I have been doing Tribulus cycles for about 6 months. The first time I took it it worked really well but every next cycle the effect is smaller. Right now it doesn’t really work any more.
I take a very high dose so there isn’t much room for raising the dose. I intend to take a long break from Tribulus - maybe a month and a half at least.
In the meantime, I want to try something else. Has anyone experienced improvement in sexual symptoms with any other herb or supplement?
Previously I took Maca and felt nothing, although I took a normal dose and not a super high dose, which is what I do with Tribulus.
I wouldn’t mind trying some of the herbs in CDnuts protocol - after all Tribulus is part of that protocol and it does work (for a while) - but there are too many things there. I want to try just one thing for a start. What should I try?
Give boron a shot, gave me a window. worked for a few days, never worked after, but still, something. Especially since i have had like 2 windows in 2 years.
Well, there are a lot of things that are said to be 5ari. I guess we’ll see. I just ordered Maca, Tongkat Ali and Ashwagandha. Will try high doses of each, consecutively.
I completed my trial of the following supplements:
Tongkat Ali
Ashwagandha
Maca
Pine Pollen
Mucuna Pruriens
I took each one of them separately, for at least a week, at doses exceeding the recommended one by a factor of 2 or more.
None of them had any effect.
So far two things have worked for me.
Tribulus, when I take a dose of 6x750mg/day (6 times the recommended dose). I have written about this before. It works but the effect goes down with continuous use, and with each successive cycle. I am currently taking a multi-month break from it.
Transdermal DHT when applies to the penis, perineum and general genitalia area. The effects are: stronger and more pleasurable orgasms, higher sensitivity, harder erections, easier to achieve and maintain erections.
(WARNING: this may be dangerous, as it may lead to cancer! It certainly leads to pain in most of these tissues when I apply a higher dose. The cause may be due to rapid proliferation of cells and changes of tissue. Presumably this is the same kind of pain people get when they stop finasteride - even if they don’t have PFS - when DHT goes back up. Or maybe the nerve endings themselves are sensitive to DHT and undergo a transformation.)
Conversely, when I apply DHT eslewhere on the skin, which is equivalent to systemic administration, there is some effect on some symptoms such as joint pain (90% reduction in joint pain, which in itself is a material relief) but a very small, though positive, effect on sexual symptoms. Effect on sexual symptoms is much higher with genital application.
The above evidence contributes to the idea that sexual problems in PFS may be caused by faulty gene expression of 5-ar type II. Additional evidence that may also point towards this conclusion is:
The persistent upregulation of the AR in genital tissue. With insufficient local production of DHT, the AR will remain upregulated. I am not familiar with any study that has tested genital tissue concentrations of DHT in PFS subjects. Anybody please correct me if I am wrong.
DHT in local tissue (prostate) is approximately 10 times as high as in serum in normal subjects.
Further evidence from paper above: serum DHT concentration is a poor predictor of tissue concentrations. In other words, having normal serum concentrations of DHT does not mean tissue concentrations are adequate. Consequently, raising serum concentrations systemically would not result in adequate tissue concentrations. This would explain why most people who have tried systemic DHT supplementation have had little effect from it on core PFS symptoms.
Evidence from the latest Melcangi study for the methylation of the gene encoding for 5-ar type II in PFS subjects.
Evidence that raising testosterone - either marginally through Tribulus or substantially through TRT - helps some people. This would work through providing more substrate (Testosterone) for 5-a reduction (to produce DHT locally). The magnitude of the effect would depend on how much of the enzyme is present, which could vary in different subjects.
My own anecdotal evidence for an extremely low serum DHT baseline, which may point towards an even bigger insufficiency or a complete absence of DHT in genital tissue, paper above notwithstanding.
There is other evidence as well. I may write some more about this theory in another thread at a later time. Anyone please let me know if you are aware of any evidence contradicting any of the above.
I believe this is the most productive avenue for future research.
Melcangi himself, after having found the methylation of the gene encoding for 5-ar type II in PFS subjects, concluded it was not known whether this methylation was caused by finasteride or whether it existed before finasteride in affected subjects.
It is thus only natural that the next study – of the highest possible priority – should attempt to observe a causal effect of finasteride on the expression of this gene. This can easily be accomplished in a rat study, as I have long advocated.
