[quote]Zell959 wrote:
Is the mechanism that causes some people joint pain from winstrol use known at this point? Are there any working theories?
[/quote]
I uhh…just found this thread doing a search last night, so I figure I’d put my theory forward…
Winstrol is a DHT-Derivative, and DHT administration has been found to decrease estrogen levels because the majority of circulating estrogen in men is derived from peripheral conversion of androgens or androgenic precursors (1). DHT directly inhibits estrogens activity on tissues, either by acting as a competitive antagonist to the estrogen receptor or by decreasing estrogen receptor binding. Either way way, it has two mechanisms of possible action in peripheral tissue.
DHT and its metabolites have also been shown to inhibit aromatiziation (conversion of testosterone to estrogen via the aromatase enzyme). Indeed, DHT, androsterone, and 5alpha-androstandione are all potent inhibitors of the formation of estrone from androstenedione. Finally, DHT acts on the HPTA to decrease the secretion of gonadotropins (it inhibits it). In fact, it’s so potent at reducing estrogen that transdermal DHT gel has been used to treat gynocomastia by applying pure DHT gel to the affected area(5)(6), since estrogen is the primary culprit in gyno (8), although we know that progesterone can be synergistic with estrogen in this (and other) respects(s).
DHT also has a negative effect on Progesterone biosynthesis in cells (7),and even has the ability to inhibit progesterone elevation caused by estrogen (10).
Therefore DHT would be (and is) very effective in reducing gyno because it reduces both estrogen as well as progesterone. This property holds with DHT-derived steroids, for the most part as well, since Masteron has been found to have similar effects in reducing breast tissue tumors(9), which is what gyno is (albeit benign).
You still with me? Good, because I want you to hold that first idea (DHT reduces estrogen and progesterone), and put it in the back of your mind while you read this next part, which is about your immune system. Bear with me…
T helper 1 (TH1) cells secrete proinflammatory cytokines as well as promoting cell-mediated immune responses, whereas TH2 cells trigger antibody production (2). Simple enough? . Sex hormones (such as progesterone) that promote the development of a TH2 response also happen to antagonize the emergence of TH1 cells. Hence, when progesterone levels are (or the PgR, progesterone receptor) is stimulated, you’ll have more anti-inflammatory cytokines floating around and less proinflammatory cytokines. Aspirin, Tylenol, and all of the over the counter anti-inflammatories are also useful as painkillers. Anti-inflammatory effects are often highly correlated with pain killing activity. What happens when women with arthritis get pregnant? Yeah, thats right, a reduction in symptoms and pain in their joints. Is this due to pregesterone and estrogen increasing during pregnancy, and the inti-inflammatory effects they bring? Yeah, probably…I’ll support that leap.
If you’re still with me, you now know that progesterone, like testosterone, both stimulates humoral immunity (the TH2) and suppresses cellular immunity (TH1 response). Ergo, progesterone has anti-inflammatory action. Deca is what, boys and girls? Thats right, it’s a progestin, meaning it stimulates the progesterone receptor. And thats why it alleviates joint pains. Remember that old idea that deca promotes “water-retention” in the joints, and thats why it helps your joints feel soothed? Bullshit. You just read the real reason deca helps joints. Deca actually works both as an androgen, which have the well documented ability to exert effects on corticosteroids to diminish inflamation, and it also acts as progestin to reduce inflammation.
Lets move on…
Estrogen exerts what is known as a a biphasic ( two phase) effect. At low amounts, it is proinflammatory, because it stimulates the TH1 arm of the immune system (cellular immunity) and inflammation. In high(er) amounts, it is actually an anti-inflamatory (2). So when you take very strong anti-estrogens (or aromatase inhibitors), you both lose water (because estrogen causes water retention) as well as get sore joints because of the proinflammatory effects you get from having such low levels of estrogen. Letrozole, which reduces blood plasma levels of estrogen due to aromatase inhibition, is the best example of this, because it is infamous for causing aching joints. Letrozole, decreases both aromatase activity (aromatase is the enzyme responsible for conversion of testosterone to estrogen as you already know) as well as (obviously) plasma levels of estrogen, and in addition reduces progesterone levels (3)…and you only need 100mcg of Letrozole to inhibit aromatase activity(4)- making it a very potent aromatase inhibitor. This is why when people take Letrozole, they claim it takes “water out of their joints” and makes them ache.
Again, this is total bullshit. You now know the real reason that Letro can make your joints ache. Lowering estrogen will lower your water retention, but also take away some of your body’s ability to have estrogen mediated anti-inflammatory reactions to weight training. You lose water and your joints hurt…hence…people say you lose water from your joints, and that makes them hurt. Its true that you lose subcutanous water, but it’s simply not true that losing this water will make your joints hurt…it’s the loss of estrogen and progesterone that is behind the aching joints here. We can also make the claim that Testosterone, can have some anti-inflamatory effects both through it’s aromatization to estrogen is as well as it’s effects on corticosteroids. This too, is well documented.
Now, lets see if we can recall that first bit I asked you to remember…the bit where I told you that DHT reduces estrogen and progesterone? Well, by now, you should be aware that a reduction in both of those hormones (Estrogen and Progesterone) is caused by DHT, and therefore, by DHT-Derivations, which carry many of the same properties and produce similar metabolites…
…And this reduction in Estrogen/Progesterone, caused by DHT, reduces your body’s production anti-inflammatory and painkilling cytokines. And this, finally, is what causes Winstrol, Masteron, etc… to cause Joint Pain. And the opposite is what causes Deca to help your joints.
References:
MacDonald PC, Madden JD, Brenner PF, Wilson JD, Siiteri PK 1979 Origin of estrogen in normal men and in women with testicular feminization. J Clin Endocrinol Metab 49:905?916
Science, Vol 283, Issue 5406, 1277-1278 , 26 February 1999
Eur J Obstet Gynecol Reprod Biol. 2002 Nov 15;105(2):161-5.
J Clin Endocrinol Metab. 1995 Sep;80(9):2658-60.
Successful percutaneous dihydrotestosterone treatment of gynecomastia occurring during highly active antiretroviral therapy: four cases and a review of the literature.
Clin Infect Dis. 2001 Sep 15;33(6):891-3. Epub 2001 Aug 10.
Androgens and the immunocompetence handicap hypothesis: unraveling direct and indirect pathways of immunosuppression in song sparrows.
Am Nat. 2004 Oct;164(4):490-505. Epub 2004 Sep 1.
Nippon Sanka Fujinka Gakkai Zasshi. 1988 Mar;40(3):331-7.
Progesterone is not essential to the differentiative potential of mammary epithelium in the male mouse. Freeman, Topper. Endocrinology. 1978 Jul;103(1):186-92
Eur J Cancer Clin Oncol. 1983 Sep;19(9):1231-7.
Biol Reprod. 1989 Jun;40(6):1201-7.
