Friday, May 30, 2014

Stanozolol by Accordo RX and muscular development


Pharmacology is the study of drugs and their effects. Anabolic pharmacology is the study of drugs that have a growth-promoting effect in muscle. This article will explore anabolic pharmacology by profiling a different anabolic drug and its effects each month. The focus of discussion this month will be the anabolic androgenic steroid, Stanozolol.

Stanozolol is a highly-modified synthetic version of dihydrotestosterone (DHT) that was originally sold under the trade name Winstrol. As you can see, there is an additional ring system attached to the traditional A-ring of the anabolic steroid structure. The binding data for Stanozolol shows it to have very poor binding for the androgen receptor. However, the half-life of nine hours for this anabolic steroid is quite long— making up for the lower affinity. Stanozolol is incapable of being converted to estrogenic metabolites through aromatization, and is already 5-alpha reduced, so it cannot be reduced further— but does seem to have some anti-aromatase activity.

Stanozolol has minimal binding to sex hormone-binding globulin (SHBG), so it circulates for the most part in the ‘free’ state. It has been shown that although stanozolol does not interact directly with the glucocorticoid receptor, it does interact with two glucocorticoid-binding proteins known as STBP and LAGS. This interaction ‘bumps off’ bound cortisol into free circulation. At the same time, Stanozolol has been shown to interfere with cortisol release from the adrenal gland. This results in reduced cortisol levels, with chronic usage. In fact, many people notice severe joint pain when using Stanozolol, especially when used alone. This can result in a rebound effect in cortisol production when going off Stanozolol.

 Even though Stanozolol has a very large anabolic-to-androgenic ratio, it is quite androgenic. The anti-glucocorticoid effect of this drug likely augments its anabolic/androgenic ratio beyond that of its androgen receptor-binding effects alone. Stanozolol decreases thyroxine-binding globulin (TBG) levels but not as much as some of the other common anabolic-androgenic steroids.

 In addition to tablets for oral administration, Stanozolol is available as water-based suspension for injection. Because it is not esterified, this steroid needs to be injected every day. Also, water-based injections are a lot more prone to bacterial contamination, so more care is needed to keep a multi-use bottle sterile. The relatively large crystal size of some preparations limits the size of needle that can be used, because the crystals will jam smaller needles. There are some formulations available that have smaller crystal size; however, these seem to have a shorter half-life— most likely due to the crystals dispersing faster within the muscle.

Because Stanozolol is C-17 alpha-alkylated, it has the potential for liver toxicity— but this is somewhat reduced with the injectable form because a lower overall dose is often used. Stanozolol has a favorable anabolic-to-androgenic ratio, but most do not consider it to be very effective. This is largely due to the fact that Stanozolol does not result in large water weight gains.

Friday, May 23, 2014

Proviron (mesterolone) by Jintani Labs


Proviron (mesterolone) is oral androgen mesterolone (1-methyl dihydrotestosterone). Similar to dihydrotestosterone, mesterolone is a strong androgen with only a weak level of anabolic activity.This is due to the fact that like dihydrotestosterone, mesterolone is rapidly reduced to inactive diol metabolites in muscle tissue where concentrations of the 3-hydroxysteroid dehydrogenase enzyme are high. The belief that the weak anabolic nature of this compound indicates a tendency to block the androgen receptor in muscle tissue, thereby reducing the gains of other more potent muscle-building steroids, should likewise not be taken seriously. In fact, due to its extremely high affinity for plasma binding proteins such as SHBG, mesterolone may actually work to potentate the activity of other steroids by displacing a higher percentage into a free, unbound state. Among athletes, mesterolone is primarily used to increase androgen levels when dieting or preparing for a contest, and as an antiestrogen due to its intrinsic ability to antagonize the aromatase enzyme.

Mesterolone is a modified form of dihydrotestosterone. It differs by the addition of a methyl group at carbon, which helps protect the hormone from hepatic metabolism during oral administration. The same structural modification is also used with oral Primobolan (methenolone) tablets. Alkylation at the one position slows hepatic metabolism of the steroid during the first pass, although much less profoundly than c-17 alpha alkylation. Mesterolone is resistant enough to breakdown to allow therapeutically beneficial blood levels to be achieved, although the overall bioavailability remains much lower than c-17 alpha alkylated oral steroids. Mesterolone also has a very strong binding affinity for Sex Hormone Binding Globulin/1o This may act to displace other steroids more weakly bound to SHBG into a free (active) state.

