Is a patient with normal Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels but low testosterone considered to have primary hypogonadism?

Normal LH and FSH with Low Testosterone is NOT Primary Hypogonadism

A patient with normal LH and FSH levels but low testosterone does not have primary hypogonadism, but rather has secondary hypogonadism or adult-onset hypogonadism. 1

Types of Hypogonadism

• Primary hypogonadism (hypergonadotropic): Caused by testicular dysfunction with low testosterone levels and elevated LH and FSH levels above normal as a compensatory response 1
• Secondary hypogonadism (hypogonadotropic): Results from impairment of the hypothalamic-pituitary-gonadal axis with low testosterone and normal or low LH and FSH levels 1, 2
• Adult-onset hypogonadism: Characterized by testosterone deficiency with normal or low gonadotropins, suggesting physiologic failure of both the testicles and hypothalamic-pituitary system 1

Diagnostic Classification Based on Laboratory Values

• Normal LH/FSH with low testosterone indicates secondary hypogonadism or adult-onset hypogonadism 1
• In primary hypogonadism, testosterone levels are low while LH and FSH are elevated above normal 1, 3
• The pattern of normal gonadotropins with low testosterone is inconsistent with primary testicular failure 2, 4

Common Causes of Secondary Hypogonadism

• Obesity: Increased aromatization of testosterone to estradiol in adipose tissue, with subsequent estradiol-mediated negative feedback suppressing pituitary LH secretion 1
• Medications: Opiates, GnRH agonists/antagonists, glucocorticoids, estrogens, progestogens 1
• Pituitary disorders: Tumors, inflammatory conditions, traumatic brain injury 1
• Systemic conditions: Type 2 diabetes, metabolic syndrome, chronic illness 1
• Functional causes: Nutritional deficiencies, excessive exercise, stress 1, 2

Evaluation Approach

• Confirm low testosterone with repeat morning measurements (between 8-10 AM) 1
• Measure free testosterone by equilibrium dialysis, especially in obese patients 1
• Check sex hormone-binding globulin levels, as low levels can affect total testosterone measurements 1
• Consider further evaluation for secondary hypogonadism including:
  • Prolactin levels to rule out hyperprolactinemia 1
  • Iron saturation studies 1
  • Pituitary function testing 1
  • MRI of the sella turcica if clinically indicated 1

Clinical Implications

• Secondary hypogonadism patients can potentially achieve both fertility and normal testosterone levels with appropriate treatment 1
• Primary hypogonadism patients can only receive testosterone therapy, which compromises fertility by suppressing the HPG axis 1
• In men interested in fertility, testosterone monotherapy should not be prescribed as it can suppress spermatogenesis 1
• Treatment options for secondary hypogonadism may include:
  • Lifestyle modifications for obesity-related hypogonadism 1
  • Gonadotropin therapy (hCG, FSH) for those desiring fertility 1
  • Addressing underlying conditions (e.g., treating hyperprolactinemia) 1

Key Takeaway

The combination of normal LH/FSH with low testosterone definitively rules out primary hypogonadism and points to secondary hypogonadism or adult-onset hypogonadism, requiring evaluation of the hypothalamic-pituitary axis and potential underlying causes.