Androgel®, Testim® and Axiron®: Comparison of Three Topical Testosterone Gels

Testosterone is a male sex hormone produced in the testicles. With the onset of puberty in males, testosterone secretion is responsible for a number of physiologic changes including increase in genital size, changes in hair growth, increase in height, enlargement of the prostate and seminal vesicles, lowering of the voice and changes in the psyche. Male hypogonadism is a disorder in which a man has testosterone deficiency, which results in symptoms such as reduced sex drive and infertility.

Two primary causes of testosterone deficiency can be:

  1. Impaired testicular function: It is commonly referred to as primary hypogonadism or testicular failure. This condition arises due to an abnormality in the testicles preventing them from producing testosterone.
  2. Impaired pituitary or hypothalamus function: It is commonly referred to as secondary hypogonadism. This condition arises due to the impaired functioning of the glands regulating the hormone production in the brain, namely, the pituitary and/or hypothalamus.

Types of testosterone replacement therapies are listed below.

  • Injection - Testosterone intramuscular injections are safe and effective.
  • Patch - A patch containing testosterone is applied each night to your back, abdomen, upper arm or thigh.
  • Gel - There are several gel preparations available in the market.
  • Gum and cheek (buccal cavity) - A small putty-like substance delivers testosterone through the buccal cavity. This product quickly sticks to your gum line and allows testosterone to be absorbed into your bloodstream.
  • Nasal - Testosterone can be pumped into the nostrils as a gel.
  • Implantable pellets - Testosterone-containing pellets are surgically implanted under the skin every three to six months.
  • Oral - Testosterone tablets are not recommended for long-term hormone replacement because they might cause liver problems.

The focus of this article is to review testosterone gel formulations, with an emphasis on their compositions and their effect on absorption of drug across the skin. Table 1 lists details on the currently marketed testosterone gel and solution formulations. The gel formulations contain ethanol, which acts as a solvent for testosterone and helps its penetration through the stratum corneum. The gel is applied on the shoulder and upper arm areas in a circular motion and allowed to dry for at least one hour for it to get absorbed. Hands must be washed carefully to prevent the transfer of testosterone to another person. The percentages of ethanol in Androgel® and Testim® were reported to be 67% and 74%, respectively (Lakshman and Basaria). The bioavailability of testosterone from gel formulations is about 10 to 15%. Table I also lists the Tmax and Cmax values for various products (Ref. Androgenic agents). The values showed a lot of variability. In another article, the median Tmax values of Testim and Androgel were reported to be 18 hours and 24 hours, respectively (Marbury et al.) which are significantly different than the values reported in Table I. Marbury et al. analyzed blood samples for total testosterone, free testosterone and dihydrotestosterone. Almost 10% of the testosterone produced by an adult each day is converted to dihydrotestosterone, by the testes and prostate in men, and by the ovaries in women. In this study, Testim® produced higher Cmax and AUC values of total testosterone and free testosterone compared to those for AndroGel®.

Table 1. Details on the currently marketed testosterone gel and solution formulations.
Table 2. %Weight loss values for three topical testosterone products at 40°C. Values were calculated as the percent of weight of product used for analysis.

We evaluated two testosterone gel formulations and one testosterone solution formulation for their weight loss profiles when exposed to 40°C. We spread about 0.5 g, 1.5 g and 3.0 g of gel formulation over 50-55 cm2 area on a plastic plate and checked the weights over 20 minutes. Figure 1 depicts the percent weight loss profiles for the Axiron® solution formulation (0.56 g, 1.5 g and 3.2 g of solution applied). The rate of weight loss decreased as the amounts of applied formulations were increased. Table 2 lists the same data for all the products. The products were also kept at 40°C for 24 hours to obtain the maximum weight loss values. When 0.5-gram product was applied, 90% weight loss occurred in 20 minutes. Axiron, being a solution, showed fastest weight loss. All the water and ethanol from the products must have evaporated during 24 hours. Androgel® showed the highest total weight loss (97%) whereas Testim® showed the least (84%). Testim was reported to have a stickiness issue, which could be related to other excipients such as PG, PEG, and glycerin. At the same time, these excipients are known as penetration enhancers for topical products. This may explain Testim’s superior pharmacokinetic properties. These products specify the amount of gel to be used at a time, but do not specify the surface area to be covered. If one spreads on larger surface area, it would allow ethanol and water to evaporate faster, and it may reduce the absorption of testosterone. A study needs to be conducted to understand this issue. Daily topical use of ethanol may have deleterious effects on the skin (D. W. Lachenmeier) and the user of testosterone gels should observe the skin area where they apply the gel every day.

