GOND Module 5 Infographic

Chapter 31 · Module 5

Androgen Pharmacology

Testosterone · 5-Alpha-Reductase Inhibitors · Anti-Androgens · Anabolic Steroids

Testosterone vs. Dihydrotestosterone — Tissue-Selective Actions

Testosterone — Primary Actions

Muscle, Bone, Erythropoiesis, Libido

Skeletal muscle protein synthesis
Bone mineral density maintenance
Erythropoiesis stimulation
Libido and mood
Aromatized to estradiol in adipose tissue → bone + gonadotropin feedback
Excess aromatization → gynecomastia, fluid retention

Dihydrotestosterone (via 5-alpha-reductase)

Prostate, Skin, Scalp, External Genitalia

Prostate growth (benign prostatic hyperplasia)
Male-pattern hair loss (androgenetic alopecia)
Beard and body hair development
External genital virilization (fetal)
Sebaceous gland activity → acne
3–5x greater androgen receptor affinity than testosterone

5-Alpha-Reductase Inhibitors

Drug	Isoform Selectivity	Approved Uses	PSA Effect	Key Safety
Finasteride	Type 2 selective	Benign prostatic hyperplasia (5 mg), hair loss (1 mg)	Reduces by ~50% — must double measured value	Sexual dysfunction; teratogenic (male fetus); Post-Finasteride Syndrome
Dutasteride	Dual type 1 + 2	Benign prostatic hyperplasia	Reduces by ~50% — must double measured value	Same sexual effects; semen contains drug up to 6 months; teratogenic

Anti-Androgens Compared

Drug	Mechanism	Clinical Use	Key Adverse Effects / Notes
Spironolactone	MR antagonist + AR antagonist (high doses)	PCOS, hirsutism, gender-affirming (feminizing)	Hyperkalemia (monitor K+ with ACE-I/ARBs); teratogenic (male fetus); menstrual irregularity
Bicalutamide	High-affinity AR antagonist; no HPG suppression	Prostate cancer (with GnRH agent); hirsutism	Hepatotoxicity (monitor LFTs); gynecomastia; testosterone rises 1.5x (LH feedback intact)
Enzalutamide	2nd-gen AR antagonist; inhibits nuclear translocation + DNA binding	Castration-resistant prostate cancer, mCSPC	Seizure risk (~0.5%/yr, GABA-A modulation); AR-V7 resistance; fatigue, cognitive effects
Cyproterone acetate	Steroidal AR antagonist + progestin + anti-gonadotropic	Prostate cancer, hirsutism (not US-approved)	Meningioma (dose/duration-dependent); VTE; hepatotoxicity

Anabolic-Androgenic Steroid Toxicity

Oral AAS (C17-Alpha-Alkylated)

Hepatotoxicity — Not Seen with Injectables

C17-alpha methyl group blocks hepatic oxidation at C17-beta hydroxyl
Steroid accumulates in hepatocytes → cholestasis
Progression: cholestasis → peliosis hepatis → adenoma → carcinoma
Injectable AAS (nandrolone decanoate, etc.): undergo normal ester cleavage → no hepatotoxicity

All Routes — Systemic Toxicity

Cardiovascular, Endocrine, Psychiatric

Cardiovascular: LVH (pathological), HDL reduced, accelerated coronary artery disease
Erythrocytosis → VTE risk
HPG suppression → testicular atrophy, azoospermia (recovery 6–24 months)
Gynecomastia (excess aromatization to estradiol)
Acne, tendon rupture
Psychiatric: aggression, hypomania during use; withdrawal dysphoria

Key Rules — Androgen Pharmacology

PSA on 5-alpha-reductase inhibitors: always double the measured value. Testosterone replacement therapy suppresses spermatogenesis: use human chorionic gonadotropin or clomiphene if fertility desired. Oral anabolic-androgenic steroids (C17-alpha-alkylated) cause hepatotoxicity; injectables do not. Enzalutamide carries seizure risk. AR-V7 resistance means switch to taxane chemotherapy.