testosterone

Testosterone is the natural male steroid hormone (androgen) responsible for the development of male reproductive organs, their normal functioning, and male secondary sexual characteristics such as increased muscle mass, bone mass and strength, body hair and deep voice.

Testosterone is used to treat low testosterone levels caused by certain medical conditions, delayed puberty in males and advanced breast cancer in women.

Testosterone is mainly produced in the testes in males and smaller amounts are produced in the ovaries in women and the adrenal glands in both sexes. Testosterone is important for normal ovary function and libido, and bone strength in women. Testosterone used as a medication is a synthetic preparation that supplements natural deficiency. Testosterone formulations include oral medications, injections, skin patches, intranasal sprays, and buccal systems in which a tablet is placed on the gum.

Testosterone is used to treat patients above 12 years of age with the following conditions:

• Hypogonadism, is a genetic or acquired condition in which the testes (male gonads) don’t function normally, leading to low testosterone levels
• Delay in the onset of male puberty
• Metastatic inoperable breast cancer in postmenopausal women; testosterone counteracts estrogen’s effects in hormone-sensitive breast cancer

Testosterone has an orphan designation and is being investigated for use in:

• Androgen deficiency in human immunodeficiency (HIV) positive patients with associated weight loss
• Delayed growth and puberty in adolescent males of age 14 to 17 years.

Testosterone is approved by the FDA only for use in men who lack or have low testosterone levels in conjunction with an associated medical condition, including failure of the testicles to produce testosterone because of reasons such as genetic problems or chemotherapy. Testosterone has a high potential for abuse and dependence, and is often used in combination with anabolic androgenic steroids by athletes and bodybuilders to build muscle and boost performance.

• Do not administer testosterone to:
  • Patients who are hypersensitive to testosterone or any of its components
  • Men with breast cancer or known or suspected prostate cancer
  • Men with hypogonadism who do not have an associated genetic or acquired medical condition
  • Patients with serious heart, liver or kidney disease
  • Women who are pregnant or have the prospect of pregnancy
• Specific to testosterone undecanoate (Aveed):
  • Can cause a serious lung problem known as serious pulmonary oil microembolism (POME) reactions, in which tiny droplets of oil get into the lungs; symptoms may include shortness of breath, tightening of throat, urge to cough, chest pain, dizziness, sweating and fainting; use with caution and monitor
  • Can cause severe life-threatening allergic reaction (anaphylaxis) which may occur after the first dose or after more than one doses; Aveed should be administered in a well-equipped healthcare setting and the patient should be monitored for 30 minutes after the injection
  • Testosterone undecanoate is available only through restricted program under a risk evaluation and mitigation strategy (REMS) called the Aveed REMS Program because of the risks for POME and anaphylaxis
• Testosterone causes an increase in blood pressure which can increase the risk for major adverse cardiovascular events such as heart attack or stroke; assess the patient’s risk, use with caution and continue monitoring blood pressure
• Testosterone can cause increase in the volume of red blood cells (hematocrit); evaluate hematocrit levels and reduce dosage or discontinue if necessary
• Testosterone use in patients with prostate enlargement (benign prostatic hyperplasia) may worsen symptoms; monitor carefully
• Testosterone treatment increases the risk for prostate cancer; evaluate the patient before initiating therapy and monitor during treatment
• There have been reports of blood clots in the vein (deep vein thrombosis/DVT) and lungs (pulmonary embolism/PE); monitor patients for symptoms of DVT and PE
• Testosterone use may increase calcium levels (hypercalcemia); use with caution in immobilized or cancer patients; discontinue if hypercalcemia occurs
• Prolonged use of testosterone in high doses can result in serious hepatic conditions such as liver inflammation (hepatitis), liver cancers and peliosis hepatis, a condition that causes blood-filled cavities to form in the liver
• Testosterone is prone to being abused, usually at doses higher than recommended and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions
• Testosterone can cause breast tissue growth in men (gynecomastia) treated for hypogonadism
• Testosterone may promote sodium and water retention; patients with pre-existing heart, liver or kidney disease are at a higher risk for developing edema, with or without congestive heart failure (CHF)
• Large doses of testosterone can suppress sperm production (spermatogenesis)
• Testosterone should not be used in women, except for the approved indication; can lead to development of masculine characteristics (virilization)
• Testosterone therapy may potentiate sleep apnea in some patients, particularly those with chronic lung disease or obesity
• Blood lipid profile may change; monitor periodically
• May decrease concentrations of thyroxine-binding globulin, a protein that transports thyroid hormone, leading to reduced total T4 serum concentrations and increased resin uptake of T3 and T4; there is, however, no evidence of thyroid dysfunction
• Depression and suicidal ideation and behavior, including completed suicide, have occurred during clinical trials
• Cellulitis and abscess have occurred with testosterone pellets
• Use testosterone with caution in healthy males with delayed puberty and monitor the effect on bone maturation; may cause early maturation compromising adult height; the younger the child, the higher the risk
• Metabolism of testosterone may cause a decrease in blood glucose levels; use with caution in patients on diabetic medications

