Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of a benign prostatic hyperplasia (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefits occur. It is usually taken by mouth.
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The most commonly reported side effects of dutasteride, although rare, include sexual dysfunction. In the largest available study of 6,729 men with BPH, 9% experienced erectile dysfunction (compared to 5.7% treated with a placebo), 3.3% experienced decreased sex drive (vs 1.6% of placebo), and 1.9% had enlarged breasts (vs 1% of placebo). Exposure during pregnancy is specifically contraindicated because antiandrogens such as dutasteride have been shown to interfere with the sexual development of male fetuses.
Medical uses
Benign prostatic hyperplasia and prostate cancer
Dutasteride is used for treating BPH, colloquially known as an "enlarged prostate". It is approved by the Food and Drug Administration (FDA) in the U.S. for this indication. A 2010 Cochrane review found a 25–26% reduction in the risk of developing prostate cancer with 5α-reductase inhibitor chemoprevention.
Scalp hair loss and excessive hair growth
Dutasteride is approved for the treatment of male androgenetic alopecia in South Korea and Japan at a dosage of 0.5 mg per day. The superior effectiveness of dutasteride relative to finasteride for this indication is because the inhibition of 5α-reductase and consequent reduction of dihydrotestosterone (DHT) production within the hair follicles is more complete with dutasteride. Dutasteride is also used off-label in the treatment of female pattern hair loss.
Other 5α-reductase inhibitors such as finasteride (a type 2 inhibitor) have been used off-label to treat excessive hair growth in women with hirsutism. Since dutasteride is an inhibitor of both type 1 and 2 5α-reductases, it could theoretically be a more effective therapy for hirsutism. However, dutasteride is not recommended for this indication due to a lack of supportive clinical evidence and a substantial risk of birth defects in female patients who inadvertently become pregnant.
Transgender hormone therapy
Dutasteride is sometimes used as a component of hormone therapy for transgender women in combination with an estrogen and/or another antiandrogen such as spironolactone. This is due to its antiandrogenic effects similar to what is seen in 5α-reductase deficiency.
Adverse effects
Dutasteride has overall been found to be well tolerated in studies of both men and women, producing minimal side effects. Adverse effects include headache and gastrointestinal discomfort.
The FDA added a black-box warning to dutasteride in 2011 describing an increased risk of high-grade prostate cancer in those who take the drug. No direct mechanistic link between 5α-reductase inhibitors and prostate cancer has been established. This is thought to delay cancer diagnosis so that patients taking 5α-reductase inhibitors present with a higher-grade tumor at the time of diagnosis. The American Urological Association <!-- (AUA) --> advises that increased risk for patients taking these drugs leads to higher prostate cancer-specific and all-cause mortality. The AUA also advises that this effect can be alleviated with more frequent screening and lower PSA cutoffs for diagnostic biopsies in men taking dutasteride or other 5α-reductase inhibitors. A 2018 meta-analysis found no higher risk of breast cancer with 5α-reductase inhibitors.
Sexual and mood side effects, such as erectile dysfunction, loss of libido, depression, and reduced semen volume occur in as many as 4.8% of patients taking 5α-reductase inhibitors including dutasteride. with a smaller subgroup of patients also experiencing a decrease of sperm motility of 6 to 12%. These negative effects reverse by 3–4 months after discontinuation of the drug. whether self-report questionnaires are reliable for this data, The Post-Finasteride Syndrome Foundation (PFSF) was created with a medical advisory board to study the topic (finasteride is a similar 5α-reductase inhibitor) and lawsuits alleging harm from the drug are ongoing. Concerns from the PFSF and other patient advocates led the FDA to add a black-box warning to Finasteride for possible risks of suicide in June 2022. Some experts have questioned the basis of the black-box warning, given that it relies on anecdotal patient-reported outcomes rather than prospective trials.
Overdose
No specific antidote for overdose of dutasteride is known, since the drug is extremely safe and well tolerated. Research studies show that even at 100 times the normal dose, dutasteride is not lethal. Treatment of dutasteride overdose should be based on symptoms and should be with supportive therapies.
Ongoing clinical trials are investigating whether dutasteride may be an effective treatment for premenstrual dysphoric disorder (PMDD), because dutasteride may inhibit the conversion of progesterone to allopregnanolone, a neurosteroid metabolite, which may be responsible for some of the debilitating symptoms of PMDD.
Pharmacology
Pharmacodynamics
Dutasteride belongs to a class of drugs called 5α-reductase inhibitors, which block the action of the 5α-reductase enzymes that convert testosterone into DHT. It inhibits all three forms of 5α-reductase, and can decrease DHT levels in the blood by up to 98%. Specifically it is a competitive, mechanism-based (irreversible) inhibitor of all three isoforms of 5α-reductase, types I, II, and III ( values are 3.9 nM for type I and 1.8 nM for type II). This is in contrast to finasteride, which is similarly an irreversible inhibitor of 5α-reductase but only inhibits the type II and III isoenzymes. In spite of the differential reduction in circulating DHT levels, the two drugs decrease levels of DHT to a similar extent of approximately 85 to 90% in the prostate gland, Among the studies analyzed, there was no statistically significant change in testosterone levels from 5α-reductase inhibitors overall, though men with lower baseline testosterone levels did show an increase. For this reason, decreased neurosteroid production is one hypothesized mechanism for sexual dysfunction and depression associated with 5α-reductase inhibitors such as dutasteride. It is an analogue of finasteride in which the tert-butyl amide moiety has been replaced with a 2,5-bis(trifluoromethyl)phenyl group. The patent protection of dutasteride expired in November 2015, so the drug has since become available in the United States in a variety of low-cost generic formulations.
It was approved for the treatment of scalp hair loss in South Korea in 2009 and in Japan in 2015. It has not been approved for this indication in the United States, though it is often used off-label both orally and topically.
Society and culture
thumb|200px|right|Avodart (dutasteride) 500 μg soft capsules
Generic names
Dutasteride is the generic name of the drug Avodart and its international nonproprietary name, United States Adopted Name, British Approved Name, and Japanese Accepted Name.
Brand names
Dutasteride is sold primarily under the brand name Avodart, but also in combination with tamsulosin under the brand names Combodart, Duodart, and Jalyn.