Practical Use of Pharmacotherapy for Obesity

Gastroenterology

Volumn 152, Issue 7, 2017, Pages 1765-1779

  Igel, Leon I ^a   Kumar, Rekha B ^a   Saunders, Katherine H ^a   Aronne, Louis J ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

Obesity; Pharmacotherapy; Testosterone; Weight Management

Indexed keywords

AMFEBUTAMONE PLUS NALTREXONE; ANTICONVULSIVE AGENT; ANTIDEPRESSANT AGENT; ANTIDIABETIC AGENT; ANTIHISTAMINIC AGENT; ANTIHYPERTENSIVE AGENT; CONTRACEPTIVE AGENT; GLUCOCORTICOID; LIRAGLUTIDE; LORCASERIN; NEUROLEPTIC AGENT; PHENTERMINE; PHENTERMINE PLUS TOPIRAMATE; STEROID; TESTOSTERONE; TETRAHYDROLIPSTATIN; AMFEBUTAMONE; ANDROGEN; ANOREXIGENIC AGENT; ANTIOBESITY AGENT; BENZAZEPINE DERIVATIVE; DRUG COMBINATION; FRUCTOSE; LACTONE; NALTREXONE; NALTREXONE-BUPROPION COMBINATION; TOPIRAMATE;

ABDOMINAL PAIN; ARTICLE; BEHAVIOR DISORDER; BEHAVIOR MODIFICATION; CONSTIPATION; DIARRHEA; DIET; DIZZINESS; DYSGEUSIA; DYSPEPSIA; ELEVATED BLOOD PRESSURE; EXERCISE; FATIGUE; FECES INCONTINENCE; FLATULENCE; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; HYPOGONADISM; INSOMNIA; LIFESTYLE MODIFICATION; NAUSEA; OBESITY; PARESTHESIA; PRIORITY JOURNAL; SLEEP DISORDER; TREATMENT INDICATION; VOMITING; WEIGHT GAIN; WEIGHT REDUCTION; XEROSTOMIA; ANALOGS AND DERIVATIVES; COMPLICATION; DRUG COMBINATION; DRUG EFFECTS;

ANDROGENS; ANTI-OBESITY AGENTS; ANTIDEPRESSIVE AGENTS; ANTIHYPERTENSIVE AGENTS; ANTIPSYCHOTIC AGENTS; APPETITE DEPRESSANTS; BENZAZEPINES; BUPROPION; DRUG COMBINATIONS; FRUCTOSE; HUMANS; HYPOGLYCEMIC AGENTS; HYPOGONADISM; LACTONES; LIRAGLUTIDE; NALTREXONE; OBESITY; PHENTERMINE; TESTOSTERONE; WEIGHT GAIN;

EID: 85018625078     PISSN: 00165085     EISSN: 15280012     Source Type: Journal    
DOI: 10.1053/j.gastro.2016.12.049     Document Type: Article

References (111)

