Testosterone is an androgen, or male sex hormone, that defines the masculine characteristics of the male reproductive system. It is synthesized primarily in the Leydig cells, which are found between the seminiferous tubules in the male testes. However, it is also produced indirectly in smaller quantities in the adrenal glands; the adrenal hormones dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S) androstenedione, and androstanediol are converted in the peripheral tissues to testosterone and estrogen. In women, testosterone is produced within the female ovaries.Handelsman, D.J., “Androgen Physiology, Pharmacology, Use and Misuse”, Endotext. October 2020. Available: https://www.ncbi.nlm.nih.gov/books/NBK279000/Antoniou-Tsigkos, A., Zapanti, E., Ghizzoni, L., Mastorakos, G.,”Adrenal Androgens”, Endotext. January 2019. Available: https://www.ncbi.nlm.nih.gov/books/NBK278929/
Even though testosterone serves primarily to develop secondary characteristics in men, it serves other essential functions within the human body. Some additional roles performed by testosterone include the following:Tyagi, V., Scordo, M., Yoon, R.S., Liporace, F.A., Greene, L.W., “Revisiting the role of testosterone: Are we missing something?”, Reviews in Urology, vol. 19 issue 1, pp. 16-24. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434832/Coviello, A.D., Kaplan, B., Lakshman, K.M., Chen, T., Singh, A.B., Bhasin, S., “Effects of Graded Doses of Testosterone on Erythropoiesis in Healthy Young and Older Men”, Journal of Clinical Endocrinology and Metabolism, vol.93 issue 3, pp.914-919. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266950/“Additional Studies of Testosterone Therapy”, Testosterone and Aging: Clinical Research Directions. Available: https://www.ncbi.nlm.nih.gov/books/NBK216178/
- In the skeletal system, testosterone aids in bone maintenance as well as growth. By decreasing the amounts of bone osteoclasts, testosterone helps decrease bone resorption and, consequently, increase bone density. This action is performed through the aromatization of testosterone to estradiol, which then activates alpha and beta receptors on the bone. Additionally, testosterone is converted to the active metabolite dihydrotestosterone (DHT) by means of the enzyme 5-alpha reductase; DHT is two to three times more potent than testosterone and it stimulates the osteoblasts within the bones and promote bone growth.
- In the muscles, testosterone helps in the development of lean body mass, muscle volume, muscle strength, and the loss of fatty tissue.
- Studies have indicated that testosterone is beneficial in the production of red blood cells. This effect is generally seen more in older rather than younger men. However, this may also lead to erythrocytosis as an adverse effect in men receiving exogenous testosterone supplements.
- Through mechanisms that have not been fully defined, testosterone has been shown to play a role in individuals’ mood and mental state. Research studies carried out indicated that men suffering from low testosterone had an improvement in their cognitive abilities as well as mood after receiving exogenous testosterone supplements.
Generally, testosterone levels do not begin to increase until around the age of puberty. Once puberty is achieved, testosterone levels increase significantly until about the third or fourth decade of life, after which they begin to decrease gradually. When this occurs, males may manifest with varied symptoms such as loss of body hair, decreased bone density, decreased libido and erectile dysfunction, decreased lean body mass, and increased body fat, among other symptoms. Individuals manifesting signs and symptoms of low testosterone levels may benefit from exogenous testosterone administration.Rivas, A.M., Mulkey, Z., Lado-Abeal, J., Yarbrough, M., “Diagnosing and managing low serum testosterone”, Proceedings (Baylor University Medical Center), vol.27 issue 4, pp. 312-324. October 2014. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255853/
There are certain conditions under which exogenous testosterone should not be administered or, if necessary, administered with extreme caution. Some of these indications include the following:Petering, P.C., Brooks, N.A., “Testosterone Therapy: Review of Clinical Applications”, American Family Physician, vol.96 issue 7 pp.441-449. Available: https://www.aafp.org/afp/2017/1001/p441.htmlCunha, J.P., “Testosterone”, RxList. Available: https://www.rxlist.com/consumer_testosterone-medication/drugs-condition.html
- Prostate cancer: This is an absolute contraindication to administering exogenous testosterone supplements. This is because testosterone can stimulate the growth of cancerous cells in individuals with prostate cancer.
- Polycythemia Vera: Individuals with this blood dyscrasia should not receive exogenous testosterone supplementation. With polycythemia, hematocrit levels are higher than normal; testosterone administration may further increase hematocrit levels, which may result in a worsening of the symptoms in individuals suffering from this condition.
- Breast cancer: Breast cancer is an absolute contraindication to exogenous testosterone administration because, just like prostate cancer, it is hormone-dependent.
- Venous thromboembolism: This is a relative contraindication to exogenous testosterone administration; there have been reported instances of deep venous thrombosis and pulmonary embolism in some individuals while receiving testosterone supplementation.
- Cardiovascular disease: Care should be exercised when administering testosterone supplements to individuals with a history of coronary artery disease or myocardial infarction as there have been reported instances of strokes in some people after receiving testosterone replacement therapy.
Testosterone supplements belong to the Food and Drug Administration (FDA) category X. Studies performed have shown fetal abnormalities and evidence of increased fetal risks in pregnant mothers taking testosterone supplements. The risks of developing significant fetal abnormalities far outweigh any benefits that may be gained from its administration of pregnant women. Testosterone replacement therapy should be immediately discontinued in women if pregnancy occurs. Additionally, testosterone and its metabolites are excreted in human breast milk; as such, it should also not be administered to lactating mothers.“Testosterone Pregnancy and Breastfeeding Warnings”. Available: https://www.drugs.com/pregnancy/testosterone.html
There are a number of side effects that could occur in individuals receiving exogenous testosterone supplements. These side effects may range from mild to potentially life-threatening conditions. Some possible adverse reactions that could occur while on exogenous testosterone therapy include, but are not limited to, the following:“Testosterone Injection”. Available: https://www.drugs.com/testosterone.html
- Women may experience signs of virilization such as male-pattern hair growth, enlarged clitoris, and a deep or hoarse voice, among others.
- Urinary retention and worsening of other features associated with benign prostatic hypertrophy (BPH).
- Features of myocardial infarction such as chest pain, cough, wheezing, shortness of breath, and coughing up blood.
- Abdominal pain and loss of appetite.
- Generalized body itching, jaundice, and clay-colored stools.
- Features of deep venous thrombosis such as pain, warmth, swelling, or redness in one or both legs.
- Features of fluid retention such as weight gain and swelling of the ankles or feet.
Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.
