Testosterone

What Is Testosterone and What Is It Used For?

Testosterone is the primary male sex hormone (androgen) that is naturally produced by the testes. When prescribed as medication, it provides testosterone replacement therapy (TRT) for adult men with confirmed testosterone deficiency (male hypogonadism), restoring normal hormone levels and alleviating symptoms such as low libido, erectile dysfunction, fatigue, and loss of muscle and bone mass.

Testosterone plays a crucial role in male sexual development and the maintenance of male secondary sex characteristics throughout life. It is responsible for the development of the male reproductive organs, deepening of the voice during puberty, growth of facial and body hair, and the regulation of muscle mass, bone density, and fat distribution. In adulthood, testosterone continues to be essential for maintaining libido, erectile function, sperm production, mood, energy levels, and overall wellbeing.

When the body fails to produce adequate amounts of testosterone – a condition known as male hypogonadism – a range of debilitating symptoms can occur. Hypogonadism may be caused by problems in the testes themselves (primary hypogonadism) or by dysfunction of the pituitary gland or hypothalamus, which regulate testosterone production (secondary hypogonadism). Common causes include Klinefelter syndrome, undescended testes, testicular injury, pituitary tumors, and certain chronic illnesses.

Testosterone replacement therapy is prescribed to restore serum testosterone concentrations to the normal physiological range. According to the Endocrine Society Clinical Practice Guidelines, TRT should only be initiated in men who have unequivocally low testosterone levels, confirmed by at least two morning blood samples, and who also present with consistent clinical signs and symptoms of deficiency. It is important to note that testosterone replacement is not recommended for age-related declines in testosterone in otherwise healthy older men, as the benefits in this population remain uncertain and the risks may outweigh the benefits.

The symptoms of testosterone deficiency that may qualify a patient for TRT include:

• Sexual dysfunction: decreased libido, erectile dysfunction, and reduced spontaneous erections
• Reduced fertility: decreased sperm production and infertility
• Physical changes: loss of muscle mass and strength, increased body fat, reduced bone mineral density (osteoporosis), and breast enlargement (gynecomastia)
• Psychological symptoms: fatigue, depression, difficulty concentrating, and decreased motivation
• Other effects: hot flushes, decreased body hair growth, and anemia

Available formulations

Testosterone is available in several formulations, each with different administration routes, dosing schedules, and pharmacokinetic profiles:

• Transdermal gel (Testogel, AndroGel, Tostrex): Applied daily to the skin of the shoulders and upper arms. Provides steady-state testosterone levels with once-daily application. Most commonly prescribed formulation.
• Intramuscular injections (Testosterone Enanthate, Testosterone Cypionate): Injected every 1–4 weeks into the gluteal muscle. Can cause fluctuations in testosterone levels between injections.
• Long-acting injections (Testosterone Undecanoate, Nebido): Injected every 10–14 weeks. Provides more stable levels with less frequent dosing.
• Transdermal patches: Applied daily to the skin. May cause skin irritation at the application site.
• Oral capsules (Testosterone Undecanoate): Taken with food. Absorbed via the lymphatic system to avoid first-pass liver metabolism.

What Should You Know Before Taking Testosterone?

Testosterone is strictly for adult men with confirmed hypogonadism. It must not be used by women, children, or men with known or suspected prostate cancer or breast cancer. Before starting therapy, testosterone deficiency must be confirmed by at least two separate blood tests along with clinical symptoms. Important contraindications include severe heart, liver, or kidney disease, untreated sleep apnea, and high red blood cell counts.

Before initiating testosterone replacement therapy, your doctor will perform a thorough evaluation including a detailed medical history, physical examination, and laboratory testing. This assessment is critical for confirming the diagnosis of hypogonadism, ruling out contraindications, and establishing baseline values for ongoing monitoring. The decision to start TRT should always be a shared one between patient and physician, with a clear understanding of both the expected benefits and potential risks.

