Hypogonadism, aka testosterone deficiency or low-T, is primarily diagnosed by low total testosterone levels. However, more and more research is showing that free testosterone, which is the active fraction of total circulating testosterone, is independently associated with important health outcomes.
Levels of free testosterone decline more steeply than total testosterone as menage.[1-7 In many cases, total testosterone levels can be relatively high, but free testosterone low. Therefore it is important to assess both total and free testosterone levels in order to get a clear picture of the androgen status.
A recent study specifically assessed if baseline testosterone (total and free) levels predict muscle loss in middle-aged and elderly Japanese men over a 10 year period.
Data were collected from community-dwelling 957 middle-aged and elderly men.
Leg and arm (appendicular) muscle mass muscle mass) was measured with dual-energy X-ray absorptiometry (DHEXA) at baseline and 10 year follow-up examinations.
Total testosterone (TT) and free testosterone (FT) were measured with a radioimmunoassay.
The calculated FT (cFT) was determined with Vermeulen's formula, based on total testosterone, albumin, and sex hormone-binding globulin (SHBG) levels.
After adjusting for baseline age, leisure-time physical activity, nutrition intake (total energy, total protein, vitamin D), medical history (stroke, heart disease, cancer, diabetes, osteoporosis, rheumatoid arthritis), and smoking habit at baseline, no association was found for total testosterone levels and muscle mass loss.
However, there was a significant association of free testosterone levels (both measured and calculated) with loss of muscle mass.
Men with the lowest free testosterone levels (calculated), below 46.3 pg/ml, had approximately a 2.1- to 2.7-fold risk of significant muscle loss compared to those with level above 46.3 pg/ml).
Men with the lowest measured free testosterone levels, below 7.7 pg/ml, had approximately a 1.8- to 2.9-fold risk of significant muscle loss compared to those with level above 46.3 pg/ml).
This study shows that middle-age and older men with low free testosterone levels are at 2-3 fold greater risk of losing a significant amount of muscle. It is notable that this significant association between low free testosterone levels (regardless of whether free testosterone was calculated or measured) and muscle loss remained after adjusting for age, medical history, nutrition intake and physical activity.
Thus, this study shows that low free testosterone levels are independently associated with muscle loss in middle-aged and elderly men, and may be an indicator of future muscle loss. Therefore, increasing free testosterone levels with appropriate therapies, such as TRT (testosterone replacement therapy) and/or fat loss, may reduce the risk of muscle loss during ageing and prevent the onset of sarcopenia and frailty.
- Orwoll E, Lambert LC, Marshall LM, et al. Testosterone and estradiol among older men. The Journal of clinical endocrinology and metabolism. 2006;91(4):1336-1344.
- Rohrmann S, Platz EA, Selvin E, et al. The prevalence of low sex steroid hormone concentrations in men in the Third National Health and Nutrition Examination Survey (NHANES III). Clinical endocrinology. 2011;75(2):232-239.
- Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. The Journal of clinical endocrinology and metabolism. 2001;86(2):724-731.
- Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. The Journal of clinical endocrinology and metabolism. 2002;87(2):589-598.
- Liu PY, Beilin J, Meier C, et al. Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts. The Journal of clinical endocrinology and metabolism. 2007;92(9):3599-3603.
- Lapauw B, Goemaere S, Zmierczak H, et al. The decline of serum testosterone levels in community-dwelling men over 70 years of age: descriptive data and predictors of longitudinal changes. European journal of endocrinology / European Federation of Endocrine Societies. 2008;159(4):459-468.
- Yeap BB, Almeida OP, Hyde Z, et al. In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study. European journal of endocrinology / European Federation of Endocrine Societies. 2007;156(5):585-594.
- Yuki A, Otsuka R, Kozakai R, et al. Relationship between low free testosterone levels and loss of muscle mass. Scientific reports. 2013;3:1818.
Medical Writer & Nutritionist
University of Stockholm & Karolinska Institute, Sweden
Baylor University, TX, USA
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