Question about 17-aa steroids

dropface

New member
I believe there`s a difference between some of the 17-aa steroids on which some of them are more stressing to the liver?

I`ve heard many ppl say how milder the tbol is compared to dbol/anadrol, even though tbol is also has the 17-aa binding.

How is this so? Is there another factor that have an effect on the liver except the 17-aa binding?
 
the 17aa structure allows the drug to be administered orally, does not change how it affects the liver. what you are asking about is the differences in drug toxicity, which varies from drug to drug.
 
Oh.. I thought the 17aa structure made the oral drug survive the first pass in the liver and then again causes the liver heavy stress. Which in other words means possibility for liver damage?
 
good question.

there's a little more to it than just that. i'll see what i can find something to back up what i'm going to say or sum it up.
 
I'll be damned. I can't throw answer you bro because I'm not sure and very skeptical of any answer I come up with myself. I'm having a VERY difficult time finding answers to my questions. I bumped a good read on something of relation to your question. I read 5 articles on both oral steroids and prescripted drus and their affects on the liver.

What I can't find is: Is it the actual structure (17aa) that causes the enzymes to go up as you mentioned dropface, or is the 17aa simply a prevention of being completely metabolized by the liver?

This is why I said there is more to it than just a simple answer, and I can't seem to find it. Hopefully someone with more concrete knowledge will chime in.
 
Take from another Place, posted by Mudge

From an athletic standpoint, certain types of anabolic steroids are frequently mentioned as having bad effects on liver function. They’re usually oral drugs that are classified as 17-alpha ankylated drugs.

The designation “17-alpha ankylated” refers to a change made on position 17 of the basic steroid structure. Scientists developed the testosterone derivatives after noticing that orally taken testosterone is degraded in the liver in a process called first-pass metabolism. Drug developers circumvented that formidable problem by making testosterone available in an injectable form, which bypasses initial first-pass liver metabolism, and by manipulating the basic steroid chemical structure, as is the case with oral 17-alpha ankylated anabolic steroids.

While the structural change in oral anabolic steroids did result in a far slower rate of breakdown in the liver, it also led to an inordinate buildup of such drugs in the liver. Since the injectable versions of steroids don’t build up in the liver as much as oral versions, the injectables are considered less of a problem in terms of normal liver function.

The oral drugs adversely affect the liver through several mechanisms. For example, they interfere with the function of certain liver enzymes. Anabolic steroids are known to increase the activity of some liver enzymes while downgrading that of others. One enzyme that’s increased with oral anabolic steroid use is hepatic triglyceride lipase, which degrades high-density lipoprotein (HDL), a beneficial cholesterol carrier in the blood. A lowered HDL level is considered a risk factor for cardiovascular disease. Athletes who use oral anabolic steroids nearly always show depressed HDL levels. The buildup of 17-alpha ankylated oral anabolic steroids in the liver leads to a type of toxic or chemical hepatitis. Hepatitis, by the way, is a general word for an inflammation of the liver and can be caused by various factors, such as drug use and viruses. Oral steroids cause liver inflammation by promoting an increase in the size of liver cells, which leads to a congestion of bile flow through ducts in the liver that empty into the gallbladder, where bile is stored.

The interference with bile flow induced by the effects of anabolic steroids on liver cells is called cholestasis. It usually occurs only in people who use higher doses of oral steroids or who use such steroids for extended periods of time. Certain oral steroids are reputed to have more potent toxic effect in the liver and to promote the liver swelling that can lead to cholestasis. They include oxymetholone (Anadrol-50) and fluoxymesterone (Halotestin), although it may be that those drugs cause problems because they’re often used in higher doses than other oral steroids. Both drugs are 17-alpha ankylated, as are most oral steroids.

