Slartibartfast's Story

[Slartibartfast]

Howdy ropcat.

As I commented elsewhere, it's strange that this issue wasn't considered in the clinical trials or FDA approval process. Although I'm a non-scientist, I'd expect that such research on a new drug would involve figuring out where 5AR-I is present in the body, what its functions are, and what the consequences of eliminating it could be. But there's no mention in the approval applications, to my knowledge.

No, I don't think 5AR-I is discussed in detail in any Glaxo or FDA literature, in fact nothing beyond the fact that Dutasteride inhibits it. I suppose really I've been content to believe that commercial self-preservation, when combined with the expertise of Glaxo's scientists, would be sufficient to produce fundamentally safe compounds. In light of the recent, high-profile drug safety scares this may now seem just slightly naive. Although I still find it incredible if it's the case that, out of the entire team responsible for developing dutasteride, not one scientist thought it worthwhile to investigate the consequences of a significant reduction in 5AR-I - I hope they weren't leant on to limit the scope of their studies.

Like you I'd be very interested in picking the brain of an endocrinologist or two, assuming that's the appropriate speciality for our questions. Is finding someone a simple matter of running a search on google (or wherever) and then firing off questions to all and sundry?

Onto your other topic... I've been taking the genuine Avodart all along. Someone pointed me to the http://www.merlonipharma.ch website (no online purchase facility, transaction is arranged via e-mail - as discussed in earlier posts) and I've ordered 3 boxes of 90 capsules, at 140 Euros a pop, without any problems.

Slarti - getting gradually more wavy haired.

 

[Slartibartfast]

Hey raider, that's sounding pretty damn good at 4 months. You've actually reminded me that it's almost time for my next update, amazingly that will be 8 months since my daily dosing got under way. Time flying and all that.

Hope those baby hairs keep on coming through at the temples and that your crown keeps thickening - it's a nice feeling to get positive feedback from the hairdresser.

Later my friend, Slarti

 

[ropcat]

Although I still find it incredible if it's the case that, out of the entire team responsible for developing dutasteride, not one scientist thought it worthwhile to investigate the consequences of a significant reduction in 5AR-I - I hope they weren't leant on to limit the scope of their studies.

Hey again. Thanks for the response. Regarding this 5AR-I/brain issue, here's a comment from HairLossTalk.com, 22 Nov 2003:

"CNS Toxicity: At 425 and 315 fold the expected clinical drug some rats and dogs exhibited signs of non-specific, reversible, centrally-mediated toxicity without associated histopathological changes.

Note that only 'some' and not all rats and dogs had signs of neural toxicity. I think if you ate 300 times the table salt you normally now do, you would probably have "non-specific, reversible, centrally-mediated [CNS] toxicity". Actually, you would probably wouldn't survive very long.

Also, does dutasteride cross the blood-brain barrier readily and enough quantity when taken at 0.5 mg/day to reduce 5AR-1 activity in the brain? The blood-brain barrier is a formidable deterrent against relatively small concentrations of substances entering the brain. Testosterone, which is chemically similar to dutasteride, does cross the blood-brain barrier, but dutasteride has many modifications in its chemical structure (it's quite electronegative) that may prohibit it's crossing that barrier except at high does (for example, 300 times the normal dose).

5AR-1 does play a role in the CNS - it's thought to prevent neurological toxicity by catabolism of neurotoxic steriods. It also functions to convert progesterone to dihydroprogesterone (DHP) in the brain - a beneficial neurosteroid. 3-alpha-HSD (another enzyme in the brain) converts DHP to allopregnanolone. Allopregnanolone is a neurosteroid which exhibits anxiolytic (anti-anxiety) and anticonvulsant activities through potentiation of the GABA(A) receptor. So if you start feeling more anxiety or have seizures, stop taking dutasteride and tell your doctor (and Glaxo)."

So one of the key issues here is whether it crosses the blood-brain barrier. Just to repeat a sentence from above, "[D]utasteride has many modifications in its chemical structure (it's quite electronegative) that may prohibit its crossing that barrier except at high doses." I wonder if more recent research has answered this barrier question for us? It's encouraging that lab animals needed over 300 times the expected clinical dose to exhibit toxicity symptoms, but that's probably not a final answer. And I'm encouraged by the possibility (at least) that the drug doesn't cross the barrier -- although getting it confirmed would be terrific. This post isn't cited so I'm not sure where HairLossTalk.com got that study from.

