Male hypogonadism

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

The hypothalamus releases pulsatile gonadotrophin-releasing hormone, the pituitary releases LH and FSH, and the testes produce testosterone and sperm. Primary hypogonadism reflects testicular failure and typically raises gonadotrophins. Secondary hypogonadism reflects inadequate hypothalamic or pituitary drive. Combined disease and functional suppression can blur this pattern, particularly during illness or obesity.

Specific sexual symptoms such as reduced libido, fewer spontaneous erections and erectile dysfunction are more informative than fatigue alone, but none is diagnostic. Delayed puberty, reduced shaving, low muscle mass, gynaecomastia, small testes, infertility, low-trauma fracture and hot flushes add weight. Depression, sleep loss, vascular erectile dysfunction and medicines commonly mimic the syndrome.

The central decisions are whether biochemical deficiency is reproducible, whether gonadotrophins localise a testicular or central problem, whether fertility is a present goal, and whether testosterone can be used safely. Treatment is replacement for established deficiency, not an anti-ageing intervention or a shortcut for nonspecific tiredness.

Key points

Male hypogonadism requires compatible symptoms or signs plus consistently low testosterone; a single result in an asymptomatic or acutely unwell person is not the diagnosis.
Obtain testosterone on two separate early-morning samples under appropriate fasting and stable-health conditions, using the local assay and reference range.
Sex hormone-binding globulin alters total testosterone interpretation in obesity, liver disease, thyroid disease and some medicines; calculated free testosterone can help in borderline or discordant cases.
High LH and FSH with low testosterone indicates primary testicular failure, whereas low or inappropriately normal gonadotrophins suggest hypothalamic-pituitary suppression or disease.
Obesity, obstructive sleep apnoea, severe illness, undernutrition, opioids and anabolic steroid withdrawal can produce functional secondary hypogonadism; treat reversible drivers while excluding structural pathology.
Very low testosterone with low gonadotrophins, raised prolactin, additional pituitary deficits, headache or visual symptoms requires pituitary evaluation rather than routine replacement alone.
Exogenous testosterone suppresses LH, FSH and intratesticular testosterone and can cause azoospermia; do not use it when current biological fertility is desired.
Before testosterone replacement, clarify fertility, prostate and breast symptoms, haematocrit, cardiovascular stability, sleep apnoea, lower urinary tract symptoms and product-specific contraindications.
Monitor clinical benefit as well as serum testosterone, full blood count and prostate safety; stop or reformulate treatment when adverse effects or absent benefit outweigh gains.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Primary testicular failure

Genetic disease, testicular injury, infection, surgery, chemotherapy or radiotherapy reduces testosterone and sperm production despite increased gonadotrophin drive.

Hypothalamic-pituitary deficiency

Pituitary lesions, hyperprolactinaemia, opioids and other central disorders provide inadequate LH and FSH stimulation to otherwise capable testes.

Functional suppression

Obesity, severe illness, sleep disruption and undernutrition can reversibly reduce gonadal signalling, complicating interpretation of a single testosterone result.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Testosterone production falls
Testicular damage or inadequate LH stimulation reduces circulating testosterone and androgen action in sexual, skeletal, muscle and blood-forming tissues.
2
Feedback reveals localisation
Loss of testicular feedback raises LH and FSH in primary disease, whereas central failure leaves gonadotrophins low or inappropriately normal.
3
Spermatogenesis may fail separately
FSH, intratesticular testosterone and intact seminiferous tissue are required for sperