Dr Proctor

In the first rogaine studies it was found that the vehicle-alone-treated group showed about 40% (or so) of the increase in hair numbers of the vehicle plus minoxidil group. At first, it was thought that this was merely an artifact of the experimenters getting better at counting hair with time. Follow-up studies showed that it was a real effect. That is, the Rogaine vehicle stimulates some hair growth. The vehicle is a combination of propylene glycol, ethyl alcohol, and water. Of the three agents, the most likely hair growth stimulator is propylene glycol. Mechanism ? It has been known since ancient times that agents effective against seborrheic dermatitis ( "tars", ketoconazole, etc. ) have some activity against pattern hair loss. Propylene glycol has some activity against seborrheic dermatitis. Peter H. Proctor, PhD,MD

Dr Proctor sez: Good questions. Nobody knows the answers. I will prescribe finasteride up to age 50 or so, after advising the patients accordingly, naturally. Over 40 is a "relative contraindication", mostly because the oldest person in the trial was 41. This seems appropriate most of the time because of the general reversibility of any sexual problems. Over 50, I start to worry. One reason is the significantly increased incidence of sexual dysfunction. The other is that, while finasteride early may retard the development of prostate cancer, it may promote the progression of the last precancerous stage to frank prostate cancer. As a practical matter, this is probably not an issue under age 50, if it is an issue at all. Peter H. Proctor, PhD,MD

Yes, fiansteride (propecia) does have some side-effects. The most distressing of these is arguably decreased libido or sex drive. But the incidence of this in males under 40 years old is less that 5%. How much less is open to debate, but in any case low. Matters are different over age 50, where the incidenc of sclinically-significant sexual dysfunctions is 25% or so. But the drug is not generally recommended for people past their early 40's anyway. In any case, these problems seem to reverse within a few weeks of stopping treatment. I have heard anecdotal stories of a few persons in whom libido dicrease, etc. did not reverse. But htis seems to be rare, if it exists at all. Peter H. Proctor, PhD,MD

Over a broad range (IIRC, from .4 mg/day to 5 mg/day) the dose response curve for finasteride is essentially flat. That is, every dose works about the same. This pretty much moots any differences in the size of the quartered Proscar tablets. Peter H. Proctor, PhD,MD wwww.doctorproctor.com

As I explain elswhere, It is not an easy thing to reliably and reproducably distribute a drug in a tablet inhomogeneously. Likewise, because of the strong binding of finasteride to type-2 5-AR, it probably doesn't make much difference anyway. But if anybody is worried about this, just crush proscar tablets and take what looks to be about one-fifth tablet per day. The flat dose-response curve covers a lot of sins. As for the persistence of Finasteride-- IIRC, the blood half-life is about 8 hours or so. Considering the flat dose-response curve ( a little works about as well as a lot), you get pharmacologically active amounts in blood for a day or so. However, blood levels are really secondary-- finasteride binds in an essentially non-equilibrium manner to type-2 5-alpha-reductase, strongly and non-diffusibly. That is, once it binds it sticks. Thus, as a practical matter restoration of activity likely strongly depends upon synthesis of new enzyme, a matter of several days. Peter H. Proctor, PhD,MD

Probably not. First, other than in serial coatings, the technical problems inherent in reliably and reproducably distributing a drug inhomogeneously in a tablet are pretty significant. Why bother unless there is some specific reason? In any case, the flat dose-response curve for finasteride (a little works the same as a lot) combined with the strong binding of the drug to type-2 5-AR probably make the issue moot. Remember, while the blood half-life of finasteride is only a few hours, becasue binding is essentially irreversible, restoration of type-2 5 AR activity after inhibition requires synthesis of new enzyme, a matter of several days. Back in the days before finasteride became available as 1 mg Propecia, some physicians used to prescribe one Proscar tablet every three days or so. By report, this worked reasonably well.. So even it the drug is inhomogeneuoos (which I seriously doubt), it should make no significance difference, as a practical matter.. Peter H. Proctor, PhD,MD www.drproctor.com

Same drug, same side-effects. Naturally Merck would prefer to sell you Propecia at about the same cost per tablet. Thus, Proscar tablets are very small and irregularly-shaped to discourage quartering. However, the dose-response curve for finasteride is very flat--- a little works about as well as a lot. Combine this with the fact that finasteride forms an almost unbreakable bond with type-2 5-AR. I.e., though the blood half-life is only eight hours or so, synthesis of new enzyme is required to restore activity. This takes several days. This means the amount you take in any one day is almost irrelevant, within limits. So quarter the tablets as well as you can and don't worry. On general principles, I suggest skipping treatment every 5th day more or less, so that the averaged dose is 1 mg per day. Peter H Proctor, PhD,MD