Contraindications

Testosterone replacement therapy must not be used in the following situations:

• Known or suspected prostate cancer: Testosterone can stimulate the growth of prostate cancer cells. All men should have a digital rectal examination and PSA test before starting therapy.
• Known or suspected breast cancer in men: Although rare, male breast cancer is an absolute contraindication.
• Allergy to testosterone or any excipient in the specific formulation being considered.
• Women and children: Testosterone replacement is not indicated for women at any age, and must not be used in boys under 18 years of age due to the risk of premature closure of bone growth plates and virilization.

Warnings and precautions

Discuss the following conditions with your doctor before starting testosterone, as they may require special monitoring or dose adjustment:

• Cardiovascular disease: Testosterone may increase the risk of heart attack, stroke, and other cardiovascular events. The FDA has issued a warning requiring manufacturers to include cardiovascular risk information on testosterone product labels. Patients with pre-existing heart disease, hypertension, or risk factors for cardiovascular disease require careful monitoring.
• Polycythemia (elevated red blood cell count): Testosterone stimulates erythropoiesis (red blood cell production). An excessively high hematocrit increases the risk of blood clots, stroke, and heart attack. Regular blood count monitoring is essential.
• Benign prostatic hyperplasia (BPH): Testosterone may worsen urinary symptoms in men with an enlarged prostate.
• Sleep apnea: Testosterone can worsen obstructive sleep apnea, particularly in obese patients or those with pre-existing respiratory conditions.
• Liver, kidney, or severe heart disease: Testosterone can cause fluid retention (edema), which may worsen heart failure or kidney disease.
• Thrombophilia or history of blood clots: Testosterone may increase the risk of venous thromboembolism (deep vein thrombosis, pulmonary embolism). Risk factors include previous blood clots, smoking, obesity, immobility, and cancer.
• Epilepsy or migraine: These conditions may be exacerbated by testosterone therapy due to fluid retention.
• Diabetes mellitus: Testosterone may alter insulin sensitivity, potentially requiring adjustment of diabetes medications including insulin.
• Bone metastases: In patients with cancer that has spread to the bones, testosterone can increase calcium levels (hypercalcemia), requiring careful monitoring.

Pregnancy and breastfeeding

Testosterone must not be used by women under any circumstances. It can cause serious harm to a developing fetus, including virilization (development of male sex characteristics) of a female fetus. Pregnant women must avoid all contact with testosterone gel or any skin areas where it has been applied.

If accidental skin contact occurs, the affected area should be washed immediately and thoroughly with soap and water. If you are a man using testosterone gel and your partner is or may become pregnant, you must strictly follow the precautions for preventing transdermal transfer (see section on application technique).

Effects on fertility

Testosterone replacement therapy suppresses spermatogenesis (sperm production) and can significantly reduce sperm count, often to zero (azoospermia). This effect is usually reversible after discontinuation, but recovery may take 6–24 months. Men who wish to preserve fertility should discuss alternative treatments with their doctor before starting TRT. Options may include clomiphene citrate or human chorionic gonadotropin (hCG), which stimulate the body's own testosterone production while maintaining spermatogenesis.

How Does Testosterone Interact with Other Drugs?

Testosterone interacts with several medications including oral anticoagulants (blood thinners) such as warfarin, corticosteroids, and insulin. These interactions may require dose adjustments. Always inform your doctor about all medications you are taking, including over-the-counter drugs and supplements, before starting testosterone therapy.

Drug interactions with testosterone can affect the efficacy or safety of both testosterone and the co-administered medication. Some interactions are clinically significant and require dose modification or enhanced monitoring, while others are relatively minor. The following table summarizes the most important known interactions.

Major interactions

Minor interactions

Other medications that may interact with testosterone include:

• Oxyphenbutazone: May increase testosterone levels when used concurrently
• Thyroid hormones (levothyroxine): Testosterone may alter thyroid-binding globulin levels, potentially affecting thyroid function tests but usually not requiring dose changes
• CYP3A4 inhibitors (ketoconazole, erythromycin): May theoretically increase testosterone exposure, though clinical significance is usually minimal with replacement doses
• CYP3A4 inducers (rifampicin, phenobarbital, carbamazepine): May increase testosterone metabolism, potentially reducing its effectiveness

Always provide your doctor and pharmacist with a complete list of all medications, vitamins, and herbal supplements you are taking. Some over-the-counter products and supplements may interact with testosterone. In particular, products containing saw palmetto, DHEA, or other hormonal supplements should be discussed with your healthcare provider.

