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Avodart/Dutasteride

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A new 4-year study, published in the journal European Urology, found that men who take dutasteride (part of a class of medications called 5-alpha reductase inhibitors) and drink heavily (more than seven alcoholic drinks per week) have a greater risk of developing high-grade prostate cancer than men who take dutasteride and do not drink. ((Fowke J.H., Howard L., Andriole G.L., Freedland S.J. Alcohol Intake Increases High-grade Prostate Cancer Risk Among Men Taking Dutasteride in the REDUCE Trial. European Urology, 2014, Dec;66(6):1133-8.))

The authors of the study concluded that heavy alcohol intake negates dutasteride’s protective benefit against high-grade prostate cancer. This result confirmed a prior study ((Gong Z., Kristal A.R., Schenk J.M., Tangen C.M., Goodman P.J., Thompson I.M. Alcohol consumption, finasteride, and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Cancer, 2009, Aug 15;115(16):3661-9)) which showed that high alcohol intake negatively affected prostate cancer prevention in patients taking finasteride, another 5-alpha reductase inhibitor.

The researchers recommend that patients taking 5-alpha reductase inhibitors may wish to eliminate alcohol intake if they are concerned about prostate cancer.

The reason why this paper is important for our readership is that dutasteride (Avodart) is used, by some doctors, to treat hair loss. Although effective in genetic baldness, its use for male pattern alopecia is not approved by the FDA and its long-term safety is not clear.

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Could the 5α-reductase inhibitors (5ARIs) dutasteride and finasteride increase the risk of developing male breast cancer?

In 2012, male breast cancer was identified as a possible new risk of 5ARIs by the FDA; however, a 2013 study published in the Journal of Urology ((Bird ST, Brophy JM, Hartzema AG, Delaney JA, Etminan M. Male breast cancer and 5α-reductase inhibitors finasteride and dutasteride. J Urol. 2013 Nov;190(5):1811-4. doi: 10.1016/j.juro.2013.04.132.)) found no evidence for a relationship between male breast cancer and finasteride (Proscar®) and dutasteride (Avodart®), both of which are used to treat enlarged prostate (benign prostatic hyperplasia).

The study excluded finasteride (Propecia®), used to treat androgenic alopecia, because previous research considered a relationship between Propecia 1mg and male breast cancer unlikely.

So how did dutasteride and finasteride become implicated in the possible development of male breast cancer?

The Hypothesized Link Between Finasteride & Dutasteride and Male Brest Cancer

Going back to 1992, researchers ((Thomas DB, Jimenez LM, McTiernan A, Rosenblatt K, Stalsberg H, Stemhagen A, Thompson WD, Curnen MG, Satariano W, Austin DF. Breast cancer in men: risk factors with hormonal implications. Am J Epidemiol. 1992 Apr 1;135(7):734-48.)) had hypothesized that an increased ratio of estrogen-to-testosterone could lead to an increase risk of male breast cancer.

This hypothesis seemed to be supported when, in 2009, the Medicines and Health care products Regulatory Agency (MHRA) in England ((Niraj K Shenoy, Sangolli M Prabhakar. Finasteride and male breast cancer: Does the MHRA report show a link? J Cutan Aesthet Surg 2010; 3: 102.)) received reports of male breast cancer developing in patients using 5ARIs, which are known to alter the normal estrogen/testosterone balance. Specifically, as of November 2009, MHRA had received 50 worldwide reports of male breast cancer developing within an average of 44 months after starting treatment with 5mg finasteride for enlarged prostate. MHRA also received three reports of male breast cancer developing in men using Propecia ® 1 mg for hair loss, but because of relatively short onset times of the disease after starting treatment, the MHRA considered any link between Propecia and male breast cancer unlikely.

Even though both finasteride and dutasteride alter the normal estrogen/testosterone balance in men, the fact that 50 individuals developed male breast cancer after starting to use a 5ARI does not constitute evidence that 5ARIs contribute to the development of male breast cancer: it is possible that these 50 individuals would have developed cancer whether or not they used a 5a-reductase inhibitor.

