What is the best course of treatment for a patient with normal total testosterone levels and decreased libido?

Evaluation and Management of Decreased Libido with Normal Total Testosterone

Measure free testosterone and sex hormone-binding globulin (SHBG) levels, as normal total testosterone does not rule out hypogonadism—particularly in obesity where low SHBG can mask truly low free testosterone. 1

Initial Diagnostic Workup

Your total testosterone of 569 ng/dL falls within the normal range (300-800 ng/dL), but this does not exclude hypogonadism as the cause of your decreased libido. 1

Essential next steps:

• Obtain morning (8-10 AM) free testosterone by equilibrium dialysis on at least two separate occasions to confirm any abnormality, as assay variability is significant 1, 2
• Measure SHBG levels, especially if obesity is present, since low SHBG can result in normal total testosterone despite frankly low free testosterone 1
• Check serum prolactin if free testosterone is low or low-normal with concurrent low/normal LH levels to rule out hyperprolactinemia 2
• Measure LH and FSH if free testosterone is confirmed low on repeat testing to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism 1, 2

Understanding the Mechanism in Obesity

If you have obesity, decreased testosterone is frequently due to low SHBG concentrations, which can result in normal total testosterone but normal free testosterone levels. 1 However, a subset of men with obesity will have frankly low free testosterone due to increased aromatization of testosterone to estradiol in adipose tissue, causing estradiol-mediated negative feedback that suppresses pituitary LH secretion. 1

When to Consider Testosterone Replacement

Testosterone replacement should only be considered when:

• Morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments 1
• The hypogonadism workup is completed to rule out etiologies unrelated to obesity 1
• Total morning testosterone is less than 300 ng/dL 1

Important caveat: A history of decreased libido alone cannot predict hypogonadism—objective laboratory confirmation is essential. 3 Additionally, low libido can occur even with high-normal testosterone levels in rare cases of pituitary pathology. 4

Primary vs. Secondary Reduced Libido

Primary reduced libido (not associated with hypogonadism, hyperprolactinemia, or psychopathology) is characterized by disturbances in domestic and dyadic relationships, and these patients typically have healthier metabolic profiles. 5

Secondary reduced libido is associated with underlying conditions:

• Hypogonadism substantially increases reduced libido prevalence 5
• Psychopathology nearly doubles the prevalence 5
• Hyperprolactinemia causes universal presence of reduced libido 5

Treatment Algorithm Based on Free Testosterone Results

If Free Testosterone is Low (<300 ng/dL total):

For men desiring fertility:

• First-line: Gonadotropin therapy with hCG initially, followed by FSH addition after testosterone normalization 2
• Alternative: Selective estrogen receptor modulators (SERMs) to stimulate GnRH secretion and increase pituitary gonadotropin release 2
• Alternative: Aromatase inhibitors to decrease estrogen production and inhibit negative feedback 2
• Avoid exogenous testosterone as it provides negative feedback to the hypothalamus and pituitary, inhibiting gonadotropin secretion and impairing fertility 2

For men not concerned with fertility:

• Testosterone replacement therapy improves libido, erectile function response to PDE5 inhibitors, and metabolic parameters including weight loss, fasting glucose, insulin resistance, triglycerides, HDL cholesterol, and lean body mass 1, 6
• Transdermal preparations (gel, patch) provide stable day-to-day testosterone levels 1
• Intramuscular injections avoid daily administration but cause fluctuating levels 1

If Free Testosterone is Normal:

Evaluate for non-hormonal causes:

• Relationship and psychosocial factors: Assess domestic and dyadic relationship disturbances, as these are strongly associated with primary reduced libido 5
• Medications: SSRIs cause decreased libido in 6% of patients (sertraline specifically) and ejaculatory dysfunction in 14% of male patients 7
• Psychiatric conditions: Depression and anxiety commonly cause decreased libido; consider anxiolytics, antidepressants, or integrative therapies 1
• Refer to sexual health specialist for comprehensive evaluation of low desire, libido, or intimacy issues 1

Additional Considerations

Lifestyle modifications should be implemented regardless of testosterone status, as weight loss and exercise can improve testosterone levels in obesity-associated secondary hypogonadism. 2

Cardiovascular risk assessment is warranted, as erectile dysfunction and sexual dysfunction identify increased cardiovascular disease risk even in the absence of CVD symptoms or history. 1 Men with primary reduced libido actually have lower cardiovascular risk profiles compared to those with secondary reduced libido. 5

Common pitfall: Do not assume normal total testosterone excludes hypogonadism—free testosterone measurement is essential, particularly in obesity. 1, 3 Approximately 50% of patients with low total testosterone will have normal free testosterone, avoiding unnecessary further endocrine evaluation. 3