Chemical Names: 4-androsten-3-one-17beta-ol, 17beta-hydroxy-androst-4-en-3-one
Estrogenic Activity: moderate
Progestational Activity: low
Agovirin Depot, a brand name for testosterone isobutyrate, is an injectable steroid preparation that contains the isobutyrate ester of testosterone in a water base. Among bodybuilders, testosterone isobutyrate is often considered analogous to testosterone suspension (no ester). Although both are usually found as water-based suspensions, the pharmacokinetics of the two products are admittedly very different. While testosterone (free) suspension is very fast-acting, requiring injections to be given every few days, testosterone isobutyrate is much slower to release, and is usually administered once every two weeks in a clinical setting. As an injectable testosterone, testosterone isobutyrate is favored for its ability to promote rapid gains in muscle mass and strength.
Injectable testosterone isobutyrate microcrystal suspension was first described in 1952.379 This agent was developed in an effort to create an injectable (depot) form of testosterone that would be slower acting that regular (free) testosterone suspension or testosterone propionate, the most widely prescribed forms of testosterone at the time. This is accomplished by providing a microcrystalline depot with very low water solubility, delaying the release of free steroid into the bloodstream. Although effective for this purpose, testosterone isobutyrate was developed at a time when many new esters of testosterone were being introduced to the market. By the mid-1950’s, testosterone enanthate would emerge as the dominant slow-acting injectable testosterone, and the isobutyrate ester would ultimately see little commercial success.
The only modern steroid product to use testosterone isobutyrate is Agovirin Depot, developed by Biotika in Czechoslovakia. It is primarily prescribed to treat males with insufficient androgen levels and adolescents with delayed puberty, although it is indicated for a variety of other purposes including the treatment of Klinefelter syndrome (a disease where an extra chromosome results in an imbalance of androgenicity and estrogenicity), aplastic anemia, Cushing’s syndrome (as an anabolic agent to preserve lean tissue), postmenopausal osteoporosis, advanced breast cancer, mastodynia (breast pain), and cachexia (wasting of the body due to severe illness). Agovirin Depot is still produced by Biotika (currently in the Slovak Republic), and remains a popular export to European black markets.
Testosterone isobutyrate suspension is available on the human drug market in the Slovak Republic as Agovirin Depot (Biotika). It contains 25 mg/ml of steroid mixed in a water-based solution; packaged in a 2 mL ampule (5 ampules per box). Testosterone isobutyrate has low water solubility; the steroid will noticeably separate from the water-based solution when an ampule is left to sit. A quick shake will temporarily place the drug back into suspension, so that the withdrawn dosage should always be consistent.
Testosterone isobutyrate is a modified form of testosterone, where a carboxylic acid ester (2-methyl propionic acid) has been attached to the 17-beta hydroxyl group. Esterified forms of testosterone are less polar than free testosterone, and are absorbed more slowly from the area of injection. Once in the bloodstream, the ester is removed to yield free (active) testosterone. Esterified forms of testosterone are designed to prolong the window of therapeutic effect following administration, allowing for a less frequent injection schedule compared to injections of free (unesterified) steroid. Testosterone isobutyrate microcrystalline suspension is designed to provide physiological androgen concentrations for approximately 2 weeks following injection.
Side Effects (Estrogenic):
Testosterone is readily aromatized in the body to estradiol (estrogen). The aromatase (estrogen synthetase) enzyme is responsible for this metabolism of testosterone. Elevated estrogen levels can cause side effects such as increased water retention, body fat gain, and gynecomastia. Testosterone is considered a moderately estrogenic steroid. An anti-estrogen such as clomiphene citrate or tamoxifen citrate may be necessary to prevent estrogenic side effects. One may alternately use an aromatase inhibitor like Arimidex® (anastrozole), which more efficiently controls estrogen by preventing its synthesis. Aromatase inhibitors can be quite expensive in comparison to anti-estrogens, however, and may also have negative effects on blood lipids.
Estrogenic side effects will occur in a dose-dependant manner, with higher doses (above normal therapeutic levels) of testosterone more likely to require the concurrent use of an anti-estrogen or aromatase inhibitor. Since water retention and loss of muscle definition are common with higher doses of testosterone, this drug is usually considered a poor choice for dieting or cutting phases of training. Its moderate estrogenicity makes it more ideal for bulking phases, where the added water retention will support raw strength and muscle size, and help foster a stronger anabolic environment.
Side Effects (Androgenic):
Testosterone is the primary male androgen, responsible for maintaining secondary male sexual characteristics. Elevated levels of testosterone are likely to produce androgenic side effects including oily skin, acne, and body/facial hair growth. Men with a genetic predisposition for hair loss (androgenetic alopecia) may notice accelerated male pattern balding. Those concerned about hair loss may find a more comfortable option in nandrolone decanoate, which is a comparably less androgenic steroid. Women are warned of the potential virilizing effects of anabolic/androgenic steroids, especially with a strong androgen such as testosterone. These may include deepening of the voice, menstrual irregularities, changes in skin texture, facial hair growth, and clitoral enlargement.
In androgen-responsive target tissues such as the skin, scalp, and prostate, the high relative androgenicity of testosterone is dependant on its reduction to dihydrotestosterone (DHT). The 5-alpha reductase enzyme is responsible for this metabolism of testosterone. The concurrent use of a 5-alpha reductase inhibitor such as finasteride or dutasteride will interfere with site-specific potentiation of testosterone action, lowering the tendency of testosterone drugs to produce androgenic side effects. It is important to remember that anabolic and androgenic effects are both mediated via the cytosolic androgen receptor. Complete separation of testosterone’s anabolic and androgenic properties is not possible, even with total 5-alpha reductase inhibition.
