Testosterone Propionate/ Testosterone Phenylpropionate/ Testosterone Isocaproate/ Testosterone Decanoate

Registered South African indications: 

• Testosterone replacement therapy in males for conditions associated with primary and secondary hypogonadism (either congenital or acquired)

Contraindications

Registered contraindications in South Africa & other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients including arachis oil, and is therefore contraindicated in patients allergic to peanuts or soya
• Known or suspected prostatic carcinoma or breast carcinoma
• Pregnancy
• Breastfeeding

Cautions

Recommendations in South Africa & other jurisdictions

Caution in the following patient groups

• Renal impairment
• Hepatic impairment
• Elderly
• Male reproductive potential
• Female reproductive potential (Recommendations in other jurisdictions)
• Latent or overt cardiac failure 
• Patients who experienced myocardial infarction, cardiac insufficiency (Recommendations in other jurisdictions)
• Hypertension or a history therof
• Epilepsy or a history therof
• Migraine or a history therof

Medical examination and monitoring (see Monitoring)

• Testosterone levels should be monitored at baseline and regularly during treatment to maintain eugonadal levels, with dosage adjustments made as necessary
• Conduct a digital rectal examination (DRE) of the prostate and measure prostate-specific antigen (PSA) levels to exclude benign prostatic hyperplasia or sub-clinical prostate cancer before starting treatment
• Monitor haematocrit and haemoglobin levels to exclude polycythemia

Tumours

• Monitor patients, particularly the elderly, for the development of mammary carcinoma, hypernephroma, bronchial carcinoma, and skeletal metastases
• Treat hypercalcemia appropriately before resuming hormone therapy once normal calcium levels are restored
• Use cautiously in men with benign prostatic hypertrophy

Other pre-existing conditions

• In patients suffering from severe cardiac, hepatic, or renal insufficiency or ischaemic heart disease, treatment with testosterone may cause severe complications characterised by oedema with or without congestive cardiac failure.  In such case, treatment must be stopped immediately

Diabetes mellitus

• Testosterone can improve glucose tolerance and blood glucose control in diabetic patients

Anti-coagulant therapy

• Testosterone can enhance the anti-coagulant action of warfarin (coumarin-type agents)

Sleep apnoea

• There is limited evidence guiding the safety of testosterone esters, in men with sleep apnoea
• Use caution when administering to patients with risk factors such as obesity or chronic lung diseases like COPD, as it may exacerbate sleep apnoea

Adverse events

• If adverse reactions related to androgens occur, treatment should be stopped. After symptoms resolve, consider resuming treatment at a reduced dosage
• A decrease in protein bound iodine (PBI) may be observed, although it is clinically insignificant

Clotting disorders

• Use testosterone with caution in patients with thrombophilia or risk factors for venous thromboembolism (VTE), due to findings from post-marketing studies and reports indicating a potential increased risk

Misuse in sports (see Drugs in Sports)

• Misusing testosterone to enhance athletic performance can pose serious health risks and is strongly discouraged
• Athletes governed by the World Anti-Doping Agency (WADA) should consult the WADA code before using testosterone, as it can affect anti-doping tests

Virilisation

• Patients should be informed about the potential occurrence of signs of virilisation. In particular, singers and women with speech professions should be informed about the risk of deepening of the voice
• The voice changes may be irreversible. If signs of virilisation develop, the risk/benefit ratio has to be newly assessed with the individual patient

Drug abuse and dependence

• Testosterone is often abused, usually at doses higher than approved for medical use and in combination with other anabolic androgenic steroids
• Abuse can lead to severe adverse reactions, including cardiovascular complications (sometimes fatal), liver issues, and psychiatric events
• Dependence on testosterone can develop, with withdrawal symptoms occurring if the drug is significantly reduced or abruptly stopped
• The abuse of testosterone and other anabolic steroids presents serious health risks and should be actively discouraged

Paediatric population

• Testosterone esters should not be used in pre-pubertal boys as premature epiphyseal closure or precocious sexual development may occur
• In pre-pubertal children statural growth and sexual development should be monitored since testosterone in high dosages may accelerate epiphyseal closure and sexual maturation

Excipient precautions

• Arachis oil (peanut oil) and should not be taken/ applied by patients known to be allergic to peanut. As there is a possible relationship between allergy to peanut and allergy to soya, patients with soya allergy should also avoid (see Contraindications)
• Contains 100mg benzyl alcohol per ml solution and must not be given to premature babies or neonates
• Benzyl alcohol may cause toxic reactions and anaphylactoid reactions in infants and children up to 3 years old

Effects on laboratory tests

• Androgens may decrease levels of thyroxine-binding globulin resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction

Additional South African recommendations

Cardiovascular risks

• There is a potential increase in the risk of heart attacks and strokes when using testosterone treatments
• Patients should not discontinue testosterone therapy without first consulting their healthcare professionals
• Consider whether the benefits of treatment are likely to exceed the potential risks of treatment

