Testosterone Enanthate Injection

Generic Name:

Testosterone Enanthate

Brand Name Equivalent:

Delatestryl®

Overview of Testosterone Enanthate Injection

Dosage Strengths of Testosterone Enanthate Injection

Commercial: 200 mg/mL 5 mL Vial (Sesame Oil)
Compounded: 200 mg/mL 5 mL Vial (Grapeseed Oil)

General Information

Testosterone is a sex hormone primarily found in males and functions to trigger the development of both primary and secondary sexual characteristics that occur during puberty. It is also found in females to a lesser amount and serves several important roles in the female physiological system.

The effects of testosterone typically begin to manifest in the first few weeks of intra-uterine life. At about the seventh week of gestation within the uterus, the presence of the Y chromosome leads to the development of the primordial testes. Once developed, the primordial testes begin to produce testosterone and Mullerian Inhibiting Factor, which are essential for the differentiation of the fetus into a male rather than a female. The release of testosterone in the uterus leads to the development of the male primary physical characteristics such as epididymis, vas deferens, seminal vesicles, penis, prostate gland, and the descent of the testicles into the scrotum in the last months of fetal life.12 

During puberty in males, there is a significant surge in testosterone produced and released within the body. This increase in testosterone production is under the control of the hypothalamic-pituitary-gonadal axis. The hypothalamus releases Gonadotropin-releasing hormone (GnRH) in the brain, which then travels down to the anterior pituitary gland by means of the hypothalamic-hypophyseal portal system. In the anterior pituitary gland, GnRH causes the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). The released LH acts on the Leydig cells within the testes to increase the amount of testosterone produced. Once released, testosterone facilitates the development of secondary sexual characteristics in males, such as enlarged genitalia, increased libido, sperm production, deepening of the voice, and growth of male hair patterns on the body. 

In addition to the development of male secondary sexual characteristics, testosterone also serves other essential functions within the body. Some of these functions include: 

  • Skeletal muscle: Testosterone has a hypertrophic and hyperplastic effect on the muscle fibers within the skeletal muscular system. There is a significant increase in muscle growth during puberty due to the hypertrophic effects of testosterone. In men experiencing muscle loss due to aging, testosterone administration has been shown to aid in reversing this condition.3
  • Bone: Testosterone has a significant impact on the development and maintenance of bone growth. It is converted to estradiol by means of the enzyme aromatase; estradiol minimizes the breakdown of bone by inhibiting the resorption of bone by osteoclasts. Additionally, testosterone is converted into dihydrotestosterone (DHT) by the enzyme 5-alpha reductase; DHT stimulates bone osteoblasts and the laying down of bone.4
  • Blood: Testosterone stimulates the production of red blood cells in males. This is one of the reasons that males generally tend to have higher red blood cell levels compared to females. The process by which testosterone stimulates red blood cell production is not yet fully understood and is undergoing research.5
  • Brain: Some studies have shown that testosterone levels in the body have an impact on the ability of males to reason and perform other higher mental functions. These studies indicate that most men suffering from hypogonadism due to low testosterone may experience some degree of memory impairment as well as impaired verbal and visual performance.6
  • Mood: Though also poorly understood, testosterone levels in the body have been shown to have an effect on the mood and behaviors in males. There is an association between hypogonadism in men and depressive moods. Research performed revealed an improvement in moods in men with hypogonadism after treatment with testosterone supplements.7

Testosterone enanthate is an injectable testosterone supplement that is usually administered to treat low testosterone and other symptoms of hypogonadism in males. It is a slow-release oil-based ester that can be administered either intramuscularly or subcutaneously, depending on the health care provider's preference or the individual receiving the injection. It was first used clinically as a treatment of low testosterone in 1937, and its use by men has since then significantly increased in popularity.8

Mechanism of Action

Testosterone exerts its actions in the body primarily by means of its binding to and interaction with androgen receptors. In tissues within the body, the testosterone secreted by the testes is converted into a more potent metabolite known as dihydrotestosterone (DHT); this conversion of testosterone to its more active form is facilitated by the cytoplasmic enzyme known as 5 alpha-reductase. DHT then binds to the androgen receptors inside the cytoplasm of the target cells and forms a DHT-receptor complex. After the formation of the DHT complex, it passes into the nucleus of the target cells, where it binds to the relevant nucleotide sequences on the chromosomal DNA, which then results in the synthesis of the relevant proteins by nuclear transcription. 