1. 1 Greenway, F.L., Physiological adaptations to weight loss and factors favouring weight regain. Int J Obes (Lond) 39 (2015), 1188–1196.
2. 2 Dhindsa, S., Miller, M.G., McWhirter, C.L., et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care 33 (2010), 1186–1192.
3. 3 Jensen, M.D., Ryan, D.H., Apovian, C.M., et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 63:25 Pt B (2014), 2985–3023.
4. 4 Apovian, C.M., Aronne, L.J., Bessesen, D.H., et al. Pharmacological management of obesity: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab 100 (2015), 342–362.
5. 5 Garvey, W.T., Mechanick, J.I., Brett, E.M., et al. American Association of Clinical Endocrinologist and American College of Endocrinology Comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract 22:Suppl 3 (2016), 1–203.
6. 6 Saunders, K.H., Igel, L.I., Shukla, A.P., et al. Drug-induced weight gain: rethinking our choices. J Fam Pract 65 (2016), 780–782 784−786, 788.
7. 7 Garber, A.J., Abrahamson, M.J., Barzilay, J.I., et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm−2016 Executive Summary. Endocr Pract 22 (2016), 84–113.
8. 8 Aronne, L.J., Drug-induced weight gain: non-CNS medications. Aronne, L.J., (eds.) A Practical Guide to Drug-Induced Weight Gain, 2002, McGraw-Hill, Minneapolis, MN, 77–91.
9. 9 Malin, S.K., Kashyap, S.R., Effects of metformin on weight loss: potential mechanisms. Curr Opin Endocrinol Diabetes Obes 21 (2014), 323–329.
10. 10 Igel, L.I., Sinha, A., Saunders, K.H., et al. Metformin: an old therapy that deserves a new indication for the treatment of obesity. Curr Atheroscler Rep, 18, 2016, 16.
11. 11 Ferrannini, E., Solini, A., SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects. Nat Rev Endocrinol 8 (2012), 495–502.
12. 12 Van de Laar, F.A., Lucassen, P.L., Akkermans, R.P., et al. Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care 28 (2005), 154–163.
13. 13 Hong, E.S., Khang, A.R., Yoon, J.W., et al. Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study. Diabetes Obes Metab 14 (2012), 795–802.
14. 14 Arnolds, S., Dellweg, S., Clair, J., et al. Further improvement in postprandial glucose control with addition of exenatide or sitagliptin to combination therapy with insulin glargine and metformin: a proof-of-concept study. Diabetes Care 33 (2010), 1509–1515.
15. 15 Scheen, A.J., DPP-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials. Diabetes Metab 38 (2012), 89–101.
16. 16 Hollander, P.A., Levy, P., Fineman, M.S., et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care 26 (2003), 784–790.
17. 17 Aronne, L., Fujioka, K., Aroda, V., et al. Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. J Clin Endocrinol Metab 92 (2007), 2977–2983.
18. 18 Messerli, F.H., Bell, D.S., Fonseca, V., et al. Body weight changes with beta-blocker use: results from GEMINI. Am J Med 120 (2007), 610–615.
19. 19 Pischon, T., Sharma, A.M., Use of beta-blockers in obesity hypertension: potential role of weight gain. Obes Rev 2 (2001), 275–280.
20. 20 Sharma, A.M., Pischon, T., Hardt, S., et al. Hypothesis: beta-adrenergic receptor blockers and weight gain: a systematic analysis. Hypertension 37 (2001), 250–254.
21. 21 Manrique, C., Whaley-Connell, A., Sowers, J.R., Nebivolol in obese and non-obese hypertensive patients. J Clin Hypertens (Greenwich) 11 (2009), 309–315.
22. 22 The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Project. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA 283 (2000), 1967–1975.
23. 23 Bray, G.A., Bouchard, C., Drugs that cause weight gain and clinical alternatives to their use. Bray, G.A., Bouchard, C., (eds.) Handbook of Obesity. Volume 2: Clinical Applications, Fourth Edition, 2014, CRC Press, Boca Raton, FL, 220–229.
24. 24 Landsberg, L., Aronne, L.J., Beilin, L.J., et al. Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment—a position paper of the The Obesity Society and The American Society of Hypertension. Obesity (Silver Spring) 21 (2013), 8–24.
25. 25 Serretti, A., Mandelli, L., Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 71 (2010), 1259–1272.
26. 26 Norris, S.L., Zhang, X., Avenell, A., et al. Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus. Cochrane Database Syst Rev(1), 2005, CD004096.
27. 27 Domecq, J.P., Prutsky, G., Leppin, A., et al. Clinical review: drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab 100 (2015), 363–370.
