MALE
HYPOGONADISM
Definition
Hypogonadism relates
to a failure of the testes to produce sufficient testosterone. It can be
divided into primary or secondary hypogonadism according to whether the
gonadotrophins are elevated or not in the presence of a low 09.00 testosterone
level, respectively (Figure 28.1). Patients present with failure to progress
through puberty, infertility, erectile dysfunction and/or reduced libido. The
clinical presentation depends on the severity, age of onset and duration of
disease (Figure 28.2).
Primary
hypogonadism
This occurs as a
result of testicular failure. Causes include the following.
• Klinefelter’s syndrome, affecting 1 in 500–1000
men. Most commonly caused by a 47XXY karyotype.
• Other chromosomal disorders (e.g. XX males,
mixed gonadal dysgenesis, XYY syndrome).
• Cryptorchidism. Although undescended testes are
common in male neonates, most will descend into the scrotum. Postpubertal
cryptocrchidism occurs in <0.5%. There is an increased risk of testicular
malignancy in addition to infertility.
• Testicular torsion, trauma or castration.
• Infection (e.g. mumps orchitis, HIV).
• Chemotherapy and radiotherapy (e.g. for
lymphoma). Alkylat-ing agents in particular are gonadotoxic.
• Other causes including systemic illness such as
renal failure, haemochromatosis (which can cause combined primary and secondary
hypogonadism), liver cirrhosis, and drug or surgical treatment for prostate
cancer.
Secondary
hypogonadism
This occurs as a
result of hypothalamic or pituitary disease. In addition to the causes of
hypopituitarism listed in Chapter 5, specific causes of secondary hypogonadism
include the following.
• Kallmann’s syndrome. A genetic
disorder arising from disrupted migration of GnRH producing neurons into the
hypothalamus. Leads to isolated gonadotrophin deficiency, often but not
invari-ably with ansomia (from failure of olfactory lobe development).
• Drugs. Anabolic steroids and opiates.
Potentially reversible with drug cessation but recovery can take a long time.
• Systemic illness of any kind.
• Type 2 diabetes and metabolic syndrome. Total
testosterone levels are lower in men with these conditions related to central
obesity and insulin resistance. Routine treatment with testoster-one is not
currently indicated in the absence of symptoms.
Late onset
hypogonadism
Testosterone levels
decline with age, at an average of 1–2% per year, because of both testicular
and hypothalamic pituitary dysfunction. As a result, a significant number of
older men have testosterone levels below the lower end of the reference range
for healthy young men. There is currently much uncertainty about the risks and
benefits of testosterone replacement in this group, hence a decision to treat
should be undertaken on an individual basis. This should be considered only in
men with confirmed hypogonadism on more than one occasion and with definite
symptoms of androgen deficiency.
Assessment
Because testosterone
levels show a circadian variation, blood samples for testosterone should be
taken in the morning when concentrations are at their highest. If the initial
result is in the mildly hypogonadal range, a repeat sample is recommended
because up to 30% of men have a normal result on repeat testing. LH and FSH
should be measured to distinguish primary from secondary hypogonadism. In men
with secondary hypogonadism, further evaluation for hypothalamic and/or
pituitary disease is needed with measurement of prolactin, ferritin (to screen for
haemochromatosis) and pituitary function in addition to MRI (Chapter 2). In men
with primary hypogonadism where the aetiology is unclear, a karyotype should be
requested to test for Klinefelter’s syndrome.
Treatment
Androgen replacement
can improve libido, erectile function, mood, muscle mass and strength, reduce
fat mass and improve bone mineral density. Treatment is given as a testosterone
gel or injection (monthly or 3-monthly depot preparations) and should be
considered in symptomatic patients with biochemically confirmed hypogonadism
provided the patient does not have prostate or breast cancer. Caution is needed
in patients with benign prostate hyperplasia, polycythaemia or sleep apnoea.
Assessment of response to treatment and a screen for adverse effects should be
undertaken at 6-12 month intervals via symptomatic enquiry, rectal examination
of the prostate and measurement of prostate-specific antigen (PSA), haematocrit
and testosterone levels. Dosage should be adjusted according to symptomatic and
biochemical response, aiming for a testosterone level in the mid-normal range.
Fertility is not
improved with androgen replacement therapy. In men with secondary hypogonadism,
substitution of testosterone replacement with gonadotrophin therapy can help
initiate and maintain spermatogenesis. Men with primary hypogonadism will not
respond to gonadotrophin therapy, and may require assisted conception via
testicular sperm extraction and intra-cytoplasmic sperm injection (ICSI).