Mesterolone is not aromatized by the body, and is not measurably estrogenic. An anti-estrogen is not necessary when using this steroid, as the drug is unlikely to induce gynecomastia, water retention, or other estrogen-related side effects. Mesterolone is actually believed to act as an antiaromatase in the body, preventing or slowing the conversion of steroids into estrogen.

The result is somewhat comparable to Arimidex, although less profound. The anti-estrogenic properties of mesterolone are not unique, and a number of other steroids have demonstrated similar activity. Dihydrotestosterone and Masteron (2-methyl-dihydrotestosterone), for example, have been successfully used as therapies for gynecomastia and breast cancer due to their strong androgenic and potentially anti-estrogenic effect. It has also been suggested that nandrolone may even lower aromatase activity in peripheral tissues where it is more resistant to estrogen conversion (the most active site of nandrolone aromatization seems to be the liver).The antiestrogenic effect of all of these compounds is presumably caused by their ability to compete with other substrates for binding to the aromatase enzyme. With the aromatase enzyme bound to the steroid, yet being unable to alter it, an inhibiting effect is achieved as it is temporarily blocked from interacting with other hormones.

Mesterolone is classified as an androgenic steroid. Androgenic side effects are common with this substance, especially with higher doses. This may include bouts of oily skin, acne, and body/facial hair growth. Anabolic/androgenic steroids may also aggravate male pattern hair loss. Women are also warned of the potential virilizing effects of anabolic steroids. These may include a deepening of the voice, menstrual irregularities, changes in skin texture, facial hair growth, and clitoral enlargement. Additionally, the 5-alpha reductase enzyme does not metabolize mesterolone, so its relative androgenicity is not affected by finasteride.

Mesterolone is not c17-alpha alkylated, and not known to produce hepatotoxic effects; liver toxicity is unlikely.

Anabolic/androgenic steroids can have deleterious effects on serum cholesterol. This includes a tendency to reduce HDL (good) cholesterol values and increase LDL (bad) cholesterol values, which may shift the HDL to LDL balance in a direction that favors greater risk of arteriosclerosis. The relative impact of an anabolic/androgenic steroid on serum lipids is dependant on the dose, route of administration (oral vs. injectable), type of steroid (aromatizable or non-aromatizable), and level of resistance to hepatic metabolism. Mesterolone is an oral non-aromatizable androgen,and expected to have a notable negative effect on lipids. Studies administering 100 mg of mesterolone per day to hypogonadal men for approximately 6 months demonstrated a significant increase in total cholesterol (18.80/0) and LDL cholesterol (65.20/0), accompanied by a significant decrease in HDL cholesterol (-35.7°;6).

Mesterolone should not be used when cardiovascular risk factors preclude the use of other oral steroids. To help reduce cardiovascular strain it is advised to maintain an active cardiovascular exercise program and minimize the intake of saturated fats, cholesterol, and simple carbohydrates at all times during active anabolic steroids administration. Supplementing with fish oils (4 grams per day) and a natural cholesterol/antioxidant formula such as Lipid Stabil or a product with comparable ingredients is also recommended.

To treat androgen insufficiency, mesterolone is usually given in a dose of 1 tablet (25 mg) three times per day at the initiation of therapy. The drug is later continued at a lower maintenance dose, which usually consists of taking 1 tablet (25 mg) one to two times per day. Similar doses are used to support male fertility, usually in conjunction with other fertility drugs like injectable FSH. The usual dosage among male athletes is between 50 mg and 150 mg of mesterolone per day, or two to six 25 mg tablets. The drug is typically taken in cycles of 6-12 weeks in length, which is usually a sufficient period of time to notice the benefits of drug therapy. Many bodybuilders favor the use of mesterolone during dieting phases or contest preparation, when low estrogen and high androgen levels are particularly desirable. This is especially beneficial when anabolics like Winstrol, Anavar, or Primobolan are being used alone, as the androgenic content of these drugs is relatively low.

Mesterolone can be effectively used here to adjust the androgen to estrogen ratio upwards, bringing about an increase in the hardness and density of the muscles, supporting libido and general sense of well being, and increasing the tendency to burn body fat. It is also commonly used (at a similar dosage) to prevent gynecomastia when other aromatizable steroids are being administered, often in conjunction with 10-20 mg
per day of Nolvadex.

