Is testosterone replacement therapy recommended for a patient with functional hypogonadotropic (low sex hormone) hypogonadism due to obesity and prior alcohol use?

From the Guidelines

Testosterone replacement therapy is recommended for this patient with functional hypogonadotropic hypogonadism due to obesity and prior alcohol use, given his low free testosterone level and significant symptoms. The patient's low free testosterone level of 123, despite a total testosterone level of 6.9, indicates a need for testosterone replacement therapy, as suggested by the study 1. This study emphasizes the importance of measuring morning serum free testosterone in men with obesity, as low total testosterone due to low sex hormone-binding globulin may not necessarily indicate hypogonadism. However, in this case, the patient's low free testosterone level, combined with his symptoms of low libido, fatigue, reduced muscle strength, and increased body fat, suggests that testosterone replacement therapy may be beneficial.

Key considerations for testosterone replacement therapy in this patient include:

• The method of testosterone replacement, with transdermal preparations (gel or patch) being favored due to their ability to provide stable testosterone levels and avoid the discomfort of intramuscular injections 1.
• Monitoring of testosterone levels after treatment initiation, with testing 2-3 months after starting therapy and/or after any dose change, to ensure normal serum testosterone concentrations are being achieved 1.
• Potential safety concerns, including an increased risk of heart attack and stroke, as well as cardiovascular events, hospitalizations, and deaths associated with testosterone injections 1.

Given the potential benefits of testosterone replacement therapy in improving symptoms and metabolic parameters, testosterone replacement therapy should be considered for this patient, with careful monitoring and individualized treatment. The study 1 supports the use of testosterone replacement therapy in men with obesity and hypogonadism, demonstrating favorable results in terms of weight loss, improvements in fasting plasma glucose, insulin resistance, and lean body mass.

From the FDA Drug Label

Testosterone cypionate injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired)-idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.

The patient has functional hypogonadotropic hypogonadism due to obesity and prior alcohol use. The FDA drug label for testosterone cypionate injection indicates it is used for replacement therapy in conditions associated with symptoms of deficiency or absence of endogenous testosterone, including hypogonadotropic hypogonadism. However, the label specifies that this condition should be congenital or acquired due to idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. Since the patient's hypogonadotropic hypogonadism is due to obesity and prior alcohol use, which is not explicitly mentioned in the label as an indication for treatment, testosterone replacement therapy may not be recommended based solely on the information provided in the drug label 2.

From the Research

Testosterone Replacement Therapy for Functional Hypogonadotropic Hypogonadism

• The patient's symptoms, such as low libido, fatigue, reduced muscle strength, and increased body fat, are consistent with hypogonadism 3.
• The diagnosis of functional hypogonadotropic hypogonadism due to obesity and prior alcohol use has been confirmed by endocrinology.
• Testosterone replacement therapy (TRT) may be beneficial for patients with hypogonadism, as it can improve sexual function, increase lean body mass, and decrease body fat 3, 4.
• However, TRT also carries potential risks, such as stimulating the growth of an occult prostate cancer, and the benefits and risks must be carefully considered 3, 4.

Considerations for Testosterone Replacement Therapy

• The patient's total testosterone level is 6.9, which is low, and the free testosterone level is 123, which is also low 3.
• The patient's FSH and LH levels are 1.9 and 1.4, respectively, which are consistent with hypogonadotropic hypogonadism 3.
• The patient's prolactin level is 16.8, which is slightly elevated, but this may not be a contraindication for TRT 3.
• The patient's prior alcohol use and obesity may be contributing factors to their hypogonadism, and lifestyle modifications may be beneficial in addition to TRT 3, 5.

Treatment Options

• Several treatment options are available for TRT, including weekly-to-biweekly injections of testosterone cypionate or testosterone enanthate, once-daily transdermal therapies, and intramuscular injection of testosterone undecanoate 3, 6, 7.
• The choice of treatment should be based on patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden, and cost 4.
• Regular monitoring of serum testosterone levels, hematocrit, and prostate-specific antigen is recommended to ensure safe and effective treatment 3, 4.