Testosterone Levels: How Do They Change Over Time?

We all go through a range of dynamically regulated hormonal changes through different stages of our lives. These changes are characteristic to many variables such as age, sex, pathological condition, and exogenous administration of drugs or in the form of dietary steroids. These hormonal changes stimulate, regulate, and control the function of various tissues and organs.

The expression levels of a wide range of hormones vary in a temporal and context dependent manner, and when the context is male menopause, the most common hormone attributed to these changes is the testosterone. However, the testosterone deficiency in males is not a state strictly analogous to female menopause.

The testosterone production is regulated by gonadotropin releasing hormone (GnRH) which leads to production of luteinizing hormone (LH) & Follicle stimulating hormone (FSH) by the pituitary gland. While FSH stimulates the testicular Sertoli cells and promotes spermatogenesis, LH, on the other hand, stimulates the testicular Leydig cells to secrete testosterone, in pulses and in a rhythm that maintains peak levels in the morning and lowest levels in the evening.

There is an age associated gradual decline in testosterone levels that can manifest itself in a variety of ways in the human male body. Various clinical manifestations of testosterone deficiency may include, amongst others, depression, anxiety, irritability, insomnia, weakness, diminished libido, impotence, poor memory, reduced muscle and bone mass etc.

The loss of testosterone is a multi-factorial phenomenon and may be because of one or more of the following reasons:

1. Increase in Age: Increase in age leads to gradual loss of existing LH as well as a decrease in the production of LH in response to GnRH. With age, the number and volume of leydig cells in the testicles decrease at about 1% per year after the age of 50 years.

2. Pathological Condition & General Health: Concurrent ill health has been found to depress testosterone levels. Further, some opiate associated medications or anticonvulsants administered in certain disorders have shown to have a direct effect on the serum testosterone levels. Diabetes is one of the factors that may lead to decrease in testosterone levels in patients as compared to their BMI-matched, non-diabetic counterparts. Various lung disorders, cardiovascular diseases, chronic illness, depression, prescription medication, & obesity have all been associated with a substantial reduction in testosterone levels.

3. Alcohol & Smoking: Although alcohol is known to inhibit testosterone production by testicular cytotoxicity but surprisingly, sustained stable alcohol intake in healthy older men has not been found to influence total testosterone levels. The reported effects of smoking on total testosterone levels are contradictory and unclear to the date.

4. SHBG Binding: In normal men, approximately 2% of testosterone is in the unbound form, while the rest of it is bound to sex hormone-binding globulin (SHBG) and an increase in SHBG also leads to a further decrease in free testosterone levels. If some of the factors like genetic composition and age associated hormonal changes are beyond our control, others like alcohol, smoking, dietary factors etc. are certainly within our reach.