Chemical Structure and Synthesis
Endogenous testosterone belongs to $C_{19}$-steroids (contains 19 carbon atoms). Normally in males, it is synthesized primarily in Leydig cells (in the testes) from androstenedione. Extra-gonadal synthesis occurs in small amounts in the adrenal cortex (in both sexes) and in the ovaries in females. Precursors include androstenedione and dehydroepiandrosterone (DHEA), which themselves possess only weak androgenic activity.
Testosteroni propionas 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
When administered intramuscularly as an oil solution, the drug forms a depot in adipose tissue. Absorption is slow due to the poor vascularization of subcutaneous adipose tissue and the properties of the oil vehicle. In the body, the ester is gradually hydrolyzed to release free testosterone. Propionate has a short duration of action, thus requiring daily administration (unlike long-acting esters like isocaproate, which are given every 3–4 weeks).
The drug is metabolized in the liver by the major cytochrome P450 isoenzyme group—CYP3A4 / CYP3A5.
In tissues, testosterone undergoes two major pathways of conversion:
- To dihydrotestosterone (DHT): via $5\alpha$-reductase (in the prostate, liver, and external genitalia). This process is irreversible. DHT has a higher affinity for androgen receptors than testosterone.
- To estradiol: via aromatase (in the liver, adipose tissue, ovaries, and CNS).
Pharmacological Effects
The drug mimics the physiological effects of native testosterone and its metabolites:
- Anabolic effect: Stimulation of muscle mass growth (pubertal effect).
- Androgenic effect: Development of libido and potency. Conversion to DHT stimulates the maturation of external genitalia and male-pattern hair growth.
- Hematologic effect: Stimulation of erythropoiesis.
- Bone effects: Conversion to estradiol maintains bone mineral density, and at the end of puberty, causes epiphyseal plate closure (cessation of longitudinal bone growth).
Indications
In oncology, the drug is indicated for breast cancer in women. Important condition: Preserved menstrual function or menopause of less than 5 years duration. The therapeutic effect in this case is due to potent suppression of estrogen production, which otherwise stimulates tumor growth.
Adverse Effects and Risks
Potential adverse reactions include:
- Virilization (development of male secondary sex characteristics in women).
- Dizziness and nausea.
- Pathophysiological risk: Excessive stimulation of prostate cells by dihydrotestosterone can lead to prostatic hyperplasia (development of benign prostatic hyperplasia and prostate cancer in males).
Formulations and Dosing
The drug is available in two main formulations:
- Capsules: 0.04 g. Administered orally, 1–2 capsules 2 times daily after meals.
- Ampoules (5% oil solution — 1 mL): Administered strictly intramuscularly.
- Maximum single dose (MSD) — 0.05 g.
- Maximum daily dose (MDD) — 0.1 g.
Note: Oil solutions must be administered with caution as they provide depot storage and slow release of the active substance into the bloodstream.