Methyltestosterone is a synthetic derivative of testosterone. It is 2.5 times more potent than testosterone. It is used in males with hypogonadism and delayed puberty. It may be used in females with breast cancer.

Methyltestosterone Uses:

• Males:

  • Delayed puberty:
    • Used on carefully chosen guys with blatantly delayed puberty to promote puberty.
  • Hypogonadotropic hypogonadism (congenital or acquired):
    • Treatment for pituitary hypothalamic impairment brought on by radiation, tumours, or idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency.
  • Primary hypogonadism (congenital or acquired):
    • Treatment of testicular failure caused by bilateral torsion, orchitis, cryptorchidism, vanishing testis syndrome; or orchidectomy.

• Females:

  • Metastatic Breast cancer:
    • Primarily in women who are 1 to 5 years postmenopausal and have advanced, incurable, metastatic (skeletal) mammary cancer.
    • Additionally, it has been applied to premenopausal breast cancer patients who have benefited from oophorectomy and are thought to have a hormone-responsive tumour.

Methyltestosterone Dose in Adults:

Note:

• In adult men with androgen deficiency syndromes (eg, hypogonadism), withhold initial treatment with hematocrit more than 50 percent (stop therapy if hematocrit exceeds 54 percent), untreated obstructive sleep apnea, uncontrolled severe heart failure, or with severe untreated BPH with IPSS symptom score more than 19.

Methyltestosterone Dose in the treatment of metastatic Breast cancer in females:

• Oral: 50 to 200 mg each day.

Methyltestosterone Dose in the treatment of Delayed puberty in males:

• Oral: 10 to 50 mg each day;
• Limit treatment duration to 4 to 6 months;
• Use a lower range of dosing and individualize dose-dependent on response and tolerability.

Methyltestosterone Dose in the treatment of Hypogonadotropic hypogonadism (congenital or acquired) and primary hypogonadism (congenital or acquired) in males:

• Oral: Initial: 10 to 50 mg each day;
• Individualize dose-dependent on tolerability and response.

Methyltestosterone Dose in Children:

Refer to adults dosing.

Pregnancy Risk Factor X

• It is not recommended for use by women who may be pregnant.
• Exposure to the environment during pregnancy can cause virilization (virilization) of the female fetus' external genitalia, such as abnormal vaginal development and clitoromegaly.
• It may also result in fusion of genitalfolds to form an scrotal-like structure.
• Dose-related factors determine the degree of masculinization. It is most common to see it in the first trimester when androgens have been administered.
• Use of methyltestosterone can impair fertility. Oligospermia in males may occur, while amenorrhea in females may occur.
• Patients who become pregnant after taking androgens should be advised about the possible dangers to their unborn baby.

Methyltestosterone use during breastfeeding:

• Breast milk contains more methyltestosterone than is known.
• Nursing infants could experience serious adverse reactions.
• It is important to decide whether to stop nursing or stop using the drug.
• This decision must be made in consideration of the importance of the mother's treatment.

Dose in Kidney Disease:

The manufacturer’s labeling doesn't provide any dosage adjustments (has not been studied). However, patients with renal disease may be at an increased risk of fluid retention.

Dose in Liver disease:

The manufacturer’s labeling doesn't provide any dosage adjustments (has not been studied). However, patients with renal disease may be at an increased risk of fluid retention.

Side effects of Methyltestosterone:

• Cardiovascular:

  • Edema

• Central Nervous System:

  • Depression
  • Headache
  • Anxiety
  • Paresthesia

• Dermatologic:

  • Acne Vulgaris
  • Androgenetic Alopecia

• Endocrine & Metabolic:

  • Hirsutism (Females)
  • Hypercalcemia
  • Hypercholesterolemia
  • Change In Libido
  • Gynecomastia (Males)
  • Menstrual Disease (Includes Amenorrhea)

• Gastrointestinal:

  • Nausea
  • Vomiting

• Genitourinary:

  • Oligospermia (Males; At High Doses)
  • Priapism (Males)
  • Testicular Atrophy (Males)
  • Benign Prostatic Hypertrophy (Males)
  • Impotence (Males)
  • Mastalgia (Females)
  • Virilization (Males And Females)

• Hematologic & Oncologic:

  • Clotting Factors Suppression
  • Polycythemia
  • Prostate Carcinoma (Males)

• Hepatic:

  • Cholestatic Hepatitis
  • Hepatic Insufficiency
  • Hepatic Necrosis
  • Jaundice
  • Abnormal Liver Function Tests
  • Peliosis Hepatitis

Contraindications to Methyltestosterone:

• Men who have been diagnosed with breast cancer or prostate cancer.
• Women who may or are pregnant.

Patients with hypersensitivity reactions to other androgens might experience cross-reactivity.

