Endocrinology & Urology & Dermatology
Dihydrotestosterone (DHT)
Dihydrotestosterone (DHT) is a steroidal androgen derived from testosterone, produced by the action of the enzyme 5-alpha-reductase (5-AR), which catalyzes the irreversible reduction of the 4,5 double bond of the A nucleus of testosterone → DHT. DHT is the most biologically active androgen in the human body: its affinity for the androgen receptor (AR) is 2 to 10 times greater than that of testosterone, and its dissociation from the receptor is 5 times slower (half-life of the DHT-AR complex of 5 hours vs. 1 hour for testosterone-AR), conferring a markedly amplified androgenic effect at equal concentration. DHT cannot be aromatized to oestradiol (unlike testosterone) - it therefore exerts a pure androgenic effect, with no concomitant oestrogenic effect. There are two isoforms of 5-alpha-reductase with distinct tissue distributions: 5-AR type 1 (SRD5A1 - expressed in liver, skin, scalp, sebaceous glands, adrenals) and 5-AR type 2 (SRD5A2 - expressed mainly in prostate, seminal vesicles, epididymis, genital skin, scalp hair follicles) - the latter is the main target of 5-AR inhibitors used in therapeutics. DHT is produced mainly in peripheral target tissues (prostate, skin, scalp) from circulating testosterone (intra-tissue conversion) - its plasma concentration therefore reflects only a fraction of local andrological activity. The physiological roles of DHT are crucial: male sexual differentiation in utero (virilization of the external genitalia - scrotum, penis, prostatic urethra - from the 8th week), male puberty (maturation of the prostate, development of body and facial hair, acne), and maintenance of prostate function in adulthood. In pathology, DHT is involved in three major clinical conditions: male and female androgenetic alopecia, benign prostatic hyperplasia (BPH) and acne/hirsutism - all three improved by 5-AR inhibitors (finasteride, dutasteride).
Reference Values and Pre-analytical Conditions
- Reference values (LC-MS/MS method recommended — immunoassay less precise at low concentrations): adult male (18–50 years): 1.03–2.92 nmol/L (30–85 ng/dL); male >50 years: 0.69–2.51 nmol/L (20–73 ng/dL); premenopausal female: 0.14–0.76 nmol/L (4–22 ng/dL); postmenopausal female: 0.10–0.55 nmol/L (3–16 ng/dL); values vary by laboratory and method — always interpret according to the reference intervals of the laboratory used
- Factors modifying plasma DHT: 5-AR inhibitors (finasteride reduces DHT by 65–70 %; dutasteride by 90–95 %); exogenous androgens (therapeutic testosterone — increases DHT by 15–25 pending on route of administration — topical gel increases DHT more than IM injection); pregnancy (slight increase); liver failure (reduced hepatic conversion of T to DHT)
- Pre-analytical conditions: morning collection (modest circadian variations for DHT – less pronounced than for testosterone); dry tube or gel tube; rapid centrifugation; assay not available in all laboratories – often sent to a reference laboratory; not reimbursed by the RAMQ in routine – specific indications required
- Dosage Indication: DHT is rarely needed in routine practice — total testosterone and SHBG (calculated free testosterone) are sufficient for the majority of androgen assessments; DHT testing is specifically useful in: the workup of ambiguous genitalia (5-AR2 deficiency — DSD — disorder of sex development), monitoring under 5-AR inhibitors, the workup of refractory hirsutism, and the investigation of severe androgenetic alopecia in women.
