Testosterone

Registered South African indications: 

• Testosterone replacement therapy for male hypogonadism

Registered South African contraindications

• Known sensitivity to testosterone, tree nuts (almond oil) or any of the excipients
• Men with known or suspected carcinoma of the breast or prostate
• Pregnancy

South African recommendations

Caution in the following patient groups

• Breastfeeding
• Elderly
• Epilepsy
• Migraine
• Hypertension

Renal and hepatic impairment

• No studies have been conducted to ascertain the efficacy and safety of testosterone cream in patients with renal or hepatic impairment. Close monitoring is advised for patients with pre-existing conditions

Reduced risk of hepatotoxicity

• Testosterone cream, being a non-oral form of testosterone, does not carry a risk of hepatotoxicity

Pre-existing conditions

• Androgens may accelerate the progression of sub-clinical prostate cancer and benign prostatic hyperplasia
• 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

Restrictions for specific demographics

• Testosterone is not suitable for use by women or children due to potential virilization effects
• Use in patients over 65 years old should be cautious due to limited data on safety and efficacy in this age group

Diagnosis confirmation

• Testosterone therapy should only be initiated after confirming hypogonadism (both hyper- and hypogonadotropic types), ruling out other causes for the symptoms
• Diagnosis must be supported by clinical features such as regression of secondary sexual characteristics, changes in body composition, fatigue, reduced libido, and erectile dysfunction, and corroborated by two separate blood testosterone measurements

Laboratory consistency

• To minimise variability in test results, all testosterone measurements should be conducted in the same laboratory

Monitoring requirements

• Before initiating testosterone cream, a comprehensive evaluation for pre-existing prostate cancer is mandatory
• Regular monitoring, including digital rectal examinations and serum Prostate Specific Antigen (PSA) tests, should be conducted annually, and biannually for elderly or at-risk patients

Monitoring during transition

• Monitor testosterone levels when transitioning a patient from another testosterone product
• Also monitor when changing the application site of testosterone cream (from upper body to scrotal application or vice versa) to ensure consistent testosterone concentrations

Monitoring during testosterone therapy

• Elevations in serum dihydrotestosterone (DHT) are common with testosterone therapy, but they don't negatively impact prostate or cardiovascular health
• Continuous monitoring is essential for patients on long-term androgen therapy, including tests for haemoglobin, haematocrit, liver function, and lipid profile
• High haematocrit levels may require a reduction or cessation of therapy due to increased thromboembolic risk
• Adjustments in testosterone dosage may be needed based on changes in the lipid profile

Skin reactions

• Erythrocytosis and skin reactions present minimal risk with transdermal testosterone systems like testosterone cream
• Severe application site reactions may necessitate a reevaluation and possible discontinuation of treatment

Male sterility

• Testosterone therapy, is not a treatment for male sterility or impotence in men who have normal serum testosterone levels

Spermatogenesis

• High doses of exogenous androgens, like testosterone, can suppress spermatogenesis by inhibiting pituitary follicle-stimulating hormone (FSH), potentially leading to reduced sperm count and other changes in semen parameters

Clinical signs of excessive androgen exposure

• Symptoms such as irritability, nervousness, weight gain, and prolonged or frequent erections suggest excessive androgen exposure, necessitating a dosage adjustment

Severe complications in certain conditions

• Testosterone treatment can lead to severe complications such as oedema, with or without congestive heart failure, in patients with severe cardiac, hepatic, or renal insufficiency, or ischemic heart disease. Treatment must be halted immediately in such cases

Gynecomastia

• Gynecomastia may develop and persist in some patients undergoing androgen treatment for hypogonadism

Increased risk of sleep apnoea

• Testosterone therapy in hypogonadal men, particularly those with obesity or chronic respiratory conditions, has been associated with an increased risk of sleep apnoea

Cancer patients

• Testosterone should be used cautiously in cancer patients at risk of hypercalcemia and associated hypercalciuria, particularly those with bone metastases
• Regular monitoring of serum calcium concentrations is recommended for these patients

Insulin sensitivity

• Changes in insulin sensitivity may occur in patients treated with androgens who achieve normal testosterone plasma concentrations following replacement therapy

Athletes

• May give positive results in an anti-doping test (see Drugs in Sports)

Muscular development 

• Androgens are not indicated for enhancing muscular development in healthy individuals

Potential for transfer

• Transdermal testosterone cream can transfer to others through close skin contact, potentially causing increased testosterone levels and adverse effects
• In women: Potential effects include facial/body hair growth, voice deepening, and menstrual irregularities
• In children: May cause premature puberty and genital enlargement if contact is repeated
• Testosterone therapy should be discontinued immediately if virilization occurs
• Patients should be thoroughly informed about the risk of testosterone transfer and the importance of adhering to safety instructions
• Testosterone cream is not recommended for patients likely to ignore safety measures, such as those with severe alcoholism, drug abuse, or severe psychiatric disorders
• The risk of transfer can be greatly reduced by covering the application area with clothing and washing the area with soap and water before potential skin-to-skin contact (see Additional Prescribing Points for further details)
• To improve partner safety the patient should be advised to wear a T-shirt covering the upper body application site during the contact period or to shower before sexual intercourse
• To improve partner safety using scrotal application wash the genital area with a damp warm flannel before sexual intercourse
• It is recommended to wear clothing covering the upper body application site during contact periods with children to avoid transference to children
• Pregnant women must avoid any contact with testosterone cream application sites. In case of pregnancy of the partner, the patient must be particularly careful to avoid potential transfer