Mesterolone is not approved for use in women.This agent is not recommended for women for physique- or performance-enhancing purposes due to its strong androgenic nature and tendency to produce virilizing side
effects. Some women do favor the drug, however, and find a single 25 mg tablet enough to efficiently shift the hormone balance in the body, greatly impacting the look of definition to the physique. Intake is usually limited to no longer than four or five weeks in such situations to minimize the chance of developing lasting virilizing effects. One tablet used in conjunction with 10 or 20 mg of Nolvadex can be even more efficient for muscle hardening, creating an environment where the body is much more inclined to burn off extra body fat, especially in female trouble areas like the hips and thighs. Extreme caution should be taken with such use, however.

Friday, May 16, 2014

Testosterone for Women


A women in her late twenties, came to see me complaining about her difficulty in losing weight. After taking a medical history, it was very difficult to tell what the basis of her problem was. She was working out daily, with a balance of aerobic exercise and weight training under the guidance of a qualified personal trainer. Her diet was a basic low carbohydrate/ high protein diet. Even more perplexing, she had been taking a caffeine/ephedrine thermogenic stack and had previously experimented with some diet drugs as well. Something was obviously wrong. I did blood tests to check all of her hormone levels. When the results came back, all of her hormones were in the normal range except for, you guessed it, testosterone! She had very low free testosterone level. It was equal to that seen in a postmenopausal women. This was an obvious source of her fat loss problem .

While the role of testosterone in maintaining muscle mass and losing body fat may be obvious to bodybuilders and athletes, it is a basic hormonal fact that is often absent in the medical community. It is known that many women begin to gain fat rapidly about ten to fifteen years before the menopause and also after. The connection between low to absent testosterone production and the deterioration of a healthy body composition is rarely made. Most women are often only given estrogens and progestins as hormone replacement therapy, but not testosterone. I have found in my medical practice that giving women estrogen and progesterone and not testosterone makes it almost impossible for them to lose weight/fat. With the scourge of increasing obesity in the USA, one would expect the medical community to pay closer attention to these issues. Yet the connection between sex hormones, and body composition is highly controversial.

Why is there such a controversy? Why is a hormone commonly used by farmers to fatten up livestock given to postmenopausal women at risk for obesity? Many doctors point to a recent study showing that when postmenopausal women given estrogen actually gained less weight than those not given estrogen. In this study 875 women were either put on .625 mg of oral estrogen a day or a placebo for three years. So does this mean that estrogen is actually a good fat-loss agent? Hardly! In this study, in spite of the publicity it was given, the authors note that when you control for lifestyle factors such as physical activity the effects of estrogen replacement therapy were insignificant.

From my clinical experience I have found that on the average when a young woman goes on birth control pills a 3-5 pound gain in fat mass can be expected, and at menopause with oral estrogens 4-8 pounds of fat mass gain can be anticipated - especially when oral estrogens are used. A recent controlled study showed that oral estrogens caused a gain in fat mass and loss in muscle, with a decrease in IGF-1 levels. This study is more consistent with my clinical observations.

So why isn’t testosterone more commonly given for weight loss in women? The medical community actually commonly believes testosterone causes obesity. This is due to a number of studies linking upper body obesity /abdominal obesity in women to elevated testosterone levels. Once again, this is a case of blaming one hormone as a "villain". In these women, they do in fact have higher than normal testosterone levels but their whole hormonal system is out of balance. Not only do they have high testosterone levels, but they also have poor insulin sensitivity as well as high insulin levels. Often these women have a metabolic problem of insulin resistance—which is associated with obesity. There is no serious evidence that testosterone replacement therapy for women will result in greater body fat – in fact the opposite is true.

With the social stigma against testosterone and anabolic steroids in general, and it is difficult enough to get a study approved on testosterone in men. Imagine how difficult it is to get a human use committee to approve a study on testosterone in women! However, there is one study that helped to illuminate the potential for androgens to help women lose fat. Lovejoy et al, in 1996, compared the effects of nandrolone decanoate and the anti-androgen drug spironolactone on body composition in obese, postmenopausal women. The dose given the nandrolone group was low – 30 mg every other week. All women in the study were put on a calorie restricted diet (500 calories below lean mass maintenance), and were told not to change their exercise habits. After nine months, the women receiving nandrolone lost an average of 3.6 percent of their bodyfat while the placebo group lost only 1.8 percent and the spirolactone (an anti-androgen) only .5 percent. Nandrolone doubled the rate of fat loss over the placebo and the anti-androgen group barely lost any fat at all – the role of androgens in fat loss is clearly demonstrated. Even more impressive, the nandrolone group actually gained an average of roughly four pounds of lean mass in spite of the calorie restriction while the placebo and anti-androgen groups lost over two pounds of lean mass. Nandrolone also did not produce insulin resistance as androgens have been previously believed to do.

