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Official Accutane Thread

Discussion in 'Post-Finasteride Syndrome & Accutane Sufferers' started by Took_accutane, Mar 16, 2012.

  1. Took_accutane

    Took_accutane Member

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    I've seen a number of people requesting an Accutane (isotretinoin) thread on the board - mods, if we can get a sticky on this, it'd be greatly appreciated. There are a great number of posts all over various forums from people experiencing long-term problems from taking this drug. I won't bore you with my own story.

    This is the current state of play:

    - Some people who take Accutane develop libido and erectile dysfunction problems, along with other symptoms. There are a hundreds, probably thousands of postings all over the internet about guys experiencing libido problems, erectile problems, and related problems after taking isotretinoin. There are public cases in the media of men who have this ongoing problem and there are cases in the literature of erectile dysfunction during isotretinoin. The symptoms experienced very similar to Post-Finasteride Syndrome. Interestingly there are many connections between isotretinoin and finasteride, it's deeply interesting that these two drugs exhibit these shared effects:

    - We know that Accutane negatively affects levels of dihydrotestosterone (1).
    - It also suppresses neurogenesis in the hippocampus of the brain (2).
    - Finasteride shares these effects (3) (4).
    - Accutane is a 5-AR suppressor (5).
    - Finasteride is a 5-AR suppressor (6).

    At this time we don't know the mechanism of why the problems persist, but we do know that Accutane affects the way genes are expressed, and that this can cause persistence of any side-effects after ceasing the drug (7). Cases of sexual dysfunction as a side effect during Isotretinoin use have been recorded in the literature (8). Read that again and let me spell it out for you: Accutane affects the way genes are expressed and this can cause persistence of any side-effect after discontinuing the drug.. and erectile dysfunction has been recorded as a side-effect of the drug. Finasteride, likewise, has been associated with sexual dysfunction and there is information about a study into the epigenetic effects of finsteride on the propeciahelp.com forum (9). Cases of sexual dysfunction following finasteride use are also documented in the literature. (ref to be provided).

    The pattern, from reading many, many posts from men affected by this problem, seems to be that they seek help from their doctor and try various treatments but none seems to help. Often the doctor will say the issue is psychological or depression-related. This is the exact same pattern which has been highlighted by the doctors investigating finasteride. They have ruled out the depression/psychological cause. In their studies they specifically rule out guys from participating who have had psychological difficulties (anxiety, depression, etc).

    - The propeciahelp.com guys are have been through a significant journey and a number of international universities are conducting is a study into the effects of finasteride. It's hoped this could explain why some users of the drugs experience persistent negative effects. The results of this research could have strong implications for former users of Accutane who are experiencing ongoing erectile dysfunction, sexual dysfunction, orgasmic anhedonia, etc.

    - We need to read as much as we can, like the finasteride guys, and to support research into these medications. Connections with the research they are carrying out could be very helpful and we need to try to read and support any basic scientific research intowhy and how the 5-AR inhibitors, finasteride and isotretinoin, cause ongoing sexual dysfunction after a person is no longer taking it.

    (1) Effect of oral isotretinoin treatment on skin androgen receptor levels in male acneic patients.

    http://jcem.endojournals.org/content/80/4/1158.abstract
    (2) www.pnas.org/content/101/14/5111.full.pdf
    (3) http://jcem.endojournals.org/content/78/5/1064.abstract
    (4) http://www.ncbi.nlm.nih.gov/pubmed/20486040
    (5) Evidence for decreased androgen 5 alpha-reduction in skin and liver of men with severe acne after 13-cis-retinoic acid treatment.

    http://jcem.endojournals.org/content/78/5/1064.abstract
    (6) http://jcem.endojournals.org/content/78/5/1064.abstract
    (7) http://www.ncbi.nlm.nih.gov/pubmed/19501473
    (8) http://www.ncbi.nlm.nih.gov/pubmed/16447596
    (9) Refer to propeciahelp.com forum, in the studies section - www.propeciahelp.com.
     
    Last edited: Feb 22, 2014
  2. Matty

    Matty Member

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    Hey all,

    Haven't posted in a while. But still a Canadian patient of Dr. John's and doing well.

    I popped on here because I have some important things to report on the subject of Accutane/sexual function - that may benefit those of you who have suffered endocrine issues since taking it. You will remember I posted the very first thread on this subject here:

    http://www.allthingsmale.com/forum/showthread.php?653-Accutane-and-hormones&highlight=accutane

    I have always believed that Accutane at the very least, aggravated an existing condition, which resulted in my almost complete endocrine collapse.

