Description:

Testosterone enanthate is a slow-acting injectable form of the androgen testosterone. This medication is designed to release testosterone steadily into the bloodstream for about 2 to 3 weeks following deep intramuscular injection. To maintain normal physiological levels of testosterone during androgen replacement therapy, it is necessary to inject testosterone at least once every two weeks, though some clinicians may advise weekly administration. Like all testosterone injections, testosterone enanthate has a potent ability to increase muscle mass and strength in athletes.

History:

Testosterone enanthate first appeared in the western pharmaceutical market in the early 1950s. It was the first widely used long-acting injectable testosterone ester in oil, effectively replacing testosterone propionate and testosterone suspension for most therapeutic applications. The first brand of this drug sold in the United States was Squibb's Delatestryl. Over the years, the Delatestryl brand has changed hands several times, most notably to Mead Johnson, BTG, Savient, and then to Indevus in December 2005. Outside the United States, the most prominent brand of testosterone has been Testoviron, which has been produced continuously for over 50 years by the same manufacturer (Schering AG, Germany). The Testoviron brand from Schering is the most widely used injectable testosterone preparation globally.

Availability:

Testosterone enanthate is widely used in both human and veterinary markets. Compositions and dosages may vary by country and manufacturer but typically contain steroids dissolved in oil at concentrations of 50mg/ml, 100mg/ml, 200mg/ml, or 250mg/ml.

Structural Characteristics:

Testosterone enanthate is a modified form of testosterone, where a carboxylic acid ester (enanthate) is 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 injection site. Once in the bloodstream, the ester is removed to yield free (active) testosterone. The esterified form of testosterone is designed to prolong the therapeutic effect after administration, allowing for less frequent injection schedules compared to injections of free (unesterified) steroids. The half-life of testosterone enanthate is approximately 8 days post-injection.

Figure 1. Pharmacokinetics of a 194mg testosterone enanthate injection.

Testosterone is easily aromatized in the body to estradiol (estrogen). The aromatase enzyme (estrogen synthetase) is responsible for this metabolism. Elevated estrogen levels can cause side effects such as increased water retention, increased body fat, and the development of gynecomastia. Testosterone is considered a moderate estrogenic steroid. Anti-estrogens such as clomiphene citrate or tamoxifen citrate may be 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 a negative impact on blood lipids.

Estrogenic side effects occur in a dose-dependent manner; higher doses (above normal therapeutic levels) of testosterone are more likely to require the simultaneous use of anti-estrogens or aromatase inhibitors. Due to water retention and muscle loss common with higher doses of testosterone, this drug is generally considered a poor choice for dieting or cutting phases. Its moderate estrogenicity makes it more suitable for bulking phases, where the additional water retention can provide raw strength and size and help promote a better 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 to hair loss (androgenic alopecia) may notice accelerated balding. Those concerned about hair loss might find a more comfortable option in less androgenic steroids such as nandrolone. Women are also warned of the virilizing potential of anabolic/androgenic steroids, especially potent androgens like testosterone. These side effects may include voice deepening, menstrual irregularities, changes in skin texture, facial hair growth, and clitoral enlargement.

In androgen-responsive tissues such as skin, scalp, and prostate, testosterone's high relative androgenicity is due to its reduction to dihydrotestosterone (DHT). The 5-alpha reductase enzyme is the primary reason for testosterone metabolism. Using 5-alpha reductase inhibitors such as 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 exhibit hepatotoxic effects; thus, 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 administered 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 adversely affect serum cholesterol. This includes a tendency to lower 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. injectable), 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 can 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, indicating 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.

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 enanthate requires a dose of 50-400 mg every 2-4 weeks. Although it is active in the body for an extended period, testosterone enanthate is typically needed weekly to promote muscle development. The common dosage for physique or performance enhancement purposes ranges from 200-600 mg per week, administered in cycles of 6 to 12 weeks. This level is sufficient for most users to notice significant increases in muscle size and strength.

Testosterone is often used during training phases where muscle quality is more important than hardness. 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 enanthate is a highly effective anabolic drug, often used alone with significant benefits. However, sometimes it may need to be stacked 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.

Use (Women):

Testosterone enanthate 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, tendency to produce toxic side effects, and slow-acting characteristics (making blood levels difficult to control), testosterone enanthate is not recommended for physique or performance enhancement purposes in women.

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