28. 28 Rosenzweig-Lipson, S., Beyer, C.E., Hughes, Z.A., et al. Differentiating antidepressants of the future: efficacy and safety. Pharmacol Ther 113 (2007), 134–153.
29. 29 Gadde, K.M., Xiong, G.L., Bupropion for weight reduction. Expert Rev Neurother 7 (2007), 17–22.
30. 30 Arterburn, D., Sofer, T., Boudreau, D.M., et al. Long-term weight change after initiating second-generation antidepressants. J Clin Med, 5(4), 2016.
31. 31 Leucht, S., Cipriani, A., Spineli, L., et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382:9896 (2013), 951–962.
32. 32 Simpson, G.M., Glick, I.D., Weiden, P.J., et al. Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Am J Psychiatry 161 (2004), 1837–1847.
33. 33 Komossa, K., Rummel-Kluge, C., Hunger, H., et al. Ziprasidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev, 4, 2009, CD006627.
34. 34 Meyer, J.M., Mao, Y., Pikalov, A., et al. Weight change during long-term treatment with lurasidone: pooled analysis of studies in patients with schizophrenia. Int Clin Psychopharmacol 30 (2015), 342–350.
35. 35 Musil, R., Obermeier, M., Russ, P., et al. Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf 14 (2015), 73–96.
36. 36 Maayan, L., Correll, C.U., Weight gain and metabolic risks associated with antipsychotic medications in children and adolescents. J Child Adolesc Psychopharmacol 21 (2011), 517–535.
37. 37 Hasnain, M., Vieweg, W.V., Hollett, B., Weight gain and glucose dysregulation with second-generation antipsychotics and antidepressants: a review for primary care physicians. Postgrad Med 124 (2012), 154–167.
38. 38 Lieberman, J.A., Stroup, T.S., McEvoy, J.P., et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353 (2005), 1209–1223.
39. 39 Allison, D.B., Casey, D.E., Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry 62:Suppl 7 (2001), 22–31.
40. 40 Ratliff, J.C., Barber, J.A., Palmese, L.B., et al. Association of prescription H1 antihistamine use with obesity: results from the National Health and Nutrition Examination Survey. Obesity (Silver Spring) 18 (2010), 2398–2400.
41. 41 He, M., Deng, C., Huang, X.F., The role of hypothalamic H1 receptor antagonism in antipsychotic-induced weight gain. CNS Drugs 27 (2013), 423–434.
42. 42 Antel, J., Hebebrand, J., Weight-reducing side effects of the antiepileptic agents topiramate and zonisamide. Handb Exp Pharmacol 209 (2012), 433–466.
43. 43 Verrotti, A., D'Egidio, C., Mohn, A., et al. Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes Rev 12 (2011), e32–e43.
44. 44 DeToledo, J.C., Toledo, C., DeCerce, J., et al. Changes in body weight with chronic, high-dose gabapentin therapy. Ther Drug Monit 19 (1997), 394–396.
45. 45 Gaspari, C.N., Guerreiro, C.A., Modification in body weight associated with antiepileptic drugs. Arq Neuropsiquiatr 68 (2010), 277–281.
46. 46 Ben-Menachem, E., Weight issues for people with epilepsy—a review. Epilepsia 48:Suppl 9 (2007), 42–45.
47. 47 Gallo, M.F., Lopez, L.M., Grimes, D.A., et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev, 1, 2014, CD003987.
48. 48 Lopez, L.M., Ramesh, S., Chen, M., et al. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev(8), 2016 Aug 28, CD008815.
49. 49 Dal'Ava, N., Bahamondes, L., Bahamondes, M.V., et al. Body weight and composition in users of levonorgestrel-releasing intrauterine system. Contraception 86 (2012), 350–353.
50. 50 Fardet, L., Fève, B., Systemic glucocorticoid therapy: a review of its metabolic and cardiovascular adverse events. Drugs 74 (2014), 1731–1745.
51. 51 Apovian, C.M., Aronne, L., Powell, A.G., Clinical Management of Obesity. 2015, Professional Communications, Inc, West Islip, NY.
52. 52 Rothman, R.B., Baumann, M.H., Dersch, C.M., et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39 (2001), 32–41.
53. 53 Kaplan, L.M., Pharmacologic therapies for obesity. Gastroenterol Clin N Am 39 (2005), 69–79.
54. 54 Aronne, L.J., Wadden, T.A., Peterson, C., et al. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity (Silver Spring) 21 (2013), 2163–2171.
55. 55 Xenical [package insert], 2016, Genentech USA, Inc, San Francisco, CA Available at: http://www.gene.com/download/pdf/xenical_prescribing.pdf Accessed September 26, 2016.
56. 56 Torgerson, J.S., Hauptman, J., Boldrin, M.N., et al. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 27 (2004), 155–161.
57. 57 Allison, D.B., Gadde, K.M., Garvey, W.T., et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring) 20 (2012), 330–342.
