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Older Men and Testosterone Therapy

Current State

A 2017 JAMA study documented the huge increase in direct-to-consumer advertising for testosterone supplementation, which has also been associated with increased prescribing trends.1 In 2013, testosterone supplementation brought in $2 billion in sales for pharmaceutical companies.2 Although trends suggest that that rapid growth in prescriptions has slowed,3 many men visit the doctor specifically seeking a testosterone prescription. Yet 80-85% of men supplementing testosterone discontinue treatment after a year.4

In healthy men under 50 years of age, serum testosterone ranges from 300–1,000 ng/dl, and levels start to drop after the age of 50.5 The American Urological Association (AUA) guidelines state that testosterone therapy can be considered if serum levels of testosterone are under 300 ng/dl and clinical symptoms are present.6 The AUA also points out that up to 25% of men receiving testosterone therapy did not have their levels tested prior to the prescription, and nearly half of patients’ blood levels are not monitored after testosterone therapy.6

The dose of testosterone needed to create specific effects in the body varies widely,7 and ongoing monitoring is needed to ensure supplementation is reaching the desired range of free testosterone.6 Furthermore, testosterone therapy can cause a range of side effects,6,8 such as:

• Reduced fertility
• Fluid retention
• Obstructive sleep apnea

There may be other risks, including cardiovascular and respiratory risks,9 although data is not yet conclusive10 and those risks may be due to flaws in study design.11 At least one study suggests testosterone may actually be cardioprotective.12 In addition, the as-yet-inconclusive role of testosterone in prostate cancer continues to garner controversy and attention.13,14

Lifestyle Interventions

Luckily, suboptimal testosterone levels are often amenable to lifestyle interventions. For instance, high-intensity interval training increases free testosterone in older, sedentary men,15 as well as masters athletes.16 Reducing alcohol intake also increases free testosterone.17

One intervention to consider prior to exogenous testosterone is nutritional: natural aromatase inhibitors. A range of foods and vitamins naturally inhibit aromatase, which decreases the conversion of testosterone into estradiol, resulting in increased testosterone levels.

FREE TOOLKIT ITEM on Foods and Botanicals That Act as Aromatase Inhibitors

In one large trial, aromatase inhibitors and testosterone supplementation resulted in similar outcomes to placebo for many cardiovascular measures, but aromatase inhibitors significantly reduced abdominal fat, which did not happen for the testosterone group.18 In both the exogenous testosterone and aromatase inhibitor groups, testosterone levels were significantly increased.19 Other studies support the finding of increased testosterone in men with aromatase inhibition.20 However, in this study at least, estradiol increased in the testosterone group and decreased in the aromatase inhibitor group.19 This may be of particular interest because the role of estradiol as a male hormone has been drawing increasing interest.20

For men with suboptimal testosterone, addressing lifestyle considerations and nutritional interventions first is not only safe, but may lead to the desired results. IFM’s toolkit contains numerous patient education materials that can help in working with men and women with hormonal imbalances.

LEARN MORE ABOUT RE-ESTABLISHING HORMONAL BALANCE >

References

  1. Layton JB, Kim Y, Alexander GC, Emery SL. Association between direct-to-consumer advertising and testosterone testing and initiation in the United States, 2009-2013. JAMA. 2017;317(11):1159-1166. doi:10.1001/jama.2016.21041
  2. Bhasin S. A perspective on the evolving landscape in male reproductive medicine. J Clin Endocrinol Metab. 2016;101(3):827-836. doi:1210/jc.2015-3843
  3. Baillargeon J, Kuo YF, Westra JR, Urban RJ, Goodwin JS. Testosterone prescribing in the United States, 2002-2016. 2018;320(2):200-202. doi:10.1001/jama.2018.7999
  4. Bandari J, Ayyash OM, Emery SL, Wessel CB, Davies BJ. Marketing and testosterone treatment in the USA: a systematic review. Eur Urol Focus. 2017;3(4-5):395-402. doi:1016/j.euf.2017.10.016
  5. Seftel AD. Male hypogonadism. Part I: epidemiology of hypogonadism. Int J Impot Res. 2006;18(2):115-120. doi:1038/sj.ijir.3901397
  6. American Urological Association. Evaluation and management of testosterone deficiency. Published 2018. Accessed May 21, 2019. https://www.auanet.org/guidelines/testosterone-deficiency-guideline
  7. Finkelstein JS, Lee H, Burnett-Bowie SM, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369(11):1011-1022. doi:1056/NEJMoa1206168
  8. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. doi:1210/jc.2018-00229
  9. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109-122. doi:1056/NEJMoa1000485
  10. Mohler ER 3rd, Ellenberg SS, Lewis CE, et al. The effect of testosterone on cardiovascular biomarkers in the testosterone trials. J Clin Endocrinol Metab. 2018;103(2):681-688. doi:1210/jc.2017-02243
  11. Hackett GI. Testosterone replacement therapy and mortality in older men. Drug Saf. 2016;39(2):117-130. doi:1007/s40264-015-0348-y
  12. Cheetham TC, An J, Jacobsen SJ, et al. Association of testosterone replacement with cardiovascular outcomes among men with androgen deficiency. JAMA Intern Med.2017;177(4):491-499. doi:1001/jamainternmed.2016.9546
  13. Klap J, Schmid M, Loughlin KR. The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy. J Urol. 2015;193(2):403-413. doi:1016/j.juro.2014.07.123
  14. Claps M, Petrelli F, Caffo O, et al. Testosterone levels and prostate cancer prognosis: systematic review and meta-analysis. Clin Genitourin Cancer. 2018;16(3):165-175.e2. doi:1016/j.clgc.2018.01.005
  15. Hayes LD, Herbert P, Sculthorpe NF, Grace FM. Exercise training improves free testosterone in lifelong sedentary aging men. Endocr Connect. 2017;6(5):306-310. doi:1530/EC-17-0082
  16. Herbert P, Hayes LD, Sculthorpe NF, Grace FM. HIIT produces increases in muscle power and free testosterone in male masters athletes. Endocr Connect. 2017;6(7):430-436. doi:1530/EC-17-0159
  17. Sandher RK, Aning J. Diagnosing and managing androgen deficiency in men. 2017;261(1803):19-22.
  18. Dias JP, Shardell MD, Carlson OD, et al. Testosterone vs. aromatase inhibitor in older men with low testosterone: effects on cardiometabolic parameters. Andrology. 2017;5(1):31-40. doi:1111/andr.12284
  19. Dias JP, Melvin D, Simonsick EM, et al. Effects of aromatase inhibition vs. testosterone in older men with low testosterone: randomized-controlled trial. Andrology. 2016;4(1):33-40. doi:1111/andr.12126
  20. Russell N, Grossmann M. Mechanisms in endocrinology: estradiol as a male hormone. Eur J Endocrinol. Published online May 1, 2019. doi:1530/EJE-18-1000

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