Testosterone vs. aromatase inhibitor in older men with low testosterone: effects on cardiometabolic parameters
Open accessAbstract
Summary Testosterone (T) replacement is being increasingly offered to older men with age‐related decline in testosterone levels. The effects of long‐term testosterone replacement and aromatase inhibition (AI) on glucose homeostasis and cardiometabolic markers were determine in older non‐diabetic men with low testosterone levels. Men ≥65 years, mean age 71 ± 3 years with serum total T < 350 ng/dL were randomized in a double‐blind, placebo‐controlled, parallel‐group, proof‐of‐concept trial evaluating the effects of 5 g transdermal testosterone gel (TT) (n = 10), 1 mg anastrozole (n = 10) or placebo (n = 9) daily for 12 months. Homeostatic Model Assessment of insulin resistance (HOMAIR) was the primary outcome. Secondary outcomes included OGIS in response to OGTT, fasting lipids, C‐reactive protein (CRP), adipokines, and abdominal and mid‐thigh fat by computed tomography. All outcomes were assessed at baseline and 12 months. After 12 months, absolute changes in HOMAIR in both treatment arms (TT group: −0.05 ± 0.21); (AI group: 0.15 ± 0.10) were similar to placebo (−0.11 ± 0.26), as were CRP and fasting lipid levels. Adiponectin levels significantly decreased in the TT group (−1.8 ± 0.9 mg/L, p = 0.02) and abdominal subcutaneous fat (−60.34 ± 3.19 cm2, p = 0.003) and leptin levels (−1.5 ± 1.2 ng/mL, p = 0.04) were significantly lower with AI. Mid‐thigh subcutaneous fat was reduced in both treatment arms (TT group: −4.88 ± 1.24 cm2, p = 0.008); (AI group: −6.05 ± 0.87 cm2, p = 0.0002). In summary, in this proof‐of‐concept trial, changes in HOMAIR AI were similar in all three groups while the effects of intervention on subcutaneous fat distribution and adipokines were variable. Larger efficacy and safety trials are needed before AI pharmacotherapy can be considered as a treatment option for low T levels in older men.
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After 12 months of AI treatment, fasting glucose, insulin, and lipid levels were not different between men treated with AI and men treated with testosterone therapy.
“After 12 months, fasting glucose, insulin, and lipid levels were not different between men treated with AI and men treated with testosterone therapy (68).”
From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [68]
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Cites
Adverse Events Associated with Testosterone Administration
Basaria, S., Coviello, A. D., Travison, T. G., Storer, T. W., Farwell, W. R., Jette, A. M., Eder, R., Tennstedt, S., Ulloor, J., Zhang, A., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1000485 · Cited by 1,494 · see citing works
Self-citationVigen, R. (2013) · JAMA · doi:10.1001/jama.2013.280386 · Cited by 1,003 · see citing works
Katznelson, L., Finkelstein, J. S., Schoenfeld, D. A., Rosenthal, D. I., Anderson, E. J., & Klibanski, A. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.12.8954042 · Cited by 791 · cited 2× · see citing works
“, 2001) and this decline has been associated with loss of muscle mass, reduced muscle strength, low bone mass, and sexual dysfunction (Katznelson et al., 1996).”
BackgroundIncreased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men
Finkle, W. D., Greenland, S., Ridgeway, G. K., Adams, J. L., Frasco, M. A., Cook, M. B., Fraumeni, J. F., & Hoover, R. N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085805 · Cited by 735 · see citing works
Stellato, R. K., Feldman, H. A., Hamdy, O., Horton, E. S., & McKinlay, J. B. (2000) · Diabetes Care · doi:10.2337/diacare.23.4.490 · Cited by 618 · see citing works
Boyanov, M. A., Boneva, Z., & Christov, V. G. (2003) · The Aging Male · doi:10.1080/tam.6.1.1.7 · Cited by 381 · see citing works
Bhasin, S., Pencina, M., Jasuja, G. K., Travison, T. G., Coviello, A., Orwoll, E., Wang, P. Y., Nielson, C., Wu, F., Tajar, A., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-3012 · Cited by 355 · see citing works
Basaria, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61126-5 · Cited by 328 · see citing works
Self-citationRibas, V., Nguyen, M. T. A., Henstridge, D. C., Nguyen, A.-K., Beaven, S. W., Watt, M. J., & Hevener, A. L. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00504.2009 · Cited by 309 · see citing works
The diversity of sex steroid action: regulation of metabolism by estrogen signaling
Faulds, M. H., Zhao, C., Dahlman-Wright, K., & Gustafsson, J.-Å. (2012) · Journal of Endocrinology · doi:10.1530/joe-11-0044 · Cited by 230 · see citing works
Yialamas, M. A., Dwyer, A. A., Hanley, E., Lee, H., Pitteloud, N., & Hayes, F. J. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0454 · Cited by 220 · see citing works
Corona, G., Giagulli, V. A., Maseroli, E., Vignozzi, L., Aversa, A., Zitzmann, M., Saad, F., Mannucci, E., & Maggi, M. (2016) · European Journal of Endocrinology · doi:10.1530/eje-15-0262 · Cited by 217 · see citing works
Testosterone therapy decreases subcutaneous fat and adiponectin in aging men
Frederiksen, L., Højlund, K., Hougaard, D. M., Mosbech, T. H., Larsen, R., Flyvbjerg, A., Frystyk, J., Brixen, K., & Andersen, M. (2012) · European Journal of Endocrinology · doi:10.1530/eje-11-0565 · Cited by 93 · see citing works
Juang, P. S., Peng, S., Allehmazedeh, K., Shah, A., Coviello, A. D., & Herbst, K. L. (2014) · The Journal of Sexual Medicine · doi:10.1111/jsm.12368 · Cited by 36 · cited 1× · see citing works
“In contrast, two recent mechanistic studies in young men showed that withdrawal of estradiol had no impact on insulin sensitivity (Rubinow et al., 2012; Juang et al., 2014); however, the role of estradiol in older men with age-related low testosterone remains unclear.”
