Hormonal Changes in the Aging Male

The aging of the world's population
During recent decades, the world population's birth and death rates have undergone a remarkable decline. Consequently, the increasing proportion of older persons is becoming a major concern. Today, one out of every ten persons is age 60 or more; by 2050, the proportion is expected to be one out of five (Figure 1). In the twenty-first century, human beings are expected to break the 100-year barrier and reach their biological limit—their longest possible lifespan—of almost 120 years. The socioeconomic impact on society that may result from an increasing old-age dependency ratio is an area of growing research and public debate.

Figure 1. Aging of the world's population.

Aging can refer to the progressive deterioration of cells, tissues and organs associated with increased age. A distinction must be made between biological and chronological aging because the primary objective is not only to prolong life but to allow aging in a state of good health. Starting at middle age, the death rate doubles every 7 to 10 years as a result of degenerative geriatric conditions such as cardiac disease, cancer, osteoporosis, arthropathy, diabetes, dementia and autoimmune disease. One hundred million Americans are currently being treated for one or more degenerative diseases at a healthcare cost of more than $700 billion per year. Ninety percent of all healthcare dollars are spent on extraordinary care in the last two to three years of life.

The aging male
Due to genetic predisposition, typical "male" lifestyle, and emotional and social factors, men in the Western world die on average seven years earlier than women. Female menopause has been known for centuries, but only recently has it been discovered that males go through a similar phenomenon, with analogous symptoms. Names for this phenomenon include male climacteric and andropause. Menopause represents a landmark in the female chronobiology and indicates the end of reproductive capacity. In contrast to this clearly defined event for women, aging of the male endocrine system, beginning in middle-aged or elderly men, is a less abrupt, less clearly demarcated and highly variable process (Figure 2). A gradual decrease in nearly all physiological functions accompanies aging and is reflected clinically by a decrease in muscle mass and strength, sexual function and activity, cognitive functions, and the feeling of well-being; and by the development of abdominal obesity, insulin resistance and atherosclerosis.

Figure 2. General patterns of age-related decline in estradiol levels in women and total testosterone levels in men.

Hormonal changes and replacement therapies
The most potent androgen in man is testosterone. It is released by the testes under the control of LH, which, in turn, is secreted in a pulsatile manner by the pituitary gland. As men age, the testes may become less responsive to these LH pulses. Serum total testosterone and calculated free and non-SHBG-bound testosterone decrease with age; SHBG is reported to increase. Serum LH and FSH exhibit a mild associated increase. Cortisol and insulin also increase with age. Both sexes experience similar declines in DHEA and DHEA-SO4, hGH, IGF-I and melatonin, with a general reduction in sense of well-being, libido and cognitive abilities. TSH, another hormone secreted from the pituitary, declines slightly with age, whereas the concentrations of T3 and T4 do not appear to be affected.

To follow up these alterations and their clinical and physiological effects, a knowledge of the hormonal profile is mandatory. Hormone measurements allow detection of pathological states and provide the necessary information for proper therapeutic monitoring in such contexts as testosterone replacement therapy and DHEA intake. Additionally, supplemental hGH, estradiol, melatonin, vitamin complexes and antioxidants are administered in specific conditions.

Replacing the hormones that decline with age can help give both women and men longer and healthier lives. As hormone levels vary widely from one individual to another, hormone replacement must be carefully balanced and monitored by measuring the hormonal status of the patient for optimal results.

The IMMULITE® Aging Male Study
The aim of the study was to verify age-dependent hormonal changes in males and to establish age-related male reference ranges for these parameters. Venous blood samples were collected from 300 apparently healthy German males aged 20 to 86 years, divided into the following age groups of 50 individuals each: 21 - 30, 31 - 40, 41 - 50, 51 - 60, 61 - 70, and > 70 years. Total testosterone, SHBG, DHEA-SO4, estradiol, LH, FSH, TSH, free T4 and free T3 were measured using the IMMULITE system. The total testosterone and SHBG results were used to generate free androgen index (FAI) and calculated free testosterone (cFT) values.1 Medians and central 95% ranges were determined for all parameters and age groups.

Median testosterone declined from 18 (21 - 30 y) to 11 nmol/L (> 70 y), the median FAI from 60 to 22.5, and the median cFT from 0.43 to 0.18 nmol/L; whereas SHBG increased from 31 to 46 nmol/L. Table 1 shows the percentage of subjects by age group with testosterone, FAI and cFT values lower than the 2.5th percentile of the 21 - 30 year age group.

Median DHEA-SO4 declined from 9.2 (21 - 30 y) to 2.4 ┬Ámol/L (> 70 y) and median estradiol from 107 to 68 pmol/L. Gonadotropin medians increased from 4.2 to 5.0 IU/L for LH, and from 3.7 to 11.2 IU/L for FSH. TSH levels declined only slightly from 1.4 to 1.0 mIU/L. There was no significant change in the median free T4 (16.7 to 15.4 pmol/L) or in the median free T3 (4.9 to 4.5 pmol/L). (See Figures 3 and 4.)

Table 1. Percentage of healthy men with testosterone, FAI and cFT values lower than the 2.5th percentile of the 21-31 year age group.










Figure 3. Box-and-whisker plots, by age group, for total testosterone, SHBG, free androgen index (FAI), calculated free testosterone (cFT), LH, FSH and DHEA-SO4. The IMMULITE system was used for all direct measurements. cFT and FAI values were derived from IMMULITE results for total testosterone and SHBG. (Data for TSH, free T4 and free T3 not shown.)









Figure 4. Regression plots of concentration versus age for total testosterone, SHBG, free androgen index (FAI), calculated free testosterone (cFT), LH, FSH and DHEA-SO4. The IMMULITE system was used for all direct measurements. cFT and FAI values were derived from IMMULITE results for total testosterone and SHBG. (Data for TSH, free T4 and free T3 not shown.)


This study clearly demonstrates the importance of determining complete profiles of the androgenic, gonadotropic, thyroid and pituitary hormones in middle-aged and elderly men to obtain correct clinical diagnoses for various hormonal disorders. Even in healthy men, a significant decrease in bioactive testosterone levels, as reflected by a decreased FAI or cFT, is observed starting with the 41 - 50 year age group. The detection of a decrease in bioactive testosterone in combination with clinical symptoms may lead to a diagnosis of hypoandrogenism and indicate the need for therapy. An automated random access analyzer such as the IMMULITE or IMMULITE® 2000, each offering a complete test menu, is a useful tool in diagnosing and managing age-related hormonal disorders

1. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666-72.


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