Testosterone is a synthetic form of the endogenous androgenic steroid testosterone. In vivo, testosterone is irreversibly converted to dihydrotestosterone (DHT) in target tissues by the enzyme 5-alpha reductase. Testosterone or DHT ligand-androgen receptor complexes act as transcription factor complexes, stimulating the expression of various responsive genes. DHT binds with higher affinity to androgen receptors than testosterone, activating gene expression more efficiently. In addition, testosterone is irreversibly converted to estradiol by the enzyme complex aromatase, particularly in the liver and adipose tissue. Testosterone and DHT promote the development and maintenance of male sex characteristics related to the internal and external genitalia, skeletal muscle, and hair follicles; estradiol promotes epiphyseal maturation and bone mineralization. Due to rapid metabolism by the liver, therapeutic testosterone is generally administered as an ester derivative.
Testosterone undecanoate is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels in men. It is also used in hormone therapy for transgender men. It is taken by mouth two to three times per day with food or given by injection into the muscle once every 12 weeks or so. Testosterone undecanoate is an esterified form of testosterone which is attached to a long fatty acid chain. The lack of a methylated site on the carbon 17 eliminates the adverse effects on the liver found in other testosterone analogs. It is currently getting further developed to be an alternative to testosterone enanthate or testosterone cypionate by Paddock labs, and this new injectable has an FDA status of tentative approval.
Mechanism of Action of Testosterone
The effects of testosterone in humans and other vertebrates occur by way of two primary mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of specific estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5-alpha-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5-alpha-reductase. The T-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing androgen effects.
Indications of Testosterone
- Hypogonadism, male
- Gender dysphoria
- Delayed puberty, male
- Klinefelter syndrome
- Breast cancer, palliative
- Postpartum breast pain
- Hypergonadotropic hypogonadism
- Hypogonadotrophic hypogonadism
- Deficient activity of the testis
- Rare X chromosome abnormality – klinefelter syndrome
- Deficient activity of testes or ovaries due to chemotherapy
- Surgical removal of both testicles
- Primary testicular failure due to torsion of both testes
- Undescended testicle
- Pituitary hormone deficiency
- Absence of testicles
- deficiency of gonadotropin releasing factor
- Primary testicular Failure due to inflammation of Testis
- Deficiency of a substance that promotes masculinization
- Male with unusually late sexual maturity
Contra-Indications of Testosterone
- Cancer of the prostate gland
- Polycythemia vera
- Increased calcium in the blood from cancer
- Diabetes
- High cholesterol
- Overweight
- High blood pressure
- Heart attack
- Lung embolism
- Chronic heart failure
- Stroke
- Blood clot formation in veins
- Chronic lung disease
- Liver Problems
- kidney disease with reduction in kidney function
- Enlarged Prostate
- Enlarged Breasts
- Temporarily stops breathing while sleeping
- Visible water retention
- Pregnancy
- A Mother who is producing milk and breastfeeding
- Abnormal increase in red blood cells
Dosages of Testosterone
Hypogonadism – Male
IM INJECTION
- Testosterone Undecanoate: 750 mg (3 mL) IM injection followed by 750 mg (3 mL) injected after 4 weeks, then 750 mg (3 mL) every 10 weeks thereafter
- Testosterone Enanthate and Cypionate: 50 to 400 mg IM injection every 2 to 4 weeks
IMPLANT
- 2 to 6 pellets (75 mg each) implanted subcutaneously every 3 to 6 months.
- The number of pellets to be implanted depends upon the minimum daily requirements of testosterone propionate administered parenterally. Thus, implant two 75 mg pellets for each 25 mg testosterone propionate required weekly.
- Mucoadhesive Oral Patch: Apply a 30 mg patch to the gum region twice a day; morning and evening (about 12 hours apart).
Breast Cancer-Palliative
Testosterone Enanthate
- 200 to 400 mg IM injection every 2 to 4 weeks
Delayed Puberty – Male
IM INJECTION
- Testosterone Enanthate: 50 to 200 mg every 2 to 4 weeks for 4 to 6 months
IMPLANT
- 2 pellets (each pellet contain 75 mg of testosterone) implanted subcutaneously every 3 to 6 months
- Duration of therapy: 4 to 6 months
Side Effects of Testosterone
The most common
- Gum or mouth irritation
- chest pain, irregular heartbeat, or shortness of breath
- incresed appetite
- weight loss
- dry mouth
- headache
- joint pain
- nausea and vomiting
- Severe stomach ache
- diarrhoea,
- anorexia,
- flatulence,
- headache,
- fainting, fast or pounding heartbeats.
More common
- bleeding gums
- blemishes on the skin
- breast pain
- change in taste
- fever
- Back pain
- dizziness
- headache
- increased cough
- Acid or sour stomach
- decreased appetite
- Agitation
- chest congestion
- chest pain
- cold sweats
- confusion
- decreased sexual ability or desire
- diarrhea or loose stools
- heartburn
- sleepiness or unusual drowsiness
- stomach or abdominal cramps, gas, or pain
- trouble sleeping
Less common
- Abnormal dreams
- change in sense of taste
- congestion
- discouragement, feeling sad, or empty
- Acting on dangerous impulses
- Aggressive or violent behavior
- Thoughts about suicide or dying
- New or worse depression
- New or worse anxiety or panic attacks
- Agitation, restlessness, anger, or irritability
- Trouble sleeping
- An increase in activity or talking more than normal
Drug Interactions of Testosterone
Testosterone undecanoate may interact with following drugs, supplements & may change the efficacy of the drug
- adrenocorticotropic hormone (ACTH)
- corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
- cyclosporine
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- cyclosporine
- estrogens (e.g., conjugated estrogen, estradiol, ethinyl estradiol)
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine,paroxetine, sertraline)
- thiazide diuretics (e.g., chlorothiazide, hydrochlorothiazide)
- nateglinide
- octreotide
- pasireotide
- somatostatin acetate
- sulfonamide antibiotics (“sulfas”; e.g., sulfisoxazole, sulfamethoxazole)
- warfarin
Pregnancy & Lactation of Testosterone
Pregnancy
This medication is not recommended for pregnant women.
Lactation
This medication is not recommended for breastfeeding women. The safety and effectiveness of using this medication have not been established for children. This medication is not recommended for children under 18 years of age.
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