Lovejoy’s group were impressed by the ability of nandrolone to produce increased muscle mass in spite of overall weight loss. Keep in mind that dose was fairly small and only given every other week, and that these women were put only somewhat extreme calorie restricted diets without being put on a weight training program. Imagine the improvement in body composition had these women been put on a balanced exercise program and were given a high protein diet in addition to their nandrolone!

Despite the positive result, the authors cautioned against using nandrolone decanoate as a weight loss therapy. There was a mild abnormality of blood lipids and a slight increase in abdominal fat in the nandrolone group. While these side effects were minor, I believe that if testosterone was used in this study instead of nandrolone, these effects would be smaller or non-existent. I also think that daily use of a testosterone gel would be more effective than a bi-monthly shot, since the gel would keep testosterone at a more physiological and consistent level whereas injections lead to huge up and down fluctuations.

It is clear to me, both from my clinical practice and from research, that testosterone is vital for women to preserve their lean mass and to prevent obesity. Not only will testosterone help mobilize body fat and negate some of the fat storing effects of estrogen, it is also extremely effective in building lean mass in women - even at small doses. Hormone replacement therapy that only includes estrogen and progesterone but leaves out testosterone is a curse of many a women’s fat loss program. This is not only a concern for postmenopausal women. Young women should think twice about using birth control pills. Birth control pills elevate estrogen and progesterone levels while drastically lowering testosterone levels. This is reason why many women experience large gains in fat as well as a decreased libido when using birth control pills.

Thursday, May 8, 2014

Melanotan and Melanotan II


Melanotan  and Melanotan II  are both analogs of the alpha-melanocyte stimulating hormone (α-MSH) which is produced within the pituitary gland. Along with other melanocortins, they are responsible for various internal human functions including skin and hair pigmentation, appetite, libido and physical sexual arousal. Whilst these effects have been observed in both sexes, it is worth noting that increases in libido and sexual function are exclusive to Melanotan-II.

Prompted by ultraviolet (UV) exposure, α-MSH release consequently stimulates production of melanin from the melanocytes within the skin. Melanin, as I'm sure you are aware, is a brown pigment and responsible for the tanning of the skin. Simply put, more α-MSH means more melanin, resulting in greater skin pigmentation. Since bodybuilding is such an aesthetic pursuit, and with darker skin that accentuates muscularity, it's little wonder that these drugs are in such high demand.

Both Melanotan and Melanotan II have been shown in the clinical setting to increase pigmentation without exposure to UV, a feature that is also confirmed anecdotally by users that report tanning in areas of the body that would seldom see the light of day! However, the process of tanning is greatly expedited by UV exposure. It is worth noting that tanning effects may not be uniform throughout the skin. This is in part due to the half life and distribution of the drug itself, but primarily in response to the concentration of melanocytes within certain areas of the skin. Most will notice the greatest tanning effect on the face, arms, abdominal region. Interestingly, the genitals have one of the highest concentrations of melanocytes enabling these particular areas to respond very well to the peptide in conjunction with UV exposure.

Suggested Cycles/Uses

If you look hard enough out there, you will find some weird and wonderful dosaging schedules whereby the user calculates their daily dosage by multiplying their bodyweight by a cofactor. Perhaps this approach has been adopted since this has been the method employed in the ongoing clinical studies. Typically, this type of formula would suggest a dose of 1mg of Melanotan-II per day for someone weighing in at a mere 110lb (50kg). The cynical among us might be forgiven for thinking that these formulae are constructed by those with a personal interest in the sale of the product as I believe this to be more than necessary to achieve a great result. Indeed, there are many instances whereby users feel they have become too dark. While I have no problem with a bodyweight dosage scale in principle, I can't help thinking that it's not only unnecessary (particularly for the mathematically challenged), but also avoids the ability to gradually increase dosages from a relatively low level; something which I would advocate to assess individual tolerance levels to side effects, especially in the case of Melanotan-II.

