Testosterone Topical

Introduction Overview

Generic Name

testosterone topical

Brand Name

AndroGel

Dosage Form

topical gel for transdermal application

Drug Class

Androgens and anabolic steroids

Pharmacokinetics

Absorption

AndroGel is administered as a topical gel applied to the skin, and testosterone is absorbed through the epidermis into systemic circulation. Absorption varies based on skin site, hydration, and integrity. Peak serum testosterone levels are generally reached within 2 to 4 hours after application. The gel formulation facilitates steady and sustained absorption, avoiding sharp peaks seen with injectable formulations. Factors such as sweating, washing the application site, or application to damaged skin can significantly alter absorption. Clinical studies indicate an approximate bioavailability of 10% to 15% from topical testosterone gels compared to parenteral administration.

Distribution

Once absorbed, testosterone is extensively bound to plasma proteins, primarily sex hormone-binding globulin (SHBG) and albumin. Approximately 98% of circulating testosterone is protein-bound, with only the unbound 'free' fraction being biologically active. Testosterone distributes widely throughout body tissues, including muscle, fat, bone, skin, prostate, and the central nervous system. The volume of distribution is relatively large due to tissue uptake, especially in androgen-responsive tissues. Distribution kinetics are influenced by SHBG levels, which may fluctuate based on age, liver function, and other hormonal states.

Metabolism

Testosterone undergoes extensive first-pass metabolism in the liver after systemic absorption. It is biotransformed primarily by cytochrome P450 enzymes via hydroxylation and oxidation to various metabolites, including androstenedione and estradiol. Further metabolism leads to conjugation as glucuronides and sulfates, which are inactive and water-soluble. The metabolism also occurs in peripheral target tissues where testosterone is converted by 5-alpha-reductase to dihydrotestosterone (DHT), a more potent androgen mediating many androgenic effects. Aromatase enzymes convert testosterone to estradiol, influencing estrogenic activity.

Elimination

The majority of testosterone metabolites are excreted via the kidneys in the urine as conjugates of glucuronides and sulfates. A smaller fraction is eliminated via the bile into feces. The plasma half-life of testosterone after topical application is approximately 2 to 4 hours, but the pharmacodynamic effects can persist longer due to tissue uptake and receptor interactions. Renal or hepatic impairment can influence elimination and thus warrant dosage adjustments or careful monitoring in affected patients.

Dosage Forms

Adults

AndroGel is available as a metered-dose pump or packet for topical application on the shoulders, upper arms, and/or abdomen. The usual starting dose for adult males with hypogonadism is 50 mg of testosterone applied once daily, which may be titrated based on serum testosterone measurements and clinical response. Patients are instructed to apply the gel to clean, dry skin once daily, typically in the morning after showering. Dose adjustments are guided by monitoring serum testosterone levels mid-day approximately 2 to 4 hours post-application.

Adolescents

AndroGel is not approved for use in pediatric populations under 18 years old. Safety and efficacy have not been established in adolescents. Use in this population is contraindicated due to potential effects on growth and development.

Special Populations

In elderly men (over 65 years), AndroGel should be used with caution due to increased risk of prostate enlargement or prostate cancer; benefits versus risks should be carefully evaluated. In patients with hepatic or renal impairment, no specific dosage adjustments are provided, but monitoring is recommended. Use is contraindicated in women, especially during pregnancy due to risk of virilization of the fetus; accidental exposure must be avoided. Patients with cardiovascular disease or history of thromboembolism require careful consideration owing to potential increased risks associated with testosterone therapy.

Mechanism Of Action

AndroGel delivers exogenous testosterone that is systemically absorbed through the skin to restore physiological levels of this endogenous androgen hormone. Testosterone acts primarily by binding to intracellular androgen receptors in target tissues. Upon binding, the steroid-receptor complex translocates to the nucleus where it modulates gene transcription, resulting in anabolic and androgenic effects. The androgen receptor-mediated genomic effects regulate development and maintenance of male secondary sexual characteristics, muscle mass, bone density, and libido.

In peripheral tissues, testosterone is enzymatically converted to dihydrotestosterone (DHT) by 5-alpha-reductase, which binds androgen receptors with greater affinity and potency, mediating many androgen-dependent biological effects such as prostate growth and hair follicle modulation. Testosterone is also aromatized to estradiol in various tissues, contributing to bone metabolism and other estrogen-dependent functions.

Clinically, restoring normal testosterone levels alleviates symptoms of hypogonadism including low energy, decreased libido, depressed mood, and muscle weakness. Compared to parenteral testosterone formulations, transdermal application via AndroGel provides more stable serum testosterone concentrations, minimizing peaks and troughs and reducing fluctuation-related side effects. Clinical trials support the efficacy of AndroGel in normalizing testosterone levels and improving quality of life in men with testosterone deficiency.

Pharmacological Actions

Replacement of endogenous testosterone in males with hypogonadism.
Binding to androgen receptors leading to anabolic effects such as increased muscle mass and strength.
Promotion of male secondary sexual characteristics, including facial and body hair growth and deepening of the voice.
Stimulation of erythropoiesis by increasing red blood cell mass.
Maintenance of libido and erectile function.
Regulation of mood and cognitive function through central nervous system androgen receptor interaction.
Influencing lipid metabolism and body fat distribution.
Modulation of bone density and prevention of osteoporosis.
Conversion to dihydrotestosterone (DHT) and estradiol mediating androgenic and estrogenic effects.

