Testosterone
Pronunciation
(tes TOS ter one)
U.S. Brand Names
Androderm®; AndroGel®; Delatestryl®; Depo®-Testosterone; Striant™; Testim™; Testopel®
Synonyms
Testosterone Cypionate; Testosterone Enanthate
Generic Available
No
Canadian Brand Names
Andriol®; Androderm®; AndroGel®; Andropository; Delatestryl®; Depotest® 100; Everone® 200; Virilon® IM
Use
Injection: Androgen replacement therapy in the treatment of delayed male puberty; male hypogonadism (primary or hypogonadotropic); inoperable female breast cancer (enanthate only)
Pellet: Androgen replacement therapy in the treatment of delayed male puberty; male hypogonadism (primary or hypogonadotropic)
Buccal, topical: Male hypogonadism (primary or hypogonadotropic)
Restrictions
C-III
Pregnancy Risk Factor
X
Pregnancy Implications
Testosterone may cause adverse effects, including masculinization of the female fetus, if used during pregnancy. Females who are or may become pregnant should also avoid skin-to-skin contact to areas where testosterone has been applied topically on another person.
Lactation
Enters breast milk/contraindicated
Contraindications
Hypersensitivity to testosterone or any component of the formulation (including soy); severe renal or cardiac disease; benign prostatic hyperplasia with obstruction; undiagnosed genital bleeding; males with carcinoma of the breast or prostate; pregnancy
Warnings/Precautions
When used to treat delayed male puberty, perform radiographic examination of the hand and wrist every 6 months to determine the rate of bone maturation. May accelerate bone maturation without producing compensating gain in linear growth. Has both androgenic and anabolic activity, the anabolic action may enhance hypoglycemia. Use caution in elderly patients or patients with other demographic factors which may increase the risk of prostatic carcinoma; careful monitoring is required. May cause fluid retention; use caution in patients with cardiovascular disease or other edematous conditions. Prolonged use has been associated with serious hepatic effects (hepatitis, hepatic neoplasms, cholestatic hepatitis, jaundice). May potentiate sleep apnea in some male patients (obesity or chronic lung disease). Transdermal patch may contain conducting metal (eg, aluminum); remove patch prior to MRI. Gels and buccal system have not been evaluated in males <18 years of age; safety and efficacy of injection have not been established in males <12 years of age.
Adverse Reactions
Frequency not always defined.
Cardiovascular: Flushing, edema, hypertension, vasodilation
Central nervous system: Aggressive behavior, amnesia, anxiety, dizziness, emotional lability, excitation, headache, mental depression, nervousness, sleeplessness
Dermatologic: Acne, allergic contact dermatitis (transdermal 4%), alopecia, burn-like blisters (transdermal 12%), dry skin, erythema (transdermal 7%), hirsutism (increase in pubic hair growth), pruritus
Endocrine & metabolic: Breast soreness, gynecomastia, hypercalcemia, hypoglycemia, menstrual problems (amenorrhea), virilism
Gastrointestinal: GI irritation, nausea, vomiting
Following buccal administration: Bitter taste, gum edema, gum or mouth irritation, gum tenderness, taste perversion
Genitourinary: Bladder irritability, epididymitis, impotence, priapism, prostatic carcinoma, prostatic hyperplasia, testicular atrophy, urination impaired
Hepatic: Cholestatic hepatitis, hepatic dysfunction, hepatic necrosis
Hematologic: Leukopenia, polycythemia, suppression of clotting factors
Neuromuscular & skeletal: Paresthesias, weakness
Miscellaneous: Diaphoresis, hypersensitivity reactions
Drug Interactions
Substrate (minor) of CYP2B6, 2C8/9, 2C19, 3A4;
Inhibits CYP3A4 (weak)
Increased toxicity: Effects of oral anticoagulants may be enhanced
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: St John's wort may decrease testosterone levels.
Stability
Androderm®: Store at room temperature; do not store outside of pouch. Excessive heat may cause system to burst.
Androgel®, Delatestryl®, Striant™, Testim™: Store at room temperature.
