ANDROGEL​ ​GEL

Indications

• Hypogonadism
• Low sexual desire in postmenopausal women (administered on expert advice)
• Certain aplastic anemias
• Androgen deficiency in males

Dosage

Adults: Refer to the BNF for specific dosing recommendations

Mechanism of action

Testosterone exerts its effects by binding to the androgen receptor, which is located in the cytoplasm bound to heat shock proteins. Upon binding, the receptor dissociates from these chaperones and undergoes a conformational change. The androgen-receptor complex is then transported into the nucleus, where it binds to DNA and recruits other transcriptional regulators to induce the expression of specific genes. This process promotes the development of male reproductive organs and secondary sexual characteristics such as increased muscle mass and body hair.

Pharmacodynamics

Testosterone antagonizes the androgen receptor to induce gene expression that leads to the growth and development of masculine sex organs and secondary sexual characteristics. The duration of action of testosterone varies among individuals, with a half-life ranging from 10 to 100 minutes. The therapeutic index is considered wide, as normal testosterone levels in adult men typically range from 300 to 1000 ng/dL. Caution is advised regarding the risk of secondary exposure to topical testosterone products, especially in children.

Pharmacokinetics

Testosterone is absorbed following administration and metabolized primarily by the liver. It has a variable half-life, and its plasma levels are influenced by factors such as the method of administration and individual patient characteristics. Testosterone undergoes conversion into dihydrotestosterone (DHT) and estradiol, which contribute to its physiological effects. Excretion occurs primarily through urine, with metabolites being eliminated from the body. Regular monitoring of testosterone levels and related parameters is recommended during therapy.

Contra-indications

• Pregnancy
• Breastfeeding
• Metastatic prostate cancer
• Known hypersensitivity to testosterone or any of its excipients
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Acne
• Gynaecomastia
• Polycythaemia
• Mood changes
• Sleep apnoea
• Fluid retention
• Increased risk of thromboembolic events
• Increased prostate-specific antigen (PSA) levels

Interactions

• Somatrogon: Unknown (decreases concentration)
• Anticoagulants: Potential for enhanced anticoagulant effect
• Corticosteroids: Increased risk of fluid retention
• Insulin: May affect insulin sensitivity

Precautions

• Monitor haematocrit and haemoglobin before treatment
• Regular monitoring of prostate and PSA levels in men over 45 years
• Consider potential androgen toxicity in elderly patients
• Careful risk/benefit assessment in patients with cardiovascular conditions
• Caution in patients with a history of liver disease

Pregnancy

Avoid as it can cause masculinisation of the female fetus.

Breast-feeding

Avoid as testosterone may be excreted in breast milk.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Injectable solution
• Transdermal patch
• Topical gel
• Oral capsule

Indications

• Androgen deficiency in males
• Delayed puberty in males
• Breast cancer in women (long-term palliative therapy)
• Prevention of tumor flare with gonadorelin analogue therapy

Dosage

Children: Child (male): 1.25–2.5 mg daily for 3–6 months for stimulation of late pre-pubertal growth. Child (female): 0.625–2.5 mg daily in combination with growth hormone for similar indications.

Adults: Initially 250 mg every 2–3 weeks; maintenance 250 mg every 3–6 weeks. For androgen deficiency, 200–300 mg daily in 2–3 divided doses may be used.

Mechanism of action

Testosterone propionate binds to androgen receptors in various tissues, leading to the activation of gene expression involved in anabolic processes such as protein synthesis, muscle growth, and erythropoiesis. The drug enhances nitrogen retention and increases muscle mass and strength, while also having effects on libido and mood.

Pharmacodynamics

As an androgen, testosterone propionate promotes the development of male secondary sexual characteristics and has anabolic effects on muscle and bone. It influences metabolic processes, enhancing lipid metabolism and may affect mood and cognitive functions. Its action can lead to increased red blood cell production due to its stimulatory effect on erythropoietin.

Pharmacokinetics

Testosterone propionate is absorbed rapidly after intramuscular injection, with peak serum testosterone levels typically occurring within 24 to 36 hours. The drug has a relatively short half-life, leading to the necessity for frequent dosing (typically every 2 to 3 days). It is metabolized in the liver to inactive metabolites and excreted primarily through urine.

