Testosterone Deficiency: Symptoms, Treatment, Andropause and Prostate Cancer

Testosterone in men begins rising in youth and reaches its highest levels in the 30s. From the 40s onward, it begins falling and continues to decrease gradually by 1-2% annually with aging. By age 60, almost 3 men out of whom 1 develops testosterone deficiency; after age 80, the proportion is 2 men out of whom 1. The growing population of older men in America is estimated to rise in 2025 from 40 million to 60 million, an increase of approximately 43% over the current population. Male hypogonadism and andropause will therefore become increasingly common concerns in hospitals, nursing homes and society.

Although men develop a habit of being examined for prostate disease after age 50, andropause is usually not evaluated during these examinations. This may be because men do not have enough information about it.

Also known as male menopause, andropausemeans the decline in testosterone with aging and the resulting symptoms. More medically, in men, an age-related decline in testosterone, apart from other diseases (a low serum testosterone level < 8-11 nmol/L or < 300 ng/dL), with associated clinical symptoms is called andropause (late-onset hypogonadism) .

What is the difference between hypogonadism and andropause?

The difference between andropause and hypogonadism is quite simple; andropauseis a natural part of a man's life in which hormones begin falling around age 30 and continue declining until reaching a plateau in the late 60s. Hypogonadism is a condition in which testosterone is not produced or is produced in insufficient amounts for various reasons — testicular or brain health problems, stress, poor nutrition or preexisting health conditions.

What are the symptoms of hypogonadism in men?

• low sexual desire,
• loss of morning erections and erectile dysfunction, 
• emotional tension,
• reduced bone density and muscle mass,
• and, conversely, increased fat mass (particularly around the abdomen).
• reduced intellectual activity, 
• and inability to sleep at night.

Because symptoms developing in andropause are also seen as natural consequences of aging, andropause is generally neglected. Moreover, accompanying illnesses such as diabetes and hypertension, obesityand adverse lifestyle influences such as alcohol and tobacco use and psychological stress can further reduce testosterone. Taking all these symptoms seriously and the necessary precautions is therefore important for a better quality of life in aging men.

Beyond the clinical significance of this age-related testosterone decline, its relationship with other illnesses and unhealthy lifestyle habits has led to considerable debate about whether testosterone supplementation is beneficial.

Potential benefits of testosterone treatment in older men (in andropause)

1. Effects of testosterone treatment on body composition, muscle mass and muscle strength
   Testosterone is an important regulator of muscle and fat mass. Various studies show that increasing serum testosterone in older men increases lean mass, particularly in the trunk, and reduces fat mass in the arms and legs. However, despite its contribution to body appearance, data on muscle strength are unclear. While improved muscle strength and physical function have been observed with testosterone treatment in older men receiving cortisone for chronic lung disease, a positive contribution to muscle strength in healthy older men has not been demonstrated.
2. Effects of testosterone treatment on bone metabolism
   Reduced bone density is an important problem not only in older women but also in aging men. Adequate testosterone plays an important role in protecting men against osteoporosis as they age. Studies indicate that testosterone treatment does not improve bone density in all healthy older men. The benefiting group is limited, with positive effects demonstrated only in those with low testosterone.
3. Effects of testosterone treatment on sexual function
   Sexual function in men is influenced by psychological, hormonal, neurological and vascular factors. Besides chronic diseases such as diabetes and hypertension, independent factors such as obesity, certain medications, stress and tension also affect it.
   The decline in testosterone in older men adversely affects sexual function and desire. However, studies show no clear relationship between testosterone levels and erectile dysfunction. Some studies have nevertheless shown small positive effects on sexual function (desire and erectile dysfunction), particularly when treating men with low testosterone, with much smaller effects in those whose levels are near normal or normal.
4. Effects of testosterone treatment on mood and quality of life
   Reduced testosterone may have a weak association with more depressed mood, reduced intellectual activity and Alzheimer's disease. However, the effects of testosterone treatment on depressed mood and quality of life remain unclear. Its positive contribution to sexual function may nevertheless have a favorable impact on mood and quality of life.
5. Effects of testosterone treatment on type 2 diabetes and components of metabolic syndrome
   Low testosterone is more common in men with type 2 diabetes and/or metabolic syndrome (a complex involving obesity, insulin resistance and cholesterol abnormalities). Studies show an inverse relationship between testosterone levels and obesity, insulin resistance and cholesterol abnormalities. More comprehensive studies are needed before saying that testosterone treatment will improve these conditions.