Depo® Testosterone: Store at room temperature; protect from light.
Testopel®: Store in a cool location.
Mechanism of Action
Principal endogenous androgen responsible for promoting the growth and development of the male sex organs and maintaining secondary sex characteristics in androgen-deficient males
Pharmacodynamics/Kinetics
Duration (route and ester dependent): I.M.: Cypionate and enanthate esters have longest duration, 
2-4 weeks
Absorption: Transdermal gel: ~10% of dose
Distribution: Crosses placenta; enters breast milk
Protein binding: 98% bound to sex hormone-binding globulin (40%) and albumin
Metabolism: Hepatic; forms metabolites
Half-life elimination: 10-100 minutes
Excretion: Urine (90%); feces (6%)
Dosage
Adolescents: I.M.:
Male hypogonadism:
Initiation of pubertal growth: 40-50 mg/m2/dose (cypionate or enanthate ester) monthly until the growth rate falls to prepubertal levels
Terminal growth phase: 100 mg/m2/dose (cypionate or enanthate ester) monthly until growth ceases
Maintenance virilizing dose: 100 mg/m2/dose (cypionate or enanthate ester) twice monthly
Delayed male puberty: 40-50 mg/m2/dose monthly (cypionate or enanthate ester) for 6 months
Adolescents and Adults: Pellet (for subcutaneous implantation): Delayed male puberty, male hypogonadism: 150-450 mg every 3-6 months
Adults:
I.M.:
Female: Inoperable breast cancer: Testosterone enanthate: 200-400 mg every 2-4 weeks
Male: Long-acting formulations: Testosterone enanthate (in oil)/testosterone cypionate (in oil):
Hypogonadism: 50-400 mg every 2-4 weeks
Delayed puberty: 50-200 mg every 2-4 weeks for a limited duration
Transdermal: Primary male hypogonadism or hypogonadotropic hypogonadism:
Androderm®: Initial: Apply 5 mg/day once nightly to clean, dry area on the back, abdomen, upper arms, or thighs (do not apply to scrotum); dosing range: 2.5-7.5 mg/day; in nonvirilized patients, dose may be initiated at 2.5 mg/day
AndroGel®, Testim™: 5 g (to deliver 50 mg of testosterone with 5 mg systemically absorbed) applied once daily (preferably in the morning) to clean, dry, intact skin of the shoulder and upper arms. AndroGel® may also be applied to the abdomen. Dosage may be increased to a maximum of 10 g (100 mg). Do not apply testosterone gel to the genitals.
Oral (buccal): Hypogonadism or hypogonadotropic hypogonadism: 30 mg twice daily (every 12 hours) applied to the gum region above the incisor tooth
Dosing adjustment/comments in hepatic disease: Reduce dose
Administration
I.M.: Warm to room temperature; shaking vial will help redissolve crystals that have formed after storage. Administer by deep I.M. injection into the upper outer quadrant of the gluteus maximus.
Oral: Striant™: One mucoadhesive for buccal application (buccal system) should be applied to a comfortable area above the incisor tooth. Apply flat side of system to gum. Rotate to alternate sides of mouth with each application. Hold buccal system firmly in place for 30 seconds to ensure adhesion. The buccal system should adhere to gum for 12 hours. If the buccal system falls out, replace with a new system. If the system falls out within 4 hours of next dose, the new buccal system should remain in place until the time of the following scheduled dose. System will soften and mold to shape of gum as it absorbs moisture from mouth. Do not chew or swallow the buccal system. The buccal system will not dissolve; gently remove by sliding downwards from gum; avoid scratching gum.
Transdermal (Androderm®): Apply patch to clean, dry area of skin on the arm, back, or upper buttocks. Following patch removal, mild skin irritation may be treated with OTC hydrocortisone cream. A small amount of triamcinolone acetonide 0.1% cream may be applied under the system to decrease irritation; do not use ointment. Patch should be applied nightly. Rotate administration sites, allowing 7 days between applying to the same site.