Paediatric use

• The safety and efficacy of testosterone cream in children and adolescents aged under 18 years of age has not been established  (see Additional Prescribing Points for further details)

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

Effects on ability to drive and use machines

• No studies on the effects on the ability to drive and use machines have been performed

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

South African registered indications and dosages

Testosterone replacement therapy for male hypogonadism
- When testosterone deficiency has been confirmed by clinical features and biochemical tests

Application to the upper body

• Topical (cre): Initial: 2ml of cream (approx. 100mg), applied to the upper body once daily at about the same time, preferably in the morning; Titrate by 1ml increments, depending on the clinical and/or laboratory response in individual patients; Max: 4ml/24hrs

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The application should be administered by the patient himself, onto clean, dry, healthy skin to the torso. The torso includes the abdomen and the sides of the body from the waist to just below the armpits. It is preferable to apply to areas with minimal hair and body fat

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In order to adjust the testosterone dose, serum testosterone concentrations must be measured in the morning before application after the 15th day of starting treatment. Results of clinical and/or biochemical monitoring may prompt dose titration

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Application to the scrotum

Topical (cre): Initial: 0.5ml of cream (approx. 25mg), applied to the entire scrotum once daily at about the same time, preferably in the morning; Titrate by 0.25ml increments, depending on the clinical and/or laboratory response in individual patients; Max: 1ml/24hrs

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The application should be administered by the patient himself, onto clean, dry, healthy skin on the scrotum. The scrotum is not required to be shaved prior to application

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 In order to adjust the testosterone dose for scrotal application it is recommended that two (2) serum testosterone concentrations be measured at 3 hours (peak) and 24 hours (trough) from prior application after the 15th day of starting treatment. Results of clinical and/or biochemical monitoring may prompt dose titration

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Administration directions
After opening the tube, the total contents must be extracted using the supplied dose measuring syringe and applied immediately onto the skin. The cream should be spread on the skin gently and massaged in until vanished. Typically, this takes 30 seconds or so
Wash hands with soap and water after applications. To clean the applicator after use, rinse in hot water

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See additional prescribing points for handling precautions

Not indicated for use in children and has not been evaluated clinically in males under 18 years of age

Pregnancy

South African recommendations

• Contraindicated
• Testosterone is contraindicated in women who are or who anticipate becoming pregnant
• Pregnant women must avoid any contact with testosterone cream application sites
• In case of pregnancy of the partner, the patient must be particularly careful to avoid potential transfer
• Exposure of a foetus to androgens may result in varying degrees of virilisation. In the event of contact, women are advised to wash with soap and water as soon as possible

Breastfeeding

South African recommendations

• Caution; not recommended
• Testosterone should not be used by breastfeeding women
• In the event of accidental contact, women are advised to immediately wash with soap and water

Fertility

South African recommendations

• Fertility studies in rodents and primates have shown that treatment with testosterone can impair fertility by suppressing spermatogenesis in a dose dependent manner

South African recommendations

• Caution; dose adjustment recommended
  No formal studies were conducted with testosterone involving patients with renal impairment. Lower doses may be required in renal impairment
  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
  Patients with pre-existing renal diseases need to be monitored closely when undergoing androgen treatment

South African recommendations

• Caution; dose adjustment recommended
  No formal studies were conducted with testosterone involving patients with renal impairment. Lower doses may be required in renal impairment
  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
  Patients with pre-existing hepatic diseases need to be monitored closely when undergoing androgen treatment

South African recommendations

• Caution; no information available
  There is limited experience of the use of testosterone in elderly patients over 65 years of age
  Currently, there is no consensus about age specific testosterone reference values. However, it should be taken into account that physiological testosterone serum levels are lower with increasing age

Blood and Lymphatic System Disorders

Frequency unknown

• Changes in laboratory tests (polycythaemia, lipids)
• Increased blood creatinine

Endocrine Disorders

Frequency unknown

• Increase in male pattern hair distribution
• Hirsutism

Metabolism and Nutrition Disorders

Frequency unknown

• Electrolyte changes (retention of sodium, potassium, chloride, calcium, inorganic phosphate, water) during high dose or prolonged treatment
• Increased appetite
• Oedema