58. 58 Gadde, K.M., Allison, D.B., Ryan, D.H., et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 377:9774 (2011), 1341–1352.
59. 59 Garvey, W.T., Ryan, D.H., Look, M., et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr 95 (2012), 297–308.
60. 60 Smith, S.R., Weissman, N.J., Anderson, C.M., et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 363 (2010), 245–256.
61. 61 A Study to Evaluate the Effect of Long-term Treatment With BELVIQ (Lorcaserin HCl) on the Incidence of Major Adverse Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects With Cardiovascular Disease or Multiple Cardiovascular Risk Factors (CAMELLIA-TIMI). Available at: https://clinicaltrials.gov/ct2/show/NCT02019264. Accessed October 2, 2016.
62. 62 Fidler, M.C., Sanchez, M., Raether, B., et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 96:10 (2011), 3067–3077.
63. 63 O'Neil, P.M., Smith, S.R., Weissman, N.J., et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOMDM study. Obesity (Silver Spring) 20 (2012), 1426–1436.
64. 64 Greenway, F.L., Whitehouse, M.J., Guttadauria, M., et al. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring) 17 (2009), 30–39.
65. 65 Saunders, K.H., Igel, L.I., Aronne, L.J., Update on naltrexone/bupropion extended-release in the treatment of obesity. Expert Opin Pharmacother, 2016 Oct 4 [Epub ahead of print].
66. 66 Greenway, F.L., Fujioka, K., Plodkowski, R.A., et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 376:9741 (2010), 595–605.
67. 67 Apovian, C.M., Aronne, L., Rubino, D., et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring) 21 (2013), 935–943.
68. 68 Wadden, T.A., Foreyt, J.P., Foster, G.D., et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 19 (2011), 110–120.
69. 69 Hollander, P., Gupta, A.K., Plodkowski, R., et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care 36 (2013), 4022–4029.
70. 70 Nauck, M., Frid, A., Hermansen, K., et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 32 (2009), 84–90.
71. 71 Van Can, J., Sloth, B., Jensen, C.B., et al. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond) 38 (2014), 784–793.
72. 72 Pi-Sunyer, X., Astrup, A., Fujioka, K., et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med 373 (2015), 11–22.
73. 73 Davies, M.J., Bergenstal, R., Bode, B., et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE Diabetes Randomized Clinical Trial. JAMA 314 (2015), 687–699.
74. 74 Wadden, T.A., Hollander, P., Klein, S., et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond) 37 (2013), 1443–1451.
75. 75 Marso, S.P., Daniels, G.H., Brown-Frandsen, K., et al., on behalf of the LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 375 (2016), 311–322.
76. 76 Saunders, K.H., Kumar, R.B., Igel, L.I., Aronne, L.J., Pharmacologic approaches to weight management: recent gains and shortfalls in combating obesity. Curr Atheroscler Rep, 18, 2016, 36.
77. 77 Mulligan, T., Frick, M.F., Zuraw, Q.C., et al. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract 60 (2006), 762–769.
78. 78 Luconi, M., Samavat, J., Seghieri, G., et al. Determinants of testosterone recovery after bariatric surgery: is it only a matter of reduction of body mass index?. Fertil Steril 99 (2013), 1872–1879.e1.
79. 79 Giagulli, V.A., Kaufman, J.M., Vermeulen, A., Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab 79 (1994), 997–1000.
80. 80 Wu, F.C., Tajar, A., Pye, S.R., et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 93 (2008), 2737–2745.
81. 81 Loves, S., Ruinemans-Koerts, J., de Boer, H., Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. Eur J Endocrinol 158 (2008), 741–747.
82. 82 Kelly, D.M., Jones, T.H., Testosterone and obesity. Obes Rev 16 (2015), 581–606.
83. 83 Saad, F., Aversa, A., Isidori, A., et al. Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Curr Diabetes Rev 8 (2012), 131–143.
84. 84 Saad, F., Haider, A., Doros, G., et al. Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss. Obesity (Silver Spring) 21 (2013), 1975–1981.
85. 85 Haider, A., Saad, F., Doros, G., et al. Hypogonadal obese men with and without diabetes mellitus type 2 lose weight and show improvement in cardiovascular risk factors when treated with testosterone: an observational study. Obes Res Clin Pract 8 (2014), e339–e349.
86. 86 Snyder, P.J., Peachey, H., Hannoush, P., et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab, 84, 1999, 2647.
