Description:

Testosterone cypionate is a slow-release injectable form of the male androgen testosterone. It is also a metabolic hormone for men, serving as the basis for all other anabolic/androgenic steroids. Like all testosterone injectables, testosterone cypionate is favored by athletes for its ability to promote significant increases in muscle mass and strength. Despite the existence of numerous other anabolic compounds in injectable form, it remains a primary bulking agent among bodybuilders. Unquestionably, it is one of the most potent compounds available.

History:

Testosterone cypionate first appeared on the U.S. pharmaceutical market in the mid-1950s under the brand name Depo-Testosterone, developed by the pharmaceutical giant Upjohn, and continues to be sold under the same trade name by the same company (now known as Pharmacia & Upjohn). This drug has historically been identified as a U.S. product with limited global availability, dominating the slow-acting ester market worldwide. The preference for this form of testosterone may be due to historical availability rather than its therapeutic advantages.

Testosterone propionate and testosterone enanthate offer very similar testosterone release patterns. There is no noticeable difference in the pharmacokinetic patterns between these two drugs (they are functionally interchangeable). The only significant difference is patient comfort; for a small percentage of patients, testosterone cypionate is less irritating at the injection site compared to its counterpart (testosterone enanthate). This benefit may be related to the early development of this ester as a commercial drug product.

Clinically, testosterone cypionate has been used to treat men with low levels of testosterone, although it has also been used for other therapeutic purposes. For instance, in the 1960s, it was prescribed for its benefits in bone maturation, treatment of menorrhagia (heavy menstrual bleeding), excessive lactation in women, increased muscle mass, and combating osteoporosis in the elderly. It was also recommended to enhance male fertility, including the treatment of suppressed testosterone/sperm production caused by the administration of 200 mg of testosterone weekly for 6 to 10 weeks, allowing for sperm production rebound due to temporarily elevated gonadotropin levels.

By the 1970s, the FDA had tightened control over the prescription drug market, and the broad use of testosterone was first refined. For example, "testosterone rebound therapy" as a way to increase male fertility proved unreliable, especially when faced with newer, more effective medications, and was soon removed from prescription guidelines. Recommendations for treating menorrhagia and lactation issues remained. Overall, testosterone therapy is being redirected back to treating male androgen deficiency, with less frequent use in other areas, especially when involving populations more susceptible to androgenic side effects, such as women and the elderly.

Today, testosterone cypionate is still available on the U.S. prescription drug market, approved by the FDA for male hormone replacement therapy and related conditions of endogenous testosterone deficiency, as well as an adjunct treatment for inoperable metastatic breast cancer in women (although it is no longer widely used for this purpose). Testosterone cypionate is available outside the United States, though not widely used. Known international sources include Canada, Australia, Spain, Brazil, and South Africa.

Specifications:

Testosterone cypionate is sold in both human and veterinary markets. The composition and dosage may vary by country and manufacturer but generally contain a steroid dissolved in oil at concentrations of 50 mg/ml, 100 mg/ml, 125 mg/ml, or 200 mg/ml.

Structural Characteristics:

Testosterone cypionate is a modified form of testosterone, where a carboxylic acid ester (cyclopentylpropionic acid) has been attached to the 17-beta hydroxyl group. The esterified form of testosterone is less polar than free testosterone, and is absorbed more slowly from the area of injection. Once in the bloodstream, the ester is removed to yield free (active) testosterone. Testosterone is designed in its esterified form to prolong the therapeutic window following administration, allowing for less frequent injection schedules compared to injections of free (unesterified) steroids. The half-life of testosterone cypionate is approximately eight days after injection.

Figure 1. Pharmacokinetics of a 200mg testosterone cypionate injection.

Testosterone is readily aromatized in the body to estradiol (estrogen). The aromatase enzyme (estrogen synthetase) is responsible for this metabolism. Elevated estrogen levels can lead to side effects such as increased water retention, body fat gain, and the development of gynecomastia. Testosterone is considered a moderate estrogenic steroid. Anti-estrogens such as clomiphene citrate or tamoxifen citrate are necessary to prevent estrogenic side effects. Aromatase inhibitors like anastrozole can be used to control estrogen more effectively by preventing its synthesis. However, compared to anti-estrogens, aromatase inhibitors can be quite expensive and may also have negative effects on blood lipids.

