From the Guidelines
To diagnose primary versus secondary hypogonadism, measure both total testosterone and follicle-stimulating hormone (FSH)/luteinizing hormone (LH) levels, as this approach allows for the distinction between testicular failure and inadequate pituitary stimulation 1. When evaluating patients with symptoms or signs of hypogonadism, such as decreased sexual desire or activity, or erectile dysfunction, a morning serum testosterone level should be considered for screening purposes 1. Key points to consider in the diagnostic process include:
- Measuring total testosterone levels in the morning when they are highest
- Using an accurate and reliable assay for testosterone measurement
- Considering the measurement of free or bioavailable testosterone levels, especially in cases where total testosterone levels are close to the lower limit
- Further testing, such as LH and FSH levels, to distinguish between primary and secondary hypogonadism Primary hypogonadism is characterized by low testosterone with elevated FSH/LH, indicating testicular failure, whereas secondary hypogonadism shows low testosterone with low or inappropriately normal FSH/LH, suggesting inadequate pituitary stimulation of otherwise normal testes. The distinction between primary and secondary hypogonadism is crucial for treatment planning, as the approach differs significantly between the two conditions, with primary hypogonadism generally requiring testosterone replacement therapy and secondary hypogonadism potentially being reversible by addressing the underlying cause or responding to medications that stimulate the hypothalamic-pituitary axis 1.
From the FDA Drug Label
Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).
The diagnostic criteria for distinguishing between primary and secondary hypogonadism include:
- Primary hypogonadism: defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia
- Secondary hypogonadism: failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH) 2
From the Research
Diagnostic Criteria for Primary and Secondary Hypogonadism
The diagnostic criteria for distinguishing between primary and secondary hypogonadism involve a combination of clinical evaluation, laboratory tests, and physical examination. The key factors to consider are:
- Measurement of serum testosterone levels to confirm low testosterone
- Measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels to distinguish between primary and secondary hypogonadism 3, 4, 5
- Primary hypogonadism is characterized by low testosterone and high LH and FSH levels, indicating gonadal failure
- Secondary hypogonadism is characterized by low testosterone and low or inappropriately normal LH and FSH levels, indicating hypothalamic or pituitary dysfunction
Laboratory Tests and Evaluation
The following laboratory tests and evaluations are useful in diagnosing and distinguishing between primary and secondary hypogonadism:
- Measurement of serum testosterone levels, preferably in the morning, on two different occasions 4, 5
- Measurement of LH and FSH levels to determine the type of hypogonadism
- Measurement of prolactin levels in cases of suspected secondary hypogonadism 3
- Evaluation of thyroid function, as hypogonadism can be associated with thyroid dysfunction 3
- GnRH testing and hCG testing may be useful in certain cases, such as discriminating between isolated hypogonadotropic hypogonadism and constitutional delay of growth and puberty 6
Clinical Evaluation and Diagnosis
A comprehensive health history, evaluation of signs and symptoms, and complete physical examination are essential in diagnosing hypogonadism 7. The diagnosis of hypogonadism requires a combination of clinical and laboratory evaluation, and the type of hypogonadism (primary or secondary) can be determined based on the results of LH and FSH measurements 3, 4, 5.