87. 87 Traish, A.M., Testosterone and weight loss: the evidence. Curr Opin Endocrinol Diabetes Obes 21 (2014), 313–322.
88. 88 Bhasin, S., Cunningham, G.R., Hayes, F.J., et al. Testosterone therapy in adult men with androgen deficiency syndromes: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 95 (2010), 2536–2559.
89. 89 Basaria, S., Coviello, A.D., Travison, T.G., et al. Adverse events associated with testosterone administration. N Engl J Med 363 (2010), 109–122.
90. 90 Finkle, W.D., Greenland, S., Ridgeway, G.K., et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One, 9, 2014, e85805.
91. 91 Vigen R, O'Donnell CI, Baron AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 310:1829–1836.
92. 92 US Food and Drug Administration Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm436259.htm. Published March 3, 2015. Accessed November 12, 2016.
93. 93 Layton, J.B., Meier, C.R., Sharpless, J.L., et al. Comparative safety of testosterone dosage forms. JAMA Intern Med 175 (2015), 1187–1196.
94. 94 Dobs, A.S., Meikle, A.W., Arver, S., et al. Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab 84 (1999), 3469–3478.
95. 95 Dohle GR, Arver S, Bettocchi C, et al. Guidelines on male hypogonadism 2015. Available at: http://uroweb.org/wp-content/uploads/EAU-Guidelines-Male-Hypogonadism-2015.pdf. Accessed November 12, 2016.
96. 96 Goodman, N., Guay, A., Dandona, P., et al. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of testosterone and cardiovascular risk. Endocr Pract 21 (2015), 1066–1073.
97. 97 Dimopoulou, C., Ceausu, I., Depypere, H., et al. EMAS position statement: testosterone replacement therapy in the aging male. Maturitas 84 (2016), 94–99.
98. 98 Agency of European Medicine. No consistent evidence of an increased risk of heart problems with testosterone medicines (EMA/706140). Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/11/news_detail_002218.jsp&mid=WC0b01ac058004d5c1. Published November 21, 2014. Accessed November 12, 2016.
99. 99 Snyder, P.J., Bhasin, S., Cunningham, G.R., et al. Effects of testosterone treatment in older men. N Engl J Med 374 (2016), 611–624.
100. 100 Sharma, R., Oni, O.A., Gupta, K., et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J 36 (2015), 2706–2715.
101. 101 Anderson, J.L., May, H.T., Lappé, D.L., et al. Impact of testosterone replacement therapy on myocardial infarction, stroke, and death in men with low testosterone concentrations in an integrated health care system. Am J Cardiol 117 (2016), 794–799.
102. 102 Wallis, C.J., Lo, K., Lee, Y., et al. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol 4 (2016), 498–506.
103. 103 Sharma, R., Oni, O.A., Chen, G., et al. Association between testosterone replacement therapy and the incidence of deep vein thrombosis and pulmonary embolism: a retrospective cohort study of the Veterans Administration Database. Chest 150 (2016), 563–571.
104. 104 Bhattacharya, R.K., Khera, M., Blick, G., et al. Testosterone replacement therapy among elderly males: the Testim Registry in the US (TRiUS). Clin Interv Aging 7 (2012), 321–330.
105. 105 Miner, M.M., Bhattacharya, R.K., Blick, G., et al. 12-month observation of testosterone replacement effectiveness in a general population of men. Postgrad Med 125 (2013), 8–18.
106. 106 Corona, G., Maseroli, E., Rastrelli, G., et al. Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf 13 (2014), 1327–1351.
107. 107 Albert, S.G., Morley, J.E., Testosterone therapy, association with age, initiation and mode of therapy with cardiovascular events: a systematic review. Clin Endocrinol (Oxf) 85 (2016), 436–443.
108. 108 Traish, A.M., Haider, A., Doros, G., et al. Long-term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: an observational, long-term registry study. Int J Clin Pract 68 (2014), 314–329.
109. 109 Haider, A., Gooren, L.J., Padungtod, P., et al. Concurrent improvement of the metabolic syndrome and lower urinary tract symptoms upon normalisation of plasma testosterone levels in hypogonadal elderly men. Andrologia 41 (2009), 7–13.
110. 110 Maggi, M., Wu, F.C., Jones, T.H., et al. Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME). Int J Clin Pract 70 (2016), 843–852.
111. 111 Thomas, C.E., Mauer, E.A., Shukla, A.P., et al. Low adoption of weight loss medications: A comparison of prescribing patterns of antiobesity pharmacotherapies and SGLT2s. Obesity (Silver Spring) 24 (2016), 1955–1961.