Testosterone Replacement Options | Testosterone Deficiency

Testosterone Replacement Options

Testosterone is considered an essential male sexual hormone that is required for the development of secondary sexual characteristics at the time of puberty and maintenance of male reproductive functions throughout life. Testosterone replacement therapy would be needed when for conditions we will discuss in this article. In addition, normal testosterone secretion is also required for:

• Maintenance of normal hemoglobin concentration and production of red blood cells.
• Increasing the muscle bulk, power and strength.
• Maintenance of adequate bone mineral density.

It has been observed that a moderate decrease in testosterone secretion can significantly affect the overall sense of well-being, sexual appetite and may lead to erectile dysfunction.

What May Cause Testosterone Deficiency?

Popular Cause of Testosterone Deficiency:

The secretion of testosterone decreases with physiological aging. The decline usually begins after the age 30 and continues for the rest of the life (though the pace is usually slow and unnoticeable).

Pathological Testosterone Deficiency Causes:

• Moderate injury to testicles.
• Inflammatory diseases of testicles (sarcoidosis). 
• Chronic illnesses (such as hemochromatosis) or  infections (like HIV, liver cirrhosis).
• Inherited genetic aberrations like Kallmann’s syndrome, Klinefelter’s Syndrome.
• Acute infectious conditions of testicles. 
• History of radiotherapy or chemotherapy to scrotal or genital region.
• Endocrinological abnormalities (especially pituitary dysfunction) or exogenous intake of testosterone hormone to treat prostatic dysfunction or malignancies.
• Chronic renal dysfunction.
• History of chronic alcoholism. 
• Stress and related disorders.

Sign and Symptoms of Need for Testosterone Replacement Therapy

Most cardinal sign and symptoms that may arose the suspicion of testosterone deficiency are:

• Low libido (decreased sex drive).
• Erectile dysfunction.
• Changes in mood and sense of well-being.
• Changes in concentration and memory.
• Weakening of bones (onset of osteoporosis and deficits in bone mineral density).
• Changes in hair density. 
• Altered metabolism of cholesterol. 
• Decrease in the overall muscle mass and since testosterone is responsible for maintaining a higher basal metabolic rate; testosterone deficiency in some males is often followed by weight gain and deposition of subcutaneous fat.

Testosterone Replacement Therapy and Available Options:

Research report published in Journal of Andrology (1) suggested that testosterone replacement therapy improves erectile dysfunction directly as well as indirectly by improving the response to PDE5 inhibitors. If testosterone deficiency is symptomatic; healthcare providers may advise testosterone replacement therapy after serial serum measurements.

Most Frequently Employed Options for Testosterone Replacement Therapy Are:

Testosterone Intramuscular Injections:
In most cases, the injections are introduced twice monthly or once in three weeks. The bioavailability or hormone is high and reduces the hassle of daily application. However, there are a few limitations; such as:

• The serum concentration of testosterone is not steady (the blood levels are high soon after the injection and decreases gradually as the time progress).
• The hemoglobin concentration increases with long term testosterone intramuscular injections.

Testosterone Gels:
These gels can be topically applied to abdomen, shoulders or chest region. Although there are many benefits (such as easy application) caution must be maintained to avoid the risk of accidental transfer to partner or any person in close physical contact.
Report published in Journal of Urology (2) suggested that testosterone replacement gel is also helpful in managing erectile dysfunction in males who are unresponsive to Sildenafil alone.
Testosterone replacement gel is the most frequent modality for replacement therapy, followed by injectable testosterone, testosterone replacement patches and oral tablets (3).
Testosterone Patch:
Testosterone replacement  patch is applied daily on the scrotum/ abdomen/ buttocks/thighs or back. Besides many advantages; one of the most commonly encountered problem is the high risk of rash or skin irritation.
Oral Testosterone Pills:
Oral testosterone formulations are not frequently used mainly because of the lower bioavailability (that can be managed by alkylation); however, the benefits of therapy are offset by the risk of liver cirrhosis or dysfunction. Other potential complications of oral testosterone replacement therapy are:

• Hepatic adenoma
• Cholestasis
• Changes in the metabolism of cholesterol

Some oral formulations of testosterone are; 17-methyltestosterone, Mesterolone, and fluoxymesterone. A relatively safer option is Testosterone undecanoate that has a better safety profile and bioavailability.

What Are Potential Complications Or Side Effects of Testosterone Replacement Options?

Regardless of the mode of testosterone intake; some common therapy related side effects are:

• Changes in the normal pattern of sleep.
• Shrinkage in the size of testicles.
• Mild weight gain due to retention of fluid by the body under the influence of testosterone.
• Changes in the quality of skin (higher risk of developing acne or skin lesions).

Research report by Calof (4) suggested that testosterone replacement therapy is associated with a significant increase in hematocrit (greater than 50%) and also increase the risk of prostate events.
References:
1. Shabsigh, R., Kaufman, J. M., Steidle, C., & Padma-Nathan, H. (2004). Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. The Journal of urology, 172(2), 658-663.
2. Yassin, A. A., & Saad, F. (2008). Testosterone and erectile dysfunction. Journal of andrology, 29(6), 593-604.
3. Calof, O. M., Singh, A. B., Lee, M. L., Kenny, A. M., Urban, R. J., Tenover, J. L., & Bhasin, S. (2005). Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 60(11), 1451-1457.