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Drop In Androgen Levels Causes Parkinson Disease (PD), DHT Reverses It

Discussion in 'Scientific Studies' started by haidut, Oct 30, 2019.

  1. haidut

    haidut Member

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    Yet another study demonstrating that many of the so-called chronic, degenerative and above all "mysterious" conditions often have quite a simple cause and, potentially, treatment. There is no need for mutated genes or complex interactions of genes with environment that nobody can decipher. Chronic stress leads to metabolic and endocrine changes that alone are sufficient to cause virtually all "named" pathologies we have on the books. Just as importantly, endogenous chemicals that have been declared "evil" for more than a century, now turn out to be among the most protective substances available to medicine. Case in point - the study demonstrated that all it takes for PD to develop in males is a sudden drop in androgen levels. While the study mentions both testosterone (T) and DHT as key players, the treatment regimen in this study for reversing PD used DHT instead of T. Yes, that same "evil" DHT that we have been told causes prostate cancer, baldness, obesity, PCOS, osteoporosis, etc. /s

    All it took to reverse the symptoms of PD in these castrated rodents was DHT supplementation with HED of ~2mg/kg daily, for 30 days. This dose of DHT is high, but in extreme (and sudden) cases such as castration much higher doses of an androgen may be needed to reverse severe brain pathologies. Other rodent studies have shown that DHT at a HED of 5mg-10mg daily also has robust neuroprotective effects. Interestingly, the drop in androgen levels caused a massive increase in nitric oxide (NO) synthesis. This elevation in NO resulted in destruction of dopamine-producing neurons, as well as a drop in the brain-anabolic factor GDNF. DHT administration reversed all of these pathological changes. Speaking of androgen-depleting events - physical or chemical castration is not the only possible cause. Chronic stress, emotional trauma, radiation exposure (X-rays anyone?), endocrine disruptors, infectious disease, endotoxin, SSRI drugs, PPI drugs, statins, PUFA, etc all count as "castration" events that can potentially cause such PD-inducing drop in androgen levels.

    Btw, the reason the study authors used DHT instead of T was that they were concerned about T aromatizing easily to estrogen, considering the negative effects estrogen has on brain pathologies like PD in males. In fact, the role of estrogen in PD pathology is acknowledged to the point that aromatase inhibitors are proposed as promising candidates for treating PD.

    Potential repositioning of exemestane as a neuroprotective agent for Parkinson's disease. - PubMed - NCBI

    Well, if androgen drop causes PD, androgen administration reverses it, and estrogen administration worsens it then the only conclusion is that DHT is the main protective factor here. T, aside from its conversion into estrogen, has only one other pathway it can go towards - conversion into DHT. Actually, it can convert back into androstenedione but that pathway is minor and also leads to estrogen. Finally, DHT lowers estrogen but T does not (it even increases it). So, it is fair to say that loss/decline of potent androgenic steroids can cause PD and supplementation with the most potent endogenous non-aromatizabe androgen (DHT) can reverse it. Considering the causative role elevated NO and lower dopamine (and as such higher prolactin) play in prostate cancer, the whole approach with chemical castration starts to look even more absurd. If anything, this study suggests that DHT should be used to treat prostate cancer :):

    Castration Induces Parkinson Disease Pathologies in Young Male Mice via Inducible Nitric-oxide Synthase

    "...To find out whether the observed pathological changes are due to castration-related loss of male sex hormone, we performed this experiment. However, testosterone may be converted into estrogen by aromatase. Therefore, to avoid the complexity, castrated male mice received DHT pellets (30-day release), which were implanted subcutaneously in the scapular area of the neck of castrated male mice on the day of castration (Fig. 8A). It is interesting to see that DHT supplementation protected nigral TH (Fig. 8, B and C) and preserved striatal DA (Fig. 8D) in 4–5-week-old castrated male mice. Accordingly, DHT supplementation also improved rotarod performance (Fig. 8E), horizontal activity (Fig. 8F), total distance (Fig. 8G), movement time (Fig. 8H), number of movement (Fig. 8I), and stereotypy (Fig. 8J)."

