Testosterone propionate

Chemical structure and synthesis

Endogenous testosterone belongs to $C_{19}$-steroids (contains 19 carbon atoms). Normally in men, it is synthesized primarily in Leydig cells (in the testes) from androstenedione. Extragonadal synthesis in small amounts occurs in the adrenal cortex (in both sexes) and in the ovaries in women. Precursors include androstenedione and dehydroepiandrosterone, which themselves possess only weak androgenic activity.

The drug Testosteroni propionas itself is a modification of the native hormone—esterification of the hydroxyl group at the 17th position. This sharply increases the lipophilicity of the molecule.

Pharmacokinetics and metabolism

Upon intramuscular administration of the oil solution, the drug creates a depot in adipose tissue. Absorption is slow due to poor vascularization of subcutaneous adipose tissue and the characteristics of the oil base. In the body, the ester is gradually hydrolyzed to release free testosterone. Propionate has a short duration of action, and therefore requires daily administration (unlike isocaproate, which is administered once every 3–4 weeks).

The drug is metabolized in the liver involving the largest group of isoenzymes—CYP3A4 / CYP3A5.

In tissues, testosterone undergoes two important conversion pathways:

1. To dihydrotestosterone (DHT): under the action of the enzyme $5\alpha$-reductase (in the prostate, liver, external genitalia). The process is irreversible. DHT has a higher affinity for androgen receptors.
2. To estradiol: under the action of the enzyme aromatase (in the liver, adipose tissue, ovaries, CNS).

Pharmacological effects

The drug's action replicates the physiological effects of native testosterone and its metabolites:

• Anabolic effect: stimulation of muscle mass growth (pubertal effect).
• Androgenic effect: formation of libido and potency. Due to conversion to DHT, it stimulates the maturation of external genitalia and male-pattern hair growth.
• Hematological effect: stimulation of erythropoiesis.
• Effect on bone tissue: through conversion to estradiol, bone mineral density is maintained, and at the end of puberty, epiphyseal growth plates close (cessation of longitudinal bone growth).

Indications for use

In oncology practice, the drug is prescribed for breast cancer in women. Important condition: preserved menstrual function or menopause duration of less than 5 years. The therapeutic effect in this case is due to the potent suppression of estrogen production, which stimulates tumor growth.

Side effects and risks

The following adverse reactions are possible with the use of the drug:

• Virilization (development of male traits in women).
• Dizziness and nausea.
• Pathophysiological risk: excessive stimulation of prostate cells by dihydrotestosterone can lead to its hyperplasia (development of adenoma and prostate cancer in men).

Dosage forms and dosing

The drug is available in two main forms:

1. Capsules: 0.04 g. Prescribed orally, 1–2 capsules (tablets) 2 times a day after meals.
2. Ampoules (5% oil solution — 1 ml): administered strictly intramuscularly.
3. Maximum single dose (MSD) — 0.05 g.
4. Maximum daily dose (MDD) — 0.1 g.

Note: oil solutions are administered with caution, as they provide depot formation and slow release of the drug substance into the blood.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Synthesis of endogenous testosterone in Leydig cells and extragonadal synthesis pathways.
• The role of $5\alpha$-reductase and aromatase enzymes in steroid metabolism.
• Comparative pharmacokinetics of testosterone esters (propionate, isocaproate, combination mixtures such as Omnadren).
• The effect of CYP3A4/CYP3A5 isoenzyme inducers and inhibitors on hormonal drug concentrations in the blood.
• Pharmacology of 19-nortestosterone derivatives (norethisterone, levonorgestrel, dienogest) and their receptor selectivity.

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