The Study: Male Breast Cancer and 5a-Reductase Inhibitors Finasteride and Dutasteride

To ascertain whether or not a link exists between the use of 5a-reductase inhibitors and subsequent development of male breast cancer, one would want to look at two groups of men where one group has been exposed to a 5a-reductase inhibitor and where one group has not, and then one would compare the incidence of the development of breast cancer in the two groups. However, one would also need the two groups to be matched on as many known risk factors for male breast cancer as possible, such as alcoholism, gynecomastia, Klinefelter syndrome, liver damage, obesity, oral estrogen, orchiectomy and prior radiation; in short, one would want to control for all the known risk factors for male breast cancer to see if 5ARIs were contributing any additional risk.

And this is exactly what the 2013 study did. As a result, it found that 5a-reductase inhibitors were not a significant predictor of developing male breast cancer 1 to 3 years after exposure.

Because no link between 5ARIs and male breast cancer was found, the authors of the study advised doctors to prescribe finasteride and dutasteride without fear of introducing additional risk for the development of male breast cancer in their patients.

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Q: I recently visited my dermatologist regarding my hair loss, and after checking my hair he said I am showing signs of Androgenetic Alopecia (common baldness), and said if I don’t treat it, it will progress. From my research on the net, I figured he will put me on Propecia. In fact he put me on Avodart. When I told him it is not FDA-approved for hair loss, and Propecia is, he said Avodart is better and brings DHT down more, and Propecia is nothing next to Avodart. He told me to take it every day for 2 weeks, then every other day from then on as it has a long half life. From researching on the net, many hair restoration doctors rarely prescribe Avodart for hair loss due to some dangers. What is your opinion on this? — T.G., Darien, Connecticut

A: Although dutasteride (Avodart) can be more effective for male pattern hair loss, I would start with finasteride (Propecia) as many patients do great with it and the safety profile is better. The following are things I would consider before starting dutasteride:

  1. As you point out, dutasteride is not FDA-approved for hair loss.
  2. There is no data on its safety when used for hair loss. This is important since dutasteride has been only tested on an older population of patients (with prostate disease) rather than a younger population of patients needing medical treatment for androgenetic alopecia.
  3. These is no natural model for dutasteride’s combined blockage of both type 1 and 2 5-alpha reductase (finasteride blocks only type 2 5-AR and there are families that have this deficiency and have no long-term problems. This, by the way, is how the drug was discovered).
  4. The type 1 enzyme which dutasteride blocks is present in many more tissues of the body (including the brain) compared to type 2 (which is more localized to the skin).
  5. Although so far unproven, there is a concern that finasteride may produce side effects than can be persistent after stopping the medication (post-finasteride syndrome). It this does turn out to be true, the effects from dutasteride would most likely be significantly more persistent.
  6. If you start with finasteride and do have side effects, you will most surely have side effects from dutasteride; therefore, by taking finasteride first you will have avoided the potentially more problematic side effects from dutasteride
  7. You may respond well to finasteride, and so do not need to consider dutasteride
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Q: I am 27 years old and I have been on Propecia for 12 months now. Honestly, I have seen no response from it. In my dermatologist’s opinion I am a non-responder. I asked about Avodart and he said, since Propecia didn’t help then Avodart won’t help as well since both are DHT blockers, and if one didn’t work the other won’t either. In your opinion do you think Avodart is better? I have read that it blocks more DHT than Propecia. What is the dosing for Avodart? If someone does not respond to Propecia will they also not respond to Avodart? — A.C., West University Place, Texas

A: Avodart (dutasteride) is more effective than Propecia (finasteride) and some patients will respond to dutasteride who do not respond to finasteride. Dutasteride decreases serum DHT about 90% compared to 70% for finasteride. The usual starting dose of Avodart is 0.5mg a day.

That said, dutasteride is not FDA approved for use in hair loss and if a person has sexual side effects, the side effects are more likely to be persistent after stopping the medication compared to finasteride.