Estrogenic side effects will occur in a dose-dependent manner; higher doses (above therapeutic levels) of testosterone are more likely to require the simultaneous use of anti-estrogens or aromatase inhibitors. Since water retention and muscle loss are common with higher doses of testosterone cypionate, it is generally considered a poor choice for dieting or cutting phases. Its moderate estrogenicity makes it more suitable for bulking phases where the stored water can provide raw strength and size and contribute to a more potent anabolic environment.

Side Effects (Androgenic):

Testosterone is the primary male androgen, responsible for maintaining male secondary sex characteristics. Elevated levels of testosterone can produce androgenic side effects, including oily skin, acne, and body/facial hair growth. Men with a genetic predisposition for hair loss (androgenic alopecia) may notice accelerated balding. Those concerned about hair loss may find a more comfortable option in nandrolone decanoate, a less androgenic steroid. Women are also warned of the virilizing potential of anabolic/androgenic steroids, especially potent androgens like testosterone, which can include deepening of the voice, menstrual irregularities, changes in skin texture, facial hair growth, and clitoral enlargement.

In androgen-responsive tissues like the skin, scalp, and prostate, testosterone's high relative androgenicity is because it is reduced to dihydrotestosterone (DHT). 5-alpha reductase is the primary reason for testosterone metabolism. Using 5-alpha reductase inhibitors like finasteride or dutasteride can interfere with the site-specific action of testosterone, reducing the tendency for testosterone medications to produce androgenic side effects. It is important to remember that both anabolic and androgenic effects are mediated by the androgen receptor. It is impossible to completely dissociate testosterone's anabolic and androgenic effects, even with all 5-alpha reductase inhibited.

Side Effects (Hepatotoxicity):

Testosterone does not have a hepatotoxic effect, so the occurrence of liver toxicity is unlikely. A study examined the potential for liver toxicity from high doses of testosterone by administering 400 mg of hormone per day (2,800 mg per week) to a group of male subjects. Oral steroids, compared to intramuscular injections, can reach higher peak concentrations in liver tissue. The hormone was given daily for 20 days, with no significant changes in liver enzyme values, including serum albumin, bilirubin, alanine amino transferase, and alkaline phosphatase.

Side Effects (Cardiovascular):

Anabolic/androgenic steroids can have a detrimental impact on serum cholesterol. This includes a tendency to reduce HDL (good) cholesterol values and increase LDL (bad) cholesterol values, potentially leading to a greater risk of arteriosclerosis. The relative impact of anabolic/androgenic steroids on serum lipids depends on the dose, the route of administration (oral vs. injection), the type of steroid (aromatizable or non-aromatizable), and the level of resistance to hepatic metabolism. Anabolic/androgenic steroids can also adversely affect blood pressure and triglycerides, reduce endothelial relaxation, and cause left ventricular hypertrophy, potentially increasing the risk of cardiovascular disease and myocardial infarction.

Compared to synthetic steroids, testosterone has a much smaller effect on cardiovascular risk factors, partly due to its openness to liver metabolism, which lessens its impact on cholesterol management by the liver. The aromatization of testosterone to estradiol also helps to mitigate the negative impact of androgens on serum lipids. In one study, 280 mg of testosterone ester (enanthate) per week had a negligible and statistically insignificant effect on HDL cholesterol after 12 weeks, but a strong (25%) reduction was observed when an aromatase inhibitor was used. Using 300 mg of testosterone ester (enanthate) per week for 20 weeks without an aromatase inhibitor only showed a 13% reduction in HDL cholesterol, while 600 mg reduced it by 21%. The negative effects of aromatase inhibition should be considered before testosterone therapy.

Due to the positive effects of estrogens on serum lipids and because they exhibit partial estrogenic activity in the liver, tamoxifen citrate or clomiphene citrate is preferable to aromatase inhibitors. They potentially improve lipid profiles and offset some of the negative effects of androgens. Doses of 600 mg per week or less tend to have a noticeable but not dramatic effect on the lipid spectrum, making anti-estrogens (for cardiac protection purposes) perhaps unnecessary. Doses of 600 mg per week or less also failed to significantly alter LDL/VLDL cholesterol, triglycerides, apolipoprotein B/C-III, C-reactive protein, and insulin sensitivity, suggesting their relatively weak impact on cardiovascular risk factors. When used at moderate doses, injectable testosterone esters are generally considered the safest of all anabolic/androgenic steroids.

