Dutasteride: medical indications and authorised uses

Dutasteride is one of the main drugs for the long-term treatment of benign prostatic hyperplasia. At the same time, it is increasingly being discussed as a remedy against baldness and even trying to use it outside of medical indications. The editors analysed what the drug is registered for, what evidence is behind each indication, and how the treatment is monitored.

Registered indications

Dutasteride is a prescription drug, and the list of its official indications is determined by regulatory bodies based on clinical studies. In the guidelines of the FDA and European regulators, the main indication is the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate — both to relieve symptoms and to reduce the risk of acute urinary retention and surgery.

The second registered use is combination therapy with the alpha-blocker tamsulosin. For convenience, there is a fixed combination of both substances in one capsule. This scheme combines the rapid relaxation of smooth muscles of the bladder neck (tamsulosin effect) with a slow decrease in the volume of the gland itself (dutasteride effect).

In some countries, in particular in South Korea and Japan, dutasteride 0.5 mg is also registered for the treatment of androgenetic alopecia in men. In the US and most EU countries, this indication is not included in the instructions, and such use is considered "off-label", which can only be decided by a doctor.

• BPH with enlarged prostate — monotherapy.
• BPH — in combination with tamsulosin.
• Androgenic alopecia in men — only in certain countries.

What is not in the indications is also important: dutasteride is not registered for the prevention of prostate cancer, it is not used in women and children, and it is also not prescribed as a remedy for acne or to "correct" the hormonal background in athletes.

Benign prostatic hyperplasia: evidence base

BPH is an age-related enlargement of the prostate gland, which is found in most men over the years. The growth of the gland depends on DHT, so a decrease in its formation reduces tissue proliferation. In practice, this is manifested by a gradual decrease in the volume of the prostate and the weakening of symptoms: frequent and difficult urination, weak stream, nocturia.

The key evidence base was formed by three randomised, placebo-controlled trials of ARIA, the pooled results of which were published by Roehrborn et al (2002). Over two years of treatment, dutasteride reduced prostate volume by about a quarter, improved IPSS symptoms, and roughly halved the risk of acute urinary retention and the need for surgery compared with placebo.

The CombAT study (Roehrborn et al., 2010) lasted four years and compared dutasteride, tamsulosin, and their combination in men with enlarged prostate. The combination provided the best symptom control and significantly reduced the risk of urinary retention and surgery compared to tamsulosin alone. Similar results were previously obtained for finasteride in the MTOPS study (McConnell et al., 2003).

The effect of 5-alpha-reductase inhibitors develops slowly: the first relief of symptoms is possible after several months, and it is recommended to evaluate the treatment result no earlier than after 6 months. Therefore, patients are informed in advance that the absence of a quick result does not mean ineffectiveness.

To whom and under what conditions it is prescribed

The American Urological Association clinical guideline (Lerner et al., 2021) recommends 5-alpha-reductase inhibitors in patients with lower urinary tract symptoms associated with prostate enlargement—as evidenced by ultrasound, digital rectal examination, or elevated PSA levels. In men without an enlarged gland, these drugs are ineffective.

Before prescribing, the urologist conducts an examination to exclude other causes of symptoms — infection, prostate cancer, urethral stricture, neurogenic disorders. The initial level of PSA is evaluated, because its subsequent decrease against the background of treatment must be correctly interpreted.

The standard dose for BPH indicated in the instructions is 0.5 mg once a day regardless of food intake; the capsule is swallowed whole, without chewing, because the contents can irritate the mucous membrane of the oropharynx. Dose correction for elderly patients is not provided, but the drug is contraindicated in severe liver failure.

BPH treatment is usually long-term. After discontinuation of the drug, the prostate volume and symptoms gradually return to the initial level, so the decision on the duration of therapy is made together with the urologist.

Androgenic alopecia: off-label use

Because DHT plays a key role in the miniaturization of hair follicles, dutasteride has also been studied as a treatment for male pattern baldness. In a randomised study by Olsen et al (2006), dutasteride 2.5 mg was superior to finasteride 5 mg in hair growth over 24 weeks.

Later, Gubelin Harcha et al (2014) compared multiple doses of dutasteride with finasteride 1 mg and placebo in a large phase III trial. Dutasteride 0.5 mg increased the number and thickness of hair more than finasteride with a similar incidence of side effects. These data became the basis for the registration of the drug for alopecia in Korea and Japan.

In the United States and most of Europe, dermatologists may consider dutasteride for alopecia off-label, usually in patients in whom finasteride has not been effective enough. The long half-life here has both pluses and minuses: skipping a dose does not affect the effect as much, but in case of unwanted reactions, the drug is excreted for months.

Other methods of administration are also being studied, such as mesotherapeutic injections into the scalp, but the evidence base for them is still much weaker than for the oral form.

What dutasteride does not treat

Of great interest was the REDUCE study (Andriole et al., 2010), in which dutasteride reduced the incidence of prostate cancer in men at increased risk over four years. However, the decrease was mainly in low-grade tumors, while tumors with a high Gleason score were more common in the drug group. Because of this, the FDA did not approve dutasteride for the prevention of prostate cancer and added a corresponding warning to the instructions.

The drug is not prescribed for women: it is contraindicated for women of reproductive age due to the risk to the male fetus, and the effectiveness of hirsutism or alopecia in women has not been established in registration studies. Any use in women is possible only within the limits of specialized practice under strict control of contraception.

Dutasteride is also not a treatment for prostatitis, does not have a positive effect on erectile function, and does not increase testosterone enough to be clinically relevant. The use of the drug for non-medical purposes, in particular in sports, has no evidence base of benefit.

Finally, dutasteride does not replace surgical treatment in patients with complications of BPH — recurrent urinary retention, bladder stones, deterioration of kidney function. In such cases, the urologist makes the decision based on the results of the examination.

Editorial conclusions

The official place of dutasteride in medicine is the treatment of benign prostatic hyperplasia with an enlarged gland, alone or in combination with tamsulosin. The evidence base for this application is high and is based on the large randomised trials ARIA and CombAT.

For androgenetic alopecia, the drug is registered only in certain countries; in other situations, it is an off-label use that requires a doctor's decision.

Dutasteride is not approved for the prevention of prostate cancer, is contraindicated in women who may become pregnant, and requires proper interpretation of PSA during treatment.

We also recommend our materials "Dutasteride: mechanism of action", "Dutasteride contraindications and interactions" and "Effect of Dutasteride on lipid profile and bone tissue".

List of used literature

1. Avodart (dutasteride) soft gelatin capsules. Prescribing information. GlaxoSmithKline; U.S. Food and Drug Administration.
2. Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology. 2002;60(3):434–441.
3. Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123–131.
4. McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349(25):2387–2398.
5. Lerner LB, McVary KT, Barry MJ, et al. Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA guideline part I — initial work-up and medical management. J Urol. 2021;206(4):806–817.
6. Olsen EA, Hordinsky M, Whiting D, et al. The importance of dual 5α-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride. J Am Acad Dermatol. 2006;55(6):1014–1023.
7. Gubelin Harcha W, Barboza Martínez J, Tsai TF, et al. A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia. J Am Acad Dermatol. 2014;70(3):489–498.
8. Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362(13):1192–1202.