Investigations
1st investigations to order
serum total testosterone
Test
First-line investigation in the evaluation of suspected hypogonadism.
Testosterone should be measured in all men with otherwise unexplained erectile dysfunction, anaemia, osteoporosis, gynaecomastia, vasomotor flushing/sweating, myopathy, or absence/loss of secondary sexual characteristics.[1][2]
Check fasting levels between 6 a.m. and 8 a.m. ideally; sample taken up to 11 a.m. is acceptable.
Total testosterone should be measured on at least two occasions, 1 week apart.[1]
Many experts and guidelines suggest a total testosterone level <10.4 nmol/L (<300 ng/dL) as the threshold level for hypogonadism (using a US standardised assay).[1] Below this level there is evidence of bone loss and increased fat accumulation. Assay standardisation between laboratories is encouraged.[41][42]
Some European guidelines consider a total testosterone level <8 nmol/L (<230 ng/dL) to be indicative of hypogonadism, with level >12 nmol/L (>350 ng/dL) not usually consistent with hypogonadism.[2][29][40] Intermediate results require careful clinical consideration.
Taking testosterone samples during periods of acute illness, shift work, or sleep deprivation should be avoided as these can transiently suppress the hypothalamic-pituitary-testes axis and cause inaccuracies in evaluation.
Result
a threshold of <10.4 nmol/L (<300 ng/dL) is generally accepted as being consistent with hypogonadism (using a US standardised assay); others consider a threshold of <8 nmol/L (<230 ng/dL) to be indicative of hypogonadism
Investigations to consider
serum sex hormone-binding globulin (SHBG)
Test
Should be checked in men with an equivocal or borderline total testosterone.
Measurement of sex hormone-binding globulin (SHBG) allows calculation of free testosterone.[37][39][40] In men with elevated or with low SHBG levels (in whom total testosterone will necessarily underestimate or overestimate androgenicity, respectively), calculating free testosterone level is diagnostically useful.[37][40]
Result
increased or decreased; altered SHBG levels are suspected in older men and in men with underlying conditions, such as obesity, diabetes mellitus, nephrotic syndrome, or liver or thyroid disease
calculated free testosterone
Test
In men who have conditions that alter sex hormone binding globulin (SHBG), or when total testosterone is in the borderline range for patients with clinical features suggestive of androgen deficiency, a calculated free testosterone estimate is used to confirm testosterone deficiency.[7]
Calculated free testosterone levels can be performed using validated equations based on the total testosterone, SHBG, and, in some equations, the albumin level. The Vermeulen equation for free testosterone is the most commonly used.[2]
Calculation of free testosterone is diagnostically useful in men with high or low SHBG levels, in whom total testosterone will necessarily underestimate or overestimate androgenicity, respectively.[37][40]
Close collaboration between clinical and laboratory specialists is required.[2]
Result
less than 200 picomol/L (<58 picograms/mL) consistent with hypogonadism
serum LH/FSH
Test
If testosterone levels are found to be consistently low, LH and follicle-stimulating hormone levels should be measured to determine whether the patient has primary or secondary hypogonadism.[37]
Result
in patients with low testosterone, elevated serum LH/FSH levels indicate primary hypogonadism; decreased or normal serum LH/FSH levels indicate secondary (also known as central or hypogonadotrophic) hypogonadism
semen analysis
Test
Performed in men who have low testosterone levels and report infertility, or who express a desire to start a family in the future.
Determines concentration, motility, and morphological appearance of spermatozoa.
Two semen analyses (each with samples obtained after 2 to 7 days of abstinence) are recommended to make an accurate diagnosis.
If a semen volume of less than 1 mL is seen on analysis, ask the patient if the entire sample was collected in the cup.
A normal semen analysis makes the diagnosis of hypogonadism very unlikely.
Result
normal semen quality is sperm concentration >16 million/mL, total sperm motility >40%, and normal morphology >4% (Kruger strict criteria); <16 million/mL is considered oligospermic, <5 million/mL suggests severe oligozoospermia (WHO reference ranges); sperm motility <40% indicates asthenospermia, <4% morphologically normal sperm indicates teratospermia
FBC
Test
Normochromic normocytic anaemia is a typical feature in all forms of male hypogonadism.[7]
Prior to initiation of testosterone therapy, all patients should undergo baseline assessment of haemoglobin/haematocrit.[1]
Result
low or low-normal haemoglobin or haematocrit consistent with hypogonadism; high or high-normal levels make hypogonadism unlikely
serum prolactin
Test
Prolactin is measured if results of testosterone and gonadotrophin testing suggest secondary hypogonadism (i.e., low testosterone, accompanied by low or inappropriately normal gonadotrophins).
Check fasting levels because meals can elevate prolactin levels.
Result
above 783 picomol/L (>18 nanograms/mL or 18 micrograms/L) is considered elevated, although much higher levels are generally present with a symptomatic pituitary adenoma
serum transferrin saturation and ferritin
Test
Iron studies are performed to rule out haemochromatosis.
Check in patients with secondary hypogonadism.
Result
elevated ferritin and transferrin saturation confirms haemochromatosis
MRI pituitary
Test
Performed to exclude pituitary and/or hypothalamic tumours or infiltrative disease.[7]
The optimal strategy for pituitary imaging is uncertain.[44]
Obtain if gonadotrophins (luteinising hormone and follicle-stimulating hormone) are low or inappropriately normal.
Men with serum levels of total testosterone below 5.2 nanomol/L (<150 nanograms/dL) may benefit from pituitary imaging, especially when there are other supporting clinical or biochemical anomalies.[1]
Result
mass ≥10 mm in size confirms macroadenoma; mass <10 mm in size confirms microadenoma; alternatively, may show empty or partially empty sella, or a parasellar mass
genetic testing
Test
In men with low testosterone and elevated gonadotrophin levels (primary hypogonadism) and very small testes, a karyotype or copy number variation test should be ordered to diagnose Klinefelter syndrome.[7] See Klinefelter syndrome.
In men who desire fertility, Y-chromosome microdeletion analysis and cystic fibrosis transmembrane receptor (CFTR) mutations are additional tests.
Result
47,XXY confirms Klinefelter syndrome (may be mosaic)
dual-energy x-ray absorptiometry (DEXA or DXA)
Test
Long-standing hypogonadism is associated with osteoporosis that can result in fractures occurring with unusually low levels of trauma.
Men who have had, or are at risk for, falls and bone fractures should have an assessment of their bone mineral density.
Result
hypogonadism usually causes a decrease in bone density
Use of this content is subject to our disclaimer