    Well I am shocked at my recent findings and think I have uncovered at least one potential reason for why Accutane impacts the items aforementioned by Took_accutane above. I will try not to make this long winded, and I just want to get out there what I've developed thus far. But here's what I think happened in my case:

    1. Accutane works on and significantly impacts Dopamine receptor D2 gene:

    Chambon, et. al. Regulation of dopaminergic pathways by retinoids: activation of the D2 receptor promoter by members of the retinoic acid receptor-retinoid X receptor family. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14349-54.

    Dopamine is a neuromodulator involved in the control of key physiological functions. Dopamine-dependent signal transduction is activated through the interaction with membrane receptors of the seven-transmembrane domain G protein-coupled family. Among them, dopamine D2 receptor is highly expressed in the striatum and the pituitary gland as well as by mesencephalic dopaminergic neurons. Lack of D2 receptors in mice leads to a locomotor parkinsonian-like phenotype and to pituitary tumors. The D2 receptor promoter has characteristics of a housekeeping gene. However, the restricted expression of this gene to particular neurons and cells points to a strict regulation of its expression by cell-specific transcription factors. We demonstrate here that the D2 receptor promoter contains a functional retinoic acid response element. Furthermore, analysis of retinoic acid receptor-null mice supports our finding and shows that in these animals D2 receptor expression is reduced. This finding assigns to retinoids an important role in the control of gene expression in the central nervous system.

    http://www.ncbi.nlm.nih.gov/pubmed/9405615?dopt=AbstractPlus

    2. Dopamine has a direct connection with Prolactin levels:

    Dopamine (DA) holds a predominant role in the regulation of prolactin (PRL) secretion. Through a direct effect on anterior pituitary lactotrophs, DA inhibits the basally high-secretory tone of the cell. It accomplishes this by binding to D2 receptors expressed on the cell membrane of the lactotroph, activation of which results in a reduction of PRL exocytosis and gene expression by a variety of intracellular signalling mechanisms.

    http://jop.sagepub.com/content/22/2_suppl/12.abstract

    3. Let's say reduced Dopamine levels result in sustained elevated Prolactin, what would that mean over time?

    Elevated serum prolactin levels create two problems that are inimical to sexual potency. With high serum prolactin levels, normal pulsatile GnRH and LH secretion does not proceed. This is why nursing mothers stop menstruating. Without pulsatile LH release, a man’s testicle is stranded without adequate stimulation and cannot produce its full ration of testosterone. Serum testosterone levels then fall. But giving more testosterone is not the remedy because elevated serum prolactin levels also prevent the body from responding normally to testosterone.

    http://pillsblog.info/what-is-prolactin-and-why-does-it-disrupt-male-sexual-function/

    ---

    Here's where my own personal experiences and thoughts come into play...

    I've had my T tuned for some time, taking DHEA, estrogen's in check. And yet I still have inconsistent issues with sexual performance and my mood is either dull or depressed. Surprisingly what made the connection for me was after every time I drink/smoke, the day after my sexual performance is immediately elevated. I could never understand why, it wouldn't last more than a day though. But within that was the key...

    What does drinking and smoking do to the brain?

    They both increase dopamine.

    What does dopamine do again?

    Regulates Prolactin.

    What does Prolactin do again?

    Suppresses male androgens.

    Bingo!

    Just to add to this re: mood. Always thought I had low serotonin so I would take 5HTP. 5HTP would make my sexual performance non-existent and also result in racing thoughts and terrible anxiety. I learned over the years 5HTP was a big no-no for me. I just assumed then I did not have low serotonin. In retrospect, serotonin is said to counter-balance dopamine and lower it. Was I just driving my dopamine further down? I digress...

    If Accutane potentially reduces dopamine (cat goes away), Prolactin can shoot up (mice will play!), wreaking havoc on your endocrine system from there on out. I haven't gotten too far into it, but I will be pursing the idea that without dopamine, prolactin surges, potentially resulting in a pituitary tumor (prolactinoma) that could in turn impact other hormones. In my case my adrenals aren't doing much either (cortisol, aldosterone, dhea). I haven't gotten too far into how and if this relates however, just androgens.

    But administering dopamine surrogates will shrink said tumors:

    Three medications, bromocriptine (Parlodel), pergolide (Permax), and cabergoline (Dostinex) have doparninelike properties, and any of them can

    be an effective dopamine surrogate. When hyperprolactinemic men or women are treated with bromocriptine (Parlodel), pergolide (Permax) or cabergoline (Dostinex), serum prolactin levels promptly return to normal. Continued treatment is required to keep prolactin levels fully suppressed.