The study should do the following: 1) test for this gene in rats before finasteride administration, 2) expose mice to finasteride; 3) after discontinuation of finasteride, test for sexual function and identify mice with significant and persistent sexual dysfunction; 4) test for any changes in the expression of that gene in affected mice.
Previously, there have been arguments against the feasibility of inducing PFS in fats. One such argument rests on the claim that lab rats/mice are clones or lack sufficient genetic diversity to account for the supposed genetic predisposition to PFS. There is no such limitation as far as I know.
There are certain lines of rats that are “outbred”, meaning, they are bred to preserve maximum genetic diversity.
“Outbred rat stocks are genetically diverse within the population, and there is likely genetic variability between any two animals within the population. Outbred stocks are primarily used in studies designed to evaluate or model the human population. Accordingly, mating systems aimed at maintaining outbred stocks must ensure that the genetic diversity in the population is maintained (i.e., must prevent or minimize the breeding of related individuals).” https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/outbred-rat-strain
PFS in rats, as far as I know, has never been measured in all the animal studies done with finasteride and dutasteride, of which there have been many. The data supposedly exists but it has not been analyzed properly (or studies have not been designed properly to detect such an effect). All the reported effects have been on group averages (finasteride vs. control) and not on separation of affected individuals (PFS vs. non-PFS). Thus, such studies have little relevance to PFS - in my opinion. It is high time a proper study is done looking specifically for PFS.
Again, PFS would be measured by tests for sexual function, which does not at all mean that sexual dysfunction is the only symptom of PFS. However, changes in gene expression would be another, objective measure.
Finally, and to reiterate, Melcangi himself concluded that the finding from his latest study was significant but the causal effect of finasteride was unknown. Hence, he of all people should be willing to do such a double blind placebo controlled animal study to estimate the possible causation effect of finasteride.
Finding a permanent causal effect of Finasteride on gene expression will be a revolution for our community and will lead to rapid recognition of PFS as well as to an influx of funding to study the condition. All it takes is one proper study.
This post looks rather bulletproof to me. I too would like to know if localised DHT concentrations have ever been tested in PFS patients.
A definite focus should be on ascertaining whether Finasteride can and does induce the methylation in the steroidic promoter - something testable with rats. I also agree with the importance of not focusing on averages. That being said, I’m not sure how easily this can be done, if presentation of symptoms exists across a wide enough spectrum of outcomes.
This is a fair and valid point. There needs to be an attempt to explain the existence of symptoms beyond the ones immediately following from lack of 5-ar type II, if one would argue that the main cause of PFS is lack of 5-ar type II. I will try to do that a bit later.
I have always found the cases where people improve on androgen replacement therapy to be odd in that it doesn’t reconcile with receptor signal silencing. Of course specificity of affected tissue could play a part.
For instance tissue which have unaffected receptors get ‘supercharged’ by the additional androgens whilst affected tissue reacts negatively to additional androgens. If the tissue where receptors are affected by PFS outweigh the tissue where it’s not affected or are in regions which are more critical to mental and sexual function, additional androgens will deteriorate the person’s function.
If the contrary is true, and receptors in critical tissues are largely unaffected By the PFS mechanism, androgen supplementation could improve the patient.
But tissue specificity aside, variable DHT synthesis in tissue could explain things I would imagine.
I have not found any real treatments during my time with PFS. At first, I was focused on finding a cure or at least a treatment that would completely reverse symptoms even with a life-long treatment. I burned out on trying for that, especially since the treatments I was trying were quite potent hormone therapies. I know don’t see it in black and white and see some value in trying to just alleviate symptoms or improve functioning if that is important to you.
A few of the hormone treatments I tried did have a slight bump in the beginning, but many biological systems are adaptive and your body adapts to the treatment and settles into a new normal. Its kind of like how taking testosterone injections will shut off your endogenous production but then your testicles can go dormant which is undesirable. Not everything will respond in that way, but the body can to many treatments of this nature, and I am not familiar enough to know which will.
Clomid - Got some improvement in erectile function, but definitely nothing near resolution. I might try it again but its not clear that it is healthy. It doesn’t shut off your endogenous production I think. I stopped it after a period of time to try something like hCG which is injectable and behaves similarly and I don’t even remember if it helped.