Side Effects (Hepatotoxicity):
Testosterone does not have hepatotoxic effects; liver toxicity is unlikely. One study examined the potential for hepatotoxicity with high doses of testosterone by administering 400 mg of the hormone per day (2,800 mg per week) to a group of male subjects. The steroid was taken orally so that higher peak concentrations would be reached in hepatic tissues compared to intramuscular injections. The hormone was given daily for 20 days, and produced no significant changes in liver enzyme values including serum albumin, bilirubin, alanine-amino-transferase, and alkaline phosphatases. 380
Side Effects (Cardiovascular):
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. Anabolic/androgenic steroids may also adversely effect blood pressure and triglycerides, reduce endothelial relaxation, and support left ventricular hypertrophy, all potentially increasing the risk of cardiovascular disease and myocardial infarction.
Testosterone tends to have a much less dramatic impact on cardiovascular risk factors than synthetic steroids. This is due in part to its openness to metabolism by the liver, which allows it to have less effect on the hepatic management of cholesterol. The aromatization of testosterone to estradiol also helps to mitigate the negative effects of androgens on serum lipids. In one study, 280 mg per week of testosterone ester (enanthate) had a slight but not statistically significant effect on HDL cholesterol after 12 weeks, but when taken with an aromatase inhibitor a strong (25%) decrease was seen.381 Studies using 300 mg of testosterone ester (enanthate) per week for 20 weeks without an aromatase inhibitor demonstrated only a 13% decrease in HDL cholesterol, while at 600 mg the reduction reached 21%.382 The negative impact of aromatase inhibition should be taken into consideration before such drug is added to testosterone therapy.
Due to the positive influence of estrogen on serum lipids, tamoxifen citrate or clomiphene citrate are preferred to aromatase inhibitors for those concerned with cardiovascular health, as they offer a partial estrogenic effect in the liver. This allows them to potentially improve lipid profiles and offset some of the negative effects of androgens. With doses of 600 mg or less of testosterone per week, the impact on lipid profile tends to be noticeable but not dramatic, making an anti-estrogen (for cardioprotective purposes) perhaps unnecessary. Doses of 600 mg or less per week have also failed to produce statistically significant changes in LDL/VLDL cholesterol, triglycerides, apolipoprotein B/C-III, C-reactive protein, and insulin sensitivity, all indicating a relatively weak impact on cardiovascular risk factors.383 When used in moderate doses, injectable testosterone esters are usually considered to be the safest of all anabolic/androgenic 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 AAS 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.
Side Effects (Testosterone Suppression):
All anabolic/androgenic steroids when taken in doses sufficient to promote muscle gain are expected to suppress endogenous testosterone production. Testosterone is the primary male androgen, and offers strong negative feedback on endogenous testosterone production. Testosterone-based drugs will, likewise, have a strong effect on the hypothalamic regulation of natural steroid hormones. Without the intervention of testosterone stimulating substances, testosterone levels should return to normal within 1-4 months of drug secession. Note that prolonged hypogonadotrophic hypogonadism can develop secondary to steroid abuse, necessitating medical intervention.
The above side effects are not inclusive. For more detailed discussion of potential side effects, see the Steroid Side Effects section of this book.
The design of testosterone isobutyrate (as Agovirin Depot) is slightly different than that of most testosterone esters, which are usually made as oily solutions. Agovirin Depot instead contains a microcrystalline aqueous suspension.The crystals form a repository in the muscle following injection, where they slowly dissolve over time. Injections of testosterone isobutyrate may require a large needle (21 gauge), and may result in local irritation, pain, and redness.
To treat androgen insufficiency, Agovirin Depot is usually administered in a dose of 50-100 mg every 14 days. When used for muscle-building purposes, testosterone isobutyrate suspension is often administered at a dose of 200-400 mg (4-8ml) per week. Although active for longer periods of time, weekly injections would be preferred due to the low dosage and tendency for pain at the site of injection (large injection volumes would not be advised). To reduce injection volume, the weekly dosage may be further subdivided into smaller injections, which are taken every 2nd or 3rd day. Cycles are generally between 6 and 12 weeks in length. This level is sufficient to provide noticeable gains in muscle size and strength. Testosterone drugs are ultimately very versatile, and can be combined with many other anabolic/androgenic steroids depending on the desired effect.
Agovirin Depot is not commonly used with women in clinical medicine. When applied, it is usually given in a dose of 25-50 mg every 14 days. Testosterone isobutyrate suspension is not recommended for women for physique- or performance-enhancing purposes due to its strong androgenic nature, tendency to produce virilizing side effects, and slow acting characteristics (making blood levels difficult to control).
Pharmaceutical preparations containing testosterone isobutyrate are rare. The only known product at this time is Agovirin Depot, produced in the Slovak Republic by Biotika. It contains 50 mg per 2 mL ampule; 5 packaged per box.
379. Experiences with a new testosterone isobutyrate crystal suspension. Drescher H. Dtsch Med Wochenschr. 1952 Apr 4;77(14):431-2.
380. Enzyme induction by oral testosterone. Johnsen SG, Kampmann JP, Bennet EP, Jorgensen F. Clin Pharmacol Ther (1976) 20:233-237.
381. High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered. Friedl K, Hannan C et al. Metabolism 39(1)
382. Testosterone dose-response relationships in healthy young men. Bhasin S, Woodhouse L et al. Am J Physiol Endocrinol Metab (2001) 281:E1172-81.
383. The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. Singh A, Hsia S, et al. J Clin Endocrinol Metab (2002) 87:136-43.