    This treatment has been effective in two respects. Lowering serum prolactin levels to normal restores sensitivity to the sexual effects of testosterone. As serum prolactin levels fall, serum testosterone levels increase and potency returns. Bromocriptine (Parlodel) or cabergoline (Dostinex) treatment also decreases pituitary tumor size and shrinks prolactin-secreting tumor tissue.

    http://pillsblog.info/what-is-prolactin-and-why-does-it-disrupt-male-sexual-function/

    ---

    Proof is in the pudding?

    I have always had elevated Prolactin in my blood tests. Still within normal range according to my Canadian labs and Canadian doctors (9 <18), but the point is its elevated. Fact is I think the normal range for males should be reduced to next to nothing. Unless someone can tell me the purpose of Prolactin in males, from what I know it only causes bad things. It shoots up after sex and should come back down. When it stays even slightly elevated it can wreak havoc. I don't know how much of my havoc it's caused, but I can tell you I took 240MG L-Dopa Friday night, felt immediately enhanced with great sensation down there, and had some of the best sex and feeling of my life. My T levels were tuned all the while keep in mind.

    Take it for what it's worth and I'm not sure where I go with this theory from here, but I'm pretty sure I've unlocked as I say, one of the reasons why Accutane impacts male sexual function.
     
    Last edited: Mar 18, 2012
  3. diesiel

    diesiel Active Member

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    good post matty. I have never taken accutane but i can relate to the whole post drinking next-day results.

    Except for me the day after i drink i feel better "all around", not just sexual function I have never taken accutane (have taken finasteride though).

    However my prolactin levels are always under 5 (2-19) from bloodwork over the last 3-5 years, i assume thats low enough to not be a factor... but i could be wrong. I've always wondered why i felt pretty good after moderate-heavy drinking and my friends all had hangovers
     
  4. alanc

    alanc New Member

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    My theory is, Accutane results in the suppression of pituitary hormones cortisol, T3, LH, IGF-1. (1),(2). In some people the pituitary output doesn't regulate itself back to normal levels after stopping and they end up with low metabolic rate due to reduced pititary hormones.

    I believe different people respond in different ways and it may only be one hormone that dooesn't pick back up which causes a suprresion of other hormones. They key is to identify which hormone you need to "restart" your system.

    As long as there are no primary issues, then i believe is the key if low metabolic rate holding back GH production. You can raise metabolic rate quite easily via exogenous thyriod hormone and or HC. This should hopefully see an increase in GH which should be able to "restart" your system. If raising metabolic rate doesn't see a big enough increase in GH and IGf-1 then you may need to supplement with GH releasing peptides.

    The GH theory restart works as follows:

    Increase GH > Increase IGF-1
    Increase IGF-1 > Incease cortisol production (3)
    Increase GH > Increase T4 to T3 conversion (4)

    Peptides work by increasing GH and IGF-1 (5). So supplmenting with GH releasing peptides, specifically GHRP-2 with GHRH, may be the key if raise in metabolic rate via T3 or HC doesn't cause a large enough increase in GH and IGF-1 output.

    It may be the case that GH levels are ok, and it is only IGf-1 that is low post accutane. Therefore IGf-1 only could be used.

    This is just my theory and I am not a medical professional by any means so this info is for research only and not to be taken as advice on what to do. It all seems to fit together. I believe that low metabolic rate IGF-1 is the link to all of the problems and is something that can be treated.

    (1) - http://www.ncbi.nlm.nih.gov/pubmed/21103844
    (2) - http://www.mendeley.com/research/sh...sotretinoin-affect-growth-hormone-physiology/
    (3) - http://jcem.endojournals.org/conten...a789ecc65291b03fe2ae5d30&keytype2=tf_ipsecsha
    (4) - http://www.ncbi.nlm.nih.gov/pubmed/7208169
    (5) - http://jcem.endojournals.org/conten...INDEX=0&sortspec=relevance&resourcetype=HWCIT
     
  5. alanc

    alanc New Member

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    Matty, I did a quick search on IGF-1 and dopamine and they appear to be closely linked. I'll do some more research into it but I think that IGF-1 and dopamine are the key. This article is extremely interesting....

    http://progressiveconvergence.com/Activation of Methionine Synthase.pdf

    I guess once we get all the research done, we need to find a doctor that will look at the info (hopefully agree with findings) and give treatment a try.
     
    Last edited: Mar 19, 2012
  6. tierry

    tierry Active Member

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    I've used some dopaminergics (cabergoline, ropinirole, pergolide, l-dopa and apomorphine) for libido and erection enhancement with some good successes, especially when combined with PDE5i. The 2 which have given best results to me are Pergolide and Apomorphine. The others have not given appreciable results.