Gel: AndroGel®, Testim™: Apply (preferably in the morning) to clean, dry, intact skin of the shoulder and upper arms (AndroGel® may also be applied to the abdomen). Upon opening the packet(s), the entire contents should be squeezed into the palm of the hand and immediately applied to the application site(s). Alternatively, a portion may be squeezed onto palm of hand and applied, repeating the process until entire packet has been applied. Application sites should be allowed to dry for a few minutes prior to dressing. Hands should be washed with soap and water after application. Do not apply testosterone gel to the genitals.
Monitoring Parameters
Periodic liver function tests, PSA, cholesterol, hemoglobin and hematocrit; radiologic examination of wrist and hand every 6 months (when using in prepubertal children)
Androderm®: Morning serum testosterone levels following application the previous evening
Gel: Morning serum testosterone levels 14 days after start of therapy
Reference Range
Testosterone, urine: Male: 100-1500 ng/24 hours; Female: 100-500 ng/24 hours
Test Interactions
May cause a decrease in creatinine and creatine excretion and an increase in the excretion of 17-ketosteroids, thyroid function tests
Dietary Considerations
Testosterone USP may be synthesized from soy. Food and beverages have not been found to interfere with buccal system; ensure system is in place following eating, drinking, or brushing teeth.
Patient Education
If you have diabetes, monitor serum glucose closely and notify prescriber of changes; this medication may alter hypoglycemic requirements. You may experience acne, growth of body hair, loss of libido, impotence, or menstrual irregularity (usually reversible); nausea or vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report changes in menstrual pattern; enlarged or painful breasts; deepening of voice or unusual growth of body hair; persistent penile erection; fluid retention (swelling of ankles, feet, or hands, respiratory difficulty or sudden weight gain); unresolved changes in CNS (nervousness, chills, insomnia, depression, aggressiveness); altered urinary patterns; change in color of urine or stool; yellowing of eyes or skin; unusual bruising or bleeding; or other persistent adverse reactions.
Transdermal:
Androderm®: Apply patch to clean, dry area of skin on the arm, back, or upper buttocks.
AndroGel®, Testim™: Apply gel (preferably in the morning) to clean, dry, intact skin of the shoulder and upper arms (AndroGel® may also be applied to the abdomen). Upon opening the packet(s), the entire contents should be squeezed into the palm of the hand and immediately applied to the application site(s). Alternatively, a portion may be squeezed onto palm of hand and applied, repeating the process until entire packet has been applied. Application sites should be allowed to dry for a few minutes prior to dressing. Hands should be washed with soap and water after application. Do not apply testosterone gel to the genitals.
Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to become pregnant. Male/female: Consult prescriber for instruction on appropriate contraceptive measures. This drug may cause severe fetal defects. Do not breast-feed.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause anxiety, insomnia, aggressive behavior, or depression
Mental Health: Effects on Psychiatric Treatment
May rarely cause neutropenia; use caution with clozapine and carbamazepine
Dosage Forms
Gel, topical:
AndroGel®:
25 mg/2.5 g (30s); 50 mg/5 g (30s) [1% unit-dose packet]
1.25 g/dose (75 g) [1% metered-dose pump; provides 60 doses]
Testim™: 50 mg/5 g (30s) [1% unit-dose tube]
Injection, in oil, as cypionate (Depo® Testosterone): 100 mg/mL (10 mL); 200 mg/mL (1 mL, 10 mL) [contains benzyl alcohol, benzyl benzoate, and cottonseed oil]
Injection, in oil, as enanthate (Delatestryl®): 200 mg/mL (1 mL [prefilled syringe; contains sesame oil]; 5 mL [multidose vial; contains sesame oil])
Mucoadhesive, for buccal application [buccal system] (Striant™): 30 mg
Pellet, for subcutaneous implantation (Testopel®): 75 mg (1 pellet/vial)
Transdermal system (Androderm®): 2.5 mg/day (60s); 5 mg/day (30s)
References
Borhan-Manesh F and Farnum JB, "Methyltestosterone-Induced Cholestasis. The Importance of Disproportionately Low Serum Alkaline Phosphatase Level,"Arch Intern Med, 1989, 149(9):2127-9.