ResultTestosterone therapy in older men with late-onset hypogonadism: a counter-rationale
Basaria, S. (2013) · Endocrine Practice · doi:10.4158/ep13318.ra · Cited by 18 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 29
- Basaria S Davda MN Travison TG Ulloor J Singh R Bhasin S 2013 Risk factors associated with cardiovascular events during testosterone administration in older men with mobility limitation J Gerontol A Biol Sci Med Sci 68 153 160 22562960 PMC3598355
- Bhasin S Parker RA Sattler F Haubrich R Alston B Umbleja T Shikuma CM 2007 Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity J Clin Endocrinol Metab 92 1049 1057 17164307
- Braga-Basaria M Muller DC Carducci MA Dobs AS Basaria S 2006 Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy Int J Impot Res 18 494 498 16617314
- Corona G Giagulli VA Maseroli E Vignozzi L Aversa A Zitzmann M Saad F Mannucci E Maggi M 2016a Testosterone supplementation and body composition: results from a meta-analysis study Eur J Endocrinol 174 R99 R116 26537862
- Corona G Giagulli VA Maseroli E Vignozzi L Aversa A Zitzmann M Saad F Mannucci E Maggi M 2016b Testosterone supplementation and body composition: results from a meta-analysis of observational studies J Endocrinol Invest 39 967 981 27241317
- Dias JP Melvin D Simonsick EM Carlson O Shardell MD Ferrucci L Chia CW Basaria S Egan JM 2015 Effects of aromatase inhibitor vs. testosterone in older men with low testosterone: randomized-controlled trial Andrology 4 33 40 26588809 PMC5836312
- Ding EL Song Y Malik VS Liu S 2006 Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis JAMA 295 1288 1299 16537739
- Dougherty RH Rohrer JL Hayden D Rubin SD Leder BZ 2005 Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels Clin Endocrinol (Oxf) 62 228 235 15670201
- Gao H Bryzgalova G Hedman E Khan A Efendic S Gustafsson JA Dahlman-Wright K 2006 Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice. a possible mechanism is through direct regulation of signal transducer and activator of transcription 3 Mol Endocrinol 20 1287 1299 16627594
- Gianatti EJ Dupuis P Hoermann R Strauss BJ Wentworth JM Zajac JD Grossmann M 2014 Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes: a randomized controlled trial Diabetes Care 37 2098 2107 24804695
- Harman SM Metter EJ Tobin JD Pearson J Blackman MR 2001 Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging J Clin Endocrinol Metab 86 724 731 11158037
- He J Bhasin S Binder EF Yarasheski KE Castaneda-Sceppa C Schroeder ET Roubenoff R Chou CP Azen SP Sattler FR 2013 Cardiometabolic risks during anabolic hormone supplementation in older men Obesity (Silver Spring) 21 968 975 23784898 PMC3930448
- Jasuja GK Bhasin S Reisman JI Berlowitz DR Rose AJ 2015 Ascertainment of testosterone prescribing practices in the VA Med Care 53 746 752 26196850
- Kapoor D Clarke S Stanworth R Channer KS Jones TH 2007 The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes Eur J Endocrinol 156 595 602 17468196
- Lanfranco F Zitzmann M Simoni M Nieschlag E 2004 Serum adiponectin levels in hypogonadal males: influence of testosterone replacement therapy Clin Endocrinol (Oxf) 60 500 507 15049966
- Lapauw B T’Sjoen G Mahmoud A Kaufman JM Ruige JB 2009 Short-term aromatase inhibition: effects on glucose metabolism and serum leptin levels in young and elderly men Eur J Endocrinol 160 397 402 19050164
- Layton JB Meier CR Sharpless JL Sturmer T Jick SS Brookhart MA 2015 Comparative safety of testosterone dosage forms JAMA Intern Med 175 1187 1196 25962056 PMC4494981
- Makrogiannis S Serai S Fishbein KW Schreiber C Ferrucci L Spencer RG 2012 Automated quantification of muscle and fat in the thigh from water-, fat-, and nonsuppressed MR images J Magn Reson Imaging 35 1152 1161 22170747 PMC3319811
- Malkin CJ Jones TH Channer KS 2007 The effect of testosterone on insulin sensitivity in men with heart failure Eur J Heart Fail 9 44 50 16828341
- Marin P Holmang S Jonsson L Sjostrom L Kvist H Holm G Lindstedt G Bjorntorp P 1992 The effects of testosterone treatment on body composition and metabolism in middle-aged obese men Int J Obes Relat Metab Disord 16 991 997 1335979
