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.

The male biological clock is ticking: a review of the literature

“…Both cross-sectional and longitudinal studies confirm this decline. [48][49][50][51] Decreased production of testosterone by the testes is the main reason for lower testosterone levels in older men. 51 From a clinical standpoint, the pertinent question is whether this decline in testosterone is significant enough for many older men to consider testosterone replacement therapy.…”

Aging of the Male Germline: Influence of Advanced Male Age on Reproductive Outcome

“…In fact, only a minor decline in Sertoli cell functions was observed due to a compensatory increase in follicle-stimulating hormone (FSH) levels [11,12]. Additionally, a decrease in Leydig cell function led to a decrease in overall androgen levels, especially testosterone, what compromises reproductive functions [11,13,14]. Furthermore, it has also been reported that APA has significant metabolic effects on protein and carbohydrate metabolism, incidentally influencing insulin sensitivity [14].…”

Pituitary Magnetic Resonance Imaging in Patients with Isolated Hypogonadotrophic Hypogonadism: A Single Center Experience

“…In these women, FSH alone was shown to induce a minor increase in oestradiol concentration, poor follicular luteinization and decreased oocyte fertilization rate [7,8]. Diagnosis is valuable since these may respond to treatment other than testosterone replacement therapy [9,10]. However, it remains unclear who deserves magnetic resonance imaging (MRI) of the hypothalamic-pituitary region during evaluation of hypogonadism.…”