What is Dutasteride?

Dutasteride is a 5-alpha-reductase inhibitor drug similar to the finasteride. Dutasteride or Avodart is a dual inhibitor of both type I & type II 5-alpha-reductases. It inhibits the conversion of testosterone to dihydrotestosterone which is a key mediator of male pattern hair loss. Dutasteride is commercially available as ‘Avodart’ and is manufactured by the Glaxo-Smith-Kline Pharmaceuticals.

Originally dutasteride 0.5mg or Avodart 0.5mg is approved for the treatment of the BPH (symptomatic benign prostate hyperplasia. Dutasteride is not approved by FDA for hair loss but it is available as ‘off-label’ hair loss treatment for men at a dose of 0.5mg. However, Dutasteride is approved for hair loss in South Korea after clinical trials on Korean population. It is also approved in US, Japan and is not approved in Europe yet.

Why Dutasteride for hair loss should be used?

Scientific researchers have discovered that men who are suffering from either male pattern hair loss or benign prostatic hyperplasia, have an increased level of the DHT (dihydrotestosterone) in their body. The hormone testosterone is converted into the dihydrotestosterone after the enzymatic action of 5-alpha reductase. DHT causes the hair follicles to shrink resulting in hair fall. Dutasteride acts on the DHT hormone and promotes the hair growth by increasing the number of hair follicles.

How Dutasteride stops hair loss?

Dutasteride is the first dual inhibitor of the reductase enzymes. Its dual mechanism of action results in the DHT synthesis and catalytic activity of 5-alpha reductase type 1&2 enzymes. This dual action leads to the complete suppression of the serum DHT levels more than 90%. When this transmission of DHT to the hair follicles is stopped, then there is no miniaturization of the hair follicles. When there is no transmission of the DHT to the hair follicles, this results in the elongated anagen phase (growing phase) and faster hair growth.

Dutasteride Vs. Finasteride

Both Finasteride & Dutasteride are 5 alpha reductase inhibitors but dutasteride reduces the larger amount of dihydrotestosterone levels than finasteride. Less DHT levels mean more chances of reduction in hair loss but the reduction in the DHT levels can cause other hormonal imbalances or physiological changes in the body. Unlike finasteride, dutasteride prevents both types of 5 alpha reductase enzymes from undergoing a metabolic process. Finasteride is an old drug used for the treatment of male pattern baldness while dutasteride is relatively a new drug for hair loss and is still under clinical trials.

Comparison of Dutasteride and Finasteride

Clinical Trials on Dutasteride:

Dutasteride resulted in scalp and serum dihydrotestosterone levels to decrease but increases the testosterone levels in a dose dependent manner. Dutasteride can decreases serum DHT levels by more than 90% whereas finasteride can decreases serum DHT levels by 70%.

Medical Uses of Dutasteride:

• Prostate enlargement: Dutasteride is primarily used for the treatment of benign prostatic hyperplasia (BPH) or also known as an “enlarged prostate”. Dutasteride has an approval from Food and Drug Administration (FDA) in the U.S. for the treatment of BPH.
• Prostate cancer: According to a clinical review in 2010, a 25–26% reduction has been noticed in the risk of developing prostate cancer with 5α-reductase inhibitor chemoprevention.  Although there is insufficient data to determine if they have an effect on the overall risk of death from prostate cancer.
• Scalp hair loss: In Japan and South Korea, Dutasteride has been approved for the treatment of male androgenetic alopecia (R). Dutasteride has also been used off-label for the treatment of female pattern hair loss.
• Transgender women: Dutasteride is also used sometimes as one of the component of hormone therapy in transgender women. It is given in combination with an estrogen or other anti-androgens like spironolactone. It may also be used for treating the scalp hair loss or in people who can’t tolerate spironolactone.

Dosage of Dutasteride:

The off-label recommended dosage of dutasteride for hair loss if 0.5mg  per day. It has been clinically proven in some trials that dutasteride 0.5mg per day improves more hair growth in men to a greater extent than finasteride at 2.5mg per day.

Missed  Dosage:

If you miss dose of dutasteride, then no need to worry. You can skip this dosage and continue to your next dosage as recommended by the doctor. Do not take excessive dosage or double dose of dutasteride to balance your missed dose.

Overdose of Dutasteride:

In case of over dosage of dutasteride, if you start feeling any discomfort or side effects, talk to your doctor or rush to the clinic immediately.

Dutasteride Side Effects:

The side effects of dutasteride is similar to the finasteride. Dutasteride, oral 5-alpha reductase inhibitor do not reduces the DHT levels in the target area only as they reduces DHT levels systematically. It reduces the hormone levels where DHT expression is observed.

• As finasteride inhibits the DHT, ratio of estrogen to androgen alters which can increase the risk of gynecomastia in males.
• Impotence
• Adverse effects include headache and gastrointestinal discomfort
• The FDA has added a warning to dutasteride about an increased risk of high-grade prostate cancer. But there is no positive, negative or neutral changes to the potential risk of developing prostate cancer with dutasteride has been established till now.

Interactions of Dutasteride:

5 alpha-reductase inhibitors like Dutasteride, can also stop the formation of the neurosteroid metabolites like allopregnanolone from progesterone. As a result of which it may reduce or even block the sedative, anticonvulsant, anxiolytic and different other effects of progesterone, particularly in the case of oral progesterone.

Contraindications of Dutasteride:

Women who are pregnant or are planning of pregnancy, should not take dutasteride. Dutasteride can result in birth defects, specifically ambiguous genitalia and under-masculinization, in male fetuses. This is because of its anti-androgenic activity and is mostly observed in the case of 5 alpha-reductase deficiency. If you are taking dutasteride, do not donate the blood at least for 6 months after your treatment has stopped. In the case of children or other people having hypersensitivity like serious skin reactions or angioedema, to dutasteride, should not take it.

Anatomy and Structure of Dutasteride:

Dutasteride is a synthetically derived androstane steroid and a 4-azasteroid. It is chemically known as N- [2,5-bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide. It is an analogue of finasteride in which the tert-butyl amide moiety has been replaced with a 2,5-bis(tri-fluoromethyl)phenyl group.

Clinical Data:

Dutasteride is a white to pale yellow powder with a melting point of 242° to 250°C. It is soluble in ethanol (44 mg/ml), methanol (64 mg/ml), and polyethylene glycol 400 (3 mg/ml), but it is insoluble in water.