplementation"[tw] OR "T Treatment"[tw] OR "T Treated"[tw] OR "T Administration"[tw] OR "Transdermal
T"[tw] OR "testosterone product"[tw] OR "testosterone products"[tw])
12. ((Testosterone[tw] OR androgen*[tw]) AND (intramuscular[tw] OR intravenous[tw] OR long-acting[tw] OR
oral[tw] OR parenteral[tw] OR gel*[tw] OR patch*[tw] OR topical[tw] OR transdermal[tw] OR transscrotal[tw] OR
implant*[tw] OR injectable*[tw] OR synthetic[tw] OR cream[tw] OR subcutaneous[tw] OR transdermal[tw] OR
pellet*[tw] OR sublingual[tw] OR use*[tw] OR abuse*[tw] OR misuse*[tw]))
13. ((Testosterone[tw] OR androgen*[tw]) AND (replacement[tw] OR therapy[tw] OR therapies[tw] OR
treatment[tw] OR therapeutic[tw] OR supplement*[tw] OR prescription*[tw] OR prescribing[tw] OR
substitution[tw] OR administration[tw]))
14. (Hypogonadism[tw] AND (replacement[tw] OR therapy[tw] OR therapies[tw] OR treatment[tw] OR
therapeutic[tw] OR supplement*[tw] OR prescription*[tw] OR prescribing[tw] OR substitution[tw] OR
administration[tw]))
15. #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14
16
16. Medline[sb]
17. #15 NOT #16
18. (androgen depriv*[ti] OR androgen suppress*[ti] OR androgen block*[ti] OR androgen ablation[ti] OR anti-
androgen*[ti] OR antiandrogen*[ti] OR androgen antagonist*[ti] OR testosterone depriv*[ti] OR testosterone
suppress*[ti] OR testosterone block*[ti] OR testosterone ablation[ti])
19. #17 NOT #18
20. ((Fish[ti] NOT "fish oil"[ti]) OR (snake[ti] NOT "snake oil"[ti]) OR chicken[ti] OR chickens[ti] OR chick[ti] OR
chicks[ti] OR goat[ti] OR goats[ti] OR rat[ti] OR rats[ti] OR rat's[ti] OR mice[ti] OR murine[ti] OR murinae[ti] OR
pig[ti] OR pigs[ti] OR goose[ti] OR geese[ti] OR stallion[ti] OR stallions[ti] OR bovine[ti] OR rabbit[ti] OR rabbits[ti]
OR duck[ti] OR ducks[ti] OR quail[ti] OR eggs[ti] OR bird[ti] OR canine[ti] OR gecko[ti] OR Rhea[ti] OR Ratite[ti] OR
passerine[ti] OR muskrat[ti] OR baboon[ti] OR baboons[ti] OR bat[ti] OR sheep[ti] OR bulls[ti] OR monkey[ti] OR
monkeys[ti] OR cats[ti] OR junco[ti] OR cow[ti] OR cows[ti] OR heifer[ti] OR heifers[ti] OR cattle[ti] OR livestock[ti]
OR horse[ti] OR hamster[ti] OR hamsters[ti] OR mouse[ti] OR turtles[ti] OR lamb[ti] OR lambs[ti] OR scallop[ti] OR
voles[ti] OR coyotes[ti] OR grouse[ti] OR blackbirds[ti] OR crane[ti] OR Ibis[ti] OR Stork[ti] OR sparrow[ti] OR
sparrows[ti] OR albatross[ti] OR albatrosses[ti] OR albatrosses'[ti] OR muntjac[ti] OR cervids[ti] OR gerbil[ti] OR
gerbils[ti] OR songbird[ti] OR songbirds[ti] OR rams[ti] OR dog[ti] OR dogs[ti] OR jays[ti] OR starling[ti] OR
starlings[ti] OR avian[ti] OR whale[ti] OR whales[ti] OR mollusc[ti] OR molluscs[ti] OR caecilians[ti] OR rodent[ti] OR
rodents[ti] OR swallows[ti] OR gull[ti] OR gulls[ti] OR budgerigar[ti] OR budgerigars[ti] OR finch[ti] OR finches[ti] OR
rhino[ti] OR rhino[ti]s OR rhinoceros[ti] OR toad[ti] OR toads[ti] OR hen[ti] OR hens[ti] OR degus[ti] OR gilt[ti] OR
gilts[ti] OR boar[ti] OR boars[ti] OR lizard[ti] OR lizards[ti] OR anuran[ti] OR anurans[ti] OR treefrog[ti] OR
treefrogs[ti] OR frog[ti] OR frogs[ti] OR crocodile[ti] OR crocodiles[ti] OR Colt[ti] OR Colts[ti] OR chimpanzee[ti] OR
chimpanzees[ti] OR salamander[ti] OR salamanders[ti] OR insect[ti] OR insects[ti] OR wasp[ti] OR wasps[ti] OR
snakes[ti] OR rattlesnake[ti] OR rattlesnakes[ti] OR treesnake[ti] OR treesnakes[ti] OR maggot[ti] OR maggots[ti]
OR urchin[ti] OR urchins[ti] OR alligator[ti] OR Alligators[ti] OR shrimp[ti] OR shrimps[ti] OR corals[ti] OR newt[ti]
OR newts[ti] OR Pleurodeles[ti] OR rotifer[ti] OR rotifers[ti] OR moth[ti] OR moths[ti] OR marmoset[ti] OR
marmosets[ti] OR elephant[ti] OR elephants[ti] OR trout[ti] OR flycatcher[ti] OR flycatchers[ti] OR iguana[ti] OR
iguanas[ti] OR worm[ti] OR worms[ti] OR marten[ti] OR martens[ti] OR hare[ti] OR hares[ti] OR deer[ti] OR ferret[ti]
OR ferrets[ti] OR ewe[ti] OR ewes[ti] OR tuatara[ti] OR tuataras[ti] OR pintail[ti] OR pintails[ti] OR partridge[ti] OR
partridges[ti] OR jerboa[ti] OR jerboas[ti] OR bucks[ti] OR squirrel[ti] OR squirrels[ti] OR cock OR cocks[ti] OR
capon[ti] OR capons[ti] OR reptile[ti] OR reptiles[ti] OR minnow[ti] OR minnows[ti] OR salmon[ti] OR beetle[ti] OR
beetles[ti] OR zebrafish[ti] OR mallard[ti] OR mallards[ti] OR catfish[ti] OR macaque[ti] OR macaques[ti] OR
tadpole[ti] OR tadpoles[ti] OR porcine[ti] OR porcines[ti] OR guppy[ti] OR guppies[ti] OR buffalo[ti] OR buffaloe[ti]
OR buffaloes[ti] OR buffalos[ti] OR parasite[ti] OR parasites[ti] OR teleost[ti] OR teleosts[ti] OR carp[ti] OR tilapia[ti]
