Depo®-Testosterone (testosterone cypionate)
Testosterone cypionate is a slow-acting injectable ester of the primary male androgen testosterone. Testosterone is also the principle anabolic hormone in men, and is the basis of comparison by which all other anabolic/androgenic steroids are judged. As with all testosterone injectables, testosterone cypionate is highly favored by athletes for its ability to promote strong increases in muscle mass and strength. It is interesting to note that while a large number of other steroidal compounds have been made available since testosterone injectables, they are still considered to be the dominant bulking agents among bodybuilders. There is little argument that these are among the most powerful mass drugs available, testosterone cypionate included.
Testosterone cypionate first appeared on the U.S. drug market during the mid-1950’s under the brand name of DepoTestosterone cyclopentylpropionate (soon abridged to simply Depo-Testosterone). It was developed by the pharmaceutical giant Upjohn, and is still sold to this day by the same company under the same trade name (although now they are called Pharmacia & Upjohn). This is a drug with limited global availability, and has historically been (largely) identified as an American item. It is not surprising that American athletes have long favored this form of testosterone over testosterone enanthate, the dominant slowacting ester of testosterone on the global market. This preference, however, is likely rooted in history and availability, not actual therapeutic advantages.
Testosterone cypionate and testosterone enanthate provide extremely comparable patterns of testosterone release. Not only are physical advantages not possible in one over the other, but actual differences in pharmacokinetic patterns are hard to notice (these two drugs are for all intents and purposes functionally interchangeable). The only key difference between the two seems to be in the area of patient comfort.
Cypionic acid is less irritating at the site of injection than enanthoic acid (enanthate) for a small percentage of patients. This makes testosterone cypionate a more favorable choice for those with recurring issues of injection-site pain with testosterone enanthate. This difference likely had something to do with the early development of this testosterone ester as a commercial drug product.
The main use of testosterone cypionate in clinical medicine has historically been the treatment of low androgen levels in males, although many other applications have existed for this drug as well. During the 1960’s, for example, the drug’s prescribing recommendations called for such uses as supporting bone structure maturity, treating menorrhagia (heavy menstrual bleeding) and excessive lactation in females, and increasing muscle mass and combating osteoporosis in the elderly. It was also being recommended for increasing male fertility, whereby induced testosterone/spermatogenesis suppression (caused by administering 200 mg of testosterone cypionate per week for 6 to 10 weeks) was potentially followed by a period of rebound spermatogenesis (due to temporarily higher than normal gonadotropin levels).
By the 1970’s, the FDA had been granted much stronger control over the prescription drug market, and the broad uses in which testosterone cypionate was first indicated were now being refined. For example, ‘testosterone rebound therapy’ as a way to increase male fertility was proving to be unreliable, especially in the face of newer more effective medications, and was soon eliminated from prescribing guidelines. So too was the recommendation for its use to treat things like excessive menstrual bleeding and lactation. In general, testosterone therapy was being pulled back to focus mainly on male androgen deficiency, and less on other applications, especially when involving populations more susceptible to androgenic side effects, such as women and the elderly.
Today, testosterone cypionate remains readily available on the U.S. prescription drug market, where it is FDA-approved for hormone replacement therapy in men with conditions associated with a deficiency of endogenous testosterone, and as a secondary treatment for inoperable metastatic breast cancer in women (although it is not widely used for this purpose anymore). Testosterone cypionate is currently available outside of the United States, but not widely. Known international sources for the drug include Canada, Australia, Spain, Brazil, and South Africa.
Testosterone cypionate is available in select human and veterinary drug markets. Composition and dosage may vary by country and manufacturer, but usually contain 50 mg/ml, 100 mg/ml, 125 mg/ml, or 200 mg/ml of steroid dissolved in oil.
Testosterone cypionate is a modified form of testosterone, where a carboxylic acid ester (cyclopentylpropionic 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. The half-life of testosterone cypionate is approximately 8 days after injection.
Figure 1.Pharmacokinetics of 200 mg testosteronecypionate injection. Source: Comparison oftestosterone, dihydrotestosterone, luteinizing hormone, and follicle-stimulating hormone in serumafter injection of testosterone enanthate ortestosterone cypionate. Schulte-Beerbuhl M. Nieschlag E.Fertility and Sterility 33 (1980):201-3.
Testosterone cypionate (in oil) can be positively identified with ROIDTESTTM Substance Tests B & D. The drug should produce a slightly delayed reaction with Substance Test D. turning purple color after 23 minutes. Secondary analysis should be performed with Substance Test B, which should produce an immediate (<1 minute) orangebrown color change.
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 antiestrogens, 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 cypionate more likely to require the concurrent use of an antiestrogen or aromatase inhibitor. Since water retention and loss of muscle definition are common with higher doses of testosterone cypionate, 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 5alpha 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-aminotransferase, and alkaline phosphatases.1
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 affect 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.2
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%.3 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 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/LDL cholesterol, triglycerides, apolipoprotein B/C-III, C-reactive protein, and insulin sensitivity, all indicating a relatively weak impact on cardiovascular risk factors.4 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.
As with all anabolic/androgenic steroids, it is unlikely that one will retain every pound of new bodyweight after a cycle is concluded.