Pathologies related to DHT and 5-alpha-reductase inhibitors
| Condition / Pathology | Role of DHT and Pathophysiology | 5-AR Targeting and Results |
|---|---|---|
| Male androgenetic alopecia (MAA) Common baldness — Hamilton-Norwood |
DHT is the central hormonal mediator of AGA: 5α-reductase type 2 is highly expressed in the hair follicles of the frontal and vertex regions (not the occiput—explaining the preserved character of the occipital crown) → local conversion of testosterone to DHT → activation of follicular ARs → progressive miniaturization of follicles (reduction in hair shaft diameter, shortening of anagen phase, lengthening of telogen phase) → non-pigmented vellus hairs replacing terminal hairs → progressive baldness; subjects with congenital 5α-reductase 2 deficiency do not develop baldness (foundational natural observation—Imperato-McGinley 1974, Dominican); Hamilton-Norwood (HN I–VII) classification for men | Finasteride (Propecia — 1 mg/day orally): selective 5-AR2 inhibitor → reduction of scalp DHT by 60–70 %→ slowing of follicular miniaturization; efficacy: stabilization of hair loss in 80–90 %of men + moderate regrowth in 40–65 %(PLESS 1998, Kaufman 1998 trials); time to response: minimum 3–6 months — maximum efficacy at 2 years; lifelong treatment (discontinuation → return of baldness in 9–12 months); side effects: erectile dysfunction (1–2 % ), decreased libido (1–2 % ), gynecomastia (0.4 % ), depression (controversial reports); post-finasteride syndrome (persistence of SEs after discontinuation — rare but documented); reduces PSA by ~50 % (take into account during prostate cancer screening — double the PSA value) |
| Female pattern hair loss Ludwig I–III — vertex rarefaction |
Mechanism analogous to AGA but more complex in women: local DHT plays a role, but aromatase (conversion of testosterone to estradiol — expressed in occipital follicles — occipital «protection» explaining the different pattern of FPHL) and prolactin would also modulate follicular miniaturization; free testosterone is often normal in idiopathic FPHL — local DHT can be elevated with normal circulating testosterone; Ludwig classification (I–III — diffuse thinning of the vertex with preservation of the frontal hairline — different from AGA) | Topical minoxidil 2–5 % (Rogaine — 1st-line women); spironolactone 50–200 mg/day (antiandrogen — RAMQ reimbursed); finasteride is contraindicated in women of childbearing potential (teratogen — ambiguous genitalia in male fetus — pregnancy category X); finasteride 2.5–5 mg/day used off-label in postmenopausal women on effective contraception; dutasteride (Avodart) off-label in severe forms in postmenopausal women |
| Benign prostatic hyperplasia (BPH) Androgen-dependent stromal-glandular proliferation |
The prostate is the tissue richest in 5-AR2—DHT is present there in concentrations 5–10× higher than testosterone (intraprostatic DHT concentration: 2–5 ng/g of tissue) → AR activation → stromal and epithelial cell proliferation → increased prostate volume → cervico-urethral obstruction + bladder hyperactivity → male lower urinary tract symptoms (LUTS): dysuria, nocturnal pollakiuria, weak stream, post-void residual, incomplete emptying sensation; men with 5-AR2 deficiency do not have BPH (foundational observation from the same Dominican cohort); total testosterone levels are normal in BPH—it is the local conversion to DHT that is pathogenic. | Finasteride (Proscar — 5 mg/day) or dutasteride (Avodart — 0.5 mg/day — dual 5-AR1 + 5-AR2 inhibitor): reduction of prostate volume by 20–30 % in 6–12 months (PLESS trials — McConnell 1998; CombAT — Roehrborn 2010) → improvement of LUTS (IPSS score) + reduction in risk of acute urinary retention −57 % + reduction in risk of prostate surgery −55 %; maximum efficacy on large prostates (PSA >1.4 ng/mL, volume >30–40 cc); often combined with alpha-blockers (tamsulosin, alfuzosin) for a rapid complementary effect on symptoms (MTOPS study — McConnell 2003); reduction of PSA by 40–50 % (double the value for prostate cancer screening interpretation) |
| Prostate Cancer — Prevention Controversial role of 5-AR inhibitors |
DHT is the main intraprostatic androgen stimulating the growth of normal and cancerous prostate cells (AR pathway — activation of PSA, TMPRSS2, FOXA1 genes); DHT plays a role in tumor progression (hormone-sensitive cancer → hormone-resistant via AR amplification and mutations); the PCPT study (Prostate Cancer Prevention Trial — Thompson 2003 — finasteride vs. placebo) shows a 24.8% reduction in prostate cancer risk % in the finasteride group — but an increase in the subgroup of high-grade cancers (Gleason 7–10) which is controversial (likely a detection bias related to the reduction in prostate volume). | 5-AR inhibitors are not approved as prostate cancer chemopreventive agents in Canada (despite the results of the PCPT and REDUCE trial with dutasteride) due to high-grade cancer concerns; in the context of advanced castration-resistant prostate cancer (CRPC): enzalutamide, apalutamide, darolutamide (next-generation AR inhibitors) + docetaxel/cabazitaxel ± abiraterone (CYP17A1 inhibitor—reduction of adrenal and intratumoral androgen synthesis). |
