testosterone (Delatestryl Testopel, Striant, Intrinsa, Xyosted)

Introduction

Secreted by Leydig cells of the testes in response to stimulation of LH receptors by LH. The adult testes secrete 7 mg/day of testosterone. Smaller amounts are formed from DHEA secreted by the adrenal cortex. Testosterone is transported in circulation bound to its binding globulin (TEBG). Activity of testosterone is mediated through the androgen receptor.

As pharmacologic agent: DEA controlled substance class 3. Testosterone enanthate, cypionate, propionate.

Indications

• males:
  • replacement therapy in hypogonadism & delayed puberty
  • sarcopenia
  • andropause (also see testosterone replacement therapy)
  • symptomatic androgen deficiency
  • orchitis
  • cryptorchidism
  • anorchia
  • Klinefelter's syndrome (Jatenzo)
  • LHRH deficiency
  • medically-related low plasma testosterone
• females:
  • inoperable breast cancer
  • post-partum pain & engorgement
  • diminished libido (not FDA-approved use)

Contraindications

• avoid in patients with prostate cancer
• BPH, serum PSA > 3 ng/mL
• hematocrit > 50%
• obstructive sleep apnea
• severe heart failure
• indiscriminant use as an anti-aging drug*

* testosterone therapy in the absence of testosterone deficiency is not beneficial & is associated with harm

pregnancy category = x

safety in lactation = ?

Dosage

• also see
  • testosterone transdermal patch
  • testosterone transdermal gel
• Striant: 30 mg placed in upper gum BID
  • tablet will not dissolve completely
  • remove old tablet before inserting new one
• Intrinsa: transdermal testosterone for women (not FDA-approved)
• undecenoate (oral) 80 mg PO BID {in Europe} not effective
• maintenance IM, adult men (enanthate):
  • 50-400 mg (100 mg/m2) IM every 2-4 weeks
  • 125 mg IM weekly is optimal dose
• children (delayed puberty & hypogonadism):
  • 40-50 mg/m2 monthly for 6 months
  • 100 mg/m2 monthly during terminal growth phase until growth ceases
• Testopel subcutaneous pellet: injection every 3-6 months
• breast carcinoma: 200-400 mg every 3-4 weeks

Injection (in oil)

• cypionate: 100 mg/mL (10 mL), 200 mg/mL (10 mL)
• enanthate: 200 mg/mL (10 mL)
• propionate: 100 mg/mL (10 mL)

Transdermal system:

• Testoderm: 4 mg/day, 6 mg/day
• Androderm: pathes 2 & 4 mg/day

Androgel 1% & 1.62%:

• 2.5 g & 5 g packets (doubles serum testosterone)

Striant: 30 mg buccal tablet

Testopel subcutaneous pellet

Xyosted (testosterone enanthate)

• once-weekly self-administration using disposable autoinjector
• 50 mg, 75 mg, 100 mg

oral testosterone undecanoate (Jatenzo) for Klinefelter's syndrome

Pharmacokinetics

• metabolized in the liver by cyt P450 3A4
• metabolized by aromatase to estradiol in peripheral tissues

elimination via liver

Monitor

• serum lipid levels
• serum PSA
• hematocrit (keep < 54%)
• liver function tests periodically

Adverse effects

• common (> 10%)
  • menstrual problems (amenorrhea), virilism, edema, acne, priapism, breast soreness
• less common (1-10%)
  • GI irritation, nausea/vomiting, hepatic dysfunction, prostatic hypertrophy, prostatic carcinoma, hirsutism (increase in pubic hair growth), impotence, testicular atrophy
• uncommon (< 1%)
  • hepatic necrosis, leukopenia, gynecomastia, amenorrhea, hypercalcemia, polycythemia, cholestatic hepatitis, hypersensitivity reactions
• other
  • males
    • gynecomastia
    • excessive frequency & duration of penile erections
    • male pattern baldness
    • retention of water & electrolytes
    • suppression of clotting factors
    • lipoprotein levels generally NOT affected
    • exogenous testosterone may result in irreversible decline in spermatogenesis, infertility & permanent inability to produce endogenous testosterone
    • fluctuation in mood & libido most common with IM testosterone
  • females
    • amenorrhea
    • deepening of voice
    • clitoral enlargement
    • may diminish HDL cholesterol
  • Testoderm, but NOT Androderm associated with elevated serum dihydrotestosterone levels
  • sleep apnea
  • inadvertent exposure to testosterone through contact with a person using AndroGel 1% or Testim 1%
  • increased cardiovascular risk
    • also see testosterone transdermal gel
    • testosterone supplementation (topical or parenteral) is associated with increased cardiovascular risk in older men after coronary angiography
    • testosterone may increase risk of myocardial infarction in men
  • increased risk of venous thromboembolism
  • no increased risk of prostate cancer
• high-dose androgen abuse
  • myocardial infarction
  • heart failure
  • stroke
  • depression
  • hostility, aggression
  • hepatotoxicity
  • male infertility

• drug adverse effects of androgens

Drug interactions

• increased anticoagulant effect of warfarin
• cyclosporine
• any drug that inhibits cyt P450 3A4 may increase levels of testosterone
• any drug that induces cyt P450 3A4 may diminish levels of testosterone

• drug interaction(s) of phosphodiesterase-5-inhibitor with testosterone

Test interactions

• may increase PSA

Mechanism of action

• androgen
• increases lean body mass, muscle mass, bone mineral density erythrocyte mass, libido
• may improve depressed mood
• AndroGel effective

More general terms

• androstenol
• androgen or anabolic steroid
• ketosteroid
• adrenal cortex hormone; corticosteroid

More specific terms

• 1-testosterone
• 4-hydroxytestosterone
• epitestosterone
• testosterone oral; testosterone undecanoate (Jatenzo)
• testosterone topical; testosterone transdermal

Additional terms

• androgen excess (hyperandrogenism)
• androgen insufficiency (hypoandrogenism, testosterone deficiency)
• androgen receptor; dihydrotestosterone receptor; nuclear receptor subfamily 3 group C member 4 (AR, DHTR, NR3C4)
• dehydroepiandrosterone; prasterone (DHEA, Aslera, Intrarosa)
• free testosterone
• gonadal steroid biosynthesis
• Leydig cell
• testosterone in serum
• testosterone replacement therapy; androgen therapy

Component of

• estradiol/testosterone
• tibolone
• conjugated estrogens (Premarin)/methyltestosterone Estratest

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5408
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6013