Testosterone enanthate and testosterone cypionate are long-acting injectable ester formulations administered every 1 to 2 weeks. Both are depot preparations that release testosterone gradually from the injection site. The major pharmacokinetic drawback of biweekly injection is significant peak-to-trough fluctuation: supraphysiological peaks in the first 48 to 72 hours followed by troughs that may fall below the normal range before the next dose, producing cyclical symptom variation. Weekly injection reduces this fluctuation substantially.

Testosterone undecanoate (Nebido) is a much longer-acting injectable formulation given every 10 to 14 weeks, producing more stable levels. However, it carries a risk of pulmonary oil microembolism from inadvertent intravascular injection of its castor oil vehicle — symptoms include cough, dyspnea, and chest pain within minutes of injection. All Nebido injections must be administered by a healthcare professional with a mandatory 30-minute post-injection observation period. This restriction does not apply to enanthate or cypionate.

Testosterone gels (applied daily to skin) and patches bypass hepatic first-pass metabolism and produce more stable serum testosterone concentrations than biweekly injections. The primary safety concern with gels is accidental transfer to female partners or children through skin contact, which can cause virilization. Patients must wash hands after application, cover the site with clothing, and avoid skin-to-skin contact at the application site for several hours.

Subcutaneous testosterone pellets (Testopel) are implanted in the hip or buttock every 3 to 6 months, providing compliance-independent sustained release. Disadvantages include the need for a minor insertion procedure and the inability to adjust the dose after implantation.

Oral testosterone undecanoate (Jatenzo) is absorbed via the intestinal lymphatic system rather than the portal circulation, which avoids the hepatotoxicity seen with older oral androgens (methyltestosterone) that required C17-alpha-alkylation for oral bioavailability. Blood pressure elevation is the most clinically relevant adverse effect of the oral formulation.

5-alpha-reductase exists in two clinically relevant isoforms. Type 1 is expressed predominantly in skin, sebaceous glands, and liver. Type 2 is expressed predominantly in the prostate, seminal vesicles, and hair follicles, and is responsible for the majority of intraprostatic dihydrotestosterone production.

The clinical importance of type 2 5-alpha-reductase is illustrated by the phenotype of men born with congenital type 2 5-alpha-reductase deficiency: they are born with ambiguous or female-appearing external genitalia because dihydrotestosterone is required for male external genital virilization during fetal development. However, they have normal internal male structures (wolffian duct derivatives) because those are driven by testosterone, not dihydrotestosterone. At puberty, rising testosterone levels partially compensate, producing dramatic phallic virilization. This is a high-yield pharmacogenomic example that also explains why finasteride (which blocks type 2) selectively reduces prostate and scalp androgenic effects without impairing muscle, bone, or fertility effects.

Finasteride selectively inhibits type 2 5-alpha-reductase. At 5 mg per day it is used for benign prostatic hyperplasia — reducing prostate volume, improving urinary flow, and reducing the risk of acute urinary retention and surgery with long-term use. At 1 mg per day it is used for male-pattern hair loss, stabilizing hair loss and producing modest regrowth in the vertex scalp.

Dutasteride inhibits both type 1 and type 2 5-alpha-reductase, achieving greater overall dihydrotestosterone suppression than finasteride, though this does not translate into meaningfully superior benign prostatic hyperplasia outcomes in head-to-head comparisons. Both agents are used for benign prostatic hyperplasia; finasteride is also approved for hair loss.

Both finasteride and dutasteride reduce prostate-specific antigen by approximately 50% within 3 to 6 months. This is a pharmacodynamic effect on prostate-specific antigen gene transcription, not a sign of prostate cancer suppression. The measured prostate-specific antigen must be doubled to estimate the true value in men on these agents — failure to do so will cause a clinically significant prostate-specific antigen rise (indicating possible prostate cancer) to be missed. Any upward trend in prostate-specific antigen despite 5-alpha-reductase inhibitor therapy requires investigation regardless of the absolute value.

Both agents are absolutely contraindicated in women who are pregnant or may become pregnant. Dihydrotestosterone is required for male fetal external genital virilization; exposure during pregnancy causes feminization of a male fetus. Women of childbearing potential must not handle crushed tablets. Dutasteride is present in semen for up to 6 months after stopping, requiring precautions for partners who are or may become pregnant.

Sexual adverse effects occur in approximately 5 to 9% of patients: decreased libido, erectile dysfunction, reduced ejaculate volume, and gynecomastia. These result from reduced dihydrotestosterone-mediated peripheral androgenic signaling and a shift in the androgen-to-estrogen ratio. Post-finasteride syndrome — persistent sexual, neurological, and psychological symptoms after stopping the drug — is a debated clinical entity reported by some patients that warrants mention before prescribing.

Anabolic-androgenic steroids are synthetic testosterone derivatives engineered to enhance anabolic effects (muscle protein synthesis, bone density) relative to androgenic effects. No available agent fully separates these properties because both are mediated through the same androgen receptor. Non-medical doses used for performance enhancement are typically 10 to 100 times higher than therapeutic testosterone replacement therapy doses.

The primary pharmacokinetic classification distinguishes oral from injectable forms. Oral anabolic-androgenic steroids (including stanozolol, oxandrolone, oxymetholone) require C17-alpha-alkylation to resist first-pass hepatic degradation — a chemical modification that also blocks the liver's normal mechanisms for conjugating and excreting the steroid. The result is intrahepatic cholestasis, peliosis hepatis (blood-filled cysts in liver parenchyma), and with prolonged use, hepatocellular adenoma and hepatocellular carcinoma. Injectable anabolic-androgenic steroids (nandrolone decanoate and others) undergo normal ester cleavage and hepatic metabolism after absorption — they avoid this hepatotoxicity while retaining full systemic androgenic activity.

Cardiovascular toxicity is the most life-threatening consequence of anabolic-androgenic steroid misuse and the leading cause of premature death in users. The principal mechanisms are: left ventricular hypertrophy from cardiomyocyte androgen receptor stimulation, producing pathological concentric hypertrophy with reduced diastolic compliance and predisposition to arrhythmia; a markedly adverse lipid profile (high-density lipoprotein cholesterol substantially reduced, low-density lipoprotein cholesterol increased); accelerated coronary artery disease with premature atherosclerotic calcification; and myocardial fibrosis. Erythrocytosis from supraphysiological testosterone further elevates thrombotic risk.

Exogenous anabolic-androgenic steroids suppress gonadotropin secretion through negative feedback, producing testicular atrophy and azoospermia in men, and menstrual disruption and virilization in women. Recovery of the hypothalamic-pituitary-gonadal axis and spermatogenesis after stopping can take 6 to 24 months and may be incomplete with prolonged use. Human chorionic gonadotropin and selective estrogen receptor modulators (clomiphene, tamoxifen) are used in the anabolic-androgenic steroid-using community to stimulate hypothalamic-pituitary-gonadal axis recovery after cessation.

Gynecomastia in male users occurs because supraphysiological androgens drive increased aromatization to estradiol. Additional adverse effects include acne (sebaceous gland androgen receptor stimulation), tendon rupture (muscle mass outpacing tendon tensile strength), psychiatric effects during use (aggression, hypomania, impulsivity), and withdrawal-related dysphoria and hypogonadal symptoms between cycles.