Figure 1. %Weight loss from the Axiron® solution at 40°C.

The bioavailability of different gels did not appear to be different (W. de Ronde). Out of 50 mg dose applied about 5 mg of testosterone is absorbed. The remaining is either washed away or metabolized in the skin. Rolf et al. recovered over 60% of testosterone applied to skin via a gel formulation.

It is believed that testosterone is absorbed within the first few minutes of application, while alcohol is still present on the skin. However, it is not applicable to all gels. Washing several hours after application of Testim® resulted in almost 30% lower 24 hour integrated plasma testosterone levels. It means, testosterone gets absorbed from Testim® for a long time.

Alcohol and water evaporate from the gel keeping a large reservoir of testosterone on the skin. This poses the potential of skin-to-skin transfer to people in physical contact with the man using testosterone gel (Williams et al.). Gels offer exposure to larger skin surface area, improving skin penetration and better tolerability compared to the patch. Higher surface area exposure also increases the chances of transfer to other people by skin contact. Wearing a shirt on the exposed area reduces the transfer of testosterone, but does not prevent it completely.

Grober et al. studied the efficacy of changing testosterone gel preparations (Androgel® and Testim®) in 370 men.

Changing from Testim® to Androgel® during therapy was indicated to eliminate or minimize unwanted side effects of Testim®, but it was less likely to offer patients significant symptomatic or biochemical improvements (Table 3).

Table 3. Effect of change of testosterone topical products on pharmacokinetics parameters

In conclusion, before selecting a topical testosterone product, one should consider the following aspects – skin irritation, stickiness, potential for the physical transfer to another person, effect of surface area on absorption and side-effects. One should also observe the sideeffects of daily exposure of ethanol to the same skin area over time.


  1. K.M. Lakshman and S. Basaria; Safety and efficacy of testosterone gel in the treatment of male hypogonadism; Clin. Interv. Aging 4: 397-412, (2009).
  2. Androgenic agents : Therapeutic Class Review; Provider Synergies, LLC, an affiliate of Magellan Medicaid Administration, Inc., March, 2015.
  3. T. Marbury, E. Hamill, R. Bachand, T. Sebree, and T. Smith; Evaluation of the pharmacokinetic profiles of the new testosterone topical gel formulation, Testim™, compared to Androgel®; Biopharm. Drug Disposition 24: 115-120 (2003).
  4. D.W. Lachenmeier; Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity; J. Occup. Med. Toxicol. 3: 26 -31 (2008)
  5. W. de Ronde; Hyperandrogenism after transfer of topical testosterone gel: Case report and review of published and unpublished studies; Human Reproduction 24 : 425-428 (2009).
  6. C. Rolf, U. Knie, G. Lemmnitz and E. Nieschlag; Interpersonal testosterone transfer after topical application of a newly developed testosterone gel preparation; Clin. Endocrinol. 56: 637-641 (2002).
  7. C.M. Williams, D.S. Freeborn, and K. Luthy; Comparison of testosterone replacement therapy medications in the treatment of hypogonadism; studentpub, Brinham Young University, July 27, 2016.
  8. E.D. Grober, M. Khera, S.D. Soni, M.G. Espinoza, and L.I. Lipshultz; Efficacy of changing testosterone gel preparations (Androgel or Testim) among suboptimally responsive hypogonadal men; Int. J. Impotence Res. 20: 213-217 (2007).
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