Read more about Avodart (dutasteride)

Read more about Propecia (finasteride)

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Men's Health - Hair HealthMen’s Health has published a new spotlight, called “Hair Health.” The multi-article spotlight is featured on the magazine’s website homepage and covers a wide variety of topics related to men’s hair loss and hair transplant surgery. Dr. Bernstein was asked to contribute to the series of articles, including an “expert advice” feature which answers five commonly-asked questions about hair loss myths.

The centerpiece articles in the spotlight include the article, “Scalped,” which details the best treatments for hair loss in men, and, “Keep Plugging Away,” about best-practices on finding a great doctor who can treat your hair loss.

In “Scalped,” Dr. Bernstein speaks to the urgency of halting your hair loss using Propecia and Rogaine, while he cautions younger patients on the side effects of the drug Dutasteride:

“Start [Propecia and Rogaine] as soon as your hair begins to thin for the best results.”

[…]

“The reproductive side effects [of Dutasteride] — decreased libido and ejaculation disorders — may be persistent, so I don’t usually recommend this medication for younger patients.”

On hair transplantation, Dr. Bernstein says:

“Hair transplants are most appropriate for people who have not responded to medical treatments.”

“Keep Plugging Away,” centers on hair transplant surgery and the repair of hair transplants that used out-dated, large, “pluggy” hair grafts. Dr. Bernstein – the hair transplant physician most responsible for the new pioneering techniques of follicular unit transplantation and follicular unit extraction – had this to say about hair transplant repair:

“Reversing the unnatural appearance of older plugs is more involved than using the right technique in the first place,” he says. “But in most cases, it can be accomplished with excellent results.”

Visit the “Hair Health” feature online at MensHealth.com.

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Q: I am currently taking Avodart and have done so for around 8 months. Last night I had a significant loss of hair after taking a shower, nothing like I have ever seen before and found it very distressing. Can you tell me if this is hair loss or could it be something known as shedding and could you please tell me what is the difference between hair loss and hair shedding? — M.S., New York, NY

A: Hair loss is a very general term that can refer loss of hair for any reason. Genetic hair loss is caused by the effects of DHT on hair follicles that result in miniaturization -– i.e. a slowly progressive change in hair diameter that starts with visible thinning and that may gradually end in complete baldness. Hair shedding is more sudden where hair falls out due to a rapid shift of hair from its growth phase into the resting phase. The medical term for this is telogen effluvium. This process is usually reversible when the offending problem is stopped. It can be due to stress, medication, or other issues. You should see a dermatologist to figure out which process is going on. Dutasteride can cause some shedding when it first starts to work, but it would be unusual to do this after being on treatment for eight months.

Read more about the Causes of Hair Loss in Men, view our Hair Loss Glossary, or read more about Avodart Hair Loss Medication.

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Q: It’s a question that greatly concerns me because I’m investigating getting a transplant sometime next year. I’m 28 and thought I started balding at 26, but photographic evidence suggests it had started somewhere around age 24. I’m roughly a Class 2 now, and thanks to finasteride, I’ve stayed almost exactly where I was at 26 with some improvement (not really cosmetically significant though). However, I am convinced I have some crown and top of the scalp thinning too, but not to a visible degree.

These people getting these miraculous jobs from Canada – it is a trick, right? They can’t honestly expect to be able to get away with what they’ve done over the course of their entire lives, can they? — L.M., Great Falls, V.A.

A: I think you have better insights into hair loss than many hair transplant surgeons. Patient ABI was the “rare” patient who seems to be a stable Class 3. I made that judgment due to: almost no miniaturization at the border of his Class 3 recession, no crown miniaturization, and his unusual family history. He had several older family members who stayed at Class 3 their whole lives.

Since we only have about 6,000 movable follicular units on average in our donor area, placing 3,000 at the hairline is obviously a joke and/or the doctor is playing “Russian Roulette” with the patient’s future.

As you point out, in most patients the hair loss will progress and the person will be out of luck. It is similar to the way flap patients were stuck without additional donor hair as their hair loss progressed. An additional problem was that the flaps were low on the forehead and very dense. The situation is analogous to placing 100 grafts per sq cm2 to create a low, broad hairline in a young person.