Warnings and precautions

• Cardiovascular events

  • The risk of developing major adverse cardiovascular conditions (MACE), such as stroke or nonfatal MI, is not known.
  • According to research, men who receive testosterone therapy have a higher chance of developing cardiovascular disease.
  • According to the Endocrine Society, it is prudent to limit testosterone therapy for men who have had a cardiovascular event in the last six months (eg, MI stroke, acute coronary syndrome).

• Gynecomastia

  • Hypogonadism may cause gynecomastia, which can persist in patients.

• Hepatic effects

  • High doses and prolonged use can lead to peliosis, hepatic cancer, jaundice and cholestatic liver disease.
  • If cholestatic liver disease is associated with jaundice, abnormal liver function tests or cholestatic hepatitis, stop treatment.

• Oligospermia:

  • After prolonged administration, or excessive doses, may cause oligospermia.

• Polycythemia

  • Can increase hematocrit and may require dose adjustment or discontinuation. 
  • Patients with a hematocrit greater than 50 percent should be stopped from receiving treatment.
  • If you are already receiving treatment, stop taking it if your hematocrit is higher than 54 percent. You may be able to restart the treatment at a lower dose.

• Priapism

  • Excessive sexual stimulation or priapism may be a possibility.

• Venous thromboembolism

  • Testosterone products have been linked to pulmonary embolism and deep vein thrombosis (DVT).
  • Assess patients who have symptoms such as pain, edema and warmth for DVT or those with shortness of breath and acute erythema for PE.
  • If venous thromboembolism is suspected, discontinue therapy.

• Benign prostatic hyperplasia, (BPH)

  • Androgens shouldn't be taken by patients with significant lower urinary tract symptoms (AUA/IPSS > 19).
  • If a patient with BPH develops a urethral obstruction, discontinue treatment and if the dose is increased, reduce it.

• Breast cancer

  • Patients with breast cancer may be at risk of hypercalcemia (by stimulating bone synthesis); discontinue use if hypercalcemia develops.

• Fluid retention can lead to more severe diseases

  • Fluid retention can be dangerous for patients suffering from cardiac impairment or other conditions.
  • Treatment for androgen deficiency syndromes shouldn't be given to men who have uncontrolled heart failure or poor control.

• Hepatic impairment

  • Patients with hepatic impairment should use it with caution as fluid retention may occur.

• Prostate cancer:

  • Increased risk of developing prostate cancer.
  • Patients with induration or a visible prostate tumour may be advised to postpone therapy while a urologist assesses the condition.

• Renal impairment

  • Patients with impaired renal function should be cautious as fluid retention may occur.

• Sleep Apnea

  • Some male patients may experience sleep apnea, particularly those who are obese or have chronic lung disease.
  • Patients suffering from untreated obstructive sleeping apnea should be withheld for their initial treatment.

Methyltestosterone: Drug Interaction

Monitoring parameters:

Prior to treatment initiation:

• Confirm hypogonadism by measuring morning serum testosterone on 2 separate days.
• Liver function tests, lipid panel, hematocrit, and hemoglobin (withhold starting treatment with hematocrit more than 50 percent).
• PSA and prostate exam in men more than 40 years of age with a baseline PSA more than 0.6 ng per mL.

During treatment:

• Liver function tests
• Lipid panel
• Hematocrit
• hemoglobin 
• discontinue therapy if hematocrit exceeds 54 percent.
• Observe serum calcium and urine
• Signs of virilization in women treated for breast cancer.
• Serum glucose 
• Evaluate males for the response to treatment and adverse events 3 to 6 months after initiation and then annually;
• monitor for cardiovascular events closely during therapy. Monitor serum testosterone 3 to 6 months after initial dose titration (if applicable) then annually.

Bone mineral density:

• Prepubertal children:
  • Radiologic examination of the wrist every  6 months also hand.
• Hypogonadal men with osteoporosis or low trauma fracture:
  • Monitor after 1 to 2 years of therapy.

PSA:

• In men >40 years of age with baseline PSA >0.6 ng/mL, PSA and prostate exam at 3 to 6 months, then as based on current guidelines.
• In individuals with a palpable prostate nodule, induration, or PSA >4 ng/mL or if PSA >3 ng/mL in males at high risk of prostate cancer, therapy should be postponed until urological assessment.

How to administer Methyltestosterone?

Administer orally without regard to meals.

Mechanism of action of Methyltestosterone:

• Male sex organ growth and development are aided by endogenous androgen, which stimulates receptors in tissues and organs.
• Additionally, it keeps secondary sexual traits in men who lack androgen.

Protein binding:

• 98% bound to sex hormone-binding globulin

Metabolism:

• Hepatic

Half-life elimination:

• Variable: 10 to 100 minutes

Excretion:

• Urine (~90%);
• feces (~6%)

International Brand Names of Methyltestosterone:

• Android
• Methitest
• Testred
• Build
• Gynosterone
• Menwin
• Mesteron
• Testormon
• Testotonic B
• Testovis

Methyltestosterone Brand Names in Pakistan:

There is no brand available in Pakistan.