What Is the Correct Dosage of Testosterone?

The dosage of testosterone is individualized based on the formulation, serum testosterone levels, and clinical response. For transdermal gel (e.g., Testogel 16.2 mg/g), the typical starting dose is 2 pump actuations (2.5 g gel containing 40.5 mg testosterone) applied once daily. The maximum dose is 4 pump actuations per day. Your doctor will adjust the dose based on blood test results.

Testosterone dosing is not one-size-fits-all. The goal of replacement therapy is to achieve and maintain serum testosterone levels within the normal physiological range, typically 300–1000 ng/dL (10.4–34.7 nmol/L). Your doctor will start with a standard dose and adjust it based on your testosterone blood levels (measured in the morning, when levels peak) and your clinical response to treatment. It typically takes several weeks to months to optimize the dose.

Adults – Transdermal gel (Testogel 16.2 mg/g)

How to apply testosterone gel correctly

Proper application technique is essential for both effectiveness and the prevention of testosterone transfer to others. Follow these steps carefully:

1. Press the pump head once to dispense the gel into the palm of your hand.
2. Select a clean, dry, intact area of skin on one shoulder and upper arm.
3. Spread the gel gently and evenly with your fingers. Do not rub it in.
4. If using 2 pump actuations, repeat steps 1–3 on the opposite shoulder and upper arm.
5. If using 3 or more actuations, apply a maximum of 2 actuations per shoulder/arm.
6. Wash your hands thoroughly with soap and water after application.
7. Allow the gel to dry completely (3–5 minutes) before getting dressed.
8. Cover the application area with clothing once dry.

Preventing transfer to others

Testosterone gel can be transferred to other people through direct skin-to-skin contact with the application area. This is particularly dangerous for women and children. To minimize the risk of transfer:

• Always wash your hands with soap and water immediately after applying the gel
• Cover the application area with clothing (e.g., a T-shirt) once the gel has dried
• Wash the application area with soap and water before close physical contact with another person (especially women and children)
• Wait at least 1 hour after application before showering or bathing
• If someone has been in contact with an unwashed application area, they should wash the contact area immediately with soap and water

Children

Testosterone replacement therapy is not recommended for boys under 18 years of age. There is no clinical data supporting the use of testosterone in this age group, and exogenous testosterone may cause premature closure of growth plates, leading to reduced final adult height, as well as other virilizing effects.

Elderly

There are limited data on the safety and efficacy of testosterone in men over 65. The Endocrine Society guidelines recommend against routinely prescribing testosterone for age-related decline in healthy older men. When TRT is prescribed for confirmed hypogonadism in older men, more frequent monitoring of prostate health (PSA, digital rectal examination), hematocrit, and cardiovascular risk factors is recommended.

Missed dose

If you forget to apply your testosterone gel, apply it as soon as you remember unless it is close to the time for your next dose. Do not apply a double dose to make up for a missed one. Simply continue with your regular schedule at the next dosing time.

Overdose

If you apply too much testosterone gel, contact your doctor or pharmacist. You may be asked to wash the application area immediately. Symptoms of excessive testosterone may include:

• Irritability and nervousness
• Weight gain
• Frequent or prolonged erections (priapism)
• Acne

These symptoms may indicate that your dose is too high and needs to be reduced. If accidental ingestion occurs (e.g., by a child), contact a poison control center or emergency services immediately.

What Are the Side Effects of Testosterone?

Common side effects of testosterone include application site reactions, mood changes (irritability, mood swings), acne, elevated blood pressure, increased red blood cell count (polycythemia), headache, and gynecomastia. Serious but rare side effects include liver tumors, priapism, severe cardiovascular events, and severe skin reactions. Regular monitoring with blood tests is essential during treatment.