If you do the math you can see how ridiculous this tactic is. A person’s original density is only 90-100 follicular units cm2. Patient with Class 6 hair loss lose hair over an area of about 300 cm2.

This consists of:

  • 50cm2 in the front (including a 15cm2 hairline)
  • 150 cm2 for the mid-scalp
  • 100 cm2 for the crown

Therefore, 6000 FUs transplanted to this area = 6000/300 = 20 FU per cm2. This is the number we often work with. We put up to 50cm2 at the very most in the mid-frontal forelock area and then proportionately less in other areas.

However, if you put 3,000 FUs at the hairline, in a density of 100/cm2, then you have covered only 30cm. This leaves only 3,000 FUs for the remaining 270cm2 of balding scalp for a density of a little over 11 FU/cm2.

Now, transplanting 11FU cm2 over the back part of the scalp is not a disaster EXCEPT if the front was transplanted at 100 per cm2. In this situation (as you have accurately pointed out) the patient will look very, very front heavy, with an aggressively placed, dense, broad, hairline and little hair to support it towards the back.

The gamble is that the patient’s baldness doesn’t progress, that finasteride or dutasteride can halt the process if it does progress, or that hair cloning methods will be available to save the day.

In my opinion, elective surgery should not be performed when its success depends upon these uncertainties – and particularly since a cosmetically disfiguring hair transplant can be so debilitating (and avoidable).

The reality is that doctors who claim to perform these procedures may not even be performing follicular unit transplantation. In FUT, the surgeon transplants naturally occurring intact FUs of 1-4 hairs. The extreme dense packing techniques preclude the use of 4- and sometimes even 3-hair grafts. What happens is that the larger FU are spit up. This doubles the graft counts (and the cost to the patient) without giving the patient any more hair. It also increases the risk of follicular damage and poor growth.

Patients in whom 10,000 follicular units are available to transplant are very rare and when they are shown on the internet, should be viewed as the exception rather than the rule.

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Q: Are there DHT blockers that are sold in the pharmacy over the counter? — C.C., — Fairfield County, Connecticut

A: The only effective DHT blockers are finasteride (Propecia, Proscar) and dutasteride (Avodart).

These medications require a doctor’s prescription and are not sold OTC. Nizoral is a topical shampoo for seborrhea (a type of dandruff) that is sold over the counter, but it is not effective in treating hair loss.

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Q: I heard that there is a new drug on the market called Avodart for prostate enlargement which might help with hair loss as it blocks the conversion of testosterone to DHT better than Finasteride and is more effective than Propecia. Do you recommend taking it and if so what is the dose? — Y.B., Orlando, Florida

A: I am currently not recommending that patients take Dutasteride for hair loss, although it is more effective than Propecia, finasteride 1mg. (Dutasteride 0.5, the dose generally used for hair loss, seems to be slightly more effective than finasteride 5m in reversing miniaturization.)

The reasons that I am hesitant to prescribe it at present are outlined in the Hair Restoration Answers question, “Is Avodart Safe?

In addition to the reasons that I listed in that response, I would also consider that: Dutasteride, unlike finasteride, decreases sperm counts, it can result in persistent decreased sex drive and the incidence is greater than with finasteride. Finally there are a significant number of alpha-type 1 receptors in brain, those affected by dutasteride, but not finasteride.

However, since Dutasteride is approved for older men with prostatic disease, using it for hair loss in this age group (usually in a lower dose) is reasonable.

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Q: I’m male, early thirties and in the early stages of hair loss, too early for hair transplants. I am experiencing extreme shedding. I took Avodart for 6 weeks, but because of the shedding I stopped. Now, it still continues as strong as ever. I’ve been losing about 200 hairs every day in the shower. 3 months ago I had so much more hair, what is going on? I heard that shedding can happen, but not like this. Could this have caused telogen effluvium, or something else? — M.M., Boston, Massachussetts

A: Since Avodart (dutasteride) is a more potent medication than Propecia (finasteride), the shedding (telogen effluvium) may be more dramatic. If you have made a decision to use Avodart, then you need to tolerate this short-term effect. It should subside within the first 6 months on the drug.