Clinical trials to determine efficacy of the drugs have typically used dosages up to 0.21mg/kg daily for Melanotan (16mg for a 75kg (165lb) individual), and up to 0.03mg/kg daily for Melanotan II (2.25mg for a 75kg (165lb) individual). More typically however, trials have used the dosages of 0.16mg/kg (12mg) and 0.025mg/kg (1.875mg) respectively. At this level of dosage, one such study involving Melanotan indicated the following incidences of side effects from subjects:

  • Nausea 85%
  • Facial Flushing 75%
  • Fatigue 44%
  • Vomiting 26%
  • Injection site reactions 13%
  • Zero incidence of erections
  • No change in vital signs or haematological parameters, blood biochemistry (liver and renal function)

As is the case with any drug use, the user is ideally looking to minimise unwanted side effects, whilst still achieving an acceptable outcome. With this in mind, I would suggest that a tapering up of dosages is used in order to assess the individual's personal tolerance to the side effects.

Both Melanotan and Melanotan II can be used for extended periods, whereby there is an initial daily administration of perhaps 2-3 weeks or until desired level of pigmentation has been achieved, followed by a maintenance phase of two injections per week.

Melanotan:
Start with a dose of 1mg daily for the first two or three days and, if level of side effects permit, look to increase dosage by 0.25mg every day over the next several days until you reach a daily dosage of 2-3mg. This level should be adequate for most users, though some may wish to increase yet further, perhaps as high as 5mg daily in order to achieve a very deep tan. A maintenance phase as described above is then used.

Melanotan II:
Start with a dose of 0.25mg. If side effects (primarily nausea) are not proving troublesome, attempt to increase daily dosage by 0.25mg where possible, until you reach 1-1.5mg daily. Most have found that this level will yield a very pleasing result and I can't see much point in increasing too much further unless a very deep tan was desired. As with Melanotan, once the desired level of tanning is reached, a maintenance phase is used.

Administration
Both Melanotan and Melanotan II are currently supplied as white lyophilised powder contained in a sealed multi-use vial. The peptide is susceptible to temperature degradation and should be shipped preferably with an ice pack though contrary to popular belief, the rate of degradation is very slow (weeks) in its powder form, so there's no need to be alarmed if yours wasn't shipped in this manner or you are unable to collect your package from a depot for a day or two. Once delivered, the powder is best stored in a freezer, or refrigerated if this is not possible.

To prepare for injection, it must be reconstituted with bacteriostatic water. You may use anything between 1ml and 5ml of water for your vial. Dependant upon the amount of water used will determine the concentration of your solution. For example, a 10mg vial of Melanotan II mixed with 1ml of water will provide a solution of 10mg per 1ml (10mg/ml). This means that a 1mg dose will require a shot of 0.1ml. Bearing in mind that the recommended starting dose is 0.25mg, using the example above, the actual volume of the shot would be 0.025ml (¼ of 1 tenth of a ml). This is a very small volume and very difficult to accurately dose even with a 0.5ml insulin syringe. Therefore, at least until your dosages have increased, it is suggested that you use more water for your vial.

An example of a good solution would be to mix 10mg of Melanotan II powder with 4ml of bacteriostatic water. This now provides:

10mg/4ml or 1mg/0.4ml or 0.25mg/0.1ml

0.1ml can be accurately measured using a 0.5ml or 1ml syringe.

Obviously, as your dosages become higher, you may dilute subsequent vials with lower amounts of water to reduce the volume of each shot. I would recommend that when you are using a dosage of 1mg, you reconstitute the vial with 1ml or 2ml of water so that each shot will be 0.1ml or 0.2ml respectively.

The injection is given into the sub-cutaneous layer which includes adipose tissue (fat).

If you are using insulin syringes which have short needles, you will need to enter the skin at 90°. to the skin, otherwise you can inject as shown in the illustration above with a 29 or 30 gauge, 0.5" needle.

I would suggest that you use standard 1ml syringes to which you can interchange needles as required. By doing so, you are able to attach any gauge/length you want to reconstitute and draw the solution (I use a 25guage 1" needle). Once done, simply attach your suitable needle for the injection. Following the injection, ensure that you pull back the plunger a little to 'reclaim' the solution that is contained within the needle itself. The syringe/needle is then placed in the refridgerator for storage until your next injection is due whereby you will attach a brand new injection needle. This process is repeated until you have administered all of the solution in that particular syringe.

Alternatively, you may pre-load insulin syringes and refrigerate until needed. However, because they have non-detachable needles, this can be quite cumbersome as they require loading from the rear.

Instability of the peptide is a much greater issue once reconstituted so you don't want it sitting in the fridge for months on end. Ideally one 10mg vial of Melanotan-II could be shared by two people (each having their own syringe/needles) so even during the maintenance phase of two injections per week of 1mg each; the longest it will be reconstituted for is 2.5 weeks.

