General Information

AndroGel is a hydroalcoholic gel to be applied to the clean, dry skin of the shoulders, upper arms and/or abdomen. The gel is absorbed through the skin and delivers testosterone to the patient for approximately 24 hours. This product is indicated for men with primary hypogonadism or hypogonadotropic hypogonadism which results from insufficient secretion of testosterone and is characterized by low serum testosterone concentrations.

Two types of hypogonadism for which this drug is indicated:
1. Primary hypogonadism: testicular failure; characterized by low serum testosterone levels and gonadotropins (FSH, LH) above the normal range

2. Hypogonadotropic hypogonadism: idiopathic gonadotropin or LHRH deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation; characterized by low serum testosterone levels, but with gonadotropins in the normal or low range

In addition to supplying sufficient amounts of testosterone, AndroGel, like other drugs in its class, may promote retention of nitrogen, sodium, potassium, phosphorus, and decreased urinary excretion of calcium. Furthermore, it may increase protein anabolism and decrease protein catabolism. This class of drugs (androgens) may also stimulate the production of red blood cells.

Hypogonadism affects approximately 4 to 5 million American men.

Symptoms of hypogonadism include:

• Impotence
• Decreased sexual desire
• Fatigue and loss of energy
• Mood depression
• Regression of secondary sexual characteristics (growth and maturation of prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, including facial, pubic, chest, axillary hair; laryngeal enlargement; vocal chord thickening; alterations in body musculature; fat distribution)
• Osteoporosis

Clinical Results

227 hypogonadal men participated in a research study investigating AndroGel 1%. The study was conducted in 2 phases: an Initial Treatment Period of the first 90 days and an Extended Treatment Period of the second 90 days. During both treatment stages, patients were randomized into different AndroGel dose groups and one non-scrotal testosterone transdermal system group. The first phase investigated 5 G daily and 10 daily of AndroGel and 5 mg daily of non-scrotal testosterone transdermal system. In the extended treatment phase, groups of patients continued with either 5 G daily or 10 G daily of AndroGel or 5 mg daily of non-scrotal testosterone transdermal system, and an additional treatment group taking 7.5 G AndroGel daily was added.

Results of the study showed that serum testosterone concentrations increased to the normal range within first day of treatment with doses of 5 G and 10 G. In patients continuing on AndroGel 5 G and 10 G, these mean testosterone levels were maintained within the normal range for the 180-day duration of the study. 87% of patients whose data could be analyzed achieved normal serum testosterone level on treatment day 180.

5 G, 7.5 G and 10 G doses of AndroGel all also significantly increased total body mass and total body lean mass and decreased total body fat mass and percent body fat. Furthermore, with 10 G AndroGel bone mineral density in the hip and spine increased significantly.

As a result of all doses of AndroGel, patients showed significant increases in libido and degree of penile erection and significant positive effects on mood and fatigue.

Another research study was conducted in order to investigate whether AndroGel could be transferred through skin-to-skin contact. AndroGel patients and their female partners engaged in daily vigorous skin-to-skin sessions. When evaluated, all unprotected females showed testosterone levels >2 times the baseline value at some point during the study. Wearing clothing, on the other hand, during skin-to-skin contact, prevented any transfer of the drug.

Side Effects

The following adverse effects were possibly, probably or definitely related to the use of AndroGel and reported by >1% of the patients:

• Acne*
• Alopecia
• Application site reaction*
• Asthenia
• Depression
• Emotional lability
• Gynecomastia
• Headache
• Hypertension
• Lab test abnormal*
• Libido decreased
• Nervousness
• Pain breast
• Peripheral edema**
• Prostate disorder*
• Testis disorder
• Urination impaired**

*Denotes side effect reported in long-term follow-up study
**Denotes side effect also reported in the initial clinical studies and long-term follow-up study

Precautions:

• Wash hands immediately with soap and water after application of AndroGel.
• Cover the application site(s) with clothing after the gel has dried (e.g. a shirt).
• If a non-patient comes in contact with the product, he or she should wash the local contact spot with soap and water

This product is contraindicated in men with carcinoma of the breast or prostate.

Do not apply AndroGel to the genitals.

Women should not use this product.

Pregnant women should have no contact with this product, as it may cause fetal harm.

This product has not been tested for men under 18 years of age.

Mechanism of Action

AndroGel is a hydroalcoholic formulation that dries quickly when applied to the skin surface. The skin serves as a reservoir for the sustained release of testosterone into the systemic circulation…

Circulating testosterone is chiefly bound in the serum to sex hormone-binding globulin (SHBG) and albumin. The albumin-bound fraction of testosterone easily dissociates from albumin and is presumed to be bioactive. The portion of testosterone bound to SHBG is not considered biologically active. The amount of SHBG in the serum and the total testosterone level will determine the distribution of bioactive and nonbioactive androgen. SHBG-binding capacity is high in prepubertal children, declines during puberty and adulthood, and increases again during the later decades of life. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is bound to albumin and other proteins...(From FDA Label)

Additional Information

Visit the Unimed Pharmaceuticals, Inc. web site, www.unimed.com, to learn more about AndroGel and about other products, research, and services provided by the company that developed this drug.

For more information about hypogonadism, visit www.hypogonadism.com.