Potential risks of testosterone treatment in older men (in andropause)

1. Prostatic hypertrophy (enlargement) and prostate cancer
   The adverse effects of testosterone hormone treatment on the prostate naturally cause concern for potential users. Testosterone is necessary for prostate development. However, benign prostatic enlargement (BPH) and increased PSA are influenced more by its tissue metabolite dihydrotestosterone (DHT) than by externally administered testosterone. Some drug combinations have even been shown to prevent this. An International Prostate Symptom Score (IPSS) above 19, severe prostate enlargement and lower urinary tract complaints are among the reasons for recommending against starting testosterone treatment.
   Prostate cancer and its relationship with testosterone have undergone important changes in recent years. Unlike earlier views, recent studies provide evidence that high testosterone does not contribute adversely to prostate cancer development as previously thought. Similarly, the prevailing view is that testosterone replacement does not increase prostate cancer risk.
   The REDUCE study, reported in 2012 in 8122 men, found no relationship between baseline serum testosterone or DHT and prostate cancer. A meta-analysis involving 2351 men across 22 randomized controlled studies likewise found no prostate cancer development risk from testosterone replacement.
   However, testosterone treatment is currently not recommended for patients with advanced, recurrent and metastatic prostate cancer (nor, similarly, for male patients with breast cancer). A current review of potential risks in prostate cancer patients states that testosterone treatment can now be recommended with greater confidence instead of following the excessively cautious strategies of the past. Accordingly, the safest group for consideration comprises men with Gleason 6 or lower who underwent radical prostatectomy (prostate cancer surgery) and whose serum PSA remained very low for 1 or 2 years.
2. Effects on cardiovascular disease
   Long-term studies in recent years have shown favorable changes in cholesterol with testosterone treatment. However, these positive studies are still insufficient to say that testosterone treatment has a favorable effect on cardiovascular disease . Some studies have even claimed that it worsens cardiovascular disease in older men with limited mobility. Caution is needed, along with more studies of benefits and harms.
3. Effects on blood production
   The decline in testosterone in older age is known to cause a 10-20% decrease in red blood cell hemoglobin and anemia. Testosterone treatment is therefore thought to be able to treat anemia in older men. However, its hemoglobin-raising effect also brings increased blood concentration, one of the risks limiting its use. Although the clinical significance of this rise is unclear, caution is needed when treating patients with heart failure and vascular disease. Patients receiving testosterone must therefore have hematocrit levels monitored regularly.
4. Effects on the liver
   Reported liver diseases have mostly been associated with oral forms of testosterone. Side effects include benign and malignant liver tumors, liver toxicity and liver failure.
5. Effect on sleep apnea syndrome
   Testosterone treatment is inadvisable in men with sleep apnea syndrome.

Things to consider about testosterone treatment

Men receiving testosterone are advised to have periodic follow-up to prevent adverse effects. Total blood testosterone, PSA, liver enzymes, hemoglobin, hematocrit and cholesterol profile must be checked before treatment and periodically afterward. Although the main aim is to use the lowest dose that relieves complaints, raising testosterone to the target level (250-300 ng/dl) is considered sufficient.

To summarize;

Testosterone treatment in aging men appears to have positive effects on body appearance, muscle-fat balance, increased bone density, insulin resistance and cholesterol profile. However, evidence concerning its contribution to muscle strength, sexual function and mood remains controversial.

Although many favorable studies exist, caution is recommended with long-term use, particularly concerning cardiovascular and prostate-related risks. Decisions about treatment and its necessity should be based on evidence-based recommendations and benefit-harm assessment.