Example of How to Dose Melanotan II

Draw 2ml of bacteriostatic water into the vial
On an insulin needle, start at 0.06ml (up to 6 little notches on the needle only – see diagram)
If this is ok then increase to 0.1ml on the needle
Do not use more than 0.15ml
Start every 2-3 days, then reduce as you get darker
Stored in the fridge and discard after 3 weeks

Major Differences

Melanotan's peptide structure is very closely matched to that of our endogenously produced alpha-melanocyte stimulating hormone (α-MSH). It is a specific agonist of the melanocortin-1 receptor (MC-1R) which is primarily responsible for skin colour and is found on melanocyte cells.

Melanotan II on the other hand has a much shorter sequence of amino acids and because of this quite pronounced change in length and structure, is an agonist of the range of melanocortin receptors. Perhaps more importantly, binding at receptors other than MC-1R is far greater than that of Melanotan. This 'shotgun effect' agonism of the full spectrum of different melanocortin receptors results in some effects that are only witnessed from Melanotan-II. Most notably, increases in sexual arousal are due to Melanotan-II's activation of MC-3R and MC-4R.

Because the amino acid sequence is much shorter in the case of Melanotan-II, there is therefore a much greater density of peptide chains than is present using Melanotan within a given set weight. Although the receptor binding affinity of Melanotan-II may not be quite as effective, there will be much more peptide chains than for Melanotan on a mg for mg basis so effectively you require much less in terms of milligram weight of Melanotan II to achieve similar results. This accounts for the wide difference in suggested dosages for each peptide and of course, makes Melanotan-II a much cheaper proposition.

                                     Effects / Side Effects
Melanotan                                                                         Melanotan II
Skin pigmentation                                                               Skin pigmentation
Nausea                                                                                 Nausea
Appetite suppression                                                           Appetite suppression
Flushing (esp. facial)                                                           Flushing (esp. facial)
Headache                                                                             Headache
Lethargy                                                                              Lethargy
Itching                                                                                 Itching
Dizziness                                                                             Dizziness
New mole appearance or darkening                                    New mole appearance or darkening
Hyperpigmentation                                                              Hyperpigmentation
White patches                                                                      White patches
Increased libido
Physical sexual arousal
Anaphylactic shock?

Of the above listed effects/side effects, it is worth bearing in mind that the prevalence and severity are witnessed to a greater degree from Melanotan II. Indeed, most will find Melanotan very comfortable to use, typically only experiencing minor nausea, appetite suppression and flushing.

Although side effects do become less troublesome with each administration of Melanotan or Melanotan-II, most users will experience at least some of the side effect to varying degrees, most commonly nausea, appetite suppression, facial flushing and dull headaches. These will typically become apparent within a few minutes of administration but can last for many hours. In the case of Melanotan-II, increases in libido are often seen in conjunction with outwardly physical signs of sexual arousal whereby the male user experiences prolonged periods of increased blood flow to the penis. This particular side effect does not diminish in severity over time and instances of occurrence are to be expected throughout the period of Melanotan-II use. As I'm sure you can appreciate, this aspect may prove embarrassing and perhaps quite uncomfortable, so I must stress again the importance of building dosage up gradually to assess personal tolerance and susceptibility.

Some users will notice the new appearance of freckles as these particular areas of skin have increased melanin. The good news is that as the tan is developed, the visual appearance of them will diminish, probably completely. Moles commonly become darker too as these are actually highly concentrated clusters of melanocytes. Both of these occurrences will reverse some time after discontinuation of the peptide and suntanning is ceased.

In addition to freckles and mole changes, there are fairly rare reports of a phenomenon called hyperpigmentation. This is typified by blotches of darkened skin, normally much larger than regular moles. Not all incidences of hyperpigmentation are attributable to increased melanocyte activity even though their appearance may only become apparent during melanocortin receptor agonism by Melanotan I or II. This condition is specifically referred to as diffuse hyperpigmentation, with many possible underlying causes or disorders including Addison's disease, haemochromatosis, hyperthyroidism and certain medications which may induce phototoxic reactions.

Previously unseen white spots or white patches of skin may also become apparent as the tan deepens. Again, this is not thought to occur as a direct result of using Melanotan, rather it merely uncovers the underlying condition. There are a range of actual causes. White spots (typically 2-5mm in size) may be the result of Idiopathic guttate hypomelanosis where there are reductions in the number of melanocytes and melanin in those particular areas. Larger white areas of skin may be due to Tinea versicolor which is a fungal infection caused by the yeast Malassezia furfur which is found on the skin and is not normally troublesome. Treatment would normally include an oral or topical anti-fungal though it may take many weeks for the skin tone to become consistent with surrounding areas.

