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

From the Guidelines

For a male patient with low testosterone, low Sex Hormone-Binding Globulin (SHBG), and low calculated free testosterone levels, testosterone replacement therapy (TRT) is the primary treatment approach, as it may provide small improvements in sexual functioning and quality of life, although long-term efficacy and safety are unknown 1. The recommended options include injectable testosterone cypionate or enanthate (typically 100-200mg every 1-2 weeks), daily transdermal testosterone gel (50-100mg applied to shoulders, upper arms, or abdomen), or testosterone pellets implanted subcutaneously every 3-6 months. Before initiating treatment, baseline prostate-specific antigen (PSA), hematocrit, and comprehensive metabolic panel should be obtained. Patients should be monitored with follow-up testosterone levels, hematocrit, and PSA at 3-6 month intervals initially, then annually. Lifestyle modifications are also important, including weight loss for overweight patients, regular exercise, adequate sleep, and stress management. The low SHBG is significant because it affects how testosterone is transported in the bloodstream, with lower SHBG potentially indicating metabolic issues like insulin resistance or liver dysfunction that may need additional evaluation, as suggested by the relationship between obesity-related decreases in testosterone and low concentrations of sex hormone-binding globulin 1. Treatment aims to improve symptoms like fatigue, low libido, and mood disturbances while restoring testosterone levels to the mid-normal range for the patient's age group. Key considerations in the management of hypogonadism include the measurement of morning serum free testosterone, as well as a sex hormone-binding globulin level in patients with obesity, to distinguish primary from secondary hypogonadism 1. Given the potential benefits and risks of testosterone therapy, the decision to initiate treatment should be individualized, taking into account the patient's specific symptoms, medical history, and preferences, as emphasized by the American College of Physicians 1.

From the Research

Diagnosis and Treatment of Low Testosterone

• The patient's low testosterone, low Sex Hormone-Binding Globulin (SHBG), and low calculated free testosterone levels may indicate hypogonadism, but the diagnosis should be made with caution, considering the patient's overall health and medical history 2, 3.
• According to a study published in the Journal of Clinical Endocrinology and Metabolism, pathologic hypogonadism occurs when serum testosterone is significantly and persistently reduced by irreversible organic disorders of the hypothalamic pituitary testicular (HPT) axis, and men with pathologic hypogonadism require life-long testosterone replacement 4.
• However, mild or moderate reductions in serum testosterone frequently accompany obesity and its numerous co-morbidities in men, and are best considered as non-gonadal illness syndromes, wherein reduction in serum testosterone is usually reversible upon amelioration of the underlying non-gonadal illness 4.

Treatment Options

• Testosterone replacement therapy (TRT) is the most common treatment utilized for male hypogonadism, but it may not be suitable for patients wishing to conceive, as it can lead to infertility 5.
• Alternative treatment options for patients who wish to remain fertile include nasal TRT, clomiphene citrate, exogenous gonadotropins, gonadotropin releasing hormone, and aromatase inhibitors, with different degrees of success 5.
• A study published in the International Journal of Impotence Research found that clomiphene citrate and exogenous gonadotropins are safe, offer good symptom control, and can successfully induce fertility in hypogonadism patients 5.

Considerations for Treatment

• Before initiating treatment, it is essential to exclude any form of classical hypogonadism and to assess the patient's overall health, including prostate-specific antigen (PSA), hemoglobin, and hematocrit levels 3, 6.
• Absolute contraindications to testosterone replacement therapy include prostate or breast cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone formulation 6.
• The patient's symptoms, such as lethargy, fatigue, decreased sense of well-being, reduced physical and mental activity, diminished libido, and erectile dysfunction, should be carefully evaluated and considered when determining the best course of treatment 3.