 

[Slartibartfast]

Even though I had to check what histopathological meant, apparently it's the: "study of the microscopic anatomical changes in diseased tissue" (but you probably knew that already), that's still a very interesting piece, good find. I hadn't considered the action of the blood-brain barrier on 5AR-I levels, wouldn't this fall into the realm of neuroscience rather than endocrinology? Might as well try to pick the right speciality before we choose an expert to quiz on this encouraging new avenue of thought.

I'm going to see what, if any, new research material I can find on the issue of dutasteride's electronegative state, and how this affects its diffusion into the brain - plus a bit of background reading on the blood-brain barrier.

Later, Slarti

 

[ropcat]

Yeah, probably a neurologist rather than an endocrinologist. You know, I've seen lots of posts about headaches associated with the early stages of Dutasteride treatment. I've always assumed that these were caused by the suppression of 5AR-I in the brain. But if (and that's a big if) the medication isn't crossing the blood-brain barrier, there must be another explanation. I wonder if changes in hormonal levels -- specifically, raised levels of testosterone coupled eventually with the compensating rise in estrogen -- as the body adjusts could produce temporary headaches or lightheadedness. (If this were the case, one would guess that it would also be an occasional symptom, albeit not as extreme, with the starting phase of Finasteride usage.)

 

[ropcat]

Slarti & Raider-

I'm sure you've both seen these sections from the Avodart prescribing information, but I thought I'd paste in two interesting sections from the PDF file:

http://us.gsk.com/products/assets/us_avodart.pdf

ased on the in vitro data, blood concentrations of dutasteride may increase in the presence of CUP3A4/5 inhibitors such as ritonivar, ketoconazole, verapamil, diltiazem, cimetidine, troleandomycin, and ciprofloxacin.

I found the above quote interesting because of the mention of ketoconazole, the active ingredient in Nizoral. I wonder if enough ketoconazole enters the blood stream with Nizoral usage to cause the increased Dutasteride blood concentrations. Probably not a big issue, but interesting to ponder.

Hormone Levels: In healthy volunteers, 52 weeks of treatment with dutasteride 0.5 mg/day (n=26) resulted in no clinically significant change compared with placebo (n=23) in sex hormone binding globulin, estradiol, luteinizing hormone, follicle-stimulating hormone, thyroxine (free T4), and dehydroepiandrosterone. Statistically significant, baseline-adjusted mean increased compared with placebo were observed for total testosterone at 8 weeks (97.1 ng/dL, p<0.003) and thyroid-stimulating hormone (TSH) at 52 weeks (0.4 mcIU/ml, p<0.05). The median percentage changes from baseline within the dutasteride group were 17.9% for testosterone at 8 weeks and 12.4% for TSH at 52 weeks. After stopping dutasteride for 24 weeks, the mean levels of testosterone and TSH had returned to baseline in the group of subjects with available data at the visit. In patients with BPH treated with dutasteride 0.5 mg/day for 4 years, the median decrease in serum DHT was 94% at 1 year, 93% at 2 years, and 95% at both 3 and 4 years. The median increase in serum testosterone was 19% at both 1 and 2 years, 26% at 3 years, and 22% at 4 years, but the mean and median levels remained within the physiologic range. In patients with BPH treated with dutasteride in a large Phase III trial, there was a median percent increase in luteinizing hormone of 12% at 6 months and 19% at both 12 and 24 months.

Particularly interesting to me was the rise of thyroid-stimulating hormone by 12.4%. Of course, that level is still within normal ranges, but I wonder what its effect might be. (A slightly faster-running metabolism?) Anyone know about this?

Finally, the increase in luteinizing hormone is interesting. Here are some excerpts from http://arbl.cvmbs.colostate.edu/hbooks/ ... lhfsh.html

"Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are called gonadotropins because [they] stimulate the gonads - in males, the testes, and in females, the ovaries. They are not necessary for life, but are essential for reproduction. These two hormones are secreted from cells in the anterior pituitary called gonadotrophs. Most gonadotrophs secrete only LH or FSH, but some appear to secrete both hormones. ... In both sexes, [Luteinizing Hormone (LH)] stimulates secretion of sex steroids from the gonads. In the testes, LH binds to receptors on Leydig cells, stimulating synthesis and secretion of testosterone. ... Diminished secretion of LH or FSH can result in failure of gonadal function (hypogonadism). This condition is typically manifest in males as failure in production of normal numbers of sperm. ... In general, elevated levels of gonadotropins per se have no biological effect."

