History and exam
Key diagnostic factors
common
decreased libido
Consistent with hypogonadism.
loss of spontaneous morning erections
Suggestive of organic disease, including hypogonadism.
erectile dysfunction
Potentially multifactorial, but hypogonadism should always be considered.
gynaecomastia
Firm ductal tissue that is mainly subareolar. It should be differentiated from adipose tissue in obese patients (often termed lipomastia or pseudogynaecomastia).
Gynaecomastia is more commonly seen in primary hypogonadism.[33]
infertility
A common presenting issue in men with hypogonadism.
uncommon
micropenis
Short penis (often in association with lack of scrotal hyperpigmentation and rugae) is indicative of hypogonadism that occurred before puberty and most probably in utero.
small testes
Very small or shrinking testes (especially <5 mL volume) are indicative of testosterone deficiency.
bifid or hypoplastic scrotum
A manifestation of testosterone deficiency in utero.
cryptorchidism, especially if bilateral
A potential manifestation of testosterone deficiency in utero.
segmental dysproportion
bitemporal hemianopia
Indicative of a parasellar lesion, which may be causing secondary hypogonadism.
low trauma fractures
Longstanding hypogonadism is associated with osteoporosis that can result in fractures occurring with unusually low levels of trauma.
loss of height
May be indicative of spinal compression fractures associated with low bone mineral density and osteoporosis secondary to hypogonadism.
anosmia
Seen in patients with Kallmann's syndrome.
Other diagnostic factors
common
decreased energy and fatigue
Non-specific finding that may be reported in patients with hypogonadism, may include physical exhaustion and lack of vitality.
uncommon
absent or incomplete puberty
If hypogonadism occurred prior to puberty, patients may report absent or incomplete puberty.
scrotal hypoplasia, hypopigmentation, and absent rugae
Indicative of hypogonadism that started before puberty.
decreased muscle mass and strength
Non-specific. A good tool in research but limited value in clinical practice.
loss of axillary and pubic hair
Specific, but insensitive in hypogonadism.
lack of facial hair
Absence of facial hair and a lower hairline may be noted in many men with congenital hypogonadism.
poor concentration and memory
Non-specific finding that may be reported in patients with hypogonadism.
depressed or labile mood
Non-specific finding that may be reported in patients with hypogonadism.
sleep disturbance
Non-specific finding that may be reported in patients with hypogonadism.
Severe hypogonadism may be associated with hot flushes that may influence sleep quality.
hot flushes and sweats
Hypogonadism may be associated with hot flushes that may influence sleep quality.
tall stature
fine wrinkling of facial skin
May be noted in some patients with prolonged severe hypogonadism.
Risk factors
strong
genetic anomaly
Klinefelter's syndrome is the most common congenital cause of primary hypogonadism.[9][15] Klinefelter's syndrome has a likely population prevalence of >5 per 10,000 men, but only 25% to 50% of men are diagnosed during their lifetime.[9]
Most patients have 47,XXY genotype anomaly; mosaicism is also seen in 6% to 7%.[16] Testosterone secretion may initially be well preserved, but clinically significant hypogonadism invariably presents.
Many genetic mutations may result in congenital hypogonadotrophic hypogonadism (CHH), including Kallmann's syndrome.[2]
type 2 diabetes mellitus
Chronic diseases such as metabolic syndrome and diabetes can lead to secondary hypogonadism.[29]
Secondary (also known as central or hypogonadotrophic) hypogonadism is present in around one third of male patients with type 2 diabetes.[31]
In the European Male Ageing Study (EMAS), age-related accumulation of non-gonadal co-morbidities causing gonadotrophin suppression (e.g., obesity) was a greater risk factor for falling testosterone levels than chronological age.[5][12]
use of alkylating agents, opioids, or glucocorticoids
Can be a cause of both primary and secondary hypogonadism.
Alkylating agents such as cyclophosphamide and chlorambucil can cause primary hypogonadism.[17] Males about to undergo therapy with alkylating agents should be given the option of sperm banking.
High-dose glucocorticoids and opioids reduce gonadal function mainly via direct effects on the hypothalamic-pituitary axis (suppressing gonadotrophin-releasing hormone synthesis).[22]
use of exogenous sex hormones and GnRH analogues
Gonadotrophin-releasing hormone (GnRH) analogues or antagonists (such as those used in prostate cancer treatment), exogenous oestrogens, and exogenous androgens can all cause hypogonadism.[22]
GnRH analogues cause down-regulation of receptors for gonadotrophins, while exogenous sex steroids suppress the hypothalamic-pituitary unit by negative feedback.
hyperprolactinaemia
Elevated prolactin level (from any cause) suppresses kisspeptin-mediated gonadotrophin-releasing hormone secretion.[4]
parasellar tumour or apoplexy of pituitary macroadenoma
Parasellar tumour or apoplexy (haemorrhagic infarction) of pituitary macroadenoma causes compression of gonadotrophs (basophilic cells of the anterior pituitary specialised to secrete luteinising hormone or follicle stimulating hormone), resulting in secondary hypogonadism.
testicular damage
Can occur as a result of trauma, torsion, or irradiation.[9] Also includes orchidectomy for testicular cancers, which are frequently metachronous.
With torsion, the likelihood of damage is increased with duration of unrelieved torsion.
infection
Orchitis related to mumps is the most common infection. HIV is a rare infectious cause.[9] Spermatogenesis is more affected than androgen production.
weak
varicocele
Rarely causes hypogonadism, but does cause increased temperature and/or accumulation of tissue metabolites in the testes.[18]
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