From the Guidelines
Secondary hypogonadism is diagnosed through a combination of clinical assessment and laboratory testing, requiring documentation of low serum testosterone levels and low or inappropriately normal gonadotropin levels (LH and FSH) 1. The diagnosis of secondary hypogonadism involves a comprehensive medical history focusing on symptoms such as decreased libido, erectile dysfunction, fatigue, decreased muscle mass, and mood changes.
- Morning total testosterone measurements should be obtained on two separate occasions, as levels fluctuate throughout the day.
- If testosterone is low, additional testing should include luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and sometimes estradiol.
- In secondary hypogonadism, LH and FSH will be low or inappropriately normal despite low testosterone, distinguishing it from primary hypogonadism where these hormones would be elevated. Further evaluation may include:
- Pituitary function tests
- Imaging (MRI) of the hypothalamic-pituitary region to identify potential causes such as pituitary tumors, hemochromatosis, or other structural abnormalities
- Semen analysis may be performed if fertility is a concern, as noted in the guidelines for the management of persons infected with human immunodeficiency virus 1. This diagnostic approach helps identify the underlying cause of secondary hypogonadism, which is essential for appropriate treatment planning, and is supported by recent evidence on the efficacy and safety of testosterone treatment in men 1.
From the Research
Diagnosis of Secondary Hypogonadism
- Secondary hypogonadism is the result of a dysfunction within the hypothalamus and/or pituitary, as stated in 2.
- Diagnosis of secondary hypogonadism requires a comprehensive health history, evaluation of the signs and symptoms, complete physical examination, as well as laboratory and diagnostic testing, according to 2 and 3.
- Measuring fasting serum total testosterone in the morning on at least 2 separate days, or free testosterone by equilibrium dialysis or calculated free testosterone, can confirm hypogonadism, as mentioned in 3.
- Further evaluation is performed to identify the specific cause of hypogonadism and whether it is potentially reversible or an irreversible pathologic disorder, as stated in 3.
Laboratory Tests
- Measurement of luteinizing and follicle stimulating hormones (LH and FSH respectively) is essential to establish whether the hypogonadism is primary or secondary, according to 4.
- In secondary hypogonadism, measurement of prolactin is always necessary, and measurement of other pituitary hormones, along with pituitary imaging, may be indicated, as mentioned in 4.
- Checking thyroid function may also be enlightening, and can raise additional therapeutic considerations, as stated in 4.
Evaluation and Treatment
- A systematic approach to diagnose hypogonadism initially establishes the presence of symptoms/signs of testosterone deficiency, considers other potential causes of manifestations, and excludes conditions that transiently suppress testosterone, according to 3.
- Enclomiphene citrate can stimulate the endogenous production of testosterone and sperm counts in men with low testosterone, as shown in 5.
- GnRH testing can be useful, and may be used in combination with hCG testing to discriminate between isolated hypogonadotropic hypogonadism and constitutional delay of growth and puberty, as mentioned in 6.