Contra-indications

• Pregnancy
• Prostate cancer
• Known hypersensitivity to testosterone or excipients
• Severe renal or hepatic impairment
• Hypercalcaemia

Adverse effects

• Mood alterations
• Increased appetite
• Gastrointestinal discomfort
• Diarrhea
• Musculoskeletal complaints
• Dysphonia
• Increased risk of infection
• Migraine
• Fluid imbalance
• Azoospermia
• Hair growth changes
• Cardiovascular disorders
• Hypercholesterolemia
• Gynecomastia
• Sleep apnea
• Anxiety
• Pulmonary oil microembolism

Interactions

• Anticoagulants (increased anticoagulant effect)
• Corticosteroids (increased risk of edema)
• Insulin and oral hypoglycemic agents (may alter glucose metabolism)
• Cyproterone acetate (antagonistic effect on testosterone)

Precautions

• Monitor liver function regularly
• Caution in patients with cardiovascular disease
• Assess for sleep apnea in predisposed individuals
• Monitor for signs of polycythemia
• Evaluate bone density due to potential effects on bone metabolism

Pregnancy

Testosterone propionate is contraindicated in pregnancy due to the risk of masculinization of the female fetus.

Breast-feeding

Testosterone is not recommended during breastfeeding as it may affect milk production and the infant.

Storage

Store in a cool, dry place, protected from light. Do not refrigerate or freeze.

Formulations

• Testosterone propionate solution for injection (50 mg/ml)
• Testosterone undecanoate solution for injection (250 mg/1 ml)

Mechanism of action

The androgen receptor exists in the cytoplasm bound to the heat shock proteins HSP90, HSP70, and other chaperones. After binding to an androgen, the androgen receptor dissociates from HSP90 and undergoes a conformational change to slow the rate of dissociation from the androgen receptor. The androgen-receptor complex is transported into the nucleus where it binds to DNA and recruits other transcriptional regulators to form a pre-initiation complex and eventually induce expression of specific genes. Testosterone and its active metabolite dihydrotestosterone (DHT) act as an agonist of the androgen receptor to activate the receptor and upregulate the expression of androgen receptors, promoting the development of masculine sex organs including the prostate, seminal vesicles, penis, and scrotum. Agonism of the androgen receptor is also responsible for the development of secondary sexual characteristics including facial and body hair, enlargement of the larynx, thickening of the vocal cords, and changes in muscle and fat distribution. Low-grade chronic inflammation is commonly found in patients with polycystic ovary syndrome (PCOS) who exhibit hyperandrogenism or hyperandrogenemia. Clinical studies have shown that hyperandrogenemia is closely correlated with low-grade chronic inflammation. However, the mechanism underlying this correlation remains unclear. Recent studies have suggested that adipocytes increase the production of proinflammatory mediators such as interleukin-6 (IL-6) and macrophage chemotactic protein-1 (MCP-1) when the inflammatory signal transduction cascade system is activated by external stimuli. The present study aimed to evaluate the effects of testosterone on the innate signalling and expression of proinflammatory mediators in 3T3-L1 adipocytes, which were or were not induced by lipopolysaccharide (LPS). The effects of testosterone on the expression of proinflammatory mediators, nuclear factor-kappaB (NF-kappaB), and extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathways were investigated using an enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, western blot analysis and an electrophoresis mobility shift assay. Testosterone induces IL-6 and MCP-1, and enhances LPS-induction of IL-6 and MCP-1. However, the effects are not simply additive, testosterone significantly enhanced the effects of LPS-induced inflammation factors. Testosterone induces the phosphorylation of ERK1/2 and NF-kappaB. The effect of testosterone on the expression of IL-6 and MCP-1 is inhibited by PD98059, an ERK1/2 inhibitor, and PDTC, an NF-kappaB inhibitor. The results indicate that testosterone enhances LPS-induced IL-6 and MCP-1 expression by activating the ERK1/2/NF-kappaB signalling pathways in 3T3-L1 adipocytes. Androgens reportedly stimulate the production of erythrocytes, apparently by enhancing the production of erythropoietic stimulating factor.

Pharmacodynamics

Testosterone antagonizes the androgen receptor to induce gene expression that causes the growth and development of masculine sex organs and secondary sexual characteristics. The duration of action of testosterone is variable from patient to patient with a half life of 10-100 minutes. The therapeutic index is wide considering the normal testosterone levels in an adult man range from 300-1000ng/dL. Counsel patients regarding the risk of secondary exposure of testosterone topical products to children.