According to existing medical research, most cases of serious liver ailments due to oral anabolic steroid use have involved hospitalized patients who were given oral steroids such as Anadrol-50 to combat rare blood anemias. Many stayed on oral steroids for three or more years. The consensus of medical reviews is that certain potentially adverse liver changes do occur with athletic use—with the extent of the changes again depending on the drugs used, the doses and the length of time—but the changes regress when the athletes stop using the steroids. The liver is known to have an amazing capacity for regeneration unless it’s irrevocably damaged, a scenario that rarely occurs with short-term steroid use.

Physicians often warn about elevated liver enzyme levels due to oral anabolic steroid use. While that could indicate an inflammation of the liver, the problem is that some of the measured liver enzymes aren’t specific to the liver and exist in other tissues. For example, two enzymes found in liver, ALT and AST, also exist in muscle. Any type of injury to muscle—including the kind that occurs with intense weight training—causes an elevation of those enzymes in the blood. A physician who’s not looking at the big picture—or measuring levels of other liver and muscle enzymes—may wrongly conclude that such liver enzyme increases are indicative of liver problems.1 Measuring enzymes such as creatine kinase and GGT would provide a more definitive picture of existing liver function, as would liver imaging tests.

One visible early sign of liver inflammation due to oral steroid use is jaundice, which is characterized by a retention of bile in the body, leading to a yellow discoloration in the skin and whites of the eyes. Anyone using oral anabolic steroids should stop using them immediately if such symptoms occur. If you ignore the symptoms, you’re at risk for a more serious liver complication.

Peliosis hepatis, as it’s called, consists of blood-filled cysts in the liver. It’s thought to be due to cholestasis; that is, the elevated pressure in liver tissue brought about by lack of proper bile flow in the liver leads to a breakdown of liver cells followed by the appearance of the cysts. The blood-filled cysts can rupture, leading to death. Most cases of peliosis have occurred in hospitalized patients on long-term steroid therapy, although the occurrence of peliosis isn’t dependent on dosage.

One published instance of peliosis involved a 27-year-old bodybuilder who was using a steroid stack consisting of oxandrolone (Anavar), methandrostenolone (Dianabol), nandrolone (Durabolin) and testosterone for five weeks.2 What he took before that time wasn’t disclosed in the published report. The interesting aspect is that the drug stack he used isn’t considered highly toxic to the liver. The bodybuilder may have used more toxic oral steroids over a longer period, however, or he may have taken a drug such as Nolvadex, an estrogen blocker that few bodybuilders know can also cause peliosis if used in too high a dose for too long.

The other serious liver disease often linked to oral anabolic steroid use is liver cancer. Reviews of liver cancer in various medical journals indicate that it’s of a more benign nature than other cancers. Simply put, the liver tumors that develop with steroid use usually regress if the person stops using the drugs. That’s not always the case, however.

A few published accounts document liver cancer fatalities among athletes who have used oral anabolic steroids. In most cases, though, the athletes stayed on the drugs for extended periods. For example, one 26-year-old bodybuilder used a steroid stack consisting of Dianabol, Anavar, Winstrol, Deca-Durabolin and Primobolan for four years before being diagnosed with liver cancer.3 He refused chemotherapy to treat his cancer—probably because it had progressed to a fatal stage—and died.

Another bodybuilder who succumbed to liver cancer took Anadrol-50 for five consecutive years,4 and a 27-year-old Indian bodybuilder died after a liver tumor allegedly induced by his anabolic steroid use ruptured.5 The report documenting that case failed to list his specific steroid regimen. The most recent case of a bodybuilder who had apparent steroid-induced liver cancer involved a 31-year-old man.6 His cancer was considered benign and had not spread or metastasized; however, his liver tumors didn’t decrease in size even after he’d been off steroids for 18 months.