    "...On the other hand, NO has also been implicated in several CNS disorders, including inflammatory, infectious, traumatic, and degenerative diseases (18, 3638). There is considerable evidence for the transcriptional induction of iNOS (the high output isoform of NOS) in the CNS that is associated with degenerative brain injury (18, 35, 37, 38). NO is potentially toxic to neurons and oligodendrocytes that may mediate toxicity through the formation of iron-NO complexes of iron-containing enzyme systems (39), oxidation of protein sulfhydryl groups (40), nitration of proteins, and nitrosylation of nucleic acids and DNA strand breaks (41). Here, we have described a new mechanism by which iNOS-derived NO may couple nigrostriatal degeneration (summarized in Fig. 12I). Whereas castration increased the expression of iNOS in the nigra, the level of GDNF went down drastically in the nigra after castration. "

    Sudden decline in testosterone may cause Parkinson's disease symptoms in men

    "..."While scientists use different toxins and a number of complex genetic approaches to model Parkinson's disease in mice, we have found that the sudden drop in the levels of testosterone following castration is sufficient to cause persistent Parkinson's like pathology and symptoms in male mice," said Dr. Kalipada Pahan, lead author of the study and the Floyd A. Davis endowed professor of neurology at Rush. "We found that the supplementation of testosterone in the form of 5-alpha dihydrotestosterone (DHT) pellets reverses Parkinson's pathology in male mice." "In men, testosterone levels are intimately coupled to many disease processes," said Pahan. Typically, in healthy males, testosterone level is the maximum in the mid-30s, which then drop about one percent each year. However, testosterone levels may dip drastically due to stress or sudden turn of other life events, which may make somebody more vulnerable to Parkinson's disease. "Therefore, preservation of testosterone in males may be an important step to become resistant to Parkinson's disease," said Pahan. Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson's disease. Nitric oxide is an important molecule for our brain and the body. "However, when nitric oxide is produced within the brain in excess by a protein called inducible nitric oxide synthase, neurons start dying," said Pahan."
     
  2. Broken man

    Broken man Member

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    Good one, can I ask you, why I cant use Keto dht without pregnenolone on my rat? Thank you.
     
  3. Tristan Loscha

    Tristan Loscha Member

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  4. Mauritio

    Mauritio Member

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    Great study. once again : DHT for the win !
     
  5. milk_lover

    milk_lover Member

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    It’s sadly banned in my country. What comes the closest to DHT in your opinion?
     
  6. Mauritio

    Mauritio Member

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  7. Tarmander

    Tarmander Member

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    The question is why would androgens drop so suddenly in a human?

    makes sense that lower T and PD would tie together because of T and dopamines buddy buddy relationship. I wonder though if overtime the dopamine system would adapt to the lower T levels. Women obviously don’t have high T (other then college professors) and aren’t devastated by high PD levels.
     
  8. Mito

    Mito Member

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    Why don’t men treated for prostate cancer develop PD?
     
  9. Mauritio

    Mauritio Member

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    Good question , I was looking it would totally make sense...
     
  10. Tristan Loscha

    Tristan Loscha Member

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    Didnt read those studies,high probability i wont read them later.
    But others can have insight,

    "Why don’t men treated for prostate cancer develop PD?"

    "Good question , I was looking it would totally make sense..."

    maybe they do.

    Search terms in google scholar:
    https://scholar.google.de/scholar?h...state+cancer+develop+parkinsons+disease&btnG=



    Association between Parkinson's disease and risk of prostate cancer in different populations: An updated meta-analysis.
    Chen C, et al. Sci Rep. 2017.
    Show full citation
    Abstract