None of this information, naturally, should cause any alarm. But I thought I'd point it out as we continue to chew over the various physiological and pharmacological effects of Dutasteride.

 

[Slartibartfast]

The temporary nature of the light-headedness I experienced must surely demonstrate that whatever Dutasteride alters, whether it be the level of 5AR-I in the brain, or that of any number of hormones, it is a change that the body is capable of adjusting to. Now that's not to say that there won't be any negative long-term implications from dutasteride but, if we're seeking the cause of the light-headedness/headaches, it does suggest (to me at least) hormonal over 5AR-I.

But are increased levels of testosterone and a compensatory rise in oestrogen the cause or is it another, such as the lowering of allopregnanolone discussed by Bismarck et al on the first couple of pages of this thread: http://www.hairlosstalk.com/discussions ... hp?t=15093

Forgot to say that http://www.merlonipharma.ch is a non-prescription website - though I have no idea how the US Customs people feel about importing prescribed medicine.

I have read those last two excerpts before, but I hadn't picked up on the ketoconazole being the active ingredient in Nizoral - as I don't use the stuff myself that's not exactly surprising. The increase in luteinizing hormone, that "in the testes, binds to receptors on Leydig cells, stimulating synthesis and secretion of testosterone" is presumably what boosted my sex drive.

Thanks again for all the info. in your posts,
Slarti

 

[Slartibartfast]

Two months since my half-year update and for a good portion of this time I was plagued by a nagging feeling that my hair was taking a beating from (yet another) shed. Now normally I've found it quite straightforward to spot a shed but, thanks to my decision to let my hair grow into a longer style, I had trouble determining whether this suspected increase in daily loss was anything more sinister than the tendency for longer hairs to be more noticeable when shampooing or combing. Then, last week, I paid a visit to my friendly hairdresser, got a fairly hefty chunk lopped off my hair and so am now in a position to give a mildly accurate update.

So here goes... My hair has definitely lost some density over these two months. Unusually for me this has occured on the crown and mid-scalp region rather than the oft shedding front - which continues down its own merry path of sheds and regrowth. The loss in density is not truly evident once my hair is dry but I can feel the difference by pressing down on it, and see it clearly whilst my hair is wet - when there's appreciably more scalp visible.

Now it would be premature to say that I'm certain this shed has run its course, but I am starting to feel that that may be the case - crosses fingers, touches wood and starts a frantic search for that lucky rabbits paw (obviously not so lucky for the rabbit). What about the front? Well, there's nothing conclusive to report. Somedays I'm convinced it's improving and on others I'm certain it's not. All I can say for sure is there are still plenty of thinnish hairs around, each one teasing me with the prospect they will develop into something approaching a respectable hair.

Sorry, that's not exactly a great update, in terms of the detail I go into as well as what's actually happened to my hair, but this shed has drained some of my normal ebullience and I'm struggling to type coherent sentences about hair loss.

Till next month,
Slarti

 

[Guest]

how about some pics...

 

[GoldenBear]

I just went of finasteride about 10 days ago and the past 2 days i had a mild headache and overall light headidness/dizziyness, this could be cause by my lack of eating though. I filled my prescprition in a pharmacy and the pharmacist told me I might experience this as the drug may increse my blood pressure. I also read on a site that ketoconazole should not be taken in conjunction with dutasteride, however it said nothing of using it topically.

And now for a quick question, almost every site i read about dutasteride it states that when your on it you should use a condom when humping a possibly pregant girl. Does that apply with Finasteride also?

 

[Slartibartfast]

trax - I'm cameraless at the mo' but I might put some pictures up when I get round to buying a new one, which will probably be in a couple of months. Not sure how useful they'll be though as I've no useable older ones to show for comparison.

goldenbears - a quickish answer to your quick question apropos sex & finasteride: my understanding (so it's far from definitive) is that you can have unprotected sex with a pregnant lass without risk of harming the embryo/foetus. But all you dutasteride users must be more careful, we don't know for certain whether the trace levels of dutasteride found in semen poses a risk - and the consequences could be pretty horrendous.

all and sundry - two weeks since my update and I'm now certain that the shed I discussed had indeed run its course, just in case anyone was wondering.

Slarti

 

[Slartibartfast]

Well here I am, and there you are. The other difference between us is that I've now been taking dutasteride, daily for precisely 307 days and you have not. What all that means is that I'm unnecessarily padding out this 10 month update with a(n) (un)healthy dollop of nonsense.