Progesterone - Precursor to a lot of the neurosteroids. Got a cream from a compounding pharmacy. Helped sensation for a few days but stopped working.
Adderall - This is an amphetamine and of course addictive and a pretty powerful stimulant. Don’t really recommend this because of what it is but it definitely helped sexual desire and a little bit sensation and partial orgasmic response. Took it to help mood, drive, concentration and this was a side effect. Sexual benefits wore off as soon as the drug did. It boosts dopamine in a not totally clear mechanism. Like TRTs, this is a drug to be both feared and respected given its potential abuse and I know people who have gotten addicted.
Requip - A dopamine agonist, I think primarily for Parkinsons. Helped improve orgasmic sensation but made me very slightly nauseous all the time so I tossed it. Might have been worth keeping if not for the nausea… boils down to a personal choice.
The way I think of how to deal with all of this is you’re going to want to rebuild your sexual scaffolding piece by piece. The more I learn about how biology, systems, scientific discovery works, it seems unlikely there will be a single switch to flip and turn everything back on. But maybe we’ll figure out how to demethylate a single problematic gene and that will be that. I hope so but I think we need to investigate and attack this problem from as many angles as possible.
@Sibelio any chance that it altered your hormones? I know on Zinc I feel great after the first pill but subsequent pills lose it’s effectiveness unless I wait several weeks to try again. I now realized my dose was too high and a high dose inhibits DHT.
I started using a DHT cream on my genitals (please read the warning in the earlier post). It is a liposome cream that supposedly is absorbed more slowly and also supposedly is able to be absorbed into cells. It works better than the liquid formulation I used earlier.
I get the best results when I apply the cream on a large area of the lower abdomen, on the penis and on the perineum. I assume this pattern of application maximizes the amount that gets into the pudendal nerve and the blood vessels leading to the genitals. The effect is material.
This evidence confirms, in my opinion, my earlier hypothesis that sexual dysfunction in PFS is due to lack of DHT in key tissues and in the brain secondary to malfunctioning 5a reductase type 2, rather than to androgen insensitivity.
My next step is to supplement 5a-dihydroprogesterone (5a-dhp), another key product of 5a reductase. The symptoms I am hoping to address are brain fog and neuropathy, which are some of the neurological symptoms of PFS I have experienced.
Note that I consider lack of motivation, attention and emotions (anhedonia) in PFS to be psychological symptoms, rather than neurological, secondary to lack of libido, although brain fog itself also can cause difficulty concentrating.
It is noteworthy to note that, since I started supplementing with DHT, it seems I have been getting more brain fog. I believe this is not unexpected (or, alternatively, is evidence for gradual worsening/degeneration over time) as a higher concentration of DHT likely exerts a negative feedback on progesterone production, misleadingly signalling adequate 5a reduction. Lowering progesterone will decrease even further the low level of production of 5a-dhp and allopregnanolone, which is likely to increase brain fog.
In fact, I believe I was able to measure this effect through my blood work as my progesterone fell by around 33% after I started supplementing DHT. Prior to DHT, my progesterone was above the reference range and after DHT it was just inside the reference range.
This latter fact suggests that raising T – and by extension DHT – systemically may not be the best approach if the attempt is to compensate for lack of 5a reductase. Instead, pregnenolone may be better to supplement so that both T and Progesterone are affected.
Of course this would be very hard to get right as lots of feedback loops have to be controlled for. Alternatively, if T is raised, Progesterone would also need to be supplemented. In addition, topical DHT and 5a-DHP will still have to be used.
I don’t know much about the other products of 5a-reductase yet but those are likely to be relevant too.
I just wrote in my other thread about Tribulus and how I am now way more sensitive then I used to. I did 5 cycles earlier this year and then it stopped working. Now after a 3 month break I got great results after the first pill of trib. Would be interested to see some people try it again after a longer break.
I this context it would be interesting to know if 5-ar type III (Prof. Zitzmann sees it as main reasons for the psychological symptoms as it is more present in the brain) is silenced too. A proof in brain of rats would be useful. Same study design as you proposed.
Something I don’t know much about, but could be of importance is whether these epigenetic methylations are in some people just in certain tissues (which may explain why some people have mostly sexual symptoms, others mainly psychological and again others rather systemic symptoms other that affect the whole body).
