AndroGel® (Testosterone gel) is a prescription medicine that is used to treat adult males who have low or no testosterone. It comes in a clear, colorless, hydroalcoholic gel form, and is used for hormone replacement in men. The gel is absorbed through the skin (transdermal) and helps the body reach and maintain normal testosterone levels.
Testosterone is important in the male body as it helps develop and maintain male sexual characteristics commonly associated with masculinity. This includes a deep, baritone voice, as well as body and facial hair. Testosterone also prevents bone degradation, facilitates sexual performance, and maintains muscle development.
According to the FDA, AndroGel® is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines.
Prescription Name and Overview
The US Food and Drug Administration has approved AndroGel® (Testosterone gel) for treatment of hypogonadism in men. This product is indicated for males with primary hypogonadism or hypogonadotropic hypogonadism which results from insufficient secretion of testosterone and is characterized by low serum testosterone concentrations.
Generic Name and Overview
Testosterone is important in male sexual development, as it helps develop and maintain male sexual characteristics commonly associated with masculinity. This includes a deep, baritone voice, as well as body and facial hair. Testosterone also prevents bone degradation, facilitates sexual performance, and maintains muscle development.
AndroGel® is exclusively marketed by Abbvie, and manufactured by Unimed Pharmaceuticals and is included in two NDAs. There are eleven patents protecting this drug.
OTC Name and Overview
Manufacturer
AndroGel® is manufactured by Unimed Pharmaceuticals and marketed by AbbVie from North Chicago, Illinois, United States, and marketed by the same company. AbbVie has owned AndroGel® for only part of the drug’s history. Abbott Laboratories acquired AndroGel® in 2010, and AbbVie was spun off from the company in 2013. The US FDA approved the manufacture and marketing of AndroGel® in February 2000.
Labeled Indications
AndroGel is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone due to:
- Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.
- Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range.
Active Ingredients
The active ingredient of AndroGel is testosterone.
What Is It Used For?
AndroGel is used as a hormone replacement in men who do are not able to produce enough testosterone.
How Does it Work?
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
What are the Approved Uses?
AndroGel is an androgen indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone:
- Primary hypogonadism (congenital or acquired).
- Hypogonadotropic hypogonadism (congenital or acquired)
Production Anecdotes / History
AndroGel 1% has been used for hormone replacement therapy since 2000 when the drug was approved for use in men with testicular damage from injury, chemotherapy, or other trauma. By 2004, AndoGel was used off-label to counteract the symptoms of Andropause. AndroGel 1.62% was approved in 2011.
Precautions
There are a number of contraindications for AndroGel. Specifically, it is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate. It is also contraindicated in women who are or may become pregnant, or who are breastfeeding.
The US FDA has issues several warnings and precautions against the use of AndroGel. These are mainly:
- Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer
- Potential for Secondary Exposure to Testosterone
- Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone.
- Use in women, due to lack of controlled evaluations in women and potential virilizing effects
- With large doses of exogenous androgens, including AndroGel, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count.
- Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice)
- Androgens, including AndroGel, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease
- Gynecomastia may develop and persist in patients being treated with androgens, including AndroGel, for hypogonadism.
- The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases
- Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.
- Androgens, including AndroGel, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria).
- Androgens, including AndroGel, may decrease concentrations of thyroxin-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.
Long-Term Use Considerations
Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas.
Drug Interactions
Can Interact with the Following
Androgens may decrease blood glucose and therefore may decrease insulin requirements in diabetic patients.
Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of INR and prothrombin time is recommended.
Use of testosterone with adrenocorticotrophic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease.
Can’t Interact with the Following
When To Stop Taking
The US FDA advises patients to stop taking AndroGel in the following cases:
- Changes in urinary habits such as increased urination at night, trouble starting your urine stream, passing urine many times during the day, having an urge that you have to go to the bathroom right away, having a urine accident, being unable to pass urine and weak urine flow.
- Breathing disturbances, including those associated with sleep, or excessive daytime sleepiness.
- Too frequent or persistent erections of the penis.
- Nausea, vomiting, changes in skin color, or ankle swelling.
- increased urination (many times per day), loss of bladder control;
- painful or difficult urination;
- breast pain or swelling;
- painful or bothersome erections;
- swelling, rapid weight gain, shortness of breath during sleep;
- chest pain or pressure, pain spreading to your jaw or shoulder;
- liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
- signs of a blood clot in the lung–chest pain, sudden cough, wheezing, rapid breathing, coughing up blood; or
- signs of a blood clot in your leg–pain, swelling, warmth, or redness in one or both legs.
Long-Term Side Effects
- redness, itching, burning, hardened skin or other irritation where the medicine was applied or where the skin patch was worn;
- headache, mood changes;
- increased red blood cells (may cause dizziness, itching, redness in your face, or muscle pain);
- vomiting, diarrhea;
- strange dreams;
- frequent or prolonged erections; or
- high blood pressure–severe headache, blurred vision, pounding in your neck or ears.
FDA Warnings (History Of)
AndroGel was approved by the US FDA in February 2000. In September 2009, the FDA ordered AbbVie to add a black box warning to the label of AndroGel, warning that children who were exposed to testosterone gels may develop enlarged genitals, pubic hair, increased libido, and aggressive behavior. In 2014, the US FDA required a warning on all testosterone products regarding blood clot risk. In 2015, the FDA took measures to include a warning to advise on increased risk of heart attacks when taking the drug.
Other Common Side Effects
- Bloating or swelling of the face, arms, hands, lower legs, or feet
- blurred vision
- feeling faint, dizzy, or lightheaded
- feeling of warmth or heat
- flushing or redness of the skin, especially on the face and neck
- frequent strong or increased urge to urinate
- Headache
- nervousness
- pain, redness, or swelling in the arm or leg
- pounding in the ears
- Irregular heartbeat
- sweating
- swelling of the breasts or breast soreness in both females and males
- tingling of the hands or feet
- unusual weight gain or loss
- waking to urinate at night
Lawsuits
There is a pending class action lawsuit filed by men across the United States that claim injury from testosterone replacement drugs, with about 4,200 involving market-leader AndroGel. The lawsuits allege that companies’ efforts to grow the market led them to target older men without properly warning of the risk of complications. Men claim they suffered heart attacks, strokes, and blood clots as a result of using the drugs.
Sources Cited (6)
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021015s036lbl.pdf
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process
https://www.rxlist.com/androgel-drug.htm#medguide
https://www.drugs.com/sfx/androgel-side-effects.html
https://www.webmd.com/drugs/2/drug-18248/androgel-transdermal
Tracy Everhart
Tracy Everhart is the Editor for Drug Law Journal. A highly-trained and certified medical professional, Tracy is also an accomplished medical writer. After spending years on the front lines of the medical profession, Tracy now devotes her expertise and skills to researching and reporting on new drugs and devices that enter the market, as well as their side-effects and the real-life stories involved. Prior to joining Drug Law Journal, Tracy wrote for benchmark online healthcare resources focused on families and, in particular, women’s health issues. Tracy holds post-graduate degrees from both the American College of Healthcare Sciences and the Yale School of Nursing. She is also a graduate of both Hampshire College, where she studied microbiology and the University of South Carolina school of nursing.