Should testosterone therapy be used for general health benefits (bone, glycemic control, vitality) in asymptomatic men with low T values

Description

Hypogonadism has significant deleterious effects on men’s health, with negative impact on:

Description

Testosterone therapy is commonly prescribed to men with low testosterone who suffer from symptoms that are related to testosterone deficiency, with the goal of symptom resolution. The classical approach to diagnosis of hypogonadism is if a man does not have symptoms his testosterone level does not have to be checked and he does not need testosterone therapy. However, accumulating scientific research on low testosterone and testosterone therapy shows that testosterone is not just about the typical sexual symptoms.

  • Glycometabolic and cardiometabolic functions
  • Body composition (increased total body fat mass and visceral fat mass and decreased lean mass)
  • Sexual function
  • Bone mineral density
  • Anemia

Testosterone therapy unequivocally improves:

  • Sexual function
  • Body composition
  • Glycometabolic and cardiometabolic functions
  • Mood
  • Bone mineral density
  • Anemia

The TIMES2 study evaluated the effect of testosterone therapy for 12 months on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS).1 Results showed a reduced insulin resistance (assessed by HOMA-IR) in the overall population by 15.2% at 6 months and 16.4% at 12 months. In type 2 diabetic patients, glycemic control was significantly better in the testosterone group than the placebo group at month 9 (HbA1c: treatment difference, -0.45%). Improvements in total and LDL cholesterol, lipoprotein a, body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events. It was concluded that testosterone therapy has beneficial effects on insulin resistance, total and LDL-cholesterol, Lp(a), and sexual health in hypogonadal men with type 2 diabetes and/or MetS.1

Testosterone therapy provides beneficial effects on several risk factors for cardiovascular disease.2 Many of the factors involved in the atherosclerotic process are interlinked with other increasingly prevalent pathological conditions such as obesity, the metabolic syndrome, type 2 diabetes and erectile dysfunction, which are also improved by testosterone therapy. Hence, testosterone therapy has potentially wide-ranging health benefits.

Elderly men who are fragile, have sarcopenia and/or low bone mineral density can be considered to be clinically symptomatic. Even though sexual symptoms are the most obvious symptoms of hypogonadism and most commonly contribute to the clinical diagnosis of hypogonadism, less perceptive signs like sarcopenia and low bone mineral density are important and should not be neglected. Dr. Miner is often referred men with low testosterone levels without a clear cause. After a complete workup, medical conditions emerge that warrant testosterone therapy, such as neurodegenerative diseases such as Parkinsson’s, MS, ALS, impaired mobility and reduced quality of life. Even though there is not much data in these patient populations, Dr. Miner offers these men a therapeutic trial of testosterone treatment, and they usually respond well. He also offers with testosterone therapy to hypogonadal men with osteoporosis and refractory depression. Even though these patient populations have relatively uncommon manifestations of hypogonadism, they should not be ignored. Their low testosterone levels and positive response to testosterone therapy underscores that a myopic focus on sexual symptoms may leave subpopulations of men who would benefit from testosterone therapy untreated and with unnecessary suffering.

In conclusion, testosterone therapy:

  • Decreases frailty and increases exercise capacity in older men.
  • Does not adversely affect the lipid profile (LDL and triglycerides are actually improved in obese men).
  • Improves the components of the metabolic syndrome.
  • Increases lean body mass (muscle mass and bone mineral mass)

Testosterone therapy is not just for sex but helps maintain general health and quality of life in the aging population.

Besides symptomatic improvement, testosterone therapy confers a wide range of additional health benefits on multiple outcomes, including insulin sensitivity, glycemic control, inflammation, body composition, sarcopenia, lipids, bone, anemia and vitality. Different effects matter for different patient populations. For a man with type 2 diabetes and/or obesity, the effects of testosterone therapy on insulin sensitivity, glycemic control and body composition are particularly relevant, whereas for a man with sarcopenia the effects on lean body mass would be of particular importance. Hence, it is important to consider a patient’s total clinical picture, and not just ask about symptoms.

Regarding the label symptomatic vs. non-symptomatic, it needs to be pointed out that it is difficult to be certain that a man is asymptomatic. Sometimes symptoms that were present before become obvious only after a therapeutic trial with testosterone treatment. This is because men with low testosterone can get accustomed to feeling and being in a certain way, so they don’t consider it abnormal until they get to experience the difference.

An overwhelming amount of data suggests that the classical approach to diagnosis of hypogonadism and testosterone therapy may need to be revised. Appropriate clinical indications for testosterone therapy in “asyptomatic” men with low or borderline low testosterone include:

  • Unexplained anemia
  • Low BMD
  • Sarcopenia
  • Adiposity
  • Insulin resistance

 

Speakers

Prof. Dr. med. Marija Pfeifer

Sandeep Dhindsa, M.D., F.A.C.E
Associate Professor of Medicine
Director, Division of Endocrinology and Metabolism
Saint Louis University School of Medicine
St. Louis, MO, USA

References

  • Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, Morales AM, Volterrani M, Yellowlees A, Howell JD, Channer KS; TIMES2 Investigators. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011 Apr;34(4):828-37. Return to content
  • Jones TH, Saad F. The effects of testosterone on risk factors for, and the mediators of, the atherosclerotic process. Atherosclerosis. 2009 Dec;207(2):318-27 Return to content