A second pathway by which testosterone also acts in the body is through its conversion into estradiol; the amount of testosterone that follows this pathway is considerably less than when involving DHT synthesis. In this pathway, free testosterone is converted by the cytochrome P-450 enzyme aromatase into estradiol. The estradiol that is produced then interacts with the estrogen receptors within the cells and then begins to exert its effects in the development and maintenance of bone density.91011

Pharmacokinetics

Testosterone may be exogenously administered by injection, topically as a gel, ointment, or patch, or by implantation of long-acting pellets. Testosterone enanthate, however, is typically administered as an injection either through the intramuscular route, or subcutaneously. It has a long half-life of 7 to 9 days and may persist in the body at therapeutic levels for up to 3 or 4 weeks after administration.1011

After administration, testosterone enanthate circulates in the bloodstream by binding to plasma proteins. One of the most important plasma proteins that testosterone enanthate binds to is sex hormone-binding globulin (SHBG); of the various plasma proteins in the body, testosterone has the most affinity for SHBG. Other plasma proteins that testosterone enanthate binds to in lesser amounts are albumin, corticosteroid-binding globulin, and alpha-1 acid glycoprotein. After binding to the plasma proteins, testosterone is then transported around the body until it reaches the cells in the targeted tissues. Testosterone is passively transferred across the cell membranes into the cytoplasm at the target tissues, where it is converted into DHT as previously discussed. 

The metabolism and inactivation of testosterone occur mainly in the liver; it undergoes both phases I and phases II hepatic metabolism to be readily excreted. However, testosterone can also be metabolized in the kidneys, gut, muscles, and adipose tissue. Testosterone is oxidized in the liver by the cytochrome P-450 3A family of hepatic oxidases during phase I hepatic metabolism. Following its oxidation by cytochrome P-450A, testosterone is then conjugated with glucuronic acid to make it water-soluble so that the kidneys can readily excrete it. The process by which the oxidized testosterone becomes conjugated with glucuronic acid is facilitated by the enzyme uridine diphospho glucuronosyl transferase (UGT).10 

Over 90% of exogenously administered testosterone is excreted from the body in the urine after its conjugation with glucuronic acid. The remaining 10% of the testosterone that is not excreted through the kidneys leaves the body in the stool. The testosterone that is excreted in the stool is unconjugated for that which has bound glucuronic acid.11 

Indications

Several medical conditions may indicate the need for exogenous testosterone administration. Some of these medical conditions are:1213 

  • Male hypogonadism: This may occur at birth or later in the life of males. In this condition, there are decreased levels of testosterone due to failure of the testicles for a variety of reasons such as orchitis, orchidectomy, testicular torsion, or aging, among others. 
  • Hypogonadotropic hypogonadism: This condition results from the failure of the hypothalamic-pituitary-gonadal pathway. Due to a deficiency in the production of GnRH or LH, there is a reduction in the blood levels of testosterone, thereby warranting the need for injectable testosterone supplementation. 
  • Delayed puberty: In some instances, testosterone injections may be used in boys who are experiencing delayed puberty. Before using it for this purpose, a thorough examination should be carried out to rule out the presence of other disease conditions that may be the cause of the delay in puberty. 
  • Female metastatic breast cancer: In some postmenopausal women who have advanced breast cancer that is inoperable, testosterone injections may be used as a supplemental therapy. 

Contraindications and Precautions

There are several circumstances in which testosterone injections should not be administered or administered with extra caution: 

  • Testosterone is absolutely contraindicated in men with any type of cancer to the breast or prostate. 
  • People who are hypersensitive to any of the components should not receive testosterone enanthate injections. 
  • Women who are pregnant or have a high likelihood of becoming pregnant should not receive testosterone injections as this may result in masculinization of the fetus. 
  • Caution should be exercised when administering testosterone to individuals with impaired liver or kidney functions. 

