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What are the proven benefits and side effects of testosterone therapy in my elderly male patient with hypogonadism?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , Leave a comment

The benefits and side-effects of testosterone therapy (TTh) in male hypogonadism, a common condition among elderly men, have been explored in several trials, demonstrating variable health benefits without significant side effects.1-4

A large 2016 randomized placebo-controlled trial of testosterone replacement for one year in elderly men found that TTh modestly improves muscle mass and strength (by 5%) without significant reduction in falls or frailty.1 This study also showed significant improvement in sexual desire and erectile dysfunction, but the effect of TTh on erections was weaker than that of phosphodiesterase inhibitors. Of interest, TTh did not improve fatigue in this study.1 This is important because lack of energy is probably the commonest complaint by men in ambulatory setting requesting that a serum testosterone level be checked.

Interestingly, in one study, cognition was not improved by TTh.2 Additionally, although TTh has been shown to improve bone density,3  it is not known if it has any impact on the risk of fractures due to lack of proper studies.  Hence, TTh should not be considered for treatment of osteoporosis at this time.  

TTh has been shown to be associated with a rise in hemoglobin by ~1 g/dl.4 However, some men may develop polycythemia, especially if they achieve supranormal levels of serum testosterone with therapy. Testosterone and hemoglobin concentrations should be monitored during TTh.3

Although there have been concerns about risks of cardiovascular events and prostate cancer with TTh, a recent randomized placebo controlled cardiovascular trial showed no effect of TTh on the incidence of major adverse cardiovascular events.4 TTh also does not appear to increase the risk of prostate cancer in the short term (up to 3 years), but long- term prospective trials have not yet been conducted to exclude this possibility.3

Feel free to use the above summary while discussing the pros and cons of TTh with your patients.

Bonus Pearl: Did you know that, according to the Endocrine Society Clinical Practice Guideline,3 in men with symptoms and signs consistent with testosterone deficiency, measuring fasting morning total testosterone concentrations followed by repeat testing for confirmation is recommended.  In men whose total testosterone is near the lower limit of normal or who have condition that alters sex hormone binding globulin, a free testosterone concentration using either equilibrium dialysis or estimating it using an accurate formula is recommended. 3

Contributed by Sandeep Dhindsa, MD, Director, Division of Endocrinology, Diabetes and Metabolism, St. Louis University Medical School, St. Louis, Missouri

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References

  1. Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older Men. N Engl J Med. 2016;374(7):611-24. Epub 2016/02/18. doi: 10.1056/NEJMoa1506119. PubMed PMID: 26886521.
  2. Snyder PJ, Bhasin S, Cunningham GR, et al. Lessons from the testosterone trials. Endocr Rev. 2018;39(3):369-86. Epub 2018/03/10. doi: 10.1210/er.2017-00234. PubMed PMID: 29522088; PMCID: PMC6287281.
  3. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715-44. Epub 2018/03/22. doi: 10.1210/jc.2018-00229. PubMed PMID: 29562364.
  4. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389(2):107-17. Epub 2023/06/16. doi: 10.1056/NEJMoa2215025. PubMed PMID: 37326322.

 

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What are the proven benefits and side effects of testosterone therapy in my elderly male patient with hypogonadism?

Do statins have a role in treating novel Coronavirus infection, COVID-19?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

There is currently no firm clinical evidence that statins improve the outcome of COVID-19. However, there are some theoretical reasons for believing that statins may have a role in the treatment of COVID-19.  That’s because beyond their cholesterol lowering action, statins may also have clinically relevant anti-inflammatory and antiviral (pleotropic) properties.  

Anti-inflammatory: Anti-inflammatory effect of statins is well known and is thought to occur through a variety of molecular pathways of the innate and adaptive immune systems as well as attenuation of several circulating proinflammatory cytokines.1 Although observational studies have suggested that statins lower hospitalization and mortality among outpatients hospitalized with infection, pneumonia or sepsis, several randomized controlled trials (RCTs) have failed to show any mortality benefit among ICU patients with sepsis and ARDS treated with statins.2

In contrast, an RCT involving patients with sepsis (majority with pneumonia, mean CRP 195 mg/dL) reported significant reduction in progression to severe sepsis among statin-naïve patients  placed on atorvastatin 40 mg/day at the time of hospitalization.3 So, perhaps timing of statin therapy before florid sepsis and ARDS is an important factor.  

Some have suggested that statins may decrease the fatality rate of a related Coronavirus, Middle East Respiratory Syndrome (MERS) virus, by blunting exuberant inflammatory response that may result in a fatal outcome. 4

Antiviral: Statins may also have antiviral properties, including activity against influenza, hepatitis C virus, Zika and dengue viruses.2,5 Whether statins have activity against coronaviruses such as the agent of COVID-19 is unclear at this time.

It’s interesting to note that cholesterol may have an important role in the membrane attachment, fusion and replication of many enveloped viruses, including influenza.5 Covid-19 is also an enveloped virus.

So what do we do? Based on the current data, it makes sense to continue statins in patients who have known clinical indications for their use and no obvious contraindications because of COVID-19 (eg. rhabdomyolysis).6 As for statin-naïve patients, particularly those in early stages of sepsis and increased risk of cardiovascular events, benefit may outweigh the risk.  Only proper clinical studies will give us more definitive answers.

Bonus Pearl: Did you know that lipids make up a major component of the envelope in enveloped viruses and that cholesterol makes up nearly one-half of total lipid and over 10% the total mass of influenza viruses?

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References

  1. Tousoulis D, Psarros C, Demosthenous M, et al. Innate and adaptive inflammation as a therapeutic target in vascular diseae: The emerging role of statins. J Am Coll Cardiol 2014;63:2491-2502. https://www.sciencedirect.com/science/article/pii/S0735109714011553?via%3Dihub
  2. Fedson DS. Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola. Ann Transl Med 2016;4:421. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124618/pdf/atm-04-21-421.pdf
  3. Patel JM, Snaith C, Thickette DR. Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial) Critical Care 2012;16:R231. https://ccforum.biomedcentral.com/track/pdf/10.1186/cc11895
  4. Espano E, Nam JH, Song EJ, et al. Lipophilic statins inhibit Zika virus production in Vero cells. Scientific Reports 2019;9:11461. https://www.nature.com/articles/s41598-019-47956-1
  5. Sun X, Whittaker GR. Role for influenza virus envelope cholesterol in virus entry and infection. J Virol 2003;77:12543-12551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC262566/
  6. Virani SS. Is there a role for statin therapy in acute viral infections. Am Coll Cardiol March 18, 2020. https://www.acc.org/latest-in-cardiology/articles/2020/03/18/15/09/is-there-a-role-for-statin-therapy-in-acute-viral-infections-covid-19

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Do statins have a role in treating novel Coronavirus infection, COVID-19?