Overview of Testosterone Pellets
Dosage Strengths of Testosterone Pellets
200 mg (4.5 mm trocar required)
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.12
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:345
- 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.6
Mechanism of Action
Testosterone secretion occurs within the Leydig cells located within the interstitial compartment of the male testes, between the seminiferous tubules. It is synthesized from cholesterol with the participation of some cytochrome P-450 enzymes such as 17-hydroxylase and 17,20 lyase. Some additional testosterone synthesis occurs in the adrenal cortex's zona reticularis; the quantity produced from the cortex is relatively insignificant in men, but in women, it contributes to a large proportion of the circulating testosterone.
Testosterone occurs at three major stages of life in the typical male, namely:
- A transient increase during the first trimester of intrauterine life.
- A transient perinatal surge during early neonatal life.
- Continual increase after puberty until the third or fourth decade of life when testosterone levels begin to gradually decrease.
Testosterone synthesis is regulated by the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. The released GnRH then stimulates the release of luteinizing hormone (LH) from the brain's pituitary gland. The LH that is released then triggers the synthesis of testosterone from the Leydig cells in the testes. Testosterone also has a negative feedback effect on GnRH and LH's release from then hypothalamus and pituitary glands respectively.
After its synthesis, testosterone is further metabolized before it can exert its effects in the body; there are two major pathways by which this may occur. In the first metabolic pathway, synthesized testosterone is converted into dihydrotestosterone through the action of the enzyme 5-alpha reductase; DHT then binds to and activates androgen receptors in organs such as the prostate, muscles, and skin where it exerts its effects. In the second pathway, the enzyme aromatase converts testosterone into estradiol; estradiol binds with estrogen receptors and exerts its effects on the brain and bone. In both pathways, binding to the androgen receptors causes dissociation of heat shock proteins that are bound to the receptors. This dissociation allows for the translocation into the nucleus, as well as phosphorylation, interaction, and modification of the DNA at the target genes. Once this occurs, the transcription activities that result in the synthesis of the relevant proteins then takes place.178
There are several routes through which testosterone can be exogenously administered; these are oral, intramuscular, topical as a gel, or subdermal as testosterone implants. Of the various routes of administration, testosterone implants have the longest duration of action.
After testosterone supplements have been exogenously and absorbed into the bloodstream, it is mostly bound to the plasma protein sex hormone-binding globulin (SHBG) before it is transported around the body to its site of action. Absorbed testosterone is also bound in reduced amounts to other plasma proteins in the body, such as albumin, corticosteroid-binding globulin, and alpha-1 acid glycoprotein. However, about two percent of testosterone in the body is not bound to plasma proteins and circulates in the body as free testosterone.
The metabolism and the catabolism of testosterone and its active metabolite DHT take place in the liver. Here, the enzyme 5-beta reductase converts testosterone into an inactive metabolite known as 5-beta dihydrotestosterone. This metabolite and DHT are reduced into 3-alpha, 5-alpha androstanediol, and 3-alpha, 5-beta androstanediol, respectively. These products are further broken down to produce the catabolic products androsterone and etiocholanolone.
Testosterone is primarily excreted from the body through the kidneys. Since testosterone and its metabolites are fat-soluble, they undergo conjugation in the liver with glucuronic acid to make it water-soluble prior to excretion. Once they have become water-soluble, the inactivated testosterone metabolites can then be excreted from the body in the urine. The conjugated testosterone metabolites are also excreted from the body in stool, though in much smaller quantities than the kidneys.18
- 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.
Pregnancy / Breastfeeding
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.13
Indications For Use
The most common reason individuals receive exogenous testosterone is due to late onset hypogonadism, which is the decline of serum testosterone levels later in life. Some off label uses that may be derived by individuals taking testosterone to treat late-onset hypogonadism include the following:910
- Increased libido and sexual arousal.
- Improved erectile function. Testosterone assists in the formation of nitric oxide, a substance that is key in the production of cyclic guanosine monophosphate necessary for penile tumescence.
- Improved cognition. Through its conversion into estradiol, testosterone plays a significant role in the development and survival of neuronal cells within the brain. This occurs especially around Brodman areas 8 and 24, which are the parts of the brain that control memory, higher motor actions, and strategic planning, among other functions.
- Improved mood and reduced feelings of depression.
- Reduced bone resorption and increased bone density, resulting in stronger and healthier bones. This is especially the case in post-menopausal women as they are at an increased risk of osteoporosis; testosterone administration to women in this category may be beneficial.
- Restoration of lean body mass. Exogenous testosterone helps to increase lean body mass as well as reduce overall fat mass in the body; these result in an increased overall muscle strength within the body.
- In men with Type 2 diabetes mellitus, some studies have demonstrated a positive correlation between the severity of their symptoms and low testosterone levels. The studies showed that men who received testosterone supplements in addition to their antidiabetic regimen had improved fasting blood sugar levels as well as reduced insulin resistance.
- Improved symptoms of anemia. Since testosterone is known to have a hematopoietic effect, it has been shown to be beneficial in the management of certain kinds of anemia in men.
The only approved uses for testosterone pellets are:
- Primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome; or orchiectomy.
- Hypogonadotropic hypogonadism (congenital or acquired) - gonadotropic LHRH deficiency, or pituitary - hypothalamic injury from tumors, trauma or radiation.
Adverse Reactions/Side Effects
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:14
- 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.
- 1. a. b. c. Handelsman, D.J., "Androgen Physiology, Pharmacology, Use and Misuse", Endotext. October 2020. Available: https://www.ncbi.nlm.nih.gov/books/NBK279000/
- 2. Antoniou-Tsigkos, A., Zapanti, E., Ghizzoni, L., Mastorakos, G.,"Adrenal Androgens", Endotext. January 2019. Available: https://www.ncbi.nlm.nih.gov/books/NBK278929/
- 3. 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/
- 4. 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/
- 5. "Additional Studies of Testosterone Therapy", Testosterone and Aging: Clinical Research Directions. Available: https://www.ncbi.nlm.nih.gov/books/NBK216178/
- 6. 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/
- 7. 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. 2017. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434832/
- 8. a. b. Nassar, G.N., Leslie, S.W., "Physiology, Testosterone", StatPearls. Available: https://www.ncbi.nlm.nih.gov/books/NBK526128/
- 11. 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.html
- 12. Cunha, J.P., "Testosterone", RxList. Available: https://www.rxlist.com/consumer_testosterone-medication/drugs-condition.htm
- 13. "Testosterone Pregnancy and Breastfeeding Warnings". Available: https://www.drugs.com/pregnancy/testosterone.html
- 9. Bain, J., "The many faces of testosterone", Clinical Interventions in Aging, vol.2 issue 4, pp.567-576. December 2007. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686330/
- 10. Polackwich, A.S., Tadros, N.N., Ostrowski, K.A., Hedges, J.C., "Benefits and Consequences of Testosterone Replacement Therapy: A Review", European Endocrinology, Vol.9 issue 1, pp.59-64. March 2013. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193518/
- 14. "Testosterone Injection". Available: https://www.drugs.com/testosterone.html