Angina pectoris or other circulatory disease

• Middle aged and elderly males on treatment for angina pectoris or other circulatory disease should receive this testosterone product only under very careful supervision

Polycythaemia

• Treatment with testosterone, decreases serum LDL-C, HDL-C and triglycerides and increases haemoglobin and haematocrit, which may lead to polycythaemia

Ability to drive and use machinery

• Testosterone may cause mood disturbances, paranoia, and delusions, which can impair the ability to drive or operate machinery
• Patients should avoid driving, using machinery, or performing any tasks requiring concentration until they are certain this medicine does not negatively impact their ability to perform these activities safely

Additional Recommendations in other jurisdictions

Female-to-male transsexual supportive therapy

• Before starting testosterone therapy, a thorough specialist assessment, including psychiatric evaluation, is necessary. Comprehensive personal and medical histories should be documented
• Regular check-ups adapted to individual needs should be conducted during treatment. Monitor for signs of osteoporosis and changes in the lipid profile
• For patients with personal or family histories of breast cancer, or a personal history of endometrial cancer, careful monitoring is required
• Based on specialist advice, consider hysterectomy and bilateral oophorectomy after 18-24 months of testosterone therapy to reduce potential risks of endometrial and ovarian cancers
• Continuous monitoring for osteoporosis is necessary for patients who have undergone oophorectomy, as testosterone may not fully counteract the decline in bone density
• Ongoing surveillance for endometrial and ovarian cancers is advised for long-term patients who have not had a hysterectomy and bilateral oophorectomy

Ability to drive and use machinery

• Testosterone has no influence on the ability to drive and use machines

Forms avail. in SA and covered in this monograph: inj

South African registered indications and dosages

Testosterone replacement therapy in males for conditions associated with primary and secondary hypogonadism (either congenital or acquired)
- Only when testosterone deficiency has been confirmed by clinical features and biochemical tests

Testosterone Propionate/ Testosterone Phenylpropionate/ Testosterone Isocaproate/ Testosterone Decanoate
30/60/60/100 (mg)/ ml

• IM: 1ml, every 3 weeks is adequate;  Dosage should be adjusted according to the response of the individual patient

Pregnancy

South African recommendations

• Contraindicated
• Testosterone esters are not indicated for treatment in women and therefore must not be used by pregnant women. If used during pregnancy testosterone poses a risk of virilisation of the foetus

Recommendations in other jurisdictions

• Contraindicated
• There are no adequate data on the use of testosterone esters in pregnant women. In view of the risk of virilisation of the foetus, testosterone should not be used during pregnancy
• Treatment with testosterone should be discontinued when pregnancy occurs

Breastfeeding

South African recommendations

• Contraindicated
• Testosterone esters are not indicated for treatment in women and therefore must not be used by breastfeeding women
• There are no adequate data for the use of testosterone esters during lactation. Therefore, testosterone should not be used during lactation

Recommendations in other jurisdictions

• Contraindicated
• There are no adequate data for the use of testosterone esters during lactation. Therefore, testosterone should not be used during lactation

Fertility

South African recommendations

• In men, treatment with testosterone can lead to fertility disorders by repressing sperm-formation

Recommendations in other jurisdictions

• In men treatment with androgens can lead to fertility disorders by repressing sperm-formation
• In women treatment with androgens can lead to an infrequent or repressed menstrual cycle

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended
  In patients suffering from renal insufficiency, treatment with testosterone may cause severe complications characterised by oedema with or without congestive cardiac failure. In such cases, treatment must be stopped immediately

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended
  In patients suffering from hepatic insufficiency, treatment with testosterone may cause severe complications characterised by oedema with or without congestive cardiac failure. In such cases, treatment must be stopped immediately

 Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no information available
  There is limited experience on the safety and efficacy of the use of testosterone esters in patients over 65 years of age
  Currently, there is no consensus about age specific testosterone reference values. It should be taken into account that physiologically testosterone serum levels are lower with increasing age

Neoplasms Benign, Malignant (including cysts and polyps)

Frequency unknown

• Prostatic cancer
  -  Progression of a sub-clinical prostatic cancer

Blood and Lymphatic System Disorders

Frequency unknown

• Polycythaemia

Metabolism and Nutrition Disorders

Common

• Increased weight

Frequency unknown

• Fluid retention

Psychiatric Disorders

Frequency unknown

• Depression
• Nervousness
• Mood disturbances
• Increased libido
• Decreased libido
• Aggression

Vascular Disorders

Frequency unknown

• Hypertension

Gastrointestinal Disorders

Frequency unknown

• Nausea

Skin and Subcutaneous Tissue Disorders

Frequency unknown

• Pruritus
• Acne

Musculoskeletal, Connective Tissue and Bone Disorders

Frequency unknown

• Myalgia

Reproductive System and Breast Disorders

Frequency unknown

• Gynaecomastia
• Oligozoospermia
• Decreased ejaculatory volume
• Ejaculation disorder
• Priapism
• Benign prostatic disorder
  - Prostatic growth (to eugonadal state) 