Several options have been suggested as methods of protecting the liver from steroid-induced damage. One obvious technique is to avoid taking oral steroids that are especially toxic to the liver, such as Anadrol, for extended times. A drug available in Japan called malotilate (Hepation) may reduce liver inflammation. A study showed that using ursodeoxycholic acid, a substance that thins bile secretions and is often used to treat gallstones, relieved the bile backup induced by androgens.7

Natural means of protecting the liver involve the use of various herbs. One example is Astralgus, which works by increasing glutathione levels in the liver. Glutathione is an antioxidant that also plays a major role in detoxifying substances in the liver, including anabolic steroids. Certain nutrients are known to increase glutathione synthesis in the liver, such as alpha-lipoic acid and N-acetyl cysteine. Milk thistle (silymarin) and a lesser known herbal substance, Picrorhiza kurroa, increase glutathione synthesis and also help regenerate liver cells. Both Astralgus and Picrorhiza kurroa are used in Europe to treat hepatitis and help maintain liver function. Increasing glutathione levels in the liver may be especially important, since one study of isolated liver cells treated with both injectable and oral anabolic steroids showed that the oral drugs depleted liver glutathione levels.8

Having sufficient amounts of chemicals called methyl groups in the liver also helps keep it healthy. Nutrient sources of methyl groups include lecithin, choline, betaine and S-adenosylmethionine (SAMe). Studies show that SAMe is especially useful for promoting increased bile flow in the liver and may help relieve the bile flow obstruction induced by oral anabolic steroids. SAMe, however, is quite expensive. An alternative method is to increase the intake of nutrients that promote SAMe synthesis in the liver, such as vitamins B12, B6 and folic acid.

Gamma-linoleic acid (GLA), which is found in evening primrose and borage oils, is often suggested as a way for those using oral anabolic steroids to help protect the liver. Ostensibly, the mechanism involved is a reduction in liver inflammation caused by oral steroids. GLA may help in that respect because it’s a precursor for anti-inflammatory prostaglandins that may be in short supply when the liver is inflamed.

Those who are concerned about liver cancer should be conscientious about avoiding contracting all forms of viral hepatitis, which is considered a direct cause of the type of liver cancer that’s more fatal than the type usually caused by steroid use. Since such forms of hepatitis are caused by blood contact, be wary of tattooing, body piercing, acupuncture and even sharing razors and toothbrushes (yech!). Sharing needles is a risk factor not only for hepatitis but also for HIV infection.
 
Oh.. I thought the 17aa structure made the oral drug survive the first pass in the liver and then again causes the liver heavy stress. Which in other words means possibility for liver damage?

This is my basic understanding also. Non 17aa orals can be taken such Primo Acetate, but doses must be very high because it get metabolized so fast by the liver. Also, 17aa can be injected like Winny.
 
the 17aa structure allows the drug to be administered orally, does not change how it affects the liver.


I agree.....

...I always used to beleive the opposite, that when a 17aa steroid was injected it avoided the first pass through the liver....BUT....then a read an article that totally dispelled that beleif.

Damned if I can find it though, pretty sure it was on the AF Board, perhaps macro would know?

If I remember correctly, the article even went as far as saying that injecting a 17aa steroid was actually harder on the liver than taking the same dosage orally.
 
I agree.....

...I always used to beleive the opposite, that when a 17aa steroid was injected it avoided the first pass through the liver....BUT....then a read an article that totally dispelled that beleif.

Damned if I can find it though, pretty sure it was on the AF Board, perhaps macro would know?

If I remember correctly, the article even went as far as saying that injecting a 17aa steroid was actually harder on the liver than taking the same dosage orally.

thanks a lot man, now i have 2 things i really need to research for!
 
I agree.....

...I always used to beleive the opposite, that when a 17aa steroid was injected it avoided the first pass through the liver....BUT....then a read an article that totally dispelled that beleif.

Damned if I can find it though, pretty sure it was on the AF Board, perhaps macro would know?

If I remember correctly, the article even went as far as saying that injecting a 17aa steroid was actually harder on the liver than taking the same dosage orally.

well shit, that was always my understanding but i never looked all that much into it. now you guys have got me thinking...we'll figure this out.
 
I agree.....

