What to do for a patient with low total testosterone, low Sex Hormone-Binding Globulin (SHBG), and low calculated free testosterone?

From the Guidelines

For a patient with low total testosterone, low Sex Hormone-Binding Globulin (SHBG), and low calculated free testosterone, testosterone replacement therapy (TRT) is recommended after confirming the diagnosis with repeat morning testing and ruling out reversible causes. The diagnosis of testosterone deficiency requires both a low testosterone measurement as well as the presence of select symptoms and/or signs, as suggested by the American Urological Association guideline 1.

Key Considerations

• The patient's total testosterone level is below the recommended threshold of 300 ng/dL, which is a reasonable cut-off in support of the diagnosis of low testosterone 1.
• Low SHBG indicates that a higher proportion of testosterone is in the free, biologically active form, so dosing may need adjustment.
• Treatment options include injectable testosterone cypionate or enanthate (50-100mg weekly or 100-200mg every 2 weeks), daily transdermal gels (AndroGel, Testim, or Axiron at 50-100mg/day), or testosterone pellets implanted subcutaneously every 3-6 months.
• Before initiating therapy, baseline prostate-specific antigen (PSA), hematocrit, and lipid panel should be obtained, as recommended by the American College of Physicians guideline 1.

Monitoring and Lifestyle Modifications

• Patients should be monitored for clinical improvement in symptoms, testosterone levels (aiming for mid-normal range), hematocrit (discontinue if >54%), PSA, and potential side effects including acne, fluid retention, and gynecomastia.
• Lifestyle modifications including weight loss, improved sleep, and resistance training should complement medical therapy, as these can help improve overall health and reduce the risk of adverse outcomes.
• The American College of Physicians suggests that clinicians discuss the potential benefits, harms, costs, and patient's preferences when considering testosterone treatment, and that clinicians should reevaluate symptoms within 12 months and periodically thereafter 1.

Conclusion Not Provided

As per the guidelines, the focus is on providing a direct and evidence-based answer without a conclusion section. The most recent and highest quality study, which is from 2020, provides the basis for the recommendation to use testosterone replacement therapy in adult men with age-related low testosterone 1.

From the Research

Patient Profile

• The patient has low total testosterone (203 ng/dL) which is below the reference interval of 264-916 ng/dL 2
• The patient also has low Sex Hormone-Binding Globulin (SHBG) levels (14.2 nmol/L) which is below the reference interval of 19.3-76.4 nmol/L
• The calculated free testosterone is low (56.7 pg/mL) which is below the reference interval of 34.7-150.3 pg/mL

Diagnosis and Treatment

• According to the study by Travison et al. (2017), the adult male reference interval for testosterone is based on a population of healthy nonobese males (BMI <30) between 19 and 39 years old 2
• The study by 3 suggests that although total testosterone may be sufficient, free testosterone can decrease to very low levels due to disturbances in the distribution of androgens between plasma proteins
• The Endocrine Society clinical practice guideline recommends making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels 4
• The guideline also recommends confirmation of the diagnosis by repeating the measurement of morning total testosterone and, in some men, measuring free or bioavailable testosterone level using validated assays 4
• Testosterone therapy is recommended for men with symptomatic androgen deficiency to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density 4

Considerations for Treatment

• The study by 5 suggests that late-onset hypogonadism (LOH) is a syndrome that carries many names, including male menopause or climacterium, andropause, and partial androgen deficiency of the ageing male (PADAM)
• The decrease of testosterone in LOH is often marginal, and hypogonadism can be either due to primary testicular failure or secondary to a hypothalamic-pituitary failure 5
• The European Male Ageing Study (EMAS) has defined strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum testosterone and three sexual symptoms (erectile dysfunction, and reduced frequency of sexual thoughts and morning erections) 5
• The study by 6 suggests that sex hormone-binding globulin (SHBG) levels often decline into the normal range after androgen administration, and free testosterone increases significantly in patients with hypogonadism.