Hypogonadism, Muscle Weakness, and Multi-morbidity in Men

Hypogonadism, Muscle Weakness, and Multi-morbidity in Men

STUDY: Peterson MD, Belakovskiy A, McGrath R, Yarrow JF. Testosterone Deficiency, Weakness, and Multi-morbidity in Men. Scientific reports. 2018;8(1):5897.

Low testosterone is associated with deterioration of the musculoskeletal system, commonly manifesting as osteopenia (borderline osteoporosis) and sarcopenia (age-related loss of muscle mass), and ultimately frailty.1,2 Furthermore, low testosterone is independently associated with various obesity-related chronic diseases in men, including type 2 diabetes and cardiovascular disease3-5, as well as with higher rates of all-cause mortality.6-10

However, it is unknown what optimal levels of testosterone are in men, and what effects different testosterone levels have on disease risk. Here we present the results of a study that evaluated the association between hypogonadism, also known as testosterone deficiency, muscle weakness and multi-morbidity (occurrence of several morbidities/diseases at the same time) in men.11 The prevalence of multi-morbidity was examined among young, middle-aged, and older men, with and without testosterone deficiency.

Key Points

  • Men with hypogonadism - including younger men - have a significantly higher prevalence of multi-morbidity compared to age-matched men with normal testosterone levels.
  • Compared to high testosterone levels, low and moderate testosterone levels are associated with a 2.9-fold and 1.7-fold increased risk of multi-morbidity.
  • Low and moderate testosterone levels are associated with increased risk of multi-morbidity even after adjusting for obesity and grip strength.
  • Low testosterone and weakness in men are independently associated with multi-morbidity at all ages; however, multi-morbidity is most prevalent among young and older men with testosterone deficiency.

What is known about testosterone, muscle strength / weakness and health

Low testosterone is strongly associated with worse health outcomes in men, including reduced sexual activity, obesity, insulin resistance, inflammation, dyslipidemia, metabolic syndrome, atherosclerosis, cardiovascular events and mortality, as well as depressed mood, reduced motivation, fatigue, frailty, anemia, bone loss and decreased quality of life.12-22

Testosterone also has multiple effects on muscle23, and low testosterone levels are associated with reduced muscle mass, strength and physical performance.24-26 Not surprisingly, testosterone therapy that normalizes testosterone levels (i.e. increases testosterone levels by a magnitude that is large enough to achieve health benefits) increases muscle mass and strength.27-30

However, there are scant data on the association between testosterone, muscle strength/weakness and risk of chronic disease across the adult life span among men in the general population.

What this study adds

The primary purpose of this study was to evaluate the association between hypogonadism and muscle weakness with chronic multi-morbidity in a large, population-representative sample of U.S. men. The study also analysed the effect of different testosterone levels among young, middle-aged, and older men on prevalence of multimorbidity.

Multi-morbidity was defined as the presence of at least two chronic conditions among a list of risk factors and chronic diseases; obesity BMI ≥30 kg/m2, elevated waist circumference >102 cm, high triglycerides (blood fats), low HDL cholesterol (the "good" cholesterol), high blood pressure, diabetes, arthritis, cardiovascular disease, stroke, emphysema, depression. Muscle strength was assessed using a handgrip dynamometer. Grip strength was expressed as strength per kg bodyweight.

Hypogonadism was defined as testosterone <300 ng/dL (10.4 nmol/L). Testosterone levels were defined as low, medium and high for each age group, as follows:

Testosterone status 20 - 39.9 years 40 - 59.9 years ≥60 years
High testosterone >16.9 nmol/L >15.3 nmol/L >15 nmol/L
  >488 ng/dL >440 ng/dL >433 ng/dL
Medium testosterone 12 - 16.9 nmol/L 10.1 - 15.3 nmol/L 10.1 - 15 nmol/L
  347-488 ng/dL 291-440 ng/dL 290-433 ng/dL
Low testosterone <12 nmol/L 10.1 nmol/L 10.1 nmol/L
  <347 ng/dL <291 ng/dL <290 ng/dL

Prevalence of hypogonadism (<300 ng/dL [10.4 nmol/L]) was 31% for the entire study population, and 23%, 36%, and 35% for young, middle-aged, and older men, respectively. As illustrated in figures 1-3, the prevalence of individual risk factors and chronic diseases was significantly higher in men with hypogonadism as compared to men with normal testosterone levels. In younger and older men, the prevalence of multi-morbidity was also significantly higher in men with hypogonadism compared to men with normal testosterone levels.