OR snail[ti] OR snails[ti] OR grouper[ti] OR medaka[ti] OR greyhounds[ti] OR eel[ti] OR mudsnail[ti] OR
mudsnails[ti] OR canary[ti] OR canaries[ti] OR bullfrogs[ti] OR swine[ti] OR parrot[ti] OR shrews[ti] OR "non
human"[ti] OR nonhuman[ti])
17
21. #19 NOT #20
22. (menstrual*[ti] OR premenstrual*[ti] OR vagina*[ti] OR uterus[ti] OR uterine*[ti] OR ovarian*[ti] OR ovary*[ti]
OR endometrial*[ti])
23. #21 NOT #22
24. ((child*[ti] OR adolescent*[ti] OR adolescenc*[ti]) NOT (adult*[ti] OR men[ti]))
25. #23 NOT #24
26. ("in vitro"[ti] OR "in vivo"[ti])
27. #25 NOT #26
28. #27 AND Publication date from 1990/01/01
EMBASE
#1 'testosterone'/exp/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#2 'testosterone ester'/exp/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#3 'testosterone derivative'/exp/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#4 'testosterone propionate'/exp/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#5 'testosterone cipionate'/exp/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#6 'testosterone enantate'/exp/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#7 'testosterone undecanoate'/exp/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#8 'testosterone phenylpropionate'/exp/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#9 'androgen therapy'/exp
#10 'androgen'/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#11 'hypogonadism'/exp/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#12 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11
#13 'hormone substitution'/dd_do,dd_cm,dd_dt,dd_ae,dd_to,dd_cb,dd_ct
#14 ((hormone OR hormonal OR 'sex steroid' OR 'sex steroids' OR 'sex steroidal') NEAR/3
(replacement OR therapy OR therapies OR treatment OR therapeutic OR supplement* OR prescription*
OR prescribing OR substitution OR administration)):ab,ti
#15 #13 OR #14
#16 'testosterone'/exp OR 'androgen'/de OR 'testosterone propionate'/exp OR 'testosterone
derivative'/exp OR 'testosterone ester'/exp OR 'testosterone cipionate'/exp OR 'testosterone
enantate'/exp OR 'testosterone undecanoate'/exp OR 'testosterone phenylpropionate'/exp
#17 androgen*:tn,ab,ti OR testosterone:tn,ab,ti
#18 #16 OR #17
#19 #15 AND #18
#20 'actiser-t':tn,ab,ti OR 'adrotest':tn,ab,ti OR 'andro 100':tn,ab,ti OR 'andro':tn,ab,ti OR
'androderm':tn,ab,ti OR 'androfort':tn,ab,ti OR 'androgel':tn,ab,ti OR 'android-10':tn,ab,ti OR
'androlan':tn,ab,ti OR 'androlin':tn,ab,ti OR 'andronaq':tn,ab,ti OR 'andronaq-50':tn,ab,ti OR
'andropatch':tn,ab,ti OR 'androplex':tn,ab,ti OR 'androsorb':tn,ab,ti OR 'androstenolone':tn,ab,ti OR
'androtest':tn,ab,ti OR 'androtop':tn,ab,ti OR 'androtopic':tn,ab,ti OR 'androxon':tn,ab,ti OR
'andrusol':tn,ab,ti OR 'aquaviron':tn,ab,ti OR 'aqueous testosterone suspension':tn,ab,ti OR
'atmos':tn,ab,ti OR 'axiron':tn,ab,ti OR 'beta testosterone':tn,ab,ti OR 'bio t gel':tn,ab,ti OR 'clym-
18
depositum':tn,ab,ti OR 'col 1621':tn,ab,ti OR 'col1621':tn,ab,ti OR 'cypionax':tn,ab,ti OR 'depot hormon-
m':tn,ab,ti OR 'depotrone':tn,ab,ti OR 'despamen':tn,ab,ti OR 'durateston':tn,ab,ti OR 'facovit':tn,ab,ti
OR 'first-testosterone':tn,ab,ti OR 'fluoxymesterone':tn,ab,ti OR 'folivirin':tn,ab,ti OR 'fortesta':tn,ab,ti
OR 'fortigel':tn,ab,ti OR 'geno cristaux':tn,ab,ti OR 'glutest liquid':tn,ab,ti OR 'halotestin':tn,ab,ti OR
'histerone':tn,ab,ti OR 'homosteron':tn,ab,ti OR 'hydroxyandrostenone':tn,ab,ti OR 'intrinsa':tn,ab,ti OR
'itnogen':tn,ab,ti OR 'libigel':tn,ab,ti OR 'livensa':tn,ab,ti OR 'lontanyl':tn,ab,ti OR 'lowtiyel':tn,ab,ti OR
'malogen aqueous':tn,ab,ti OR 'malogen in oil':tn,ab,ti OR 'mertestate':tn,ab,ti OR 'metesto':tn,ab,ti OR
'metharmon-f':tn,ab,ti OR 'methitest':tn,ab,ti OR 'methyl testosterone':tn,ab,ti OR
'methyltestosterone':tn,ab,ti OR 'natesto':tn,ab,ti OR 'nebid':tn,ab,ti OR 'neotestis':tn,ab,ti OR 'nsc
9700':tn,ab,ti OR 'nsc9700':tn,ab,ti OR 'numanis':tn,ab,ti OR 'nuo shi':tn,ab,ti OR 'omnadren':tn,ab,ti OR
'opterone':tn,ab,ti OR 'oreton f':tn,ab,ti OR 'oreton methyl':tn,ab,ti OR 'oreton':tn,ab,ti OR
'orquisteron':tn,ab,ti OR 'pasuma':tn,ab,ti OR 'percutacrine androgenique':tn,ab,ti OR 'polysteron
250':tn,ab,ti OR 'primoniat depot':tn,ab,ti OR 'primotest':tn,ab,ti OR 'primoteston depot':tn,ab,ti OR
'primoteston':tn,ab,ti OR 'proviron depot':tn,ab,ti OR 'reandron':tn,ab,ti OR 'restinsol':tn,ab,ti OR
'rubidiosin composto':tn,ab,ti OR 'scheinpharm testone-cyp':tn,ab,ti OR 'shotest-100':tn,ab,ti OR
'shotest-50':tn,ab,ti OR 'si te long':tn,ab,ti OR 'sostenon':tn,ab,ti OR 'sten':tn,ab,ti OR 'sterotate':tn,ab,ti