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Q: I’m 52 years old and have been taking Propecia (finasteride) for two years. It seems to maintain the status quo with no apparent regrowth. I am considering adding a dose of Avodart (dutasteride) once a week in conjunction with the daily Propecia. My question is twofold: (1) Since dutasteride blocks production of both enzymes (type I and II) that produce DHT from testosterone, is it redundant to take the finasteride that only blocks the type I enzyme? — Y.B., Orlando, Florida

A: It is redundant to take both.

However, you may not be taking the optimal dose of dutasteride which seems to be at least 0.5mg a day for hair loss.

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Q: If I use the dutasteride for one year and do not see a noticeable improvement can I quit the Avodart, continue the daily dose of Propecia and expect to retain the same “holding pattern” I have now?

A: If Avodart is helping to maintain the status quo then you can expect to lose some hair, i.e. return to where you would have been if you had used finasteride alone.

Read more about Hair Loss Medication

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Q: First off thank you for providing this Blog, it is extremely informative and gives people the opportunity to ask questions of one of the most knowledgeable hair transplant surgeons in the world. You are considered the consummate researcher in the field of hair loss, so I ask this question of you. It appears that all the current hair loss drugs, at one point or another, begin to lose their effectiveness. Have you ever entertained the idea of cycling these drugs, or reducing the dosage for a period of time, to prevent the body from becoming acclimated to these drugs and subsequently making adjustments to receptors causing this? This method is commonly used by bodybuilders and others in the sports profession to elicit the maximum effect from the drugs they employ. Though I have not found any studies along these lines, I believe there are valid reasons why this may work. I hope you may be able to share any information on this subject. — Z.Z., Chicago, I.L.

A: Excellent question. I can answer it only indirectly.

It has been our experience that when you discontinue finasteride (Propecia), or decrease the dose to a degree that it no longer works, the patient will begin to shed hair. When the drug is re-started or the dose increased again, the medications will begin working, but the patient now maintains his hair at a lower baseline. He doesn’t seem to regain the amount of hair he has before the medication was stopped. For this reason, we don’t stop and start finasteride. The same argument applies to dutasteride, although we have less experience with this medication. This experience would speak against using pulse therapy for hair loss.

On the other hand, the hair loss medications finasteride and dutasteride do not necessarily need to be used once a day. Although the serum half-life of finasteride is around 6 hours, the tissue half-life is felt to be around two days. Therefore, alternate day dosing with 2 mg of finasteride (or approx. 1/2 of a 5mg tablet) should work just as well as 1mg a day. An average daily dose of less than 1mg, however, does not seem to be as effective. Dutasteride has a half-life of 5 weeks and is found to bind to scalp tissue for many months, so with dutasteride, a dosing of even once a week will most likely be just as effective as once a day.

Note that this regular alternate day dosing is different than pulse dosing. In pulse therapy, the body is given a chance to recover. The principle here is to take advantage of the persistence of the drug in the scalp even after blood levels drop and not to let the scalp recover (which we have found to result in a net loss of hair (as discussed above).

When patients do become acclimated to these drugs (which seem to be common after 3 to 5 years) we increase the daily dose of finasteride gradually up to 5mg and then consider switching to dutasteride 0.5mg a day.

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Q: My friend just came back from Paris and said that his cousin was taking Avolve for hair loss. Can you tell me what that is and is it available in the U.S.? — N.W., Portland, Oregon

A: Avolve is the European trade name for dutasteride 0.5mg made by GlaxoSmithKline for prostate enlargement. In the U.S. dutasteride 0.5mg, under the brand name Avodart, is FDA approved to treat prostate enlargement (BPH). It has not been FDA approved for hair loss.

