Andriol

 

  • Androgenic 100
  • Anabolic 100
  • Standard Testosterone (Standard)
  • Chemical Names 4-androsten-3-one-17beta-ol, 17beta-hydroxy-androst-4-en-3-one
  • Estrogenic Activity moderate
  • Progestational Activity low

Description:

Andriol (testosterone undecanoate) is an oral testosterone preparation that contains 40 mg of testosterone undecanoate (in an oil base) in a soft gelatin capsule. This drug is very different than most oral anabolic steroids, which are usually c-17 alpha alkylated to survive first pass metabolism through the liver. Instead, esterification and suspension in oil allows the testosterone undecanoate in Andriol® to be partially absorbed through the lymphatic system along with dietary fat. This bypasses the destructive first-pass through liver, providing sustained physiological levels of testosterone to the body. The actual oral bioavailability of Andriol is estimated to be approximately 7%. In design, this steroid is essentially a non-toxic and orally active testosterone, intended to provide a unique alternative to testosterone injections and other hepatotoxic oral anabolic/androgenic steroids.

History:

Oral testosterone undecanoate capsules were developed by international drug giant Organon (now Merck/MSD), and first introduced into clinical trials during the early 1980’s. The drug was soon approved for use as a prescription agent in a number of countries around the globe, generally under the Andriol brand name, although Organon has also marketed it as Androxon, Panteston, Restandol, Undestor, and Virigen in certain markets. This drug preparation is indicated for testosterone replacement therapy in males with conditions associated with insufficient endogenous androgen production. Although there is a large market for androgen replacement drugs in the United States, the drug is not approved for sale on the U.S. market. It has been approved as a prescription agent in the bordering markets of Mexico and Canada, however.

In 2003, Organon began replacing its Andriol products with Andriol® Testocaps®. The new formulation improves on the storage limitations of the original Andriol preparations, which needed to be kept under refrigeration at the pharmacy. The drug was stored at room temperature once dispensed, as the product needed to be consumed at room temperature. Outside of refrigeration, however, the drug functionally had only a 3-month shelf life. The new Andriol Testocaps are designed to always be stored at room temperature, and have a shelf life of 3 years. The new formulation is considered to be bioequivalent to the older version, and can be substituted in patients without any change in dosage.417 Given the handling advantages and bioequivalency, it is likely that the new Testocaps will slowly come to replace all of the older Andriol preparations.

In spite of its wide availability, Andriol has never been a popular item among athletes. This is likely due to the high relative cost of the drug, and its low potency compared to other pharmaceutical preparations, particularly injectable testosterone compounds and the more potent synthetic oral anabolic steroids. Still, Andriol remains a product of choice among those athletes not interested in using injectable medications and preferring to avoid the greater risks of hepatotoxicity and lipid alterations inherent in c-17 alpha alkylated orals. Today, decades after its initial release, Merck/MSD remains the sole global producer of prescription oral testosterone undecanoate. Andriol itself has maintained a prominent share of the global hormone replacement market since the 1990’s.

How Supplied:

Oral testosterone undecanoate preparations are available in various human drug markets. The older formulations supply 40 mg of testosterone undecanoate in oleic acid, contained in small soft gelatin capsules. Andriol Testocaps supplies 40 mg of testosterone undecanoate in castor oil and propylene glycol monolaurate, contained in small soft gelatin capsules. Packaging is commonly as bottles of 30 or 60 capsules, or foil/plastic strips of 10 capsules. Subtracting the ester weight, each 40 mg Andriol capsule contains 25.3mg of (base) testosterone.

Structural Characteristics:

Andriol® contains testosterone that has been modified with the addition of carboxylic acid ester (undecanoic acid) at the 17-beta hydroxyl group. The esterified hormone is more fat soluble than base (free) testosterone, and has been dissolved in oil and encapsulated for oral administration. Significant absorption of oral testosterone undecanoate takes place through the lymphatic route, bypassing the first pass through the liver. Andriol® is designed to provide a peak in testosterone levels several hours after administration, and with repeated dosing maintain physiological concentrations for 24 hours.

andriol testosterone undecanoate pharmacokinetics graph

Figure 1. Median response pharmacokinetics after oral administration of 80 mg of testosterone undecanoate in fasted and fed states. Testosterone absorption is impaired when taken without meals. Source: Andriol Testocaps online information, Organon. Citation Bachus et al, 2001. Andriol.com.

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. Exceeding therapeutic doses will increase the likelihood of estrogenic side effects. In such cases, an anti-estrogen such as clomiphene citrate or tamoxifen citrate is commonly applied 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.

Side Effects (Androgenic):

Testosterone is the primary male androgen, responsible for maintaining secondary male sexual characteristics. Taking oral testosterone undecanoate in doses exceeding normal therapeutic levels is 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. 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 oral testosterone by administering 400 mg of the hormone per day (2,800 mg per week) to a group of male subjects. 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.418No study in which liver enzymes were examined has demonstrated an adverse hepatotoxic effect from Andriol, including an examination of patients on continuous therapy for 10 years.419

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. Therapeutic doses of oral testosterone undecanoate used to correct insufficient androgen production in otherwise healthy aging men are unlikely to increase atherogenic risk, and may actually improve lipid profiles and cardiovascular risk factors.420

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.

 

Administration (General):

Andriol should always be taken with meals, preferably containing a moderate fat content (20 grams) to maximize lymphatic absorption. Very low bioavailability has been reported when taken in the fasted state. The total daily dosage should be divided into a minimum of two applications, taken in the morning and evening, to maintain more consistent elevations of serum testosterone.

Administration (Men):

For the treatment of low androgen levels, prescribing guidelines for Andriol recommend an initial dosage of 120-160 mg daily for 2-3 weeks. Based on the level of effect, a daily maintenance dosage of 40-120 mg is usually continued at this point. For bodybuilding purposes, higher doses would be required to reach strong supraphysiological levels of testosterone. This would generally call for a minimum dosage of 240-280 mg per day (6-8 capsules), taken in cycles of 6-8 weeks. A more common effective dosage, however, would fall in the range of 400-480 mg (10 to 12 capsules) per day. These doses can be quite costly given the relative price of Andriol preparations, making injectable testosterones much more cost effective and popular. Given the relative low potency of Andriol, when taken by athletes it is most commonly used in combination with other agents. Testosterone drugs are ultimately very versatile, and can be stacked with many other anabolic/androgenic steroids depending on the desired effect.

Administration (Women):

Andriol is not prescribed to women in clinical medicine. This drug is not recommended for women for physique or performance-enhancing purposes due to its strong androgenic nature and tendency to produce virilizing side effects.

Availability:

Oral testosterone undecanoate remains widely available. It is produced almost exclusive by or under license from Organon (now Merck/MSD).

 

References:

417. Contribution of lymphatically transported testosterone undecanoate to the systemic exposure of testosterone after oral administration of two andriol formulations in conscious lymph duct-cannulated dogs. Shackleford D, Faassen W Aet al. J of Pharm and Exper Ther. 306 (2003):925–933.
418. Enzyme induction by oral testosterone. Johnsen SG, Kampmann JP, Bennet EP, Jorgensen F. 1976 Clin Pharmacol Ther 20:233-237.
419. A ten-year safety study of the oral androgen testosterone undecanoate. Gooren LJG , J Androl , 1994 , 15 , 212–5.
420. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Mårin P, Holmång S, Jöhnsson L, et al. Int J Obes , 1992 , 16 , 991-7.