This is especially true when withdrawing from a strong (aromatizing) androgen like testosterone cypionate, as much of the new weight gain is likely to be in the form of water retention, quickly eliminated after drug discontinuance. An imbalance of anabolic and catabolic hormones during the post-cycle recovery period may further create an environment that is unfavorable for the retention of muscle tissue. Proper ancillary drug therapy is usually recommended to help restore hormonal balance more quickly, ultimately helping the user retain more muscle tissue.
Another way to lessen the post-cycle ‘crash’ is to first replace testosterone cypionate with a milder anabolic such as nandrolone decanoate or methenolone enanthate. The new steroid would be administered alone for one to two more months, at a dosage of 200-400 mg per week. In this ‘stepping down’ procedure the user is attempting to eliminate the watery bulk of a testosterone-based drug while simultaneously preserving the solid muscularity underneath. This practice can prove to be effective, even if mainly for psychological reasons (some may view it as simply dividing the crash into water and hormonal stages). Testosterone-stimulating drugs are still typically used at the conclusion of therapy, as endogenous testosterone production will not rebound during the administration of nandrolone decanoate or methenolone enanthate.
The above side effects are not inclusive. For more detailed discussion of potential side effects, see the Steroid Side Effects section of this book.
To treat androgen insufficiency, the prescribing guidelines for testosterone cypionate call for a dosage of 50-400 mg every two to four weeks. Although active in the body for a longer time, testosterone cypionate is usually injected on a weekly basis for physique- or performance-enhancing purposes. The usual dosage is in the range of 200-600 mg per week, taken in cycles 6 to 12 weeks in length. This level is sufficient for most users to notice exceptional gains in muscle size and strength.
Testosterone is usually incorporated into bulking phases of training, when added water retention will be of little consequence, the user more concerned with raw mass than definition. Some do incorporate the drug into cutting cycles as well, but typically in lower doses (100-200 mg per week) and/or when accompanied by an aromatase inhibitor to keep estrogen levels under control. Testosterone cypionate is a very effective anabolic drug, and is often used alone with great benefit. Some, however, find a need to stack it with other anabolic/androgenic steroids for a stronger effect, in which case an additional 200-400 mg per week of boldenone undecylenate, methenolone enanthate,
or nandrolone decanoate should provide substantial results with no significant hepatotoxicity. Testosterone is ultimately very versatile and can be combined with many other anabolic/androgenic steroids to tailor the desired effect.
While large doses are generally not advised, some bodybuilders have been known to use excessively high dosages of this drug (1,000 mg per week or more). This was much more common before the 1990’s, when cypionate vials were usually very cheap and easy to find. A ‘more is better’ attitude is easy to justify when paying only $20 for a 10cc vial (today the typical price for a single injection). At dosages of 800-1000 mg per week or more, water retention will likely account for more of the additional weight gain than new muscle tissue. The practice of ‘megadosing’ is inefficient (not to mention potentially dangerous), especially when we take into account the typical high cost of steroids today.
Testosterone cypionate is rarely used with women in clinical medicine. When applied, it is most often used as a secondary medication during inoperable breast cancer, when other therapies have failed to produce a desirable effect and suppression of ovarian function is necessary. Testosterone cypionate 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).
Testosterone cypionate remains widely available as a prescription drug product. Its production is largely associated with American companies, although recently has been expanding into loosely regulated Asian markets that still cater to demand by bodybuilders and athletes. In reviewing some of the products and changes on the global pharmaceutical market, we have made the following observations.
Brand name testosterone cypionate Depot®-Testosterone remains available in the United States from Pfizer. It is produced in both 100 mg/mL and 200 mg/mL strengths. In addition, there are numerous generics being produced from companies such as Periggo, Sandoz, West-Ward, Mylan, Paddock, Sun, and Watson. In recent years there has been a shift to the prescribing and production of 1 mL vials, though 10 mL products are still in production domestically.
Cypiobolic from Asia Pharma (Malaysia) is now approved for sale through pharmacies in Thailand. This product comes in a 200 mg/mL strength, and is packaged in 10 mL multi-dose vials.
Landerlan produces a 200 mg/mL cypionate in Paraguay called Testoland Depot. It comes in a 100 mg/mL concentration, and is packed in 2 mL glass ampules (3 per box). Note that the manufacturer states they are overfilled by 10%.
Alpha-Pharma India produces a 250 mg/mL product called Testocyp. This comes in both 1 mL ampules and 10 mL multi-dose vials.
It appears Q Pharma (Spain) is still manufacturing Testex Prolongatum. It is packaged in 2 mL dark glass ampules containing a total of 100 mg or 250 mg of steroid. Testex has always been a high-profile item for counterfeiters. Be cautioned.
Balkan Pharmaceuticals (Moldova) makes the product Testosterona C. It is prepared in 100 and 200 mg/ml concentrations, in 1 mL ampules.
1 Enzyme induction by oral testosterone. Johnsen SG, Kampmann JP, Bennet EP, Jorgensen F. 1976 Clin Pharmacol Ther 20:233-237.
2 High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered. Friedl K, Hannan C et al. Metabolism 39(1) (1990):69-74.
3 Testosterone dose-response relationships in healthy young men. Bhasin S, Woodhouse L et al. Am J Physiol Endocrinol Metab 281 (2001):E117281.
4 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 87 (2002):136-43.