To help reduce cardiovascular strain, it is recommended to maintain an active cardiovascular exercise program and always minimize the intake of saturated fats, cholesterol, and simple carbohydrates during AAS use. It is also advisable to supplement with fish oil (4 grams per day) and natural cholesterol/antioxidant formulations such as Lipid Stabil or products with similar ingredients.

Side Effects (Testosterone Suppression):

When taken in doses sufficient to promote muscle gain, all anabolic/androgenic steroids are expected to suppress endogenous testosterone production. Testosterone is the primary male androgen, exerting strong negative feedback on endogenous testosterone production. Likewise, testosterone-based drugs have a strong effect on hypothalamic regulation of natural steroid hormones. Without interventions involving testosterone-stimulating substances, testosterone levels are expected to return to normal within 1-4 months after drug discontinuation. Note that hypogonadism may be secondary to steroid abuse and require medical intervention.

Like all anabolic/androgenic steroids, it is not possible to retain every pound of new body weight acquired during a cycle. This is especially true when discontinuing potent (aromatizable) androgens like testosterone, where the new weight gain is likely to be in the form of water and rapidly disappears after discontinuation. The imbalance of anabolic and catabolic hormones during the post-cycle recovery period may further produce an environment that is unfavorable for retaining muscle tissue. It is usually recommended to use proper ancillary drug therapy to help restore hormonal balance to assist users in retaining more muscle tissue.

Another way to reduce weight loss after the cycle ends is to first replace testosterone cypionate with milder anabolic substances, such as nandrolone decanoate and testosterone enanthate. The new steroids are initially administered alone for one to two months at doses of 200-400 mg per week. In this "tapering" process, users attempt to eliminate the water content associated with testosterone-based drugs while maintaining muscle hardness. This practice has proven effective, even if primarily for psychological reasons (some may perceive it as merely dividing the crash into water and hormone stages). At the end of treatment, drugs that stimulate testosterone production are usually used, as endogenous testosterone production does not rebound during the administration of nandrolone decanoate and testosterone enanthate.

In addition to the above side effects, other potential side effects are discussed in more detail in the steroid side effects section of this book.

Use (Men):

For the treatment of androgen deficiency, the prescription guidance for testosterone cypionate requires a dosage of 50-400 mg every 2-4 weeks. Although it is active in the body for an extended period, testosterone injections are typically needed weekly to improve physique or enhance performance. Common dosages range from 200-600 mg per week, administered in cycles of 6 to 12 weeks. This level is sufficient for most users to notice abnormal growth in muscle size and strength.

Testosterone is often used during training phases where muscle quality is more important than quantity. Some individuals use the drug in cutting cycles, but typically at lower doses (100-200 mg/week) accompanied by an aromatase inhibitor to maintain estrogen levels. Testosterone cypionate is a highly effective anabolic drug, often used alone with significant benefits. However, some may need to stack it with other anabolic/androgenic steroids for stronger effects, in which case an additional 200-400 mg per week of cholesterol octanoate, propylhexedrine butyrate, or nandrolone decanoate may provide substantial results without significant hepatotoxicity. Testosterone is very versatile and can be combined with many other anabolic/androgenic steroids to achieve desired effects.

Although generally not recommended at high doses, some bodybuilders have used high doses of this drug (1000 mg per week or more). Before the 1990s, this was more common when these vials were inexpensive and easy to find. A 10cc vial only cost $20 (the typical price for a single injection today), so a "more is better" attitude was understandable. When administered at doses of 800-1000 mg or higher per week, the stored water may increase additional body weight more than new muscle tissue. The practice of "megadosing" is inefficient (not to mention potentially dangerous), especially when considering the high cost of steroids today.

Use (Women):

Testosterone cypionate is rarely used in clinical medicine for women. When applied, it is most commonly used as an adjunct drug in inoperable breast cancer, when other therapies have failed to produce the desired effect, necessitating the suppression of ovarian function. Due to its strong androgenicity, side effects, and slow-acting characteristics (making blood levels difficult to control), testosterone cypionate is not recommended for physique or performance enhancement purposes in women.

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