Hemoglobin;

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?

Should I order a blood transfusion based on the hemoglobin (Hgb) or the hematocrit (Hct)?

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

Despite the frequent interchangeability of Hgb (g/dL) and Hct (%) by a ratio of ~1:3, directly-measured blood Hgb levels may be preferred for assessing the need for blood transfusion for at least 3 reasons:

First, in contrast to the widely-used automated measurements of Hct, Hgb is not affected by conditions that affect the size of the RBCs or the mean corpuscular Hgb concentration (MCHC). This is because the Hct is not a direct measure of Hgb; rather it’s the proportion of blood occupied by RBCs which, in automated systems, is derived by multiplying the number of RBCs by the mean corpuscular volume (MCV).1-3

This may not be a significant issue when MCHC is normal, but when MCHC is abnormal, HCT may not accurately reflect the blood Hgb concentration. For example, in patients with hypochromic iron deficiency anemia with RBCs containing less hemoglobin (ie, low MCHC), the Hct may overestimate blood Hgb levels. Conversely in hereditary spherocytosis with its attendant low RBC volume and high MCHC, the Hct may underestimate Hgb levels.

Second, Hct results may also be more subject to technical factors in the lab. For example, blood at room temperature between 6-24 h may be associated with RBC swelling and increased Hct without any change in its Hgb concentration.4

Finally, national and international guidelines on blood transfusion generally target Hgb, not Hct results.5-7

For a related pearl, go to https://pearls4peers.com/2016/11/01/should-i-use-a-hemoglobin-level-of-7-or-8-gdl-as-a-threshold-for-blood-transfusion-in-my-hospitalized-patient.

 

References

  1. Tefferi A, Hanson CA, Inwards DJ. How to interpret and pursue an abnormal complete blood cell count in adults. Mayo Clin Proc 2005;80:923-36. https://www.ncbi.nlm.nih.gov/pubmed/16007898
  2. Macdougall IC, Ritz E. The Normal Haematocrit Trial in dialysis patients with cardiac disease: are we any the less confused about target hemoglobin? Nephrol Dial Transplant 1998;13:3030-33. https://academic.oup.com/ndt/article-pdf/13/12/3030/9907456/3030.pdf
  3. Kelleher BP, Wall C, O’Broin SD. Haemoglobin, not haematocrit, should be the preferred parameter. Nephrol Dial Transplant 2001;16:1085-87. https://www.ncbi.nlm.nih.gov/pubmed/11328933
  4. Hayuanta HH. Can hemoglobin-hematocrit relationship be used to assess hydration status? CDK-237/vol 43 no.2, th. 2016 http://www.kalbemed.com/Portals/6/20_237Opini-Can%20Hemoglobin-Hematocrit%20Relationship%20Be%20Used%20to%20Assess%20Hydration%20Status.pdf
  5. Blood transfusion. NICE guideline, November, 2015. https://www.nice.org.uk/guidance/ng24/chapter/Recommendations#fresh-frozen-plasma-2 uk
  6. National Blood Authority: Australia. Patient blood management, November 2016. https://www.blood.gov.au/system/files/documents/nba-patient-blood-management-resource-guide-nov_2016_v3_sm_web_file.pdf
  7. Carson JL, Guyatt G, Heddle NM, et al. Clinical practice guidelines from the AAABB: red blood cell transfusion thresholds and storage. JAMA 2016; 316:2025-2035. https://www.ncbi.nlm.nih.gov/pubmed/27732721

 

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Should I order a blood transfusion based on the hemoglobin (Hgb) or the hematocrit (Hct)?

Should I use a hemoglobin level of 7 or 8 g/dL as a threshold for blood transfusion in my hospitalized patient?

FA Manian MD, MPH, , , , , , , , , , , 1 Comment

Unlike its previous 2012 guidelines that recommended overlapping hemoglobin level triggers of 7 g/dL to 8 g/dL for most inpatients, the 2016 guidelines from AABB (formerly known as the American Association of Blood Banks) assigns 2 distinct tiers of hemoglobin transfusion triggers: 7 g/DL for hemodynamically stable adults, including those in intensive care units, and 8 g/dL for patients undergoing cardiac or orthopedic surgery or with preexisting cardiovascular disease1 , often defined as history of coronary artery disease, angina, myocardial infarction, stroke, congestive heart failure, or peripheral vascular disease2,3.  

These recommendations are based on an analysis of over 30 randomized trials, taking into account the potential risks of withholding transfusions, including 30-day mortality, and myocardial infarction. The new 2-tier recommendation specifically excludes those with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia.

The guidelines also emphasize that good clinical practice dictates considering not only the hemoglobin level but the overall clinical context when considering blood transfusion in patients. These factors include alternative therapies to transfusion, rate of decline in hemoglobin level, intravascular volume status, dyspnea, exercise tolerance, light-headedness, chest pain considered of cardiac origin, hypotension, tachycardia unresponsive to fluid challenge, and patient preferences.

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References

  1. Carson JL, Guyatt G, Heddle NW. Clinical practice guidelines from the AABB red blood cell transfusion thresholds and storage. JAMA. Doi:10.1001/jama.2016.9185. Published online October 12, 2016. https://www.ncbi.nlm.nih.gov/pubmed/27732721
  2. Carson JL, Duff A, Poses RM, et al. Effect of anemia and cardiovascular disease on surgical mortality and morbidity. Lancet 1996;348:1055-60. https://www.ncbi.nlm.nih.gov/pubmed/8874456
  3. Carson JL, Siever F, Cook DR, et al. Liberal versus restrictive blood transfusion strategy: 3-year survial and cause of death results from the FOCUS randomized controlled trial. Lancet 2015;385:1183-1189. https://www.ncbi.nlm.nih.gov/pubmed/25499165
Should I use a hemoglobin level of 7 or 8 g/dL as a threshold for blood transfusion in my hospitalized patient?