Figure 1: Differences in prevalence of risk factors and chronic diseases in young men age 20-39.9 years with hypogonadism(<10.4nmol/L or <300 ng/dL)
vergrößern

Figure 1: Differences in prevalence of risk factors and chronic diseases in young men age 20-39.9 years with hypogonadism(<10.4nmol/L or <300 ng/dL) versus normal testosterone (>10.4 nmol/L or >300 ng/dL).

Figure 2: Differences in prevalence of risk factors and chronic diseases in middle-aged men age 40-59.9 years with hypogonadism
vergrößern

Figure 2: Differences in prevalence of risk factors and chronic diseases in middle-aged men age 40-59.9 years with hypogonadism (<10.4nmol/L or <300 ng/dL) versus normal testosterone (>10.4 nmol/L or >300 ng/dL).

Figure 3: Differences in prevalence of risk factors and chronic diseases in older men age ≥60 years with hypogonadism
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Figure 3: Differences in prevalence of risk factors and chronic diseases in older men age ≥60 years with hypogonadism (<10.4nmol/L or <300 ng/dL) versus normal testosterone (>10.4 nmol/L or >300 ng/dL).

Data from Peterson MD, Belakovskiy A, McGrath R, Yarrow JF. Testosterone Deficiency, Weakness, and Multi-morbidity in Men. Scientific reports. 2018;8(1):5897.

Both testosterone and muscle strength were associated with multimorbidity. Testosterone levels were significantly correlated with grip strength, even after adjusting for age, race/ethnicity, income and education.

Compared to the high testosterone group, the low and moderate testosterone groups had a 2.9-fold and 1.6-fold increase risk of multi-morbidity. This increased risk remained even after adjusting for muscle strength.

It was concluded that low testosterone and weakness in men are independently associated with multi-morbidity at all ages; however, multi-morbidity is more prevalent among young and older men with testosterone deficiency.

Commentary

The present study shows a higher prevalence of hypogonadism, 31%, in a large population-representative sample of U.S. men across the adult age-span than what has been previously reported. It is especially notable that among young men, nearly one out of four (22.6%) had hypogonadism and one out of five (17.4%) had multimorbidity. The finding that young men with low and moderate testosterone have a significantly higher risk of multi-morbidity than young men with high testosterone levels provides a rationale for checking testosterone levels even among young men, particularly those with existing obesity, diabetes, cardiovascular disease, hypertension, depression, low HDL cholesterol, or hypertriglyceridemia, as each of these conditions are significantly more common in those with testosterone deficiency.

Considering the strong association between low testosterone and multi-morbidity even in young men, it is possible that low testosterone may be a contributing cause to development of chronic diseases, such as obesity, metabolic syndrome, cardiovascular disease and type 2 diabetes, the prevalence of which has reached epidemic proportions over the last decade. Early detection and treatment of low testosterone in young men could possibly slow progression, or potentially stop disease development entirely.

In the present study, different thresholds were used to define low, medium and high testosterone levels for each age group. However, definitive age-specific reference ranges do not exist and there are insufficient data to define optimal target testosterone levels during treatment.31 The aim of therapy is therefore to restore testosterone levels to the mid-normal range for healthy young men32, and then adjust the dose on an individual basis based on patient response.31

It is notable that the reduced risk of multi-morbidity in the group with the highest testosterone level remained significant even after adjusting for grip strength, which is a strong predictor of physical function and risk of diabetes, cardiovascular disease, and mortality, particularly cardiovascular mortality, in men.33-40 This suggests that testosterone confers protection above and beyond its well-established beneficial effects on muscle and strength.

Low testosterone has traditionally been considered "old men‘s problem". However, as the present study shows11, as well as other studies41, low testosterone can also affect younger men. This suggests that the underlying changes in hormonal and metabolic dysregulation that lead to multi-morbidity are gradual and develop throughout the adult lifespan. Hence, a young age does not make men immune to low testosterone and its health consequences.

Another notable finding is the high prevalence of obesity and abdominal obesity among young men, especially young men with hypogonadism. In all age groups, men with hypogonadism had a significantly higher prevalence of abdominal obesity and obesity.

The present study provides a rationale for men who are obese or have elevated waist circumference, high blood pressure, low HDL, high triglycerides (blood fats), cardiovascular disease, diabetes or depression to have their testosterone levels checked regularly. Considering the significantly increased risk for multi-morbidity with low testosterone in young and older men, treatment with testosterone therapy in hypogonadal men is warranted regardless of age.

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Last updated: 2018
G.MKT.GM.MH.02.2018.0506