OR 'striant':tn,ab,ti OR 'sustanon':tn,ab,ti OR 'sustenan':tn,ab,ti OR 'sustenon 250':tn,ab,ti OR
'synandrol':tn,ab,ti OR 'tachynerg n':tn,ab,ti OR 'tesamone':tn,ab,ti OR 'teslen':tn,ab,ti OR
'testamone':tn,ab,ti OR 'testandro':tn,ab,ti OR 'testandrone':tn,ab,ti OR 'testaqua':tn,ab,ti OR 'test-
comp':tn,ab,ti OR 'testerone':tn,ab,ti OR 'test-estro':tn,ab,ti OR 'testim':tn,ab,ti OR 'testiormina':tn,ab,ti
OR 'testo enant':tn,ab,ti OR 'testocaps':tn,ab,ti OR 'testoderm':tn,ab,ti OR 'testo-enant':tn,ab,ti OR
'testogel':tn,ab,ti OR 'testoject-50':tn,ab,ti OR 'testolent':tn,ab,ti OR 'testolic':tn,ab,ti OR
'testolin':tn,ab,ti OR 'testoluton':tn,ab,ti OR 'testomax':tn,ab,ti OR 'testopatch':tn,ab,ti OR
'testopel':tn,ab,ti OR 'testoprim-d':tn,ab,ti OR 'testoral':tn,ab,ti OR 'testosteron aq':tn,ab,ti OR
'testosterone acetate':tn,ab,ti OR 'testosterone aq':tn,ab,ti OR 'testosterone aqueous
suspension':tn,ab,ti OR 'testosterone caproate':tn,ab,ti OR 'testosterone chloride':tn,ab,ti OR
'testosterone conjugate':tn,ab,ti OR 'testosterone cyclopentilate':tn,ab,ti OR 'testosterone
decanoate':tn,ab,ti OR 'testosterone fuel booster':tn,ab,ti OR 'testosterone isocaproate':tn,ab,ti OR
'testosterone prop':tn,ab,ti OR 'testosterone suspension':tn,ab,ti OR 'testosteron':tn,ab,ti OR
'testosteronum prolongatum':tn,ab,ti OR 'testotop':tn,ab,ti OR 'testoviron':tn,ab,ti OR 'testovis':tn,ab,ti
OR 'testovital':tn,ab,ti OR 'testozzard':tn,ab,ti OR 'testred':tn,ab,ti OR 'testro aq':tn,ab,ti OR
'testro':tn,ab,ti OR 'testrone':tn,ab,ti OR 'testryl':tn,ab,ti OR 'tesurene':tn,ab,ti OR 'tostran':tn,ab,ti OR
'tostrelle':tn,ab,ti OR 'tostrex':tn,ab,ti OR 't-phenylpropionate':tn,ab,ti OR 'trinestril':tn,ab,ti OR
'trioestrine-retard':tn,ab,ti OR 'triolandren':tn,ab,ti OR 'virilisterona':tn,ab,ti OR 'virosterone':tn,ab,ti OR
'vogelxo':tn,ab,ti
#21 (testosterone NEXT/1 ester*):tn,ab,ti
#22 'testosterone cipionate':tn,ab,ti OR 'andro cyp':tn,ab,ti OR 'andronaq la':tn,ab,ti OR
ciclosterone:tn,ab,ti OR depandro:tn,ab,ti OR 'depo testosterone':tn,ab,ti OR depotest:tn,ab,ti OR 'depo-
test':tn,ab,ti OR depotestosterone:tn,ab,ti OR depovirin:tn,ab,ti OR depoviron:tn,ab,ti OR
duratest:tn,ab,ti OR 'malogen cyp 200':tn,ab,ti OR pertestis:tn,ab,ti OR 'testa c':tn,ab,ti OR 'testodrin
prolongatum':tn,ab,ti OR 'testosterone 17beta cyclopentanepropionate':tn,ab,ti OR 'testosterone
17beta cypionate':tn,ab,ti OR 'testosterone beta cyclopentylpropionate':tn,ab,ti OR 'testosterone
cyclopentylpropionate':tn,ab,ti OR 'testosterone cypionate':tn,ab,ti OR 'testred cypionate':tn,ab,ti OR
'andro-cyp 100':tn,ab,ti OR 'andro-cyp 200':tn,ab,ti OR 'andronate 100':tn,ab,ti OR 'andronate
19
200':tn,ab,ti OR 'deposteron':tn,ab,ti OR 'shotest-la':tn,ab,ti OR 't-cypionate':tn,ab,ti OR 'testa-c':tn,ab,ti
OR 'testoject-la':tn,ab,ti OR 'testra-c':tn,ab,ti OR 't-ionate p.a.':tn,ab,ti OR 'testex':tn,ab,ti OR
'virilon':tn,ab,ti
#23 'testosterone enantate':tn,ab,ti OR 'andro la 200':tn,ab,ti OR 'androstenolone
enanthate':tn,ab,ti OR androtardyl:tn,ab,ti OR delatestryl:tn,ab,ti OR durathate:tn,ab,ti OR
everone:tn,ab,ti OR jenasteron:tn,ab,ti OR 'malogen la 200':tn,ab,ti OR malogex:tn,ab,ti OR
'testosterone 1 hexanecarboxylate':tn,ab,ti OR 'testosterone enanthane':tn,ab,ti OR 'testosterone
enanthate':tn,ab,ti OR 't-enanthate':tn,ab,ti OR 'testosterone ethanate':tn,ab,ti OR 'testosterone
heptanoate':tn,ab,ti OR 'testosterone heptonate':tn,ab,ti OR 'testosterone heptylate':tn,ab,ti OR
'testosterone oenanthate':tn,ab,ti OR 'testosterone oenanthic acid derivative':tn,ab,ti OR 'testosviron
depot':tn,ab,ti OR 'testoviron depot':tn,ab,ti OR 'testro-l.a.':tn,ab,ti OR 'virormone depot':tn,ab,ti OR
'andropository':tn,ab,ti OR 'andryl 200':tn,ab,ti OR 'everone':tn,ab,ti OR 'testone l.a.':tn,ab,ti OR
'testostroval p.a.':tn,ab,ti OR 'testra-e':tn,ab,ti OR 'testrin pa':tn,ab,ti OR 'ablacton':tn,ab,ti
#24 'testosterone propionate':tn,ab,ti OR akroteston:tn,ab,ti OR anderone:tn,ab,ti OR
andronate:tn,ab,ti OR 'andronex amp':tn,ab,ti OR 'androsan amp':tn,ab,ti OR 'androtest p':tn,ab,ti OR
androteston:tn,ab,ti OR androxid:tn,ab,ti OR androxil:tn,ab,ti OR 'andrusol p':tn,ab,ti OR anertar:tn,ab,ti
OR 'bio testiculina':tn,ab,ti OR 'bio teston':tn,ab,ti OR 'cosex tp 50':tn,ab,ti OR 'delta4 androstene 17beta
propionate 3 one':tn,ab,ti OR enarmon:tn,ab,ti OR entestil:tn,ab,ti OR gonadrone:tn,ab,ti OR
'homandren amp':tn,ab,ti OR hormandren:tn,ab,ti OR hormoteston:tn,ab,ti OR masenate:tn,ab,ti OR