Common side effects of testosterone include:

• Pain and inflammation at the injection site
• Hypersensitivity reactions including severe allergic reaction (anaphylaxis)
• Inappropriate male pattern hair growth in women (hirsutism)
• Menstrual irregularities
• Breast soreness
• Growth acceleration in prepubertal males
• Breast tissue growth in males (gynecomastia)
• Excessive frequency and prolonged erections (priapism)
• Suppression of sperm production with high doses
• Low sperm count (oligospermia) or absence of sperm (azoospermia)
• Increase in prostatic specific antigen (PSA)
• Prostate enlargement (benign prostatic hyperplasia)
• Increase in estradiol level
• Low testosterone level
• Increase or decrease in libido
• Male pattern baldness
• Fluid and electrolyte disturbances with retention of water, sodium, chloride, potassium, calcium and inorganic phosphates
• Acne
• Hair loss (alopecia)
• Rash
• Itching (pruritus)
• Scaly, itchy skin condition (seborrhea)
• Headache
• Hot flashes
• Fatigue
• Increase in cholesterol (hypercholesterolemia)
• Decrease in high-density lipoprotein (HDL) cholesterol
• Liver function alterations
• Liver tumor
• Peliosis hepatis, a condition with blood-filled cavities in the liver
• Jaundice due to impaired bile flow (cholestatic jaundice)
• Nausea
• Vasodilation
• Blood clotting disorders
• Bleeding in patients on concomitant anticoagulant therapy
• Increase in red blood cells (polycythemia)
• Blood clots in veins (venous thromboembolism)
• Pulmonary embolism
• Stroke
• High blood pressure (hypertension)
• Heart attack (myocardial infarction)
• Edema with or without congestive heart failure
• Aggressive behavior
• Anger
• Anxiety
• Depression
• Mood swings
• Loss of memory (amnesia)
• Insomnia
• Abnormal dreams
• Breathing problems while sleeping (sleep apnea)
• Abnormal skin sensations (paresthesia)
• Bladder irritability
• Virilization
• Fluid buildup under the retina (central serous chorioretinopathy), rare

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Adult:

Oral capsule (undecanoate): Schedule III

• 112.5 mg (Tlando)
• 158 mg (Jatenzo)
• 198 mg (Jatenzo)
• 237 mg (Jatenzo)

Injectable solution (cypionate): Schedule III

• 100 mg/mL (Depo-Testosterone)
• 200 mg/mL (Depo-Testosterone)

Injectable solution (enanthate): Schedule III

• 50 mg/0.5mL (Xyosted)
• 75 mg/0.5mL (Xyosted)
• 100 mg/0.5mL (Xyosted)
• 200 mg/mL (generic)

Injectable solution (undecanoate): Schedule III

• 750 mg/3mL (Aveed)

Pellet implant: Schedule III

• 75 mg (Testopel)
• 12.5 mg, 25 mg, 37.5 mg, 50 mg (generic)

Hypogonadism

• Testosterone cypionate: 50-400 mg intramuscular (IM) every 2-4 weeks
• Testosterone enanthate (generic): 50-400 mg IM every 2-4 weeks
• Testosterone undecanoate (restricted availability): 750 mg IM initial dose, repeat after 4 weeks, and then q10wk thereafter
• Pellet: 150-450 mg subcutaneous (SC) every 3-6 months; 150 mg of pellet approximately equivalent to 25 mg of testosterone propionate weekly

Xyosted

• Starting dose: 75 mg SC every week
• Adjust dose based upon total testosterone minimum (trough) concentrations (Cmin) (measured 7 days after most recent dose) obtained following 6 weeks of dosing and periodically thereafter
• Trough concentration (350-650 ng/dL) generally provides testosterone exposures in normal range during entire dosing interval
• Decrease dose by 25 mg if Cmin is 650 ng/dL or higher; increase dose by 25 mg if the total testosterone Cmin below 350 ng/dL
• Maintain same dose if total testosterone Cmin is 350 ng/dL to 650 ng/dL