...I always used to beleive the opposite, that when a 17aa steroid was injected it avoided the first pass through the liver....BUT....then a read an article that totally dispelled that beleif.

Damned if I can find it though, pretty sure it was on the AF Board, perhaps macro would know?

If I remember correctly, the article even went as far as saying that injecting a 17aa steroid was actually harder on the liver than taking the same dosage orally.

Yeah, I believed the exact opposite too.

I guess I have to do more research on other factors that can affect the liver and the difference between steroids that are known to cause serious liver stress or damage.
 
did you guys all skip over what I posted lol. Cholestasis seems to be a major concern and cause of liver disease with oral steroids in the literature I have read (again from the above post) :

. The buildup of 17-alpha ankylated oral anabolic steroids in the liver leads to a type of toxic or chemical hepatitis. Hepatitis, by the way, is a general word for an inflammation of the liver and can be caused by various factors, such as drug use and viruses. Oral steroids cause liver inflammation by promoting an increase in the size of liver cells, which leads to a congestion of bile flow through ducts in the liver that empty into the gallbladder, where bile is stored.

The interference with bile flow induced by the effects of anabolic steroids on liver cells is called cholestasis. It usually occurs only in people who use higher doses of oral steroids or who use such steroids for extended periods of time. Certain oral steroids are reputed to have more potent toxic effect in the liver and to promote the liver swelling that can lead to cholestasis. They include oxymetholone (Anadrol-50) and fluoxymesterone (Halotestin), although it may be that those drugs cause problems because they’re often used in higher doses than other oral steroids. Both drugs are 17-alpha ankylated, as are most oral steroids.

There are many forms of liver disease, failure and inflammation. One cause of this is that certain drugs within their first pass through the liver are broken down by the livers enzyme, one of the these primary enzymes is cytochrome 450. The drugs can be converted into metabolites that are toxins and actually damage the liver cells themselves. An example of this is acetominophen aka tylenol.

Going back to cholestasis, which seems to be one of the major factors, The liver is responsible for producing many different enzymes that are secreted. Liver cells contain a high level of Smooth Endoplasmic reticulum, hence alcohol degradation. One of these major proteins is albumin. Albumin can bind to a toxic metabolite called bilirubin. Bilirubin is produced from the breakdown of hemoglobin from old, damaged, lysed or non-functional RBCs. Bilirubin is very toxic in high levels in the blood and thus can cause tissue damage. this damaged includes the liver as well as other organs flooding the blood with the proteins ALT and AST. These are what common liver test look for. All this can happen from Cholestasis.

Now to Sum it up. THE TRUE BIOCHEMICAL REASON for this damage is Oxidants, free radicals, Oxygen. Yes Oxygen. Oxygen is one of the most toxic substances for your tissue, esp in free radical forms, It causes damages to DNA cell structures, and disrupts chemical bonds. This can be a result of often damage to mitochondria. Oxygen increase and free radicals are caused by many drugs. Remember 75% of the blood absorbed in the intestine (where your orals are absorbed into) go directly to the liver in that concentrated amount.

I left out alot of information, This was off the top of my head feel free to correct me. Hope it clears some things up.
 
good post animal.

it doesn't specifiy if it's the 17aa itself that causes this or the oral steroids themselves. my guess from the article is that the steroids are very toxic, whether or not being 17aa, they will damage the liver. if that's the case, then any steroid we take orally should damage the liver. but thats not the case. only 17aa steroids cause liver damage. i'm still unsure.

whats the source of the article bro
 
good post animal.

it doesn't specifiy if it's the 17aa itself that causes this or the oral steroids themselves. my guess from the article is that the steroids are very toxic, whether or not being 17aa, they will damage the liver. if that's the case, then any steroid we take orally should damage the liver. but thats not the case. only 17aa steroids cause liver damage. i'm still unsure.

whats the source of the article bro


It was posted by Mudge on Ironmagazineforums.com since hes a mod here maybe he can come in and elaborate more on the article, his sources and other info.
 