Psychiatric Disorders

Frequency unknown

• Mood disorders
• Nervousness
• Hostility

Nervous System Disorders

Frequency unknown

• Amnesia
• Hyperaesthesia
• Smell disorder
• Taste disorder

Vascular Disorders

Frequency unknown

• Decreased blood pressure diastolic
• Flushing
• Vasodilation

Respiratory, Thoracic and Mediastinal Disorders

Frequency unknown

• Worsening of sleep apnoea
• Dyspnoea

Gastrointestinal Disorders

Frequency unknown

• Diarrhoea

Hepatobiliary Disorders

Frequency unknown

• Abnormal liver enzyme/liver function tests (including bilirubin)

Skin and Subcutaneous Tissue Disorders

Frequency unknown

• Alopecia
• Urticaria
• Discoloured hair
• Skin reactions including seborrhoea

Musculoskeletal and Connective Tissue Disorders

Frequency unknown

• Muscle cramps
• Muscle pain

Renal and Urinary Disorders

Frequency unknown

• Prostatic disorders
• Worsening symptoms of benign prostatic hyperplasia (BPH)
• Impaired urination
• Urinary tract infections
• Urinary tract obstruction

Reproductive System and Breast Disorders

Frequency unknown

• Virilisation of foetuses, infants, children, and women
• Foetal harm
• Suppression of lactation
• Gynaecomastia/mastodynia
• Sensitive nipples
• Libido changes
• Increased frequency of erections
• Suppression of spermatogenesis
• Reduction in the size of the testicles/testicular atrophy
• Priapism

General Disorders and Administration Site Conditions

Frequency unknown

• Hypersensitivity reactions
• Asthenia
• Malaise

Investigations

Frequency unknown

• Decreased high-density lipoprotein (HDL)

• Insulin
• Anti-coagulants
• Adrenocorticotropic hormone (ACTH)
• Corticosteroids
• Bupropion
• Ciclosporin
• Substances which affect liver function

Other interactions

• Herbal medicines that affect liver function
• Ancreamica dahurica
• Chapparal
• Comfrey
• Eucalyptus
• Germander tea
• Jin Bu Huan
• Kava
• Penny royal oil
• Skullcap
• Valerian
• Laboratory tests for thyroid function (see Cautions)

• Serum testosterone levels
  - Follow up measurements should be made at intervals not exceeding one year
  - Application to the upper body: To adjust dose, serum testosterone concentrations must be measured in the morning before application after the 15th day of starting treatment
  - Application to the scrotum: To adjust dose, two (2) serum testosterone concentrations be measured at 3 hours (peak) and 24 hours (trough) from prior application after the 15th day of starting treatment
• Trough testosterone levels
• Prostate gland evaluation (at least once yearly and twice yearly in elderly and at-risk patients (those with clinical or familial risk factors)
  - Digital rectal examination
  - Estimation of serum Prostate Specific Antigen (PSA)
• Breast evaluation (at least once yearly and twice yearly in elderly and at-risk patients (those with clinical or familial risk factors))
• Haemoglobin
• Haematocrit (to avoid the risk of polycythaemia)
• Liver function
• Lipid profile
• Blood pressure
• Bone mineral density

Specific cases may require

• Serum calcium
• Serum glucose

Additional observations

• Patients with pre-existing cardiac, hepatic or renal diseases need to be monitored closely when undergoing androgen treatment
• 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)
• Signs of virilization in females treated for breast cancer

Special Handling Precautions

For the patient

• Wash hands thoroughly with soap and water after applying the cream
• Cover the application area with clothing once the cream has dried
• Wash before any situation in which skin-to-skin contact is foreseen
• Clothing or items in contact with the area of application should be washed separately

Paediatrics

• The patient should be advised to wash their hands well with soap and water after testosterone has been applied, especially in case of contact with children
• Cases of contact with children may cause premature puberty and genital enlargement, in case of repeat contact (inadvertent androgenisation)
• Keep all clothes/implements of the person treated out of sight and reach of children

For people not being treated with testosterone cream

• In the event of contact with an application area which has not been washed or is not covered with clothing, wash the area of skin onto which testosterone may have been transferred as soon as possible, using soap and water
• Report the development of signs of excessive androgen exposure such as acne or hair modification

Testosterone is an androgen replacement therapy containing the male hormone testosterone. Endogenous androgens, principally testosterone, secreted by the testes and its major metabolite dihydrotestosterone (DHT), are responsible for the development of the external and internal genital organs and for maintaining the secondary sexual characteristics (stimulating hair growth, deepening of the voice, development of the libido); for a general effect on protein anabolism; for development of skeletal muscle and body fat distribution; for a reduction in urinary nitrogen, sodium, potassium, chloride, phosphate and water excretion. Testosterone does not produce testicular development: it reduces the pituitary secretion of gonadotropins. The effects of testosterone in some target organs arise after peripheral conversion of testosterone to oestradiol, which binds to oestrogen receptors in the target cell nucleus e.g. the pituitary, fat, brain, bone and testicular Leydig cells.

Cream (per ml) 50mg

• TestaFotre (Pharmacorp)