Cunningham GR, Cordero E, and Thornby JI, "Testosterone Replacement With Transdermal Therapeutic Systems. Physiological Serum Testosterone and Elevated Dihydrotestosterone Levels,"JAMA, 1989, 261(17):2525-30.
Daigle RD, "Anabolic Steroids,"J Psychoactive Drugs, 1990, 22(1):77-80.
Moller BB and Ekelund B, "Toxicity of Cyclosporine During Treatment With Androgens,"N Engl J Med, 1985, 313(22):1416.
Ruch W and Jenny P, "Priapism Following Testosterone Administration for Delayed Male Puberty,"Am J Med, 1989, 86(2):256.
International Brand Names
Agovirin® [inj.] (CZ); Andriol® (AT, AU, BD, CA, CH, CR, CY, DE, EG, GT, HK, HN, HU, ID, IT, JO, KW, LB, MX, NL, RU, SG, SY, TH, YU); Androderm® (AU, CA, CH, DE, ES, IT); AndroGel® (BE, CA, FR); Andropatch® (GB, IE); Andropository (CA); Androtardyl® (FR); Androtop® (DE); Androxon® (BR, IL, NO, ZA); Atmos® (FI, NO, SE); Delatestryl® (CA); Deposteron® (BR); Depotest® 100 (CA); Depo-Testosterone® (NZ, SG); Enarmon® (JP); Everone® 200 (CA); Nebido® (DE); Omnadren® (PL); Pantestone® (FR); Panteston® (FI, NZ); Primoniat Depot® (CL); Primoteston Depot® (AU, CR, EC, GB, GT, HN, MX, NO, NZ, PA, SV); Restandol® (DK, GB, IE); Sostenon® [Propionate, Phenylpropionate, Isocaproate, Decanoate] (MX); Sustanon 100® [isocaproate, phenpropionate and propionate] (AU, GB); Sustanon 250® [decanoate, isocaproate, phenpropionate and propionate] (AR, AU, CY, EG, FI, GB, ID, IL, JO, KW, LB, RU, SY, TR); Sustanon® [decanoate, isocaproate, phenpropionate and propionate] (NZ, ZA); Sustenan Oral® (CL); Testex Elmu® (ES); Testinon® (JP); Testocaps® (BE); Testo-Enant® (IT); Testogel® (AT, DE, GB, IE, SE); Testogol® (DE); Testolent® (RO); Testosterona Enantato® (CL); Testosterona Enantato L.CH.® (CL); Testosteron Depot Eifelfango® (DE); Testosteron Depot Galen® (DE); Testosteron Depot Jenapharm® (DE); Testosteron Depot Rotexmedica® (DE); Testosteron depo® (YU); Testosterone Enantate® (GB); Testosterone Implant® (GB, SG); Testosterone Implants® (AU, NZ, ZA); Testosterone Propionate March® (TH); Testosteron Ferring® (AT); Testosteron Paranova® (DK); Testosteron propionat Eifelfango® (DE); Testosteron® (RO); Testosteronum prolongatum® (PL); Testosteronum propionicum® (PL); Testotop® (LU); Testoviron® (CO, SE); Testoviron Depot® [enantate and propionate] (AR); Testoviron Depot® (AT, BE, CH, CN); Testoviron Depot® [enantate and propionate] (CR, CY); Testoviron Depot® (DE, DK); Testoviron Depot® [enantate and propionate] (EG, ES); Testoviron Depot® (GT, HN, IL); Testoviron Depot® [enantate and propionate] (IT, JO, KW, LB); Testoviron Depot® (LU); Testoviron Depot® [enantate and propionate] (PA); Testoviron Depot® (PT, SE, SV, TH); Testovis® [inj.] (IT); Triolandren® [propionate, undecylenate and valerate] (HK); Undestor® (AR, BE, CZ, LU, PL, RO); Virigen® (TR); Virilon® IM (CA); Virormone® (CY, GB, MT)