napionate:tn,ab,ti OR nasdol:tn,ab,ti OR 'neo hombreol':tn,ab,ti OR neohombreol:tn,ab,ti OR 'nsc
9166':tn,ab,ti OR nsc9166:tn,ab,ti OR 'okasa mascul':tn,ab,ti OR orchiol:tn,ab,ti OR orchiormon:tn,ab,ti
OR orchisterone:tn,ab,ti OR orchistin:tn,ab,ti OR oreton:tn,ab,ti OR oretone:tn,ab,ti OR 'orquisteron
p':tn,ab,ti OR 'orquisterone p':tn,ab,ti OR pantestin:tn,ab,ti OR penandren:tn,ab,ti OR perandren:tn,ab,ti
OR perandrone:tn,ab,ti OR primoniat:tn,ab,ti OR propiokan:tn,ab,ti OR recthormone:tn,ab,ti OR
sterandryl:tn,ab,ti OR sterotest:tn,ab,ti OR 'suprasteron amp':tn,ab,ti OR suprasterone:tn,ab,ti OR
synerone:tn,ab,ti OR testaform:tn,ab,ti OR testex:tn,ab,ti OR testodet:tn,ab,ti OR testodrin:tn,ab,ti OR
testogen:tn,ab,ti OR testonique:tn,ab,ti OR testormol:tn,ab,ti OR testormon:tn,ab,ti OR testosid:tn,ab,ti
OR 'testosteron propionate':tn,ab,ti OR 'testosteron propionat':tn,ab,ti OR
testosteronepropionate:tn,ab,ti OR 'testoviron amp':tn,ab,ti OR testoxyl:tn,ab,ti OR testrex:tn,ab,ti OR
tostrin:tn,ab,ti OR uniteston:tn,ab,ti OR 'virormone x':tn,ab,ti OR 'agovirin':tn,ab,ti OR
'virormone':tn,ab,ti
#25 'testosterone undecanoate':tn,ab,ti OR andriol:tn,ab,ti OR aveed:tn,ab,ti OR nebido:tn,ab,ti OR
pantestone:tn,ab,ti OR restandol:tn,ab,ti OR 'tosterone 17 undecylate':tn,ab,ti OR 'testosterone
undecylate':tn,ab,ti OR 'undestor':tn,ab,ti OR 'understor':tn,ab,ti OR 'virigen':tn,ab,ti
#26 'testosterone phenylpropionate':tn,ab,ti OR androject:tn,ab,ti OR retandrol:tn,ab,ti
#27 'exogenous testosterone':ab,ti OR 'exogenous t':ab,ti OR 't trial':ab,ti OR 't trials':ab,ti OR 't
therapy':ab,ti OR 't therapies':ab,ti OR 't supplementation':ab,ti OR 't treatment':ab,ti OR 't treated':ab,ti
OR 't administration':ab,ti OR 'transdermal t':ab,ti OR 'testosterone product':ab,ti OR 'testosterone
products':ab,ti
#28 ((testosterone OR androgen*) NEAR/1 (intramuscular OR intravenous OR 'long acting' OR oral
OR parenteral OR gel* OR patch* OR topical OR transdermal OR transscrotal OR implant* OR injectable*
OR synthetic OR cream OR subcutaneous OR transdermal OR pellet* OR sublingual OR use* OR abuse*
OR misuse*)):ab,ti
20
#29 ((testosterone OR androgen*) NEAR/3 (replacement OR therapy OR therapies OR treatment OR
therapeutic OR supplement* OR prescription* OR prescribing OR substitution OR administration)):ab,ti
#30 (hypogonadism NEAR/3 (replacement OR therapy OR therapies OR treatment OR therapeutic OR
supplement* OR prescription* OR prescribing OR substitution OR administration)):ab,ti
#31 #12 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR
#30
#32 (Animals/exp or invertebrate/exp or 'animal experiment'/exp or 'animal tissue'/exp or 'animal
cell'/exp or nonhuman/exp) NOT (humans/exp)
#33 #31 NOT #32
#34 'female'/exp NOT 'male'/exp
#35 #33 NOT #34
#36 'antiandrogen'/exp OR 'androgen deprivation therapy'/exp
#37 #35 NOT #36
#38 (androgen NEXT/1 depriv*):ti OR (androgen NEXT/1 suppress*):ti OR (androgen NEXT/1
block*):ti OR (androgen NEXT/1 ablation):ti OR (anti NEXT/1 androgen*):ti OR antiandrogen*:ti OR
(androgen NEXT/1 antagonist*):ti OR (testosterone NEXT/1 depriv*):ti OR (testosterone NEXT/1
suppress*):ti OR (testosterone NEXT/1 block*):ti OR (testosterone NEXT/1 ablation):ti
#39 #37 NOT #38
#40 (fish:ti NOT 'fish oil':ti) OR (snake:ti NOT 'snake oil':ti) OR fishes:ti OR goldfish:ti OR chicken:ti OR
chickens:ti OR chick:ti OR chicks:ti OR goat:ti OR goats:ti OR rat:ti OR rats:ti OR mice:ti OR murine:ti OR
murinae:ti OR pig:ti OR pigs:ti OR goose:ti OR geese:ti OR stallion:ti OR stallions:ti OR bovine:ti OR
rabbit:ti OR rabbits:ti OR duck:ti OR ducks:ti OR quail:ti OR eggs:ti OR bird:ti OR canine:ti OR gecko:ti OR
rhea:ti OR ratite:ti OR passerine:ti OR muskrat:ti OR baboon:ti OR baboons:ti OR bat:ti OR sheep:ti OR
bulls:ti OR monkey:ti OR monkeys:ti OR cats:ti OR junco:ti OR cow:ti OR cows:ti OR heifer:ti OR heifers:ti
OR cattle:ti OR livestock:ti OR horse:ti OR horses:ti OR hamster:ti OR hamsters:ti OR mouse:ti OR
turtles:ti OR lamb:ti OR lambs:ti OR scallop:ti OR voles:ti OR coyotes:ti OR grouse:ti OR blackbirds:ti OR
crane:ti OR ibis:ti OR stork:ti OR sparrow:ti OR sparrows:ti OR albatross:ti OR albatrosses:ti OR
muntjac:ti OR cervids:ti OR gerbil:ti OR gerbils:ti OR songbird:ti OR songbirds:ti OR rams:ti OR dog:ti OR
dogs:ti OR jays:ti OR starling:ti OR starlings:ti OR avian:ti OR whale:ti OR whales:ti OR mollusc:ti OR
molluscs:ti OR caecilians:ti OR rodent:ti OR rodents:ti OR swallows:ti OR gull:ti OR gulls:ti OR
budgerigar:ti OR budgerigars:ti OR finch:ti OR finches:ti OR rhino:ti OR rhinos:ti OR rhinoceros:ti OR
