DHT

**Synthesis:** Testosterone is converted to DHT by 5-alpha-reductase in peripheral target tissues (prostate, skin and hair follicles, external genitalia). Type 2 is the main isoform in the prostate and genital skin. Type 1 is found mainly in skin and liver.

**Potency:** DHT binds the androgen receptor with higher affinity and dissociates more slowly than testosterone. It is therefore a more potent androgen at the receptor level.

**Physiologic roles:** - **Fetal:** DHT differentiates the male external genitalia (penis, scrotum, penile urethra) and the prostate. Testosterone itself drives the Wolffian duct derivatives: epididymis, vas deferens, seminal vesicles (mnemonic: "SEVEN UP" for seminal vesicles, epididymis, vas deferens, ejaculatory duct, and the "UP" for ureter... bud, but this belongs to mesonephric development). Remember: **T = internal, DHT = external and prostate.** - **Puberty and adulthood:** DHT drives prostate growth, facial and body hair, sebaceous gland activity (acne), and temporal/vertex scalp hair loss (androgenetic alopecia). Testosterone drives muscle mass, libido, spermatogenesis, and deepening of the voice.

**Clinical correlates:** - **5-alpha-reductase type 2 deficiency (autosomal recessive):** The 46,XY patient has normal testes, normal testosterone, and normal Müllerian-inhibiting factor (MIF/AMH). Müllerian structures regress, and Wolffian structures develop normally. The external genitalia are ambiguous or appear female at birth, there is no uterus, and the testes are intra-abdominal or in the inguinal canal. At puberty, testosterone rises and virilization occurs (penile growth, voice deepening, muscle mass). This is sometimes called "penis at 12." The lab pattern is a **high testosterone-to-DHT ratio**. The prostate is small and there is little facial hair or acne. Differential: androgen insensitivity syndrome has a normal or high DHT and testosterone, but the receptor is defective, and the patient has a blind-ending vagina and develops breasts at puberty. - **Benign prostatic hyperplasia (BPH):** DHT stimulates prostatic stromal and epithelial growth. Finasteride (type 2 inhibitor) and dutasteride (types 1 and 2) shrink the prostate over months. Alpha-1 blockers (tamsulosin) give faster symptom relief. - **Androgenetic alopecia:** Finasteride (1 mg) is used for male-pattern baldness. - **Adverse effects of 5-alpha-reductase inhibitors:** decreased libido, erectile dysfunction, gynecomastia, decreased PSA (roughly 50% after 6-12 months, so double the measured value when screening for prostate cancer). They are teratogenic (risk of ambiguous genitalia in a male fetus), so pregnant women should not handle crushed tablets. - **Hirsutism in women (e.g., PCOS):** Excess androgen is converted to DHT in the skin and drives terminal hair growth.

**High-yield pearls:** - DHT is not aromatized to estrogen, but testosterone is. - DHT is the major androgen in the prostate, and testosterone is the main circulating androgen. - 5-alpha-reductase deficiency: normal Wolffian internal structures, ambiguous external genitalia, and no Müllerian structures.