Therapeutic Clinical Uses

Treatment of adult male hypogonadism due to primary or secondary testicular failure.
Replacement therapy for testosterone deficiency syndromes.
Management of symptoms associated with low testosterone, such as decreased libido, fatigue, and muscle weakness.
Treatment of delayed puberty in males when appropriate (off-label with caution).
Improvement of mood, energy, and cognitive function in testosterone-deficient men.
Support of bone density in men with testosterone deficiency to reduce osteoporosis risk.
Potential adjunct in male infertility cases related to hypogonadism (under specialist supervision).

Side Or Adverse Effects

Local skin reactions at application site including redness, itching, burning, and irritation.
Increased hematocrit and hemoglobin leading to risk of polycythemia and thromboembolism.
Elevation of prostate-specific antigen (PSA) and potential exacerbation of benign prostatic hyperplasia (BPH).
Hypertension or increased blood pressure.
Mood changes including aggression, irritability, and strange dreams.
Frequent or prolonged erections (priapism).
Nausea and vomiting.
Peripheral edema and leg swelling.
Potential liver function abnormalities with long-term use.
Gynecomastia or breast tenderness in males due to hormonal imbalance.
Potential suppression of spermatogenesis leading to infertility.
Risk of cardiovascular events including myocardial infarction and stroke in susceptible individuals.
Accidental transfer causing virilization in women or children exposed to treated skin areas.

Precautions

Contraindicated in men with prostate or male breast cancer.
Avoid use in women and children due to risk of virilization.
Monitor prostate health regularly with PSA testing and digital rectal exams during therapy.
Monitor hematocrit to detect polycythemia early.
Caution in patients with cardiovascular disease, sleep apnea, or hematologic disorders.
Prevent accidental dermal transfer to others by covering application sites and thorough hand washing.
Advise patients on avoiding application to broken or irritated skin to minimize systemic absorption variability.
Avoid co-administration with other androgens or anabolic steroids unless under specialist guidance.
Regularly assess liver and kidney function during prolonged therapy.
Inform patients about the potential for behavioral or mood changes.
Adjust dose based on serum testosterone levels to maintain physiological range.
Advise patients to avoid showering or swimming for at least 2 hours post-application to maximize absorption.

Warnings

Do not use in patients with known hypersensitivity to testosterone or gel components.
Avoid use in presence of prostate cancer or male breast cancer due to potential growth stimulation.
Testosterone can cause serious adverse cardiovascular effects including heart attack and stroke.
Risk of secondary exposure to women and children causing virilization; immediate washing recommended if exposure occurs.
Misuse or abuse can lead to irreversible adverse effects such as infertility, liver toxicity, and psychiatric disorders.
Potential for abuse due to anabolic steroid properties; schedule III controlled substance in the US.
Monitor for signs of liver toxicity or cholestatic jaundice during therapy.
Potential to exacerbate sleep apnea and increase hematocrit requiring vigilance during therapy.
Avoid smoking or exposure to flames during application because the gel formulation is flammable until dry.
Discontinue therapy if significant breast lumps, nipple discharge, or breast pain occur to rule out malignancy.

Contraindications

Known or suspected prostate cancer.
Male breast cancer.
Women who are or may become pregnant.
Pediatric patients under 18 years of age.
Hypersensitivity to testosterone or formulation excipients.
History of hypersensitivity or allergic reactions to testosterone topical products.

Drug Interactions

Anticoagulants such as warfarin may have enhanced effects leading to increased bleeding risk; monitoring is required.
Insulin and oral antidiabetic agents may have altered effects; blood glucose monitoring is advised.
Concurrent use with corticosteroids may increase the risk of edema and exacerbate fluid retention.
Other anabolic steroids or androgen preparations may have additive adverse effects.
Drugs inducing hepatic enzymes (e.g., rifampin) may decrease testosterone levels via increased metabolism.
Cytochrome P450 inhibitors or inducers may alter testosterone metabolism affecting serum levels.
Testosterone may reduce serum thyroxine-binding globulin altering thyroid hormone levels; monitor thyroid function.
Concomitant use with cholesterol-lowering agents requires monitoring due to potential androgen impact on lipid profiles.
Interaction with drugs affecting blood pressure should be monitored due to potential hypertensive effects.

Preparations Of The Drug

AndroGel 1% topical gel pump delivering 12.5 mg testosterone per actuation.
AndroGel 1% topical gel packets containing 5 g of gel with 50 mg testosterone.
AndroGel 1.62% higher concentration topical gel pump delivering 20.25 mg testosterone per actuation.
Comes with metered-dose pumps for precise application.
Available in single-use packets for patient convenience and dose standardization.
Formulated for application on shoulders, upper arms, and/or abdomen.
Packaged with patient instructions for application site care and safety precautions.
Not for application on genitalia or broken skin.
Flammable formulation with patient instructions for fire safety during use.