Starting with my crown and mid-scalp regions: There's been no further shedding in the last two months, so the new, post-shed regrowth is beginning to add to the overall weight of my hair. At the crown this translates into a slight (so far) shrinkage of the, admittedly small, bald spot that was caused by the recent, heavy shed.

As I move from the vertex down the back of my head my hair grows in such a way that, even with a limited amount of thinning, two diagonal lines - one per side, and along which my hair naturally parts - soon make a thin strip of scalp visible. With judicious styling these can be disguised, to an extent, without detriment to other, thinned areas - such as the crown. Fortunately this area shed only to the point of slight, scalp show-through and so is quite rapidly moving back to having an effortless coverage.

In a way the mid-scalp suffered more from the shed than the crown as it entered it with a lower density, so aesthetically it became quite flat and lifeless. Again I'm surprised at how fast the improvemant has been - even if it will take perhaps 3 to 4 more months just to get back to where it was pre-shed. At least the new hairs on the crown and mid-scalp are coming in, straight-off, with a decent thickness, unlike...

The front: With a mind of its own, the front continues to tread an alternative path towards a decent (I hope) head of hair. What's more, the progress of the two sides is very much asymmetric - significantly worse on the right side. What they have in common are many thin hairs, hopefully going through various growth cycles as a means of (eventually) becoming fully mature. The problem is it's phenomenally hard to keep track of hairs that are so thin and lightly pigmented, and without keeping track of a few of them how will I know for sure they aren't stuck in the process of miniaturization.

Just last week I noticed a little group of about 5 or 6 of these 'mini' hairs, close to the middle of my hairline. They've become a new test group - if they can progress in that location I can still achieve a good hairline.

Pray for them...
Slarti

 

[Slartibartfast]

Okay, I'm a couple of weeks late with this 1 year update, well it's a year since I switched to taking dutasteride daily, more like 4 years since I started off on a finasteride/minoxidil combo. Speaking of minoxidil, I meant to say last time that I'd decided to drop down from two daily applications to just one - the irritation (flakes of unabsorbed minoxidil as well as the hassle of morning usage) had finally got to me, so I'm hoping (I have my fingers crossed as I type this) the single application will allow me to hang on to whatever gains minoxidil has provided.

Onto the hair... In my last post I said that everywhere bar the front was thickening-up pleasingly quickly post-shed. Fortunately this has continued, and with the exception of a small patch of crown thinness my hair quality is pretty much back to its pre-shed level of six months ago. But then I've always been fairly confident that dutasteride would work on those parts, even if I did have a few shed induced moments of panic along the way. The real question was, and still is, whether or not it would do the same for the front.

Well, the front continues to provide irritation and succour in equal measure. My main problem is a strip of (not very much) hair that stretches from above the temples and right around the hairline - with a depth of, say, half an inch at best to more like a full inch on the long-suffering right-side of my hairline. Irrespective of careful styling, this strip looks painfully thin in anything approaching strong light (sunny days shouldn't be a cause of stress), and the most positive thing I can say is that it hasn't deteriorated further in the past 2 months. To be fair there is still a fair smattering of 'mini' hairs who might, one day, all get round to becoming a decent size.

The little test group I mentioned last time have so far become: two not quite full-size hairs, one as short and light as 2 months back, another is one (tiny) step up from that, and the other one (or two) have vanished - hopefully as a prelude to regrowth. Behind all this, in the remainder of the frontal region, it's actually bulking-up nicely, not to the same extent as the crown or mid-scalp but definite progress nonetheless.

I suppose it's the progress in these other areas that keep me hopeful for the very front, that and the knowledge that my best results from finasteride came after 14 months.

Next update in about 6 weeks time, good luck,
Slarti

 

[damnthis]

good story, thanks for the update

 

[noorur]

thanks alot for ur update, i'll be following ur update, because it gives us all an idea of how hair regrowth occurs and etc.

 

[Slartibartfast]

As I predicted four months back, the crown and mid-scalp (basically everywhere bar the front) have managed to claw their way up to a density comparable (or slightly better) to before my tremendously enjoyable, 3 month long, dutasteride initiated shed ravaged them. Aesthetically, this translates into it once again looking like male pattern baldness has never darkened their door, even if, to my trained eye, I can tell that some diffuseness persists - particularly when wet.