toad:ti OR toads:ti OR hen:ti OR hens:ti OR degus:ti OR gilt:ti OR gilts:ti OR boar:ti OR boars:ti OR lizard:ti
OR lizards:ti OR anuran:ti OR anurans:ti OR treefrog:ti OR treefrogs:ti OR frog:ti OR frogs:ti OR
crocodile:ti OR crocodiles:ti OR colt:ti OR colts:ti OR chimpanzee:ti OR chimpanzees:ti OR salamander:ti
OR salamanders:ti OR insect:ti OR insects:ti OR wasp:ti OR wasps:ti OR snakes:ti OR rattlesnake:ti OR
rattlesnakes:ti OR treesnake:ti OR treesnakes:ti OR maggot:ti OR maggots:ti OR urchin:ti OR urchins:ti
OR alligator:ti OR alligators:ti OR shrimp:ti OR shrimps:ti OR corals:ti OR newt:ti OR newts:ti OR
pleurodeles:ti OR rotifer:ti OR rotifers:ti OR moth:ti OR moths:ti OR marmoset:ti OR marmosets:ti OR
elephant:ti OR elephants:ti OR trout:ti OR flycatcher:ti OR flycatchers:ti OR iguana:ti OR iguanas:ti OR
worm:ti OR worms:ti OR marten:ti OR martens:ti OR hare:ti OR hares:ti OR deer:ti OR ferret:ti OR
ferrets:ti OR ewe:ti OR ewes:ti OR tuatara:ti OR tuataras:ti OR pintail:ti OR pintails:ti OR partridge:ti OR
partridges:ti OR jerboa:ti OR jerboas:ti OR bucks:ti OR squirrel:ti OR squirrels:ti OR cock:ti OR cocks:ti OR
capon:ti OR capons:ti OR reptile:ti OR reptiles:ti OR minnow:ti OR minnows:ti OR salmon:ti OR beetle:ti
OR beetles:ti OR zebrafish:ti OR mallard:ti OR mallards:ti OR catfish:ti OR macaque:ti OR macaques:ti OR
21
tadpole:ti OR tadpoles:ti OR porcine:ti OR porcines:ti OR guppy:ti OR guppies:ti OR buffalo:ti OR
buffaloe:ti OR buffaloes:ti OR buffalos:ti OR parasite:ti OR parasites:ti OR teleost:ti OR teleosts:ti OR
carp:ti OR tilapia:ti OR snail:ti OR snails:ti OR grouper:ti OR medaka:ti OR greyhounds:ti OR eel:ti OR
mudsnail:ti OR mudsnails:ti OR canary:ti OR canaries:ti OR bullfrogs:ti OR swine:ti OR parrot:ti
OR shrews:ti OR "non human":ti OR nonhuman:ti
#41 #39 NOT #40
#42 menstrual*:ti OR premenstrual*:ti OR vagina*:ti OR uterus:ti OR uterine*:ti OR ovarian*:ti OR
ovary*:ti OR endometrial*:ti
#43 #41 NOT #42
#44 child*:ti OR adolescent*:ti OR adolescenc*:ti NOT (adult*:ti OR men:ti)
#45 #43 NOT #44
#46 'in vitro study'/exp
#47 #45 NOT #46
#48 'in vitro':ti OR 'in vivo':ti
#49 #47 NOT #48
#50 #49 AND [1990-2016]/py
Cochrane library
#1 MeSH descriptor: [Testosterone] explode all trees and with qualifier(s): [Administration &
dosage - AD, Adverse effects - AE, Contraindications - CT, Poisoning - PO, Therapeutic use - TU, Toxicity -
TO]
#2 MeSH descriptor: [Testosterone Propionate] explode all trees and with qualifier(s):
[Administration & dosage - AD, Adverse effects - AE, Contraindications - CT, Poisoning - PO, Therapeutic
use - TU, Toxicity - TO]
#3 MeSH descriptor: [Testosterone Congeners] explode all trees and with qualifier(s):
[Administration & dosage - AD, Adverse effects - AE, Contraindications - CT, Poisoning - PO, Therapeutic
use - TU, Toxicity - TO]
#4 MeSH descriptor: [Androgens] explode all trees and with qualifier(s): [Administration & dosage -
AD, Adverse effects - AE, Contraindications - CT, Poisoning - PO, Therapeutic use - TU, Toxicity - TO]
#5 MeSH descriptor: [Hypogonadism] explode all trees and with qualifier(s): [Diet therapy - DH,
Drug therapy - DT, Mortality - MO, Therapy - TH]
#6 {or #1-#5}
#7 MeSH descriptor: [Hormone Replacement Therapy] explode all trees
#8 ((hormone or hormonal or sex steroid*) near/3 (replacement or therapy or therapies or
treatment or therapeutic or supplement* or prescription* or prescribing or substitution or
administration)):ti,ab,kw
#9 #7 or #8
#10 MeSH descriptor: [Testosterone] explode all trees
#11 (androgen* or testosterone):ti,ab,kw
#12 {or #10-#11}
#13 #9 and #12
#14 ("Actiser-T" or "Adrotest" or "Andro 100" or "Andro" or "Androderm" or "Androfort" or
"Androgel" or "Android-10" or "Androlan" or "Androlin" or "Andronaq" or "Andronaq-50" or
22
"Andropatch" or "Androplex" or "Androsorb" or "Androstenolone" or "Androtest" or "Androtop" or
"Androtopic" or "Androxon" or "Andrusol" or "Aquaviron" or "Aqueous testosterone suspension" or
"Atmos" or "Axiron" or "Beta testosterone" or "Bio t gel" or "Clym-Depositum" or "Col 1621" or
"col1621" or "Cypionax" or "Depot hormon-m" or "Depotrone" or "Despamen" or "Durateston" or
"Facovit" or "First-testosterone" or "Fluoxymesterone" or "Folivirin" or "Fortesta" or "Fortigel" or "Geno
cristaux" or "Glutest Liquid" or "Halotestin" or "Histerone" or "Homosteron" or "Hydroxyandrostenone"
or "Intrinsa" or "Itnogen" or "Libigel" or "Livensa" or "Lontanyl" or "Lowtiyel" or "Malogen Aqueous" or