Jatenzo

• Starting dose: 237 mg orally twice a day (BID) with food
• To ensure proper dose adjustment, measure serum testosterone concentrations 6 hours after morning dose in plain tubes, clotted at room temperature for 30 minutes prior to centrifugation; adjust dose based on serum testosterone measurement
• Wait 7 days after starting treatment or adjusting the dose before checking the serum testosterone concentration; thereafter, periodically monitor serum testosterone concentrations 6 hours after morning dose
• Adjust dose based on testosterone level as follows:
• Below 425 ng/dL
  • Current BID dose 158 mg: Increase to 198 mg BID
  • Current BID dose 198 mg: Increase to 237 mg BID
  • Current BID dose 237 mg: Increase to 316 mg (two 158-mg cap) BID
  • Current BID dose 316 mg: Increase to 396 mg (two 198-mg cap) BID
• 425-970 ng/dL
  • No dose change
• Above 970 ng/dL
  • Current BID dose 396 mg: Decrease to 316 mg BID
  • Current BID dose 316 mg: Decrease to 237 mg BID
  • Current BID dose 237 mg: Decrease to 198 mg BID
  • Current BID dose 198 mg: Decrease to 158 mg BID
  • Current BID dose 158 mg: Discontinue treatment

Tlando

• Starting dose: 225 mg orally BID with food
  • Monitoring for continued use or discontinuation
  • Monitor serum testosterone (8-9 hours after morning dose) 3-4 weeks after initiating, and periodically thereafter
  • Based on serum testosterone measurements, determine if Tlando should be continued or discontinued
  • Serum testosterone 300-1080 ng/dL: Continue
  • Serum testosterone below 300 ng/dL: Discontinue
  • Serum testosterone above 1080 ng/dL: Discontinue

Delayed Puberty in Males

• Testosterone enanthate (generic): 50-200 mg IM every 2-4 weeks for 4-6 months

Inoperable Mammary Cancer in Women

• Testosterone enanthate (generic): 200-400 mg IM every 2-4 weeks

Pediatric:

Injectable solution (cypionate): Schedule III

• 100 mg/mL (Depo-Testosterone)
• 200 mg/mL (Depo-Testosterone)

Injectable solution (enanthate): Schedule III

• 200 mg/mL (generic)

Injectable solution (undecanoate): Schedule III

• 250 mg/mL (Aveed)

Pellet implant: Schedule III

• 75 mg (Testopel)
• 12.5 mg, 25 mg, 37.5 mg, 50 mg (generic)

Hypogonadism

Below 12 years

• Safety and efficacy not established

12 years and above

• Testosterone cypionate: 50-400 mg IM every 2-4 weeks
• Testosterone enanthate (generic): 50-400 mg IM every 2-4 weeks
• Pellet: 150-450 mg SC every 3-6 months; 150 mg of pellet approximately equivalent to 25 mg of testosterone propionate weekly

Delayed Puberty in Males

Below 12 years

• Safety and efficacy not established

12 years and above

• 50-200 mg IM every 2-4 weeks for 4-6 months

Dosing Considerations

Limitations of use

• Aveed: Safety and efficacy not established in adult males with “age-related hypogonadism” (also referred as “late-onset hypogonadism”) and males aged below 18 years
• Jatenzo, Tlando, Xyosted: Safety and efficacy not established in males aged below 18 years

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of testosterone include:
  • cabotegravir
• Serious interactions of testosterone include:
  • cyclosporine
  • lasmiditan
  • lonafarnib
  • pexidartinib
  • pretomanid
  • sotorasib
  • tepotinib
  • warfarin
• Testosterone has moderate interactions with at least 28 different drugs.
• Testosterone has mild interactions with at least 39 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Abuse of anabolic androgenic steroids may cause irregular menstruation and infertility in women. Women with pregnancy prospects should not use testosterone.
• Large doses of testosterone can affect male fertility and sperm production, reducing chances of pregnancy in their female partner.
• Testosterone should not be used during pregnancy; can cause fetal harm and female fetuses may develop male characteristics (virilization).
• Testosterone is present in breast milk; maternal testosterone can suppress milk production; do not use while breastfeeding.

• Testosterone is a Schedule III controlled drug with moderate potential for abuse and dependence; use with caution
• Take testosterone exactly as prescribed; do not take higher or more frequent doses
• Store safely away from reach of children