- Pre-pubertal boys specific reactions

• Precocious sexual development
• Increased frequency of erections
• Phallic enlargement
• Premature epiphyseal closure

-  Virilisation in women

• Hoarseness
• Acne
• Hirsutism
• Menstrual irregularity
• Alopecia

Investigations

Frequency unknown

• Abnormal hepatic function
• Abnormal lipids
  - Decrease in serum LDL-C, HDL-C and triglycerides
• Increased PSA

Common

• Increased haematocrit
• Increased red blood cell count
• Increased haemoglobin

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Abuse-related adverse reactions in the context of testosterone/ anabolic androgenic steroids

Endocrine disorders

Frequency unknown

• Secondary hypogonadism¹

Psychiatric disorders

Frequency unknown

• Hostility
• Aggression¹
• Psychotic disorder¹
• Mania
• Paranoia
• Delusion

Cardiovascular disorders

Frequency unknown

• Myocardial infarction¹
• Cardiac failure¹
• Chronic cardiac failure^¹,²
• Cardiac arrest
• Sudden cardiac death
• Cardiac hypertrophy¹,²
• Cardiomyopathy¹
• Ventricular dysrhythmia
• Ventricular tachycardia¹
• Venous/arterial thrombotic and embolic events (including deep venous thrombosis¹, pulmonary embolism¹, coronary artery thrombosis, carotid artery occlusion¹,², intracranial venous sinus thrombosis¹,²)
• Cerebrovascular accident
• Ischaemic stroke

Hepatobiliary Disorders

Frequency unknown

• Peliosis hepatis¹
• Cholestasis
• Liver injury
• Jaundice¹
• Hepatic failure

Skin and subcutaneous tissue disorders

Frequency unknown

• Alopecia¹

Reproductive system and breast disorders

Frequency unknown

• Testicular atrophy
• Azoospermia
• Infertility (in males)
• Enlarged clitoris
• Breast atrophy (in females)

¹ Has been reported with testosterone esters
² With fatal outcomes in some cases

• Enzyme-inducing agents
• Enzyme-inhibiting agents
• Insulin and other antidiabetic medicines
• Anti-coagulant therapy (coumarin-type agents)
• Adrenocorticotropic hormone (ACTH)
• Corticosteroids

Other interactions

• Laboratory tests for thyroid function (see Cautions)

• Serum testosterone
  - Confirm hypogonadism prior to treatment
  - Free testosterone
  - Total testosterone
• Liver function tests
• Lipid profile
• Blood parameters (before the start of treatment, at quarterly intervals for the first 12 months and yearly thereafter)
  - Haemoglobin
  - Haematocrit
• Cardiovascular risk factor evaluation
• Prostate assessment (before the start of treatment, at quarterly intervals for the first 12 months and yearly thereafter)
  - Prostate-specific antigen (PSA)
  - Digital rectal examination
• Blood pressure
• Bone mineral density

Specific cases may require

• Urine and serum calcium
• Serum glucose

Additional observations

• Monitor for symptoms of pain, oedema, warmth, and erythema in the lower extremity (evaluate for deep vein thrombosis) and acute shortness of breath (evaluate for pulmonary embolism)

Treatment of hypogonadal men with testosterone results in a clinically significant rise of plasma concentrations of testosterone, dihydrotestosterone, estradiol and androstenedione, as well as decrease of SHBG (Sex hormone binding globulin). Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are restored to the normal range. In hypogonadal men, treatment with testosterone esters results in an improvement of testosterone deficiency symptoms. Moreover, treatment increases bone mineral density and lean body mass, and decreases body fat mass. Treatment also improves sexual function, including libido and erectile function. Treatment decreases serum LDL-C, HDL-C and triglycerides and increases haemoglobin and haematocrit, which may lead to polycythaemia. No clinically relevant changes in liver enzymes and PSA have been reported. Testosterone also produces systemic effects, such as increasing the retention of sodium, potassium and chloride leading to an increase in water retention. Treatment may result in an increase in prostate size, and worsening of lower urinary tract symptoms, but no adverse effects on prostate symptoms have been observed. In hypogonadal diabeteic patients, improvement of insulin sensitivity and/or reduction in blood glucose have been reported with the use of androgens. In boys with constitutional delay of growth and puberty, treatment with testosterone accelerates growth and induces development of secondary sex characteristics. In female-to-male transsexuals, treatment with testosterone induces masculinisation.

COMBINATION PREPARATIONS

Testosterone Propionate/ Testosterone Phenylpropionate/ Testosterone Isocaproate/ Testosterone Decanoate

Injection (per ml) 30mg/60mg/60mg/100mg

• Sustanon (Adcock Ingram)