"Malogen In Oil" or "Mertestate" or "Metesto" or "Metharmon-F" or "Methitest" or "Methyl
Testosterone" or "Methyltestosterone" or "Natesto" or "Nebid" or "Neotestis" or "Nsc 9700" or
"Nsc9700" or "Numanis" or "Nuo Shi" or "Omnadren" or "Opterone" or "Oreton f" or "Oreton Methyl"
or "Oreton" or "Orquisteron" or "Pasuma" or "Percutacrine androgenique" or "Polysteron 250" or
"Primoniat Depot" or "Primotest" or "Primoteston Depot" or "Primoteston" or "Proviron Depot" or
"Reandron" or "Restinsol" or "Rubidiosin Composto" or "Scheinpharm Testone-Cyp" or "Shotest-100" or
"Shotest-50" or "Si Te Long" or "Sostenon" or "Sten" or "Sterotate" or "Striant" or "Sustanon" or
"Sustenan" or "Sustenon 250" or "Synandrol" or "Tachynerg N" or "Tesamone" or "Teslen" or
"Testamone" or "Testandro" or "Testandrone" or "Testaqua" or "Test-Comp" or "Testerone" or "Test-
Estro" or "Testim" or "Testiormina" or "Testo enant" or "Testocaps" or "Testoderm" or "Testo-Enant" or
"Testogel" or "Testoject-50" or "Testolent" or "Testolic" or "Testolin" or "Testoluton" or "Testomax" or
"Testopatch" or "Testopel" or "Testoprim-D" or "Testoral" or "Testosteron Aq" or "Testosterone
acetate" or "Testosterone Aq" or "Testosterone Aqueous Suspension" or "Testosterone caproate" or
"Testosterone chloride" or "Testosterone conjugate" or "Testosterone Cyclopentilate" or "Testosterone
decanoate" or "Testosterone Fuel Booster" or "Testosterone isocaproate" or "Testosterone prop" or
"Testosterone Suspension" or "Testosteron" or "Testosteronum Prolongatum" or "Testotop" or
"Testoviron" or "Testovis" or "Testovital" or "Testozzard" or "Testred" or "Testro AQ" or "Testro" or
"Testrone" or "Testryl" or "Tesurene" or "Tostran" or "Tostrelle" or "Tostrex" or "T-phenylpropionate" or
"Trinestril" or "Trioestrine-Retard" or "Triolandren" or "Virilisterona" or "Virosterone" or
"Vogelxo"):ti,ab,kw
#15 (testosterone ester*):ti,ab,kw
#16 ("Testosterone Cipionate" or "andro cyp" or "andronaq la" or ciclosterone or depandro or "depo
testosterone" or depotest or "Depo-Test" or depotestosterone or depovirin or depoviron or duratest or
"malogen cyp 200" or pertestis or "testa c" or "testodrin prolongatum" or "testosterone 17beta
cyclopentanepropionate" or "testosterone 17beta cypionate" or "testosterone beta
cyclopentylpropionate" or "testosterone cyclopentylpropionate" or "testosterone cypionate" or "testred
cypionate" or "Andro-Cyp 100" or "Andro-Cyp 200" or "Andronate 100" or "Andronate 200" or
"Deposteron" or "Shotest-La" or "T-Cypionate" or "Testa-C" or "Testoject-La" or "Testra-C" or "T-Ionate
P.A." or "Testex" or "Virilon"):ti,ab,kw
#17 ("Testosterone Enantate" or "andro la 200" or "androstenolone enanthate" or androtardyl or
delatestryl or durathate or everone or jenasteron or "malogen la 200" or malogex or "testosterone 1
hexanecarboxylate" or "testosterone enanthane" or "testosterone enanthate" or "T-enanthate" or
"testosterone ethanate" or "testosterone heptanoate" or "testosterone heptonate" or "testosterone
heptylate" or "testosterone oenanthate" or "testosterone oenanthic acid derivative" or "testosviron
depot" or "testoviron depot" or "testro-l.a." or "virormone depot" or "Andropository" or "Andryl 200" or
"Everone" or "Testone L.A." or "Testostroval P.A." or "Testra-E" or "Testrin Pa" or "Ablacton"):ti,ab,kw
23
#18 ("testosterone propionate" or akroteston or anderone or andronate or "andronex amp" or
"androsan amp" or "androtest p" or androteston or androxid or androxil or "andrusol p" or anertar or
"bio testiculina" or "bio teston" or "cosex tp 50" or "delta4 androstene 17beta propionate 3 one" or
enarmon or entestil or gonadrone or "homandren amp" or hormandren or hormoteston or masenate or
napionate or nasdol or "neo hombreol" or neohombreol or "nsc 9166" or nsc9166 or "okasa mascul" or
orchiol or orchiormon or orchisterone or orchistin or oreton or oretone or "orquisteron p" or
"orquisterone p" or pantestin or penandren or perandren or perandrone or primoniat or propiokan or
recthormone or sterandryl or sterotest or "suprasteron amp" or suprasterone or synerone or testaform
or testex or testodet or testodrin or testogen or testonique or testormol or testormon or testosid or
"testosteron propionate" or "Testosteron propionat" or testosteronepropionate or "testoviron amp" or
testoxyl or testrex or tostrin or uniteston or "virormone x" or "Agovirin" or "Virormone"):ti,ab,kw
#19 ("Testosterone undecanoate" or andriol or aveed or nebido or pantestone or restandol or
"tosterone 17 undecylate" or "testosterone undecylate" or "Undestor" or "Understor" or