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Q: My query is prompted by your answer to another query “Is Avodart Safe?” My son, who is in his mid-20s, has been taking Dutasteride for hair loss for about two years now. He had tried Finasteride earlier but without much benefit. Medical supervision regarding Dutasteride is not available in Australia as the drug has not been released here yet. — N.V., Melbourne, Australia

I am concerned by your remarks that there is no biologic model to show the long-term safety of Dutasteride (as opposed to Finasteride). Would you suggest that he goes back to taking Finasteride? We would be grateful for your advice.

A: It is a tough call as I have never met or examined your son, so I can only offer an opinion based on limited information. If you feel your son will be emotionally or socially debilitated by the hair loss, then I think that it may be worth the risk (if there is any) of taking the medication; otherwise, I would use Finasteride.

Please keep in mind that you don’t need to make the final decision now. You may want to defer the decision until he is 28 or so, at time when he is more mature. It is a tough call. Please let me know what you decide.

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Q: Over the past three months, my hair seems to be thinning more on one side. Is it common in male pattern hair loss for it to be more on one side? I had a lot of stress about three months ago and have heard that this could be the cause. Is this possible? Should I use Rogaine to treat it? — B.R., Landover, MD

A: Regardless of the cause, hair loss is usually not perfectly symmetric. This applies to male pattern hair loss as well.

In your case, it is important to distinguish between telogen effluvium (shedding that can be due to stress) and hereditary or common baldness. The three month interval from the stressful period to the onset of hair loss is characteristic telogen effluvium, but you may have androgenetic alopecia as an underlying problem.

The two conditions are differentiated by identifying club hairs in telogen effluvium and miniaturized hair in androgenetic alopecia. In addition, a hair pull will be positive in telogen effluvium (when a clump of hair is grasped with the fingers, more than five hairs pull out of the scalp at one time) and will be negative in common baldness. The hair loss diagnosis can be made by a dermatologist.

Hair cuts do not affect either condition.

Rogaine (Minoxidil) is only effective in androgenetic hair loss and only marginally so. Finasteride is the preferred treatment if your hair loss is genetic when it is early and a hair transplant may be indicated if the hair loss progresses.

Shedding from telogen effluvium is reversible and does not require specific treatment.

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Q: My friend is taking Avodart, he bought it over the internet. Is it safe to take? — T.G., Denver, Colorado

A: Avodart (dutasteride 0.5mg) was approved by the FDA for the treatment of prostate enlargement in men in 2002. Avodart has not been approved for the treatment of androgenetic hair loss, although physicians can use an approved medication in ways other than for which it was specifically approved. That said, the use of dutasteride certainly requires a doctor’s supervision.

Like finasteride (the active ingredient in Proscar and Propecia), dutasteride blocks the enzyme 5-alpha reductase that converts testosterone to DHT (DHT is a key hormone that causes hair loss). However, unlike finasteride, which only inhibits the Type I form of the enzyme, dutasteride inhibits both the Type I and Type II forms. This combined effect lowers circulating DHT more with dutasteride than with finasteride, but also increases the incidence of its side effects.

The Type II form of the enzyme (blocked by finasteride) is found predominantly in the hair follicle. The Type I form of the enzyme has been found in the scalp and sebaceous glands, and many other parts of the body, but its exact role in hair growth has not been determined. It is felt that dutasteride’s ability to dramatically lower serum levels of DHT is what makes it a more potent medication in hair loss.

When considering the safety of dutasteride, one should consider the following:

  • It acts on other parts of the body besides the hair follicle.
  • Unlike finasteride, where families that had a deficiency of the Type II 5-alpha reductase enzyme were followed for years without any adverse effects, there is no natural biologic model to show the safety of dutasteride.
  • Dutasteride has been approved for prostate enlargement in an older male population. It is not approved for hair loss and, in fact, the clinical trials for hair loss were discontinued, so there is no safety data for its use in younger patients. There is a greater incidence of sexual side effects with dutasteride compared to finasteride.
  • The 1/2 life of dutasteride is 5 weeks compared to 6-8 hours for finasteride. Serum concentrations of dutasteride are detectable up to 4-6 months after discontinuation of treatment.
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