17aa adds toxicity to a drug(stress to liver due to multiple liver passes) but drugs themselves can be toxic without 17aa, such as [C8H9NO2] Acetaminophen (Tylenol) which causes three times as many cases of liver failure as all other drugs combined, and is the most common cause of acute liver failure in the United States,accounting for 39% of cases. So, regardless of 17aa or non 17aa drugs can have varied levels of toxicity.
 
Wow, great thread and awesome question dropface.

I always thought that it was so the compound would pass through the first go in the liver and that the toxicity comes from the compound themselves. well, we will know for sure soon I bet.
 
[Peliosis hepatis. A clinical status inventory]

[Article in German]

Spech HJ, Liehr H.

Peliosis hepatis is a rare condition, recognizable by macroscopical view. It is characterized by multiple blood-filled cystic spaces in the liver parenchyma. According to 49 out of 152 more recent case reports (1951-1981/82) its spontaneous occurrence is frequently associated with malignant and toxic processes. However, in about 70% peliosis may be induced by the action of certain drugs, especially by 17 alpha-alkylated steroids. Usually peliosis is found by chance at autopsy or peritoneoscopy, as the clinical picture does not provide sufficient conclusive criteria to allow a definite diagnosis. The striking macroscopical appearance contrasts to the dispute on the as yet unestablished natural history. As most important complication spontaneous intraabdominal bleeding can occur in occasional cases. On the other hand, the patients predominantly die of their underlying diseases and not of a peliosis hepatis.


Hepatic lesions caused by anabolic and contraceptive steroids.

Ishak KG.

PIP: Many hepatic lesions, ranging from subcellular alterations to malignant tumors, have been attributed to the use of anabolic steroids (AS) and contraceptive steroids (CS). These lesions that have been attributed to AS and CS are discussed with focus on the following: biochemical changes; subcellular alterations; intrahepatic cholestasis; vascular complications (sinusoidal dilatation, peliosis hepatitis, Budd-Chiari syndrome); hyperplasia and neoplasia (diffuse hyperplasia, nodular transformation, focal nodular hyperplasia, hepatocellular adenoma, hepatocellular carcinoma, and miscellaneous malignant tumors); and miscellaneous effects (effects of preexisting liver disease, cholelithiasis, and pancreatitis). OCs have a number of physiologic effects on the liver. These include decreased bile flow, diminished secretion of organic anions, and decreased synthesis and secretion of bile acids. Retention of bromosulfophthalein has been noted with AS during late pregnancy and in the puerperium. It is well established that the CS can lead to elevations of serum ceruloplasmin and copper levels. Subcellular alterations have been reported in both humans and rats on AS or women on CS and involve multiple organelles of the several systems of the liver. Both AS and CS have been implicated in intrahepatic cholestasis. Jaundice usually develops after 2-5 months of therapy with AS or after 3 months of OC use. The lesions attributed to CS and AS can involve any of the systems of the liver. At times more than 1 system is affected simultaneously. Most of the steroid related lesions resemble similar ones caused by other etiologies. Some, such as peliosis hepatitis, are rarely related to other etiologies, but others can be termed steroid specific. A number of diseases associated with the CS or AS also occur in pregnancy. Acute fatty metamorphosis of pregnancy and the periportal hemorrhagic necrosis characteristic of eclampsia have not been reported in patients on CS. Spontaneous rupture of the liver during pregnancy has not been attributed to the CS.


I am having trouble finding a study that compares aa vs non aa orals and liver toxicity :scratchhe
 
reps for sure. but the question is still left unanswered lol. i've read tons of those papers already. this "in about 70% peliosis may be induced by the action of certain drugs, especially by 17 alpha-alkylated steroids" does not necessarily mean its the 17aa that's the cause. i think it just may be refering to oral steroids in general.