Like all medications, testosterone can cause side effects, although not everyone experiences them. Most side effects are dose-dependent, meaning they are more likely to occur at higher doses and may resolve with dosage adjustment. Your doctor will monitor you regularly to detect and manage any adverse effects early. It is important to report any unusual symptoms to your healthcare provider promptly.

Since testosterone gel contains alcohol (ethanol), frequent application may cause skin irritation and dryness at the application site. Avoid applying the gel to broken or damaged skin. Exercise caution around heat sources and open flames until the gel has fully dried, as ethanol is flammable.

How Should You Store Testosterone?

Testosterone gel does not require any special storage conditions. Keep it out of sight and reach of children at all times. Do not use after the expiry date printed on the packaging. Dispose of unused medication through your pharmacy – do not flush it down the toilet or throw it in household waste.

Proper storage of testosterone products is important to maintain their effectiveness and to prevent accidental exposure to others, particularly children and women. Follow these storage guidelines:

• No special temperature requirements: Testosterone gel (Testogel) can be stored at room temperature. No refrigeration is needed.
• Keep out of reach of children: This is particularly important for testosterone products, as accidental exposure can cause premature puberty and virilization in children.
• Check the expiry date: Do not use the product after the expiry date (EXP) printed on the carton and bottle. The expiry date refers to the last day of that month.
• Close the container properly after each use to prevent evaporation of the gel and accidental spills.
• Safe disposal: Do not dispose of testosterone through household waste or wastewater. Return unused or expired medication to your pharmacy for safe disposal. This helps protect the environment.

What Does Testosterone Contain?

Testogel 16.2 mg/g transdermal gel contains testosterone as its active ingredient (16.2 mg per gram of gel, with each pump actuation delivering 1.25 g of gel containing 20.25 mg of testosterone). Excipients include carbomer, isopropyl myristate, ethanol, sodium hydroxide, and purified water.

Active ingredient

The active substance is testosterone. Each gram of gel contains 16.2 mg of testosterone. One pump actuation delivers 1.25 g of gel containing 20.25 mg of testosterone. Not all of the applied testosterone is absorbed through the skin; the actual bioavailability of transdermal testosterone gel is approximately 10–14%, meaning that out of a 40.5 mg applied dose (2 pump actuations), approximately 4–5.7 mg of testosterone is absorbed into the bloodstream.

Excipients (inactive ingredients)

• Carbomer: Thickening agent that gives the gel its consistency
• Isopropyl myristate: Skin penetration enhancer that helps testosterone absorb through the skin
• Ethanol (alcohol): Solvent that helps dissolve testosterone and aids rapid drying on the skin. Each 1.25 g dose contains approximately 0.9 g of ethanol, which may cause a burning sensation on damaged skin.
• Sodium hydroxide: pH adjuster
• Purified water: Carrier base for the gel formulation

Packaging

Testogel is supplied as a colorless transdermal gel in a multidose container with a metered-dose pump. Each container holds 88 g of gel, providing a minimum of 60 doses. Packs of 1, 2, 3, or 6 containers are available, although not all pack sizes may be marketed in every country.

What Monitoring Is Required During Testosterone Therapy?

Regular monitoring during testosterone therapy includes blood tests for serum testosterone levels, complete blood count (especially hematocrit), PSA, liver function, and lipid profile. Physical examinations including digital rectal examination of the prostate should be performed before treatment and at least annually thereafter, or twice yearly in older men or those at higher risk.

Ongoing monitoring is a critical component of safe and effective testosterone replacement therapy. Both the Endocrine Society and the European Association of Urology recommend specific monitoring schedules to detect adverse effects early and optimize treatment outcomes.

Recommended monitoring schedule

If your testosterone blood level is above or below the target range, your doctor will adjust the dose accordingly. If your hematocrit rises above 54%, treatment may be paused until the level normalizes. A significant rise in PSA (>1.4 ng/mL over 12 months) or an abnormal digital rectal examination warrants further urological evaluation to rule out prostate cancer.