5-Alpha-Reductase Inhibitors: Mechanism, Clinical Uses, and Side Effects

In pharmacology and clinical medicine, 5-alpha-reductase inhibitors (5-ARIs) have a variety of life saving uses. These drugs have been widely used to manage conditions  such as benign prostatic hyperplasia (BPH) and male pattern baldness (androgenetic alopecia) which are linked to the androgen hormone dihydrotestosterone (DHT).

What is 5-Alpha-Reductase?

To understand these drugs, we first need to understand the enzyme they target (5-Alpha-Reductase)

5-alpha-reductase is an enzyme that is responsible for converting testosterone into dihydrotestosterone (DHT) its more potent form.  DHT has higher binding affinity than testosterone and has significant effects on tissues like the prostate, hair follicles, and skin.

There are three known isoenzymes of 5-Alpha-Reductase:

1. Type I (SRD5A1): this isoenzyme is Found mainly in the skin, liver, and sebaceous glands.
2. Type II (SRD5A2): this isoenzyme catalyzes the conversion of testosterone into dihydrotestosterone (DHT) and other steroids in the prostate, seminal vesicles, epididymis, and hair follicles.
3. Type III (SRD5A3): Less understood, with emerging roles in cancer biology.

Clinical Significance of DHT

• In the prostate, excess DHT contributes to prostate enlargement (BPH).
• In the scalp, DHT shrinks hair follicles, causing male pattern baldness.
• In other tissues, DHT contributes to acne and sebaceous gland activity.

What are 5-alpha-reductase inhibitors?

Five-alpha-reductase inhibitors are a class of medications that inhibit the enzyme that converts testosterone into dihydrotestosterone during its action. This leads to an increase in testosterone levels and a decrease in dihydrotestosterone levels. An excess of dihydrotestosterone has been associated with benign prostatic hyperplasia (BPH) and prostate cancer. In comparison to men who have a substantial quantity of hair, the scalp of men with androgenetic alopecia (male-pattern baldness) contains elevated levels of dihydrotestosterone and miniaturized hair follicles.

Finasteride and dutasteride are the two 5-alpha-reductase inhibitors that are currently available. There are two variants of the 5-alpha-reductase enzyme: type 1 and type 2. Finasteride exclusively inhibits type 2, while dutasteride inhibits both. Despite the fact that dutasteride offers a more substantial suppression of dihydrotestosterone, it is uncertain whether this results in a clinically significant advantage. The rates of adverse effects, including impotence, decreased libido, ejaculation disorder, and gynecomastia, are comparable.

5-alpha-reductase inhibitors may be used in the treatment of benign prostatic hyperplasia (enlarged prostate organ) and male-pattern hair loss (androgenic alopecia). They are not approved for the prevention of prostate cancer.

5-Alpha-Reductase Inhibitors Mechanism of Action of

5-ARIs inhibit 5-alpha-reductase enzymes, which prevents testosterone from being converted to DHT.

By reducing DHT levels:

• The prostate shrinks and urinary flow improves in BPH.
• Hair follicle miniaturization slows, and hair regrowth may occur in androgenetic alopecia.

Pharmacological Examples

• Finasteride: is an example of 5-Alpha-Reductase Inhibitors that Selectively inhibits type II 5-alpha-reductase. Its Brand names include: Proscar (5 mg, for BPH), Propecia (1 mg, for hair loss).

• Dosing is usually, 5 mg daily for BPH, and 1 mg daily for androgenetic alopecia.

• Dutasteride is more versatile and can Inhibit both type I and type II isoenzymes, leading to better suppression of DHT (over 90%). A good Brand name is Avodart (0.5 mg).
• Dosing is usually 0.5 mg daily (BPH). Sometimes prescribed off-label for alopecia.

Clinical Uses of 5-Alpha-Reductase Inhibitors

1. Benign Prostatic Hyperplasia (BPH)

• BPH is a common condition in older men, that leads to urinary symptoms (weak stream, hesitancy, nocturia). Usually due to enlarged prostates (>40 mL volume). 5-ARIs help to shrink the prostate gland by reducing DHT-driven growth. They are Often combined with alpha-1 blockers (e.g., tamsulosin) for faster relief.

2. Androgenetic Alopecia (Male Pattern Baldness)

• Finasteride at 1 mg daily reduces scalp DHT and helps slow hair loss. For better results patients should started early, the results may take 3–6 months.

Side Effects and Safety Profile

Like any medication, 5-ARIs come with risks.

Common Side Effects

• Can lead to Reduced libido.
• Can cause Erectile dysfunction.
• Decreased ejaculate volume.

Less Common Side Effects

• Gynecomastia (breast tenderness or enlargement).
• Depression and mood changes (reported but debated).
• Infertility (due to lowered DHT).

Finasteride vs Dutasteride: Which is Better?

• For BPH: Both medications are effective; dutasteride may be better for very large prostates.
• For hair loss: Finasteride is FDA-approved, dutasteride is off-label but often more potent.

Key Takeaways

• 5-alpha-reductase inhibitors reduce DHT, targeting conditions like BPH and androgenetic alopecia.
• Finasteride is selective for type II enzyme; dutasteride blocks both type I and II.
• Both drugs improve urinary symptoms and reduce prostate size, but take months to show results.
• Side effects are mostly sexual in nature, with additional precautions for PSA monitoring and teratogenic risk.
• These drugs remain a cornerstone in the pharmacological management of prostate disorders and male hair loss.

References & Further Reading

1. American Urological Association (AUA) Guidelines – Management of BPH.
2. European Association of Urology (EAU) Guidelines – Male LUTS.
3. Goodman & Gilman’s The Pharmacological Basis of Therapeutics.
4. FDA Drug Monographs: Finasteride, Dutasteride.
5. McConnell JD, et al. “The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia.” NEJM, 2003.