Pharmacology of Testosterone


Testosterone is a primary male sex hormone, belonging to the androgen group, and is crucial in male reproductive tissue development and maintaining secondary sexual characteristics. It is secreted predominantly in the testes of males and, to a lesser extent, the ovaries of females. The pharmacological exploration of testosterone has evolved significantly, offering insights into its multifaceted role in human physiology.

Historical Development of Testosterone Therapy

The first experimental proof that the testes produce a substance responsible for virility was provided by Berthold in 1849. He transplanted testes from roosters into the abdomen of capons and recognized that the animals with the transplanted testes behaved like normal roosters. Berthold concluded that the virilizing effects were exerted by testicular secretions reaching the target organs via the bloodstream.

Following his observation, various attempts were made to use testicular preparations for therapeutic purposes. The first testicular extracts with demonstrable biological activity were prepared by Loewe and Voss in 1930 using the seminal vesicle as a test organ. Finally, the groundstone for modern androgen therapy was laid when steroidal androgens were first isolated from urine by Butenandt in 1931, testosterone was obtained in crystalline form from bull testes by David et al. in 1935, and testosterone was chemically synthesized by Butenandt and Hanisch in 1935 and Ruzicka and Wettstein in 1935.

Chemical Structure and Properties


Testosterone is a 19-carbon steroid hormone characterized by its lipophilic nature, allowing it to easily permeate cell membranes. It typically exists as a white or slightly creamy crystalline substance and is the precursor to several other critical hormones, including dihydrotestosterone (DHT) and estradiol.

Mechanism of Action

Testosterone’s effects are mediated through multiple pathways:

  • Direct Activity: It binds to androgen receptors in target cells, influencing gene expression and cellular function.
  • Conversion to Dihydrotestosterone (DHT): In certain tissues, it is converted to DHT, a more potent androgen, by the enzyme 5-alpha-reductase.
  • Conversion to Estradiol: Testosterone can be aromatized into estradiol, an estrogen, affecting tissues through estrogen receptors.


  • Absorption: The absorption and bioavailability of testosterone vary based on the route of administration, including oral, intramuscular, transdermal, and buccal methods.
  • Distribution: It binds extensively to plasma proteins, particularly sex hormone-binding globulin and albumin.
  • Metabolism: Testosterone is primarily metabolized in the liver into various metabolites, including DHT and estradiol.
  • Excretion: The metabolites are excreted through urine and feces.

Clinical Uses

Testosterone therapy is utilized in several clinical scenarios:

  • Hypogonadism in Men: It is the standard treatment for men with low testosterone levels due to various causes.
  • Delayed Puberty: It can induce and accelerate puberty in adolescents experiencing delays.
  • Breast Cancer: Certain forms of breast cancer in women are responsive to testosterone treatment.
  • Gender Affirming Therapy: Testosterone is a cornerstone in hormone therapy for transgender men.

Adverse Effects

While testosterone therapy is beneficial, it comes with potential risks:

  • Cardiovascular Risks: There’s an increased risk of heart attack and stroke, particularly in older men.
  • Liver Toxicity: Oral formulations are particularly associated with liver damage.
  • Endocrine Effects: Including suppression of spermatogenesis, testicular shrinkage, and potential infertility.
  • Psychological Effects: Mood alterations, aggression, and other psychological changes may occur.
  • Effects on Women: Masculinization effects such as voice deepening and hirsutism can occur.

Contraindications and Precautions

  • Prostate and Breast Cancer: Testosterone is contraindicated in men with these cancers.
  • Liver Disease: Caution is advised in patients with liver impairments.
  • Cardiovascular Disease: Patients with heart conditions should use testosterone cautiously.

Drug Interactions

Testosterone can interact with various medications, affecting their efficacy or leading to increased risks, including anticoagulants, diabetes medications, and corticosteroids.

Special Considerations

  • Monitoring: Regular assessments of testosterone levels, prostate health, hematocrit, and liver function are recommended.
  • Use in Women: Requires careful dosage and administration adjustments and monitoring due to different physiological responses.


Testosterone, with its broad physiological implications, is a vital hormone in medical therapy. Its use necessitates a comprehensive understanding of its actions, potential side effects, and the careful balancing of benefits and risks in treatment plans.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always seek the advice of a healthcare provider with any questions regarding a medical condition.

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