Pregnancy/Breast-feeding

Testosterone has been classified as a category X drug by the US Food and Drug Administration. This means that research has demonstrated significant fetal abnormalities when used in pregnant women. As such, testosterone injections are absolutely contraindicated in pregnancy, and the risks of its use far outweigh any potential benefits that may be gained from its administration. Testosterone injections are also contraindicated in women who are breastfeeding as studies have shown that it is expressed in breast milk to a significant degree.14 

Adverse Reactions/Side Effects

Some side effects that may arise from exogenous administration of testosterone enanthate injections are: 

  • Liver conditions such as peliosis hepatitis as well as hepatocellular carcinomas
  • Elderly males may develop enlargement of the prostate and prostatic carcinoma
  • In individuals with pre-existing cardiovascular conditions, there may be swelling of the lower limbs due to salt and water retention
  • Some men may develop enlarged breasts, a condition known as gynecomastia

Storage

Store this medication 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. NOTE: Warming and shaking the vial should redissolve any crystals that may have formed during storage temperatures lower than recommended.
  • 1. Bain, J., "The many faces of testosterone", Clinical Interventions in Aging, vol. 2 issue 4, pp. 567-576. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686330/
  • 2. Nassar, G.N., Leslie, S.W., "Physiology, Testosterone", StatPearls. Available: https://www.ncbi.nlm.nih.gov/books/NBK526128/
  • 3. Atkinson, R.A., Srinivas-Shankar U., Roberts, S.A., Connolly, M.J., Adams, J.E., Oldham, J.A., Wu, F.C., Seynnes, O.R., Stewart, C.E., Maganaris, C.N., Narici, M.V., "Effects of Testosterone on Skeletal Muscle Architecture in Intermediate-Frail and Frail Elderly Men", The Journals of Gerontology: Series A, Vol. 65A, issue 11, pp.1215–1219. November 2010. Available: https://academic.oup.com/biomedgerontology/article/65A/11/1215/596059
  • 4. Mohamad, N. V., Soelaiman, I. N., , Chin, K. Y., "A concise review of testosterone and bone health", Clinical interventions in aging, vol. 11, pp. 1317–1324. September 2016. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036835/
  • 5. 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", The Journal of clinical endocrinology and metabolism, vol.93 issue 3, pp. 914–919. March 2008. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266950/
  • 6. Resnick, S.M., Matsumoto, A.M., Stephens-Shields, A.J., Ellenberg, S.S., Gill, T.M., Shumaker, S.A., Pleasants, D.D., Barrett-Connor, E., Bhasin, S., Cauley, J.A., Cella, D., Crandall, J.P., Cunningham, G.R., Ensrud, K.E., Farrar, J.T., Lewis, C.E., Molitch, M.E., Pahor, M., Swerdloff, R.S., Cifelli, D., Anton, S., Basaria, S., Diem, S.J., Wang, C., Hou, X., Snyder, P.J., "Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment", Journal of the American Medical Association. Vol.317 issue 7, pp.717–727. 2017. Available: https://jamanetwork.com/journals/jama/fullarticle/2603930
  • 7. Spitzer, M., Basaria, S., Travison, T. G., Davda, M. N., DeRogatis, L., Bhasin, S., "The effect of testosterone on mood and well-being in men with erectile dysfunction in a randomized, placebo-controlled trial". Andrology, vol.1 issue 3, pp.475–482. March 2013. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630276/
  • 8. Wein, H., "Understanding How Testosterone Affects Men", NIH Research Matters. September 2013. Available: https://www.nih.gov/news-events/nih-research-matters/understanding-how-testosterone-affects-men
  • 9. Funder, J.W., "The multiple actions of testosterone in men: nature knows best", Asian Journal of Andrology, vol.16 issue 2, pp. 266-267. March – April 2014. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955337/
  • 10. a. b. c. Handelsman, D.J., "Androgen Physiology, Pharmacology, Use, and Misuse", Endotext. October 2020. Available: https://www.ncbi.nlm.nih.gov/books/NBK279000
  • 11. a. b. c. "Testosterone enanthate," DrugBank. Available: https://go.drugbank.com/drugs/DB13944
  • 12. "Delatestryl", RxList. Available: https://www.rxlist.com/delatestryl-drug.htm
  • 13. "Testosterone enanthate injection, USP". Available: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=e89d6458-428c-4256-97a3-f1fa851293c1&type=display
  • 14. "Testosterone Pregnancy and Breastfeeding Warnings", Drugs.com. Available: https://www.drugs.com/pregnancy/testosterone.html

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