Testosterone is a key steroid hormone and the primary male sex hormone, essential for the development and maintenance of male characteristics like muscle mass, bone density, and body hair. In men, testosterone is mainly produced by the testes, while in women, it is produced by the ovaries and adrenal glands. In both males and females, it also plays a role in regulating mood, energy, and libido. Additionally, it is crucial for sperm production in men and contributes to bone health, red blood cell formation, and the distribution of body fat.
BRAND NAMES
Common brand names for testosterone include AndroGel, Depo-Testosterone, Xyosted, Jatenzo, Testim, and Androderm.
Oral capsules should be taken with food to ensure proper absorption. Topical gels, solutions, and patches are applied directly to the skin for absorption, and the amount used varies by brand.
MECHANISM OF ACTION
Testosterone primarily exerts its effects by binding to the androgen receptor (AR), a protein that, once activated, translocates to the cell nucleus. Inside the nucleus, the activated AR complex attaches to specific DNA sequences called androgen response elements, recruiting other proteins to regulate the transcription of target genes. Additionally, testosterone can influence gene expression indirectly by being converted into other active hormones, such as dihydrotestosterone (DHT) and estradiol, which bind to their respective receptors to modulate gene activity.
PHARMACOKINETICS
Absorption
Testosterone can be administered and absorbed through multiple routes, each with distinct absorption profiles and effectiveness. While native oral testosterone is poorly absorbed, special formulations, injections, and transdermal methods are designed to increase bioavailability and bypass first-pass metabolism in the liver.
Distribution
The volume of distribution (Vd) of testosterone is generally around 1 L/kg when administered intravenously.
Metabolism
Testosterone metabolism is the process by which the body breaks down and transforms the male sex hormone testosterone into various active or inactive metabolites. This occurs primarily in the liver, but also in other tissues like the prostate, skin, and brain, influencing a wide range of physiological functions.
Excretion
Roughly 90% of the testosterone metabolites are eliminated through urine. Around 6% of testosterone metabolites are eliminated via the feces.
PHARMACODYNAMICS
Testosterone exerts its pharmacodynamic effects primarily by activating the androgen receptor (AR) and, after conversion, the estrogen receptor (ER). The ultimate effects, which include regulating gene expression and causing rapid cellular responses, are critical for developing and maintaining masculine features and overall metabolic function.
ADMINISTRATION
Testosterone can be administered via various methods, including injections, topical gels, and transdermal patches. The best method depends on a person's specific medical needs, lifestyle, and a doctor's recommendation.
DOSAGE AND STRENGTH
Dosage forms include injections, transdermal gels and patches, oral capsules, and subdermal pellets. The standard dose is 225 milligrams (mg) taken twice a day, in the morning and evening.
DRUG INTERACTIONS
Testosterone interacts with several classes of medications, notably blood thinners like warfarin, diabetes drugs including insulin, and corticosteroids such as prednisone. These interactions can lead to increased bleeding risk with anticoagulants, hypoglycemia when combined with diabetes medications, and fluid retention (edema) with corticosteroids, which is particularly concerning for those with heart, kidney, or liver disease.
FOOD INTERACTIONS
Oral testosterone capsules, such as testosterone undecanoate, must be taken with a meal containing fat to be properly absorbed, as minimal absorption occurs on an empty stomach. Maintaining a balanced diet is essential for promoting healthy natural testosterone production. Foods rich in zinc, like oysters and red meat, or magnesium, found in leafy greens, may help support levels. Healthy fats from sources such as fatty fish, olive oil, and egg yolks can also contribute to testosterone production, while excessive alcohol, trans fats, and highly processed foods may have a negative effect.
CONTRAINDICATIONS
Testosterone therapy has several serious contraindications, including prostate and breast cancer, uncontrolled heart failure, and elevated red blood cell count. It is also not recommended for anyone trying to conceive, as it can cause infertility. All decisions about testosterone therapy should be made with a doctor to ensure a careful risk-benefit assessment.
SIDE EFFECTS
Skin reactions.
Fluid retention.
Sleep apnea.
Breast changes.
Mood swings.
Weight gain.
Fertility changes.
Sexual function.
Cardiovascular issues.
Hormonal withdrawal.
Prostate growth.
OVER DOSE
A testosterone overdose can lead to a range of symptoms, from serious cardiovascular events to mood changes.
Cardiovascular issues.
Seizures.
Blood clots.
Severe headaches or blurred vision.
Allergic reaction.
Psychiatric symptoms.
Liver issues.
Gynecomastia.
Reproductive issues.
TOXICITY
Testosterone toxicity refers to the harmful health effects caused by excessively high levels of testosterone, either from natural overproduction or the misuse of testosterone or anabolic steroids. Symptoms can differ between individuals and may include increased libido, acne, hair loss, mood swings, infertility in men, and masculinizing effects in women, such as a deeper voice or irregular menstrual cycles. More severe complications can include heightened cardiovascular risk, elevated red blood cell count, prostate issues, and possible neurotoxic effects.