"Virigen"):ti,ab,kw
#20 ("testosterone phenylpropionate" or androject or retandrol):ti,ab,kw
#21 (Exogenous testosterone or "exogenous T" or "T trial" or "T trials" or "T therapy" or "T
therapies" or "T Supplementation" or "T Treatment" or "T Treated" or "T Administration" or
"Transdermal T" or "testosterone product" or "testosterone products"):ti,ab,kw
#22 ((Testosterone or androgen*) near/1 (intramuscular or intravenous or long-acting or oral or
parenteral or gel* or patch* or topical or transdermal or transscrotal or implant* or injectable* or
synthetic or cream or subcutaneous or transdermal or pellet* or sublingual or use* or abuse* or
misuse*)):ti,ab,kw
#23 ((Testosterone or androgen*) near/3 (replacement or therapy or therapies or treatment or
therapeutic or supplement* or prescription* or prescribing or substitution or administration)):ti,ab,kw
#24 (Hypogonadism near/3 (replacement or therapy or therapies or treatment or therapeutic or
supplement* or prescription* or prescribing or substitution or administration)):ti,ab,kw
#25 {or #6, #13-#24}
#26 MeSH descriptor: [Animals] explode all trees
#27 MeSH descriptor: [Humans] explode all trees
#28 #26 not #27
#29 #25 not #28
#30 MeSH descriptor: [Female] explode all trees
#31 MeSH descriptor: [Male] explode all trees
#32 #30 not #31
#33 #29 not #32
#34 MeSH descriptor: [Androgen Antagonists] explode all trees
#35 #33 not #34
#36 (androgen depriv* or androgen suppress* or androgen block* or androgen ablation or anti-
androgen* or antiandrogen* or androgen antagonist* or testosterone depriv* or testosterone
suppress* or testosterone block* or testosterone ablation):ti
#37 #35 not #36
#38 ((Fish not "fish oil") or (snake not "snake oil") or fishes or goldfish or chicken or chickens or chick
or chicks or goat or goats or rat or rats or rat's or mice or murine or murinae or pig or pigs or goose or
geese or stallion or stallions or bovine or rabbit or rabbits or duck or ducks or quail or eggs or bird or
24
canine or gecko or Rhea or Ratite or passerine or muskrat or baboon or baboons or bat or sheep or bulls
or monkey or monkeys or cats or junco or cow or cows or heifer or heifers or cattle or livestock or horse
or horses or hamster or hamsters or mouse or turtles or lamb or lambs or scallop or voles or coyotes or
grouse or blackbirds or crane or Ibis or Stork or sparrow or sparrows or albatross or albatrosses or
albatrosses' or muntjac or cervids or gerbil or gerbils or songbird or songbirds or rams or dog or dogs or
jays or starling or starlings or avian or whale or whales or mollusc or molluscs or caecilians or rodent or
rodents or swallows or gull or gulls or budgerigar or budgerigars or finch or finches or rhino or rhinos or
rhinoceros or toad or toads or hen or hens or degus or gilt or gilts or boar or boars or lizard or lizards or
anuran or anurans or treefrog or treefrogs or frog or frogs or crocodile or crocodiles or Colt or Colts or
chimpanzee or chimpanzees or salamander or salamanders or insect or insects or wasp or wasps or
snakes or rattlesnake or rattlesnakes or treesnake or treesnakes or maggot or maggots or urchin or
urchins or alligator or Alligators or shrimp or shrimps or corals or newt or newts or Pleurodeles or rotifer
or rotifers or moth or moths or marmoset or marmosets or elephant or elephants or trout or flycatcher
or flycatchers or iguana or iguanas or worm or worms or marten or martens or hare or hares or deer or
ferret or ferrets or ewe or ewes or tuatara or tuataras or pintail or pintails or partridge or partridges or
jerboa or jerboas or bucks or squirrel or squirrels or cock or cocks or capon or capons or reptile or
reptiles or minnow or minnows or salmon or beetle or beetles or zebrafish or mallard or mallards or
catfish or macaque or macaques or tadpole or tadpoles or porcine or porcines or guppy or guppies or
buffalo or buffaloe or buffaloes or buffalos or parasite or parasites or teleost or teleosts or carp or
tilapia or snail or snails or grouper or medaka or greyhounds or eel or mudsnail or mudsnails or canary
or canaries or bullfrogs or swine or parrot or shrews or "non human" or nonhuman):ti
#39 #37 not #38
#40 (menstrual* or premenstrual* or vagina* or uterus or uterine* or ovarian* or ovary* or
endometrial*):ti
#41 #39 not #40
#42 ((child* or adolescent* or adolescenc*) not (adult* or men)):ti
#43 #41 not #42
#44 ("in vitro" or "in vivo"):ti
#45 #43 not #44
25
APPENDIX 4. ASSESSMENT OF COMPOSITE MACE OUTCOME AMONG RCTS INCLUDED IN
SYSTEMATIC REVIEWS.
