Testosterone Undecanoate 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. 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 is Testosterone Undecanoate 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 of Testosterone Undecanoate
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.
Testosterone Undecanoate 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 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.
Testosterone Undecanoate 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.418 No 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.
Testosterone Undecanoate 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.
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.
Testosterone Undecanoate 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.
Testosterone Undecanoate 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.
Testosterone Undecanoate 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.
Testosterone Undecanoate 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.
Testosterone Undecanoate Availability
Oral testosterone undecanoate remains widely available. It is produced almost exclusive by or under license from Organon (now Merck/MSD). In reviewing some of the more popular products and changes on the global pharmaceutical market, we have made the following observations.
In November 2009, Organon (a subsidiary of ScheringPlough since 2007) became part of Merck/MSD. All Organon products are expected to transition over to this label. It is unknown what (if any) changes to expect in the global distribution of Andriol products.
The softgel design of the Andriol products is extremely difficult to duplicate. Andriol is prepared as a brown/red colored capsule that contains oil inside. It is completely sealed. The Testocaps are also soft oval glossy capsules, but these are made out of a transparent orange gelatin mixture. Inside there is a yellow oily liquid. DV3 and ORG are printed on the surface of both types of capsules. Legitimate Organon oral testosterone undecanoate has been sold under the brand names Andriol, Andriol Testocaps, Androxon, Panteston, Restandol, Undestor, and Virigen. Andriol is regarded as an older version of this preparation, and remains available only in a limited number of markets worldwide.
Andriol is an orally active testosterone. The only other orally active testosterone is methyltestosterone. But unlike its counterpart, Andriol has a unique absorption method. When ingested with or after meals it is reabsorbed through the mucosal cells in the small intestine via the lymphatic system. This ester therefore avoids absorption through the portal vein in the liver and subsequent first pass deactivation. This means that a much higher level of Andriol enters the blood stream. Some of the drug is then converted into DHT (dihydrotestosterone) which has a high affinity for androgen receptors. Due to higher DHT conversion, Andriol does not aromatize (transform) into estrogen at a high rate like other testosterone. For this reason, water retention is much lower while gyno and female pattern fat deposits are far less likely. This drug has a reported low negative effect on the HTPA (hypothalamic pituitary testes axis) and therefore does not suppress natural (endogenous) androgen production to a significant degree in the lower reported dosages. For the most part it is due to estrogen's negative influences that HPTA function is decreased. However, estrogen must be present in lower levels for any steroid to reach its full potential effects. Kind of a paradox huh?
When stacked with other AAS, Andriol has provided a mild androgenic/anabolic synergistic effect at dosages of 200 mg daily. However, if this drug was administered alone, this dosage did not provide much in the way of results when compared to injectable testosterone. To rival its injectable cousins, daily dosages would need to be in the above 290-320 mg range minimum. This dosage would not only be quite expensive, it also would reach a level where suppression of the HPTA would increase a great deal due to elevated aromatization. This also increases water retention significantly. Since Andriol is quickly excreted through urine release, the drug was be taken 3-6 times daily to maintain adequate circulatory levels.
All in all Andriol was reported as a mildly Androgenic / Anabolic steroid that was best used in stacks for its excellent compatibility at dosages of 240-320 mg daily. For novice steroid users, older athletes, and safety conscience individuals, a stack of 200-240 mg Andriol daily, 200 mg of Primobolan depot (or 200-400 mg Anadur or Deca Durabolin) weekly, and 20 mg of Oxandrolone daily was reported to provide excellent lean mass and good strength gains with minimal suppression of the HPTA and other negative side effects. The good news was that athletes retained the gains quite well after use was discontinued. (Unless they were highly psychologically influenced by off periods!)