I've never been one for photographing my nugget, so to help me gauge any progress (or lack thereof) I use visual yardsticks (I have a v. good memory for images). One of these is simply the amount of scalp visible when I part my hair down its natural line, i.e. slightly off centre, over to my right side. By this measure, the non-frontal thickness broadly equates to that of 4 and a bit years ago, essentially when I started on finasteride and minoxidil to counter frontal thinning; because at that time I had no idea my crown was in the process of becoming diffuse to a point where I would develop a small bald spot - happy days.

So I could live quite happily with the crown and mid-scalp as they are now but the dutasteride hasn't finished yet, as the parting is still narrowing - it looks rather like the two sides of hair are meshing together. The parting is also becoming more definite nearer to the front, with only the last half-inch falling short of a decent density.

Unfortunately the hideously diffuse, half-inch deep strip of hair at the front persists, though behind this, on the left-side at least, some gradual progress is being made. It resembles more the look of someone in the early(ish) stages of a receding hairline rather than the "oh my God, I can't believe how much scalp is shining through" stage that it did at worst, and that the right-side is still tragically near to. Now I'm sure it's trying, bless its little heart, but how long do I have to wait for a decent number of the fine hairs that populate the area, to thicken up?

All that's left is for a quick update on my little test group: two of the hairs are now fully functioning adults, i.e. full thickness and length; one is a stage below that, good length but a bit on the thin side; whilst the only other clearly visible hair has got stuck as an early stager, adding nothing cosmetically.

If my 16 month update is on time (fat chance) it'll be here, but down a bit, in 7 weeks.

Good luck to all,
Slarti

 

[raider]

update

Hi Slarti

Sos for the extended absence period.

Unfortunately I have not seen any improvement with the dutasteride and will soon be coming off...

Im looking at transplant options and wondered what you think? Hoping I can get away with 750 grafts as all I need is to fill in the temples and I'll be away!!!

 

[Slartibartfast]

Ah, hello Raider, long time no typed messages.

I'm not that knowledgeable apropos hair transplants (or any other type surprisingly) but it seems reasonable to say you'll be able to get away with a relatively small number of grafts - as you're only doing the temples. I imagine the "surgical alternatives" forum must be worth a gander - not been in there myself.

Are you sure it's a good idea to drop the 5-AR inhibitors though? Apart from the fact that my hair is still gradually improving (touch wood) at the 15 month mark, you can't be sure that the dutasteride isn't the only thing keeping the rest of your barnet where it is.

Slarti

 

[Aplunk1]

How's the Dutasteride working now?

 

[Slartibartfast]

Hi, I'll post a full update later this week, probably on Thursday.

We've made it to Thors-day, so here's my update:

I'm somewhat later with this than I originally intended, what with all the Christmas and New Year preparations and celebrations, which means this post marks 17 months since I began my daily intake of Dutasteride.

Fortunately, or should that be unfortunately, a month either way is fairly insignificant where monitoring my hair's progress is concerned; except for when I was in the midst of my heavy dutasteride(y) shed and the quickness of change was all too apparent. Little has changed since mid-October, so little in fact that some of the observations made then are equally valid now. In the name of laziness then, here are the relevant sections from my previous update:

"So I could live quite happily with the crown and mid-scalp as they are now but the dutasteride hasn't finished yet, as the parting is still narrowing - it looks rather like the two sides of hair are meshing together. The parting is also becoming more definite nearer to the front, with only the last half-inch falling short of a decent density."

That describes perfectly what is still occuring, with the addition that the hair around the crown, and in particular that down the back of my head (above the stuff that isn't affected by male pattern baldness of course), is once more regaining the waviness of my pre-male pattern baldness days - a process that had been getting into swing just before my dutasteride shed kicked-in. Last October I also wrote that:

"Unfortunately the hideously diffuse, half-inch deep strip of hair at the front persists, though behind this, on the left-side at least, some gradual progress is being made. It resembles more the look of someone in the early(ish) stages of a receding hairline rather than the "oh my God, I can't believe how much scalp is shining through" stage that it did at worst, and that the right-side is still tragically near to."

This is also a broadly accurate description of the current situation, with the proviso that it is the right-hand side that has made modest progress - though only near to the middle, not right out on the side; and that on the left my hairline has seen no change at all (or may have thinned very slightly) - hard to be sure, my opinion vacillates from day-to-day.

One change I have noticed is a scattering of short (just a mm or two), light-brown hairs on the hairless section of my left temple. I did have these once before, way back when I was still taking dutasteride every other day, but they didn't amount to anything (obviously, otherwise the temple would be hairy) and vanished around 6 months into taking a daily dose (when I had my shed). Will update if they do anything remotely interesting.

Good luck,
Slarti