    I usually take alphablockers along with PDE5i because blocking noradrenaline enhances the PDE5i effect on the corpora cavernosa.

    Dopaminergics can produce similar results. In fact by stimulating the dopamine receptors peripherally they signal to shut down Noradrenaline release.

    Nitric Oxide release is increased as well by different routes.
    Low noradrenaline output will let more NO to be released from nitrergic nerves as they lack part of the negative feedback given from NA.
    The augmented central dopaminergic stimulation will send more signals from the brain down through the spine to the genitalia nitrergic nerves.

    Plus dopaminergics clearly and strongly increase libido due to central stimulation.

    Their effects vary based on the Dopamine receptors they stimulate.

    My best results in term of erections and libido have been with Pergolide + Cialis. I've not tried Pramipexole yet.
     
  7. Harry Hormones

    Harry Hormones Member

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    My friend who took accutane for several years had his salivary cortisol levels tested and they were very high, not low!
     
  8. alanc

    alanc New Member

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    The thing is, although we have taken accutane, there is a chance that our current conditions have nothing to do with taking it. It might just be the case that I have low cortisol due to something else. My skin isn't great 7 years on so I know that some of the effects are not permanent. However, any studies I have seen show that immediately following accutane use, pituitary hormones are reduced. I guess some people recover and their pituitary hormones return to normal and some do not. It could be that there was an underlying problem with adrenals in the first place and the stress while on tane has just amplified it...or it could have nothing to do with the tane
     
  9. alanc

    alanc New Member

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    also, how do you get your dopamine levels tested? Is there a specific test for it?
     
  10. Took_accutane

    Took_accutane Member

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    I'm very certain my problems were caused by Accutane.. before Accutane I had a strong libido, soon after Accutane it became very low. The difference was quite stark. I later developed anxiety and depression but these were some time after my libido had substantially reduced. Sometimes it can seem like a chicken vs. the egg scenario - i.e. did your libido reduce because you were depressed or did your depression happen because you have reduced libido. For me, the answer is clear because I've been free from depression and anxiety for a few years and my libido is still very low. 100% this was due to Accutane - though getting a doctor to agree to this would be a different matter. But what do most doctors know about Accutane? Barely anything. I'm certain this was caused by Accutane.
     
    Last edited: Mar 25, 2012
  11. DaveK22

    DaveK22 Member

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    A HUGE THANKS to Dr. John, other forum Administrators, & "Took_Accutane" for making this topic a "sticky". I will undoubtedly be a regular reader of this thread.
     
  12. alanc

    alanc New Member

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    Has everyone on here had their vitD levels checked? I know tane can lead to lower levels of D which can cause problems. I had mine tested a few months ago and it was low, just wandering about everyone else's levels.
     
  13. Dubya_B

    Dubya_B Member

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    Many thanks to the OP and to Dr. Crisler and whoever decided to make this thread a sticky. It's greatly appreciated!

    I noticed a slight loss of libido and light depression within the first week of using Accutane. This remained without worsening during my entire treatment, then I experienced a "PFS-like" crash around two months after my last pill (was 18, super horny and in great health before taking the drug). 13 years later I am still suffering from low libido, ED, genital numbness, emotional blunting, depression, fatigue, occasional bouts of anxiety, and pretty much lost my lust for life in general. All of this despite normal levels of T, Free T, DHT, E2, and many other hormones.

    Here is a short list of informative posts and websites concerning Accutane if anyone is interested:

    Posts on acne.org discussing accutane and sexual dysfunction-
    accutane-and-erectile-dysfunction/
    men-fancy-trading-in-your-acne-for-impotence/
    repairing-the-long-term-damage-from-accutane/
    accutane-castration-from-the-inside/
    isotretinoin-induced-sexual-dysfunction/

    Roaccutane action group forum-
    http://ragforum.freeforums.org/

    Many studies related to possible mechanisms behind accutane's long term side effects (Roaccutane Science forum)-
    http://max001.proboards.com/
     
    Last edited: Mar 25, 2012
  14. Harry Hormones

    Harry Hormones Member

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    Vitamin D levels should return to the normal range some time after finishing accutane, but having such low vitamin D levels whilst on accutane can trigger many of the chronic conditions that people are left with. It's very, very hard to get these chronic conditions under control.
     
    Last edited: Mar 26, 2012
  15. Took_accutane

    Took_accutane Member

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    It's a shame that those guys are posting on acne.org about their bad experiences because there does seem to be a lot of pro-accutane people on there who are ready to bash people. Dubya_B, if you want to share the link to this thread on these other forums then it might help to let those guys to know that there are other people out there.
     