NOW, if they ARE refering to oral steroids in general, then what about injectable steroids. If injectable steroids are swallowed they won't be effective because it will be completely metabolized (no 17aa structure), but it won't be damaging the liver either as 17aa oral steroids would.

than going back to the begining, some prescription or otc drugs don't have 17aa structures and they can have a negative impact on the liver too!
My guess is that other drugs negative impact on the liver compared to the impact on the liver from oral steroids are not the same.
 
Questions have to do with
a.) hepatotoxicity of 17 alpha-substitution
b.) hepatotoxicity of oral steroids both as related to 17aa and steroid
c.) absorption and distribution of 17aa steroids via oral vs. injection methods.
d.) detoxification vs. bioactivation during metabolic process in the liver. (other drugs having hepatotoxicity effects)

Will try to keep it simple.

BOTH the 17 alpha substitution AND the steroid itself are (in different ways) damaging to the liver. However, SOME of the steroids have different levels of absorption and excretion and metabolic transformation in the liver. In other words, SOME oral steroid get pissed out more (not absorbed or transformed). All 17aa ARE hepatotoxic - some more than others (oxandrolone seems to be the least OUT OF the anabolic ones).

Oral administration means that the 17aa steroid must go through the intestinal tract - go through the cell membranes and get transported to the liver via the hepatic artery before undergoing metabolic (biotransformation) changes AND then going into the blood system to the heart, tissues, lungs etc...

17aa administration via injection skips the intestinal tract absorption method -however, it must still be biotransformed (in toxicology it is called DETOXIFICATION) in the liver. So, it is still toxic. Might have improved absorption - so, as someone else said above it "could" be even more toxic only because MORE of the substance makes it to the liver.

Someone else brought up "tylenol" and "other" substances that are liver toxic. There are over 900 medications known to be liver toxic.

When the liver receives said substances it can detoxify them or bioactivate them. Detoxification means metabolites of lower toxicity - bioactivation means metabolites that are more toxic than the parent substance.

Tylenol is a known substance that metabolizes into a MORE TOXIC substance (NAPQi metabolized by P-450 enzymes) above a certain limit intaken. Tylenol causes adverse drug reactions classified as type A (intrinsic or pharmacological) - meaning "we" know when and why and in what quantity they occur.


BOTTOM LINE:
17aa steroids ARE toxic whether taken orally or IM.
17aa steroids in low quantities taken for SHORT periods of time haven't been proven to cause HCC (cancer) but do cause reversible (most of the time) damage.
SOME 17aa steroids are less toxic - like oxandrolone appearing to be the least so.
(for the original "post" - Tbol is toxic to the liver and WILL elevate your liver enzymes - tried it myself this summer - stopped after 4 weeks due to elevated enzymes - oxandrolone at 20mgs/day did NOT elevate enzymes - but this was JUST my experience).

Personally I wouldn't run them unless I knew my liver state prior to - and couldn't monitor during cycle at least weekly. Run vit b-complex (B6, b3, b12) run arginine - run milk thistle ... all prior to, during and after orals.

IF YOU HAVE THE FOLLOWING:
Serum bilirubin level - more that 2 times ULN with associated transaminase rise - this is an ominous sign.

If you want to know WHEN you've caused your liver injury - either (a) ALT level more than three times of upper limit of normal (ULN), (b) ALP level more than twice ULN. This indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending steroid isn't stopped (Hy's Law)

The only diagnostic test to detect HCC is a blood test known as alpha-fetoprotein (AFP). This test is one of the tumor markers (a blood test indicative of, but not diagnostic of, cancer). Normal adult level is less than 20 nanograms per milliliter (ng/ml). If the level in a person’s blood is over 400 ng/ml, then it is pretty safe to say that liver cancer is present. Levels under 400 ng/ml are unclear but I wouldn't want to see them on my result sheet.

MAKE IT A STICKY AND GOOD LUCK .. and if SCARZ's questions are answered I can sleep well - if it's not enough info for Scarz -- tell me and I swear I'll dust of my toxicology manuals in the attic somewhere.
 
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