How is low testosterone diagnosed and treated?

From the Guidelines

Low testosterone is diagnosed through a combination of blood tests, physical examination, and symptom assessment, with treatment primarily involving testosterone replacement therapy (TRT) to improve symptoms such as sexual dysfunction, fatigue, and decreased muscle mass. According to the most recent and highest quality study 1, doctors typically order morning blood tests to measure total testosterone levels, as levels naturally fluctuate throughout the day. A diagnosis usually requires at least two separate blood tests showing low testosterone levels, along with symptoms such as fatigue, reduced sex drive, erectile dysfunction, decreased muscle mass, or mood changes.

Key Points for Diagnosis and Treatment

• Morning total testosterone level should be measured using an accurate and reliable assay 1
• In men who have total testosterone levels close to the lower limit, it is reasonable to determine free testosterone concentrations either directly from equilibrium dialysis assays or by calculations that use total testosterone, sex hormone binding globulin, and albumin concentrations 1
• Additional tests may include luteinizing hormone, follicle-stimulating hormone, and prolactin to determine the cause of low testosterone
• Treatment primarily involves testosterone replacement therapy (TRT), available in several forms: injections, transdermal gels, patches, or pellets implanted under the skin
• Lifestyle modifications including weight loss, regular exercise, adequate sleep, and stress reduction can also help improve testosterone levels naturally

Considerations for Treatment

• Testosterone replacement in men with symptomatic hypogonadism may have benefits including improved sexual function, well-being, muscle mass and strength, and bone density 1
• Treatment is typically lifelong and requires regular monitoring of testosterone levels, complete blood count, and prostate-specific antigen
• TRT works by directly supplementing the body's testosterone, which helps restore normal hormone levels and alleviate symptoms, though it may reduce natural testosterone production and fertility 1

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Prior to initiating testosterone enanthate injection, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range

• Diagnosis of low testosterone is confirmed by measuring serum testosterone concentrations in the morning on at least two separate days, and the levels are below the normal range.
• Treatment of low testosterone involves replacement therapy with testosterone enanthate injection, with a suggested dosage of 50 to 400 mg every 2 to 4 weeks for male hypogonadism.
• The dosage and duration of therapy will depend on age, sex, diagnosis, patient’s response to treatment, and appearance of adverse effects 2.
• Total doses above 400 mg per month are not required due to the prolonged action of the preparation 2.
• Injections more frequently than every two weeks are rarely indicated 2.

From the Research

Diagnosis of Low Testosterone

• Low testosterone levels are diagnosed based on a serum total testosterone level of less than 300 to 350 ng/dL on two separate morning blood samples 3.
• Accurate measurement of total testosterone levels requires an accurate method, such as liquid chromatography-tandem mass spectrometry, in a laboratory certified by an accuracy-based program 4, 5.
• Free testosterone level should ideally be measured by equilibrium dialysis method, especially in men with suspected alterations in binding protein concentrations or total testosterone levels near the normal range 4, 5.
• Testosterone levels should be measured in 2 or more fasting samples obtained in the morning 4, 5.

Treatment of Low Testosterone

• Testosterone replacement therapy (TRT) is available for patients with hypogonadism, defined as a low testosterone level and signs or symptoms of hypogonadism 3.
• Numerous testosterone formulations are available, including topical gels, intramuscular injections, oral tablets, and transdermal patches 3, 6, 7.
• The choice of formulation depends on factors such as cost, patient preference, and individual needs 3, 7.
• Nonhormonal pharmacotherapies are also available for patients who wish to avoid exogenous hormones or are not candidates for TRT 3.
• Patients receiving TRT require close monitoring due to potential contraindications, adverse effects, and limited long-term safety data 3.

Clinical Manifestations of Androgen Deficiency

• Androgen deficiency can cause a range of symptoms, including reduced body hair, decreased muscle mass and strength, increased fat mass, decreased hematocrit, decreased libido, erectile dysfunction, infertility, osteoporosis, and depressed mood 6.
• The prevalence of androgen deficiency syndrome in men varies depending on age, comorbidities, and study group, and may be underestimated due to underdiagnosis or undertreatment 7.