Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men

Abstract

Many studies have shown cross-sectional (and two small studies, longitudinal) declines in total and/or free testosterone (T) levels, with age, in men. The extent to which decline in T is the result of the aging process per se, as opposed to chronic illness, medication use, and other age-related factors, remains controversial. The frequency with which aging leads to T levels consistent with hypogonadism has also not been defined. These issues bear on the potential use of T replacement in aging men, because aging and hypogonadism have, in common, reduced bone and lean body mass and muscle strength and increased total and abdominal fat. We measured T and sex hormone-binding globulin (SHBG), by RIA, in stored samples from 890 men in the Baltimore Longitudinal Study on Aging. Using a mixed-effects model, we found independent effects of age and date of sampling to reduce T levels. After compensating for date effects, which investigation suggested was artifactual, we observed significant, independent, age-invariant, longitudinal effects of age on both T and free T index (free T index = T/SHBG), with an average change of -0.124 nmol/L.yr and -0.0049 nmol T/nmol SHBG.yr. T, but not free T index, also decreased with increasing body mass index. Use of beta-blocking drugs was associated with higher T and higher free T index levels. Using total T criteria, incidence of hypogonadal T levels increased to about 20% of men over 60, 30% over 70 and 50% over 80 yr of age, and even greater percentages when free T index criteria were employed. Our observations of health factor independent, age-related longitudinal decreases in T and free T, resulting in a high frequency of hypogonadal values, suggest that further investigation of T replacement in aged men, perhaps targeted to those with the lowest serum T concentrations, are justified.

Changes in BMI modulate age-associated changes in sex hormone binding globulin and total testosterone, but not bioavailable testosterone in young adult men: the CARDIA Male Hormone Study

“…As discussed previously, Harman et al 6 proposed that ageassociated changes in potentially modifiable lifestyle factors could contribute to the decline in serum testosterone levels in men. The scarcity of longitudinal data on changes in hormones, BMI and age in a well-characterized sample of adult men has not allowed for a detailed analysis of this hypothesis.…”

“…[1][2][3][4][5][6][7] Additionally, there is an age-related increase in sex hormone binding globulin (SHBG), which binds about 44% of testosterone with high affinity. The non-SHBG-bound fraction of testosterone, the bioavailable testosterone fraction, appears to decrease with age.…”

“…The non-SHBG-bound fraction of testosterone, the bioavailable testosterone fraction, appears to decrease with age. 3,4,6,7 There is evidence that decreased Leydig cell number and secretory function appears to contribute to the decline in serum testosterone. 8 However, Harman et al 6 suggested that changes in potentially modifiable lifestyle factors associated with aging also might play an important role in this decline.…”

18F-FDG Uptake of Human Testis on PET/CT: Correlation with Age, Sex Hormones, and Vasectomy

“…Serum levels of total testosterone and free testosterone decrease in elderly men, and SHBG levels increase [9][10][11][12]. Furthermore, the numbers of major cells in the testis, such as Sertoli cells, Leydig cells, and germ cells, decrease with age [13][14][15][16][17][18].…”

Testosterone therapy and cardiovascular risk

“…About 20% of healthy men over age 60 have a total testosterone below the normal range determined in healthy young men (1). The high prevalence of lower testosterone in older men and aggressive marketing of new formulations for nonspecific symptoms have resulted in a marked increase in testosterone prescribing over the last decade (2)(3)(4).…”