No. This is because visible early shedding is caused by a combination of several factors. First, Waking up follicles inducing loss-phase hair to shed early. This does not appear to be the case in the majority of persons. Second, enough follicles being turned on at any one time that the increased shedding becomes perceptible. That is, if the follicles are turned on more slowly, over a period of time, you are less-likely to observe visible shedding. The convers is also true-- the more follicles that get turned on and the earlier they get turned on, the more likely shedding will be significant enough to be perceptible. This is why an early wave of shedding tends to be associated with a good eventual result. This is only a rule of thumb and naturally with the qualification "all else being equal". E.g., if for some reason you have an abnormal amount of loss-phase on board when you start treatment, this can also cause an apparent shed. The most common cause of this we see is stopping medical treatment several months before. Again, the hair was about to fall out anyway. Dr Proctor

It is true that ketoconazole probably does not act as an antiandrogen. The medical indication for ketoconazole is treatment of seborrheic dermatitis and that is probably why it works (some) in pattern loss. The efficacy of antiseborrheic dermatits agents in pattern loss has been known for a long time. The earliest reference I can find to is is the first-century physicians Diocorides, who recommends "tar" (presumably coal tar, pitch, or bitumen) as a treatment for pattern loss. There is another reference to it from 1640. Early 20th-century illuminaries in dermatology such as Sabaroud also recommended tar treatment for pattern loss. While continuing in Europe, this fell out of use in the US, presumably due to the "snake-oil" taint. The latest reference I can find to it in an American formulary is 1927. An attempt to patent this use about 1950 was rejected as an "incredible invention", like a cancer cure. The patent office has since revised its opinion on both cancer cures and hair loss treatments. Anyway, more recent studies suggest that standard treatments for Seb derm (ketoconazole, coal-tar, and pyrithione) all have some efficacy in pattern loss. E.g., in the clinical trials with Propecia, Merck even used a coal-tar proparation (T-Gel) in both wings of the trial to minimize seborrheic dermatitis as a contributing factor. Most likely Seborrheic dermatitis exacerbates the inflammatory-autoimmune component of pattern loss, though nobody knows for sure. Nor does anybody know the optimal agent. On the principle of "If you can, treat the disease and not the symptoms", I mildly prefer ketoconazole, which kills the yeast that probably causes Seb derm. Peter H Proctor, PhD,MD (promotional link removed) <span class="ev_code_red">Important Moderator Note:</span> This is now your second warning... Blatant Promotions and Solicitations are not allowed here. See our terms of service for more information. Failure to comply to these rules will result in suspension of posting privileges. Thank you. Bill - Moderator

Re: Ketoconazole. Antiseborrheic dermatitis agents such as "tar", ketoconazole, and pyrithione have long been known to have some efficacy in the treatment of pattern loss. The first century Greek physician Dioscorides even lists "Tar" (presumably bitumen or coal-tar) as a treatment for pattern balding. Before the discovery of minoxidil again made hair loss treatments a respectible are of research, the efficacy of seb derm treatments was eclipsed for a while, though continued in Eurpope. Until the area was revived in the late 1990's, the latest reference I can find to it is a formulary from 1927. Now, it is pretty well-established. The propecia clinical trials even used "T-gel", a coal-tar preparation, in both wings to minimize seborrheic dermatitis as a variable. Peter H. Proctor, PhD,MD (promotional link removed)

Any hair that sheds within 2-4 months of starting a treatment was already in the loss-phase when treatment started and scheduled to fall out anyway. Medical treatment may accelerate this process a few weeks because new hair starting to grow may serve as a stimulous for loss-phase hair to shed a little early. Generally, this presents as a wave of shedding starting 3-6 weeks after starting treatment. The minoxidil package insert says as early as two weeks, but this is unusual. Typically, it lasts a month or so. Every treatment that brings follicles out of dormancy (which means every treatment that works) may do this in some persons. The faster the follicles get brought out of dormancy, the more likely you are to see it. I estimate that about 10-15% of pateints see it. Also, fine "vellous" hair spends the majority of its life-span in the 2-4 month loss phase. So half or more of this is generally in the loss phase and thus sheds disproportionately. "Indeterminate" hair ( a little thincker that vellous, but still not "termainal" hair) also spends a disproportionate part of its lifespan in the loss-phase and is thus more likely to shed this way than terminal hair. The hair that replaces these tends to be progressively coarser, darker and spends longer in the growth phase In any case, the hair was about to fall out anyway. If the shed is due to treatment, it is a good sign, since it means treatment is working. Thus, as distressing as it can be, an early shed tends to be associated with a good eventual result. Peter H Proctor, PhD,MD (promotional link removed)