- Pacini G Mari A 2003 Methods for clinical assessment of insulin sensitivity and beta-cell function Best Pract Res Clin Endocrinol Metab 17 305 322 12962688
- Pitteloud N Mootha VK Dwyer AA Hardin M Lee H Eriksson KF Tripathy D Yialamas M Groop L Elahi D Hayes FJ 2005 Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men Diabetes Care 28 1636 1642 15983313
- Rochira V Madeo B Zirilli L Caffagni G Maffei L Carani C 2007 Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in men Diabet Med 24 1491 1495 17976198
- Rubinow KB Snyder CN Amory JK Hoofnagle AN Page ST 2012 Acute testosterone deprivation reduces insulin sensitivity Clin Endocrinol 76 281 288 PMC3224202 21797916
- Selvin E Feinleib M Zhang L Rohrmann S Rifai N Nelson WG Dobs A Basaria S Golden SH Platz EA 2007 Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III) Diabetes Care 30 234 238 17259487
- Snyder PJ Lawrence DA 1980 Treatment of male hypogonadism with testosterone enanthate J Clin Endocrinol Metab 51 1335 1339 6777395
- Spitzer M Huang G Basaria S Travison TG Bhasin S 2013 Risks and benefits of testosterone therapy in older men Nat Rev Endocrinol 9 414 424 23591366
- Swerdloff RS Pak Y Wang C Liu PY Bhasin S Gill TM Matsumoto AM Pahor M Surampudi P Snyder PJ 2015 Serum testosterone (T) level variability in T gel-treated older hypogonadal men: treatment monitoring implications J Clin Endocrinol Metab 100 3280 3287 26120790 PMC4570167
- Xu L Freeman G Cowling BJ Schooling CM 2013 Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials BMC Med 11 108 23597181 PMC3648456
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Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.
Bhasin, S., Brito, J. P., Cunningham, G. R., Hayes, F. J., Hodis, H. N., Matsumoto, A. M., Snyder, P. J., Swerdloff, R. S., Wu, F. C., & Yialamas, M. A. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00229 · Cited by 1,736 · see citing works
Non-testosterone management of male hypogonadism: an examination of the existing literature
Krzastek, S. C., & Smith, R. P. (2020) · Translational Andrology and Urology · doi:10.21037/tau.2019.11.16 · Cited by 34 · see citing works
“After 12 months, fasting glucose, insulin, and lipid levels were not different between men treated with AI and men treated with testosterone therapy (68).”
BackgroundEfficacy of Non-Testosterone-Based Treatment in Hypogonadal Men: A Review.
Raheem, O. A., Chen, T., Akula, K. P., Greenberg, J., Le, T. V., Chernobylsky, D., Sikka, S. C., & Walsh, T. J. (2021) · Sexual Medicine Reviews · doi:10.1016/j.sxmr.2020.08.003 · Cited by 22 · see citing works
- Authors
- Dias, J. P., Shardell, M. D., Carlson, O. D., Melvin, D., Caturegli, G., Ferrucci, L., Chia, C. W., Egan, J. M., & Basaria, S.
- Affiliations
- National Institute on Aging (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Egan, J. M.
- Basaria, S.
- ORCID
- Venue
- Andrology
- Publisher
- Wiley
- Published
- 2016-10-28
- Volume
- 5
- Issue
- 1
- Pages
- 31-40
- ISSN
- 2047-2919 (ISSN-L)
- 2047-2927
- PMC
- PMC5794008
- OpenAlex
- W2543553793
- Cited by
- 22
- References
- 15
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 1
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- onlinelibrary.wiley.com/termsAndConditions#vor (vor)
- Locations
- Andrology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- testosterone, testosterone replacement therapy, aromatase inhibitors, anastrozole, older men, insulin resistance, glucose homeostasis, cardiometabolic risk, adipokines, subcutaneous fat distribution, adiponectin, leptin, C-reactive protein, lipid profile, transdermal testosterone gel, hypogonadism, sarcopenia, frailty
- MeSH terms
- Aged, Blood Glucose, Body Composition, C-Reactive Protein, Double-Blind Method, Humans, Hypogonadism, Insulin, Insulin Resistance, Lipids, Male, Testosterone, Treatment Outcome, Hormone Replacement Therapy, Aromatase Inhibitors, Abdominal Fat, Adipokines
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