| Hirsutism and androgenic acne Excessive peripheral DHT activity |
Type 1 5-AR (expressed in the skin and sebaceous glands) converts testosterone and androstenedione locally to DHT → activation of pilosebaceous follicle ARs → excess terminal hair growth in androgen-dependent areas (upper lip, chin, cheeks, chest, abdomen, inner thighs) + sebaceous hypersecretion → inflammatory acne; causes of hirsutism include PCOS (ovarian hyperandrogenism + insulin resistance), congenital adrenal hyperplasia (NC CAH — CYP21A2), virilizing tumors (DHEA-S >700 µg/dL), acromegaly, and androgenic medications (anabolics, valproate) | Spironolactone 50–200 mg/day (anti-AR + moderate 5-AR1 inhibition — 1st line hirsutism in Canada — SOGC 2021); combined oral contraceptives (reduced free testosterone via increased SHBG); cyproterone acetate (Diane-35 — progestin antiandrogen — indicated for androgenic acne + hirsutism in Canada); finasteride 2.5–5 mg/day off-label (5-AR inhibitor — documented efficacy in hirsutism — CI women of childbearing potential without effective contraception); 2.5–5 mg/day off-label (5-AR inhibitor — documented efficacy in hirsutism — CI women of childbearing potential without effective contraception); eflornithine (Vaniqa — ornithine decarboxylase inhibitor — topical — slows facial hair growth) |
| 5-alpha-reductase type 2 deficiency (DSD) Disorders of sex development (DSD — 46,XY) |
Loss-of-function mutation of the SRD5A2 gene (autosomal recessive) → absence of testosterone to DHT conversion in genital tissues → incomplete virilization of external genitalia in 46,XY individuals despite normal testosterone: micropenis, perineoscrotal hypospadias, cryptorchidism, blind-ending urogenital sinus → female or ambiguous phenotype at birth → often raised as girls in traditional societies; at puberty, increased testosterone (partial conversion by 5-AR1 + direct action of T on AR) leads to progressive virilization (deepening of the voice, phallic growth, muscle development) → phenomenon of «sex change at puberty» (described in the Dominican cohort by Imperato-McGinley 1974, in the Guevedoces villages — Salinas, Dominican Republic); internal male genitalia are normal (epididymis, vas deferens, seminal vesicles — not DHT-dependent); no BPH, no male pattern baldness, no acne | Biological diagnosis: elevated testosterone/DHT ratio (>20–30 after hCG stimulation in children, or basal in adults) + genetic confirmation (SRD5A2 sequencing); multidisciplinary management (pediatric endocrinology, urology, psychology) — sex assignment and gender reassignment surgery décision individualized according to age, virilization, and patient/family desire; virilization at puberty may allow for satisfactory male integration without surgery in some cases |
ℹ️
Visit finasteride reduces PSA by 40-50 % and the dutasteride from 50-60 % after 6 months of treatment. This reduction is important for the interpretation of prostate cancer screening: in a patient treated with a 5-AR inhibitor, the measured PSA value should be multiplied by 2 to obtain the «corrected» value equivalent to that of an untreated patient. A PSA measured at 2.0 ng/mL while on finasteride corresponds to a true PSA of approximately 4.0 ng/mL. Failure to make this correction leads to underdetection of prostate cancer. Furthermore, finasteride and dutasteride can mask a PSA elevation related to developing prostate cancer—any increase in PSA while taking a 5-AR inhibitor, even if the absolute values remain within normal limits, should be considered a warning sign and warrant urological evaluation.
Acute urinary retention under 5-AR inhibitor
5-AR inhibitors (finasteride, dutasteride) gradually reduce prostate volume and the long-term risk of acute urinary retention (AUR) — but during the first few weeks of treatment, or upon abrupt discontinuation, an episode of AUR remains possible in patients with BPH. Compose the 911 or go immediately to the emergency room if a patient on finasteride or dutasteride presents with a Complete inability to urinate accompanied by intense hypogastric pain Emergency urine catheterization required.
Also remind patients on finasteride to teratogenicity Pregnant or potentially pregnant women should never handle crushed or broken finasteride tablets (skin absorption → risk of sexual ambiguity in male fetuses).
Consult at Clinique Omicron
The doctors at Clinique Omicron perform a complete androgen assessment (total and free testosterone, SHBG, DHT if specifically indicated, LH, FSH, prolactin), prescribe and monitor treatments with 5-AR inhibitors (finasteride, dutasteride) for male androgenetic alopecia and BPH, and manage assessments for hirsutism and female hyperandrogenism. Consultations are available at our service points in Quebec as well as via telemedicine. To make an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not substitute for the advice of a qualified healthcare professional. The dosage of DHT and the indication of 5-alpha-reductase inhibitors should be determined by a physician.
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