It has been suggested that due to the greater difference of Melanotan-II to our own α-MSH, there is a greater chance of the body to view the peptide as a 'foreign body' and produce an allergic response. This could potentially trigger anaphylaxis, a potentially life threatening situation whereby large amounts of histamine are produced by the body which can lead to a host of effects including severe bronchoconstriction and rapid drops in blood pressure.

Friday, May 2, 2014

Anabolic Steroids and Side Effects


Anabolic steroids tend to have side effects, especially when used at above therapeutic dosages. They can increase cholesterol, raise the hematocrit ("thickening" the blood), suppress natural testosterone production, and at least for oral varieties, impair liver function. Let's not forget, too, those pesky cosmetic issues like acne, accelerated male pattern hair loss, and gynecomastia. Both sides of the anabolic steroid argument readily agree on this. Where there seems to be much disagreement, however, are the long-term risks of anabolic steroid use. Are anabolic steroid-related side effects reversible and if so, does a career of anabolic steroid use still increase the likelihood of disease or death later on? While science has yet to answer the latter question, the former has been the subject of much investigation.

Before we get into the specific results, I think it is important to examine the protocols of the study. A total of 32 men participated in this investigation, each identified as a bodybuilder or powerlifter. About half of the men (15) were former anabolic steroid abusers, with an average age of 38. The amount of time since the men quit taking the drugs varied from one to 10 years, with an average of about 3.5 years. While they were using steroids, their average intake was 720 milligrams per week for 26 weeks per year over nine years. The other 17 men were current anabolic steroid abusers, with an average age of 30. They used an average of 750 milligrams per week for approximately 32 weeks per year over an eight-year period. The two groups in this study were fairly well balanced as far as history and usage patterns go, and seem to represent a formidable though fairly average history of anabolic steroid use at above therapeutic levels.

While they were using anabolic steroid, each of the subjects self-administered without a medical prescription. According to a questionnaire filled out by the subjects, the most popular injectable agents of use were Boldenone, Drostanolone, Methenolone, Nandrolone, Stanozolol and various esters of testosterone such as Testosterone enanthate and Sustanon 250. The orals most widely used included 4-chlorodehydromethyltestosterone (Oral Turinabol),  Mesterolone, Methenolone, Methandrostenolone, Oxymetholone, Oxandrolone and Stanozolol. Five ex-abusers and six current abusers had occasionally used human growth hormone (hGH) as part of their programs, at a dosage between 2 and 16 IU daily. Other non-steroid drugs commonly used by both groups included anti-estrogens and clenbuterol, as would be expected in such populations.

Now let's get to the results. To begin with, current steroid users noticed a predictable (negative) shift in cholesterol levels. In particular, HDL (good) cholesterol values were very low (< .9 nmol/L) in 15 out of 17 current anabolic steroid abusers. The cholesterol balance, of course, may reflect the ongoing disposition of plaque in the arteries during use. As such, a higher HDL level and HDL/ LDL ratio are more desirable. After a minimum of one year of abstinence, the HDL level was below the normal range in only one ex-abuser. These results are in line with other short-term administration studies, as well as the common understanding of anabolic steroid, demonstrating a strong negative impact on serum cholesterol levels, and by extension cardiovascular disease risk, during the misuse of anabolic steroids. However, they also appear to support the reversibility of anabolic steroid-related changes in serum lipids, as no consistent (negative) findings were carried over into the lab results of ex-abusers.

There were also distinct changes in the blood cell counts of current anabolic steroid users. In particular, there was a significant increase in hemoglobin (5%) and hematocrit (9%). These changes may reflect an increase in the oxygen-carrying capacity of the blood, and could improve performance. However, they may also represent an unwanted "thickening" of the blood by nature of increased red cell concentrations. This is very important because it can increase the likelihood of a cardiovascular event such as heart attack or stroke— especially in light of the other common health marker changes during anabolic steroid use, such as impaired cholesterol and elevated blood pressure. In the group of former steroid users, these changes in blood cell counts were not noticed. These findings support the position that there are distinct side effects on red blood cell counts during steroid use, but these changes are reversible when the drugs are discontinued.