Whether assessed composite MACE outcome (0/1)
Calof, 2005
[14]
Haddad,
2007 [15]
Fernandez-
Balsells, 2010
[16]
Xu, 2013
[17]
Corona,
2014 [19]
Borst, 2014
[18]
Copenhagen Study Group for
Liver Diseases 1986 [48]
-- 0 0 0 0 0
Marin et al., 1992 [49] 0 -- -- 0 -- 0
Tenover, 1992 [50] 0 -- -- -- -- -- Morley et al., 1993 [51] 0 -- 0 -- -- -- Drinka et al., 1995 [52] 0 -- -- -- 0 -- Hall et al., 1996 [31] 0 -- -- 0 0 0
Reid et al., 1996 [53] 0 -- -- -- -- --
Sih et al., 1997 [54] 0 -- -- 0 0 0
English et al., 2000 [55] 0 0 0 0 0 0
Snyder et al., 2001 [56] 0 0 0 0 0 0
Simon et al., 2001 [57] 0 -- -- -- 0 -- Munzer et al., 2001 [58] 0 -- -- -- 0 -- Kenny et al., 2002 [59] 0 -- -- -- -- -- Amory et al., 2002 [60] -- 0 -- -- 0 -- Ferrando et al., 2003 [61] 0 -- -- -- 0 0
Boyanov et al., 2003 [62] 1 -- -- -- -- --
Wittert et al., 2003 [63] 0 -- -- -- -- --
Steidle et al., 2003 [30] 0 -- 0 -- 0 --
Crawford et al., 2003 [64] 0 -- -- -- -- --
Amory et al., 2004 [65] 0 0 -- 0 0 0
Kenny et al., 2004 [66] 0 -- -- 0 0 0
Svartberg et al., 2004 [67] -- 0 0 0 0 0
Brockenbrough, 2006 [68] -- -- 1 1 1 1
Malkin et al., 2006 [69] -- -- 0 0 0 0
Merza et al., 2006 [70] -- -- -- 0 0 0
Nair et al., 2006 [71] -- -- -- 1 1 1
Emmelot-Vonk, 2008 [32] -- -- 1 1 1 1
Svartberg et al., 2008 [72] -- -- -- 0 0 0
Caminiti et al., 2009 [73] -- -- -- 0 0 0
Chapman et al., 2009 [74] -- -- -- 0 0 0
Legros et al., 2009 [75] -- -- -- 0 0 0
Aversa et al., 2010 [76] -- -- -- 0 0 0
Basaria et al., 2010 [3] -- -- -- 1 1 1
Srinivas-Shankar, 2010 [77] -- -- -- 0 0 0
Kalinchenko et al., 2010 [78] -- -- -- 0 0 0
Kenny et al.,2010 [79] -- -- -- -- -- 1
Jones et al ., 2011 [80] -- -- -- 0 0 0
Ho et al., 2011 [81] -- -- -- 0 0 0
Kaufman et al., 2011 [82] -- -- -- 0 0 0
Sheffield-Moore et al., 2011 [83] -- -- -- -- -- 0
Hoyos et al., 2012 [84] -- -- -- 1 1 1
26
Whether assessed composite MACE outcome (0/1)
Calof, 2005
[14]
Haddad,
2007 [15]
Fernandez-
Balsells, 2010
[16]
Xu, 2013
[17]
Corona,
2014 [19]
Borst, 2014
[18]
Spitzer et al., 2012 [85] -- -- -- 1 -- 1
Glintborg et al.,2013 [86] -- -- -- -- -- 0
Hildreth et al., 2013 [87] -- -- -- -- 0 0
Hackett et al., 2013 [88] -- -- -- -- 0 0
Tan et al., 2013 [89] -- -- -- -- -- 0
Borst et al., 2014 [90] -- -- -- -- -- 0
Total 1 0 2 6 7 7
Footnote: RCT–Randomized placebo-controlled clinical trial; MACE–composite assessment of major adverse
cariovascular event; 0 – did not assess MACE; 1 – assessed MACE; ‘--' the RCT is not reported in the review
27
APPENDIX 6: OPTIMAL INFORMATION SIZE (OIS) ANALYSIS
We conducted an optimal information size (OIS) analysis based on the cardiovascular event rates reported in the largest systematic review by Borst et al (6.2% or 0.062 in the testosterone group vs 5.5% or 0.055 in placebo group or a relative increase of approximately 12%). Assuming a two-sided P of 0.05 and power of 80%, we would require 17,664 participants in each arm of a randomized controlled trial to detect a statistically significant difference. As a sensitivity analysis, we also performed an OIS analysis assuming a larger minimal detectable difference of 25%, or 0.068 in the testosterone group and 0.055 in the control group, as reported by Borst et al. In this case, we would require 4,819 participants in each arm of a randomized controlled trial to detect a statistically significant difference.
References
1. Roser B. Hypothesis Testing: Categorical Data - Estimation of Sample Size and Power for Comparing Two Binomial Proportions. Fundamentals of Biostatistics. Brooks/Cole Cengage Learning. United States, 2010.
2. Statistical Sample Size Calculator. Avilable at: http://www.stat.ubc.ca/~rollin/stats/ssize/b2.html (Accessed July 5, 2016).