    Recently, growing evidence has revealed a significant association between Parkinson's disease (PD) and cancer. However, controversy still exists concerning the association between PD and prostate cancer. A comprehensive article search for relevant published studies was performed using the online databases PubMed, Web of Science and Embase up to January 1, 2017. The pooled risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated using the method of inverse variance with a random-effects model. Fifteen studies comprising 346,153 PD patients were included in this study. The results of the present study showed that PD was significantly associated with a decreased risk of prostate cancer in the Western population (RR: 0.83, 95% CI: 0.72-0.95, P < 0.01), while an increased risk of prostate cancer was shown in the Asian population (RR: 1.80, 95% CI: 1.52-2.13, P < 0.001). In the subgroup analysis, the reduced risk of prostate cancer in PD patients from Western populations was consistent regardless of study design or study quality. In conclusion, PD was significantly associated with a reduced risk of prostate cancer in the Western population. The relationship between those conditions in the Asian population needs to be confirmed by future studies.







    Parkinson's disease and cancer risk: a systematic review and meta-analysis.
    Review article
    Bajaj A, et al. Cancer Causes Control. 2010.
    Show full citation
    Abstract

    OBJECTIVE: To appraise the existing literature on cancer risk among patients with Parkinson's disease (PD), determine the overall cancer risk ratio among patients with PD, explore reasons for variations in study results, and assess the potential for publication bias.

    METHODS: Studies reporting cancer risk in patients with PD were identified by searching electronic databases through 18 November 2009 using the terms PARKINSON DISEASE, NEOPLASM, and CANCER. Reviewers individually performed data extraction and scored each study using a quality assessment instrument. Cancer risk in all patients with PD was calculated overall, and after excluding melanoma and other skin cancers. We tested for heterogeneity and publication bias, and stratified for gender, smoking-related versus non-smoking-related cancers, and study quality. We pooled effect sizes using fixed-effects and random-effects models.

    RESULTS: We included 29 studies in the overall analysis for a total of 107,598 patients with PD. Compared to controls, the aggregate risk for cancer in patients with PD was 0.73 (95% confidence interval [CI], 0.63-0.83), and after excluding skin tumors, 0.69 (95% CI, 0.62-0.78). These risks varied by gender (males, RR = 0.71, 95% CI, 0.57-0.88; females, RR = 0.82; 95% CI, 0.68-0.98). After strictly excluding skin tumors, both smoking-related (RR = 0.61; 95% CI, 0.58-0.65) and non-smoking-related cancer rates (RR = 0.76; 95% CI, 0.65-0.89) were significantly lower among patients with PD .

    CONCLUSIONS: Studies on cancer risk among patients with PD collectively show significantly reduced cancer risk ratios. Further research to explain the biological mechanisms, particularly for the association with non-smoking-related cancers, appears warranted.
     
  11. Mauritio

    Mauritio Member

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    I don't get your point, you sound like you say it is the case that there is a correlation between prostate cancer treatment and Parkinson's but the study says the opposite.
    And our point was, there might be a chronological order : first prostate cancer (and treatment) , then cancer. And not the other way around.
    Since prostate cancer treatment causes a sudden drop in androgen and this might lead to Parkinson's as per haiduts study.
     
  12. Cameron

    Cameron Member

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    Are there any countries where dht is sold as a research chemical and easy to obtain? I’m wondering if Canada is easy to obtain pure dht for research as possessing steroids is not illegal only selling them is. Finding a pre made non toxic solution seems difficult to find as well.
     
  13. Cameron

    Cameron Member

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    What is the theory on dht supplementation in humans and suppression. I’ve seen both the theory dht in any dose with suppression on hpta and testosterone. I’ve also seen the opposite that dht will have positive effect on its own production and positive effect on t and e and therefore safe to use in supplementation. Can we suspect dht is the safe form of hrt in men? Is dht actually less suppressing to the entire endocrine system? Oral dht or dht pellets for best dht type hrt in men?
     
  14. Tristan Loscha

    Tristan Loscha Member

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    True.
    I dont have a point in this matter yet.
    i wanted to post something to chew on for members.
     
  15. Tristan Loscha

    Tristan Loscha Member

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    I would also like to hear someone who have ideas about suppression or knowledge of the course and consequences of such side effects.
     
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