In the area of liver enzymes, there were notable changes in both groups. All of the current steroid users except one had elevated AST (aspartate transaminase) and ALT (alanine transaminase) values, which is often indicative of hepatic strain due to c-17 alpha alkylated (oral) anabolic steroid use. AST and ALT enzymes were elevated above normal in three and six of the former steroid abusers, respectively. The researchers discussed the potential elevation of liver enzyme values caused by exercise, and noted that both groups practiced strength training. However, changes in enzymes not related to exercise (such as GLDH) suggested the strain in current users was anabolic steroid-related. There were no signs of lasting impairment of the organ in either group upon ultrasound examination. These results are in line with numerous previous studies that show a risk of liver toxicity with current anabolic steroid misuse. However, they do not support the position that anabolic steroid misuse increases the long-term (post-administration) likelihood of hepatic health issues.

Testosterone levels were exceedingly high in steroid abusers, owing to the prominence of synthetic testosterone use in this group (the source was not natural but exogenous). This was accompanied by a severe suppression of gonadotropin levels, with LH and FSH levels lower by 91-94 %. This reflects the underlying suppression of natural testosterone production in current steroid abusers. Unlike most of the other health markers, serum testosterone did not seem to recover to normal levels after anabolic steroid misuse. A troubling 13 of the former steroid abusers had testosterone levels that measured in the lowest 20 % of the normal range for men. Two of the subjects had testosterone that measured below normal. The other hormones were within reference ranges for this group. While we generally like to view testosterone suppression during anabolic steroid use as a temporary side effect, it may not always be. If the results of this study hold true for the general population, it suggests that former steroid users are likely to struggle with sub-optimal testosterone production years after stopping use of the drugs. Therefore, this part of the study did provide distinct evidence of prolonged steroid-related side effects.

There were some other areas of effect to note during this study. For example, there was an increase in thrombocytes in current steroid abusers compared to ex-abusers. Thrombocytes are cells involved in blood clotting. Together with increased hematocrit and possibly blood pressure, this could increase the likelihood of serious adverse cardiovascular events such as blood clot or stroke. While still relatively rare, we have seen occasional reports of such in otherwise healthy anabolic steroid users. With regard to other common blood markers, there were no significant differences between groups in serum electrolytes (sodium, potassium, magnesium, calcium), iron, urea, creatinine, uric acid, glucose or HBA1. Lastly, while the researchers did not chart common cosmetic issues, they did report a high prevalence of gynecomastia in both groups (approximately two-thirds of subjects had or are currently dealing with it). Gynecomastia can be a permanent side effect of anabolic steroid misuse that requires surgery for correction. There are no surprises here.

In the context of this study, most of the short-term negative health effects of anabolic steroid misuse appeared to be reversible. In particular, former steroid users did not have the same unfavorable changes in red or white blood cell counts, serum cholesterol levels or liver enzyme values noted in current anabolic steroid users. The immediate effects of anabolic steroid on cardiovascular and liver health markers, which we know can be markedly negative, appear to go away after the drugs have been discontinued. These results do lend support for the acute safety of these drugs. They also mirror what we've seen in many short-term administration studies, which we touched on earlier in this piece. In this case, we are simply looking more broadly (and in a real-world context) at populations of users and former users for these same changes.

The reversibility of changes to basic health markers, of course, does not necessarily discount that there were changes in the first place. Disturbed health markers, even in the short term, could reflect underlying damage to our health. There is still much question as to whether a substantial period of anabolic steroid misuse could lead to a greater incidence of disease or death years later. For example, elevated cholesterol and LDL/HDL ratio are associated with heart-disease-promoting changes in the cardiovascular system. Logically speaking, one might still be contributing to atherosclerosis (hardening of the arteries) during non-prescribed anabolic steroid administration, even if these health markers return to normal after. This is an area of medicine that needs much greater examination, of course. As mentioned in the opening of this article, such studies are lacking.

In the area of hormonal health, there does appear to be a valid reason for concern if you are contemplating the use of anabolic steroids. In the men of this study, a history of anabolic steroid misuse was associated with insufficient testosterone levels long after stopping. Low testosterone may cause immediate issues such as energy loss, impaired mental focus, reduced libido, and loss of strength and muscle mass. In the long term, however, more serious issues such as heart disease, diabetes and cancer have been linked to male hormone deficiency. It is conceivable that a "minor" problem with a low or even low-end-of-normal testosterone level after steroid use could foster considerable health issues later in life if not corrected. "Low T" is certainly a growing concern for aging men in clinical medicine. Therefore, one should consider both the positive and negative findings of this study before placing any weight on the results, one way or the other. As always, be safe.