Anabolic Steroid Guide reference
Andriol is a revolutionary steroid because, besides methyltestosterone, it is the only effective oral testosterone compound. Testosterone itself, if taken orally, is ineffective since it is reabsorbed through the portal vein (1) and immediately deactivated by the liver. The substance testosterone undecanoate contained in Andriol, however, is reabsorbed from the intestine through the lymphatic system, thus bypassing the liver and becoming effective. The liver function is not affected by this. Andriol aromatizes only minimally, meaning that only a very small part of the substance can be converted into estrogen, since the dihydrotestosterone does not aromatize. The users of Andriol therefore do not experience feminization symptoms such as gynecomastia or increased body fat. Andriol's non-aromatizing quality consists of the fact that the body's own hormone production is only affected after a long-term administration of very high dosages. Andriol should be the perfect steroid; however, this is not the case.
The disadvantage of Andriol is that it only becomes effective if taken in high doses. Even if a dose of 200 mg of Andriol/day is taken, the testosterone level in the blood is still too low for a bodybuilder to gain strength and muscle growth. The capsules, therefore, are effective for only a few hours so that 6-7 capsules, that is 240- 280 mg (minimum), must be taken daily to achieve good results comparable to those of injectable compounds. This, however, puts the athlete in a dosage range which begins to influence the hormone production and the compound now more readily converts into estrogen. Such a dose can also manifest itself in a higher retention of sodium and water. This is one factor which competing athletes must consider. Another disadvantage is Andriol's high price. A package with 60 capsules costs approximately $80 and the minimum daily dose of 6-7 capsules thus costs almost $8. For those athletes who would like to try Andriol 8 capsules (320 mg daily) should be taken. The capsules should be taken three times daily (approximately every 8 hours) after meals so that the substance can be properly reabsorbed. However, even this high dosage does not guarantee satisfactory results. Those of you who believe that you need even higher doses should then consider that it might be more sensible to switch to the injectable testosterone. The Andriol/ Oxandrolone stack gives athletes who do not yet have much experience with steroids a fairly large strength increase and also often substantial muscle growth. Andriol is quickly eliminated by the body it should also be considered for use before competitions requiring doping tests. Women should avoid Andriol since the androgenic component-common with testosterone-is also strongly developed in this compound. Andriol intake can occasionally lead to high blood pressure, retention of fluids, acne, sexual overstimulation, and, in women, the well-known virilization symptoms.
Andriol should be stored in a cool place (6 - 15 C), preferably in the refrigerator. Since the capsules are extremely sensitive to heat they can easily melt into an undefinable shape if left in direct sunlight, e.g. in a car.
Newbies Research Guide reference
Andriol, is a unique version of testosterone undecanoate developed by Organon. This version of testosterone is based in oil and is sealed in a capsule to be taken orally. According to the manufacturer, this method bypasses the liver and enters the body as a fat through the lymphatic system. In theory this seems quite interesting, however, athletes find Organon’s claims don’t hold up well. In doses of less than 240mg per day effects are generally non-existent. With higher doses, effects are small at best. This leads one to think most of the steroid is not making it to circulation. Generally, steroid users experienced with any strong anabolics will be disappointed with Andriols results. Combined with other anabolics it may lend some effectiveness but should be questioned.
This product comes under the names Androxon, Undestor and Restinsol in Europe and South America. This agent is a revolutionary oral steroid. It is presented in little, oval- shaped, red capsules. An oil, which contains the testosterone, is inside of these capsules. Andriol is a unique steroid in that it is not an alpha alkylayted 17 steroid. This all but eliminates its hepatotoxicity. Andriol is actually contained in a natural ester base, one, which is very easy on the body. This product’s advantageous properties are similar to other testosterones in that it promotes rapid strength and weight gains. It, like other testosterones, promotes the storage of glycogen as well as ATP. Andriol does not seem to exhibit the degree of LH and FSH suppression that is seen with other testosterones and androgens. Aromatization is also minimal with this agent. All in all, Andriol seems to yield gains similar to other testosterone esters, while being safer to administer. This drug has a wide following in parts of Europe where it is available. If it were around in the United States, it’s popularity would be comparable to the old oral Dianabol. Effective dosages seem to be in the area of 200 mg a day taken in divided dosages.
Wlliam Llewellyn (2011) - Anabolics
L. Rea (2002) - Chemical Muscle Enhancement Bodybuilders Desk Reference
Anabolic Steroid Guide
Newbies Research Guide