  16. alanc

    alanc New Member

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    Found some really useful info on another site about a recent report into how dopamine, GH and cortisol are linked to fibromyalgia. Bearing in mind the previous information on this thread and how we have narrowed the main causes to dopamine, igf-1 and I believe cortisol (Matty, you mentioned in your post that you were unsure where low cortisol fits into your theory), this article clarifies somewhat how they are all linked together:

    http://jrheum.org/content/36/2/221.full

    I think the information and other articles references as part of this study really is dynamite material for us. This paragraph especially:

    Finally, if dopamine indeed plays a critical role in the pathophysiology of FM, then one would expect the disorder to be associated with other phenomena related to central dopamine. A review of research findings suggests this may indeed be the case. As noted, FM is associated with increased prolactin release in response to dopamine antagonism, which is indicative of a denervation hypersensitivity as would be expected in the context of reduced dopaminergic activity9. Other neuroendocrine abnormalities among subsets of FM patients include attenuated growth hormone response to physiological challenge28​ and mild hypocortisolemia29. While dopamine stimulates growth hormone release, the reactivity of striatal dopamine in response to challenge corresponds with cortisol levels such that conditions characterized by low cortisol would be expected to be similarly associated with attenuated dopamine release30​. Given that FM is associated with dysautonomia, it is noteworthy that cortical dopamine plays a role in modulating autonomic function31.

    If i'm understanding this correctly then "the reactivity of striatal dopamine" requires adequate cortisol levels, so if we can correct our low/ dysfunctional cortisol levels this should have a positive affect on dopamine levels, which should result in increased GH and lowered prolactin. What's your thoughts guys?
     
  17. alanc

    alanc New Member

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    The GH releasing peptide GHRP-2 which I mentioned in an earlier post would appear to be a possible treatment as it increases GH, IGF-1 and has the side effect of increased cortisol production and therefore could be a perfect way to treat, given the previous article i posted (increased cortisol leads to increased dopamine, leads to increased GH and lowered prolactin). However, the problem with it is that GHRP-2 also can also cause an increase in prolactin within normal ranges. Now whether this increase in prolactin would be significant given that prolactin is elevated already and due to low cortisol and GH in our condition is unknown. The reports of increased prolactin I assume will be in healthy individuals and not those with the specific problems that we have.
     
  18. alanc

    alanc New Member

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    You can probably tell that i'm getting pretty excited about this but here is another study linking cortisol and dopamine:

    Moreover, the magnitude of the salivary cortisol response to stress was significantly correlated with the reduction in [11C]raclopride binding in the ventral striatum (r = 0.78), consistent with a facilitating effect of cortisol on dopamine neuron firing

    http://www.jneurosci.org/content/24/11/2825.full
     
  19. alanc

    alanc New Member

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  20. alanc

    alanc New Member

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    Sorry to hog the thread but a lot of this is coming together now and I just want to try to clarify and put everything in order of effect. So we know that:

    1. Accutane results in lower IGF-1 (http://www.mendeley.com/research/sh...sotretinoin-affect-growth-hormone-physiology/)
    2. Lower IGF-1 results in less p450scc and therefore lowered cortisol (and dhea) produced via blunted response to ACTH(http://www.ncbi.nlm.nih.gov/pubmed/8276137) (http://www.ncbi.nlm.nih.gov/pubmed/9141522)
    3. Reduced dhea results in reduced testosterone which results in reduced dht
    4. Reduced 5 Alpha Reductase activity (mainly type1) results in reduced DHT and a reduction in sebum
    5. Lower cortisol results in a) lower dopamine levels and b) low metabolic rate via lowered T3 uptake
    6. Low dopamine leads to low mood and elevated prolactin which leads to sexual dysfunction
    7. Low metabolic rate causes chronic fatigue and hypothalamus reduces GH,LH
    8. Low GH causes reduction in T3 to T4 conversion

    I believe that this is how Accutane works and affects us.

    From the blood tests I have had done I know that I have low cortisol and lowish dhea. I also know that my T4 (top quarter of range) and TSH levels are good however my T3 level is lowish (bottom quarter of range). I have a low metabolic rate and have been diagnosed, via my symptoms, by a thyroid specialist, as being hypothyroid despite T4 and TSH levels being spot on. For the last month I have been taking T3 meds but it has had little effect, even at 80mcg per day which indicates to me that my low cortisol is the culprit in low metabolic rate. I can guess that my ACTH response is blunted due to slight hyperpigmentation (red face after short exposure to sunlight).

    Has anyone here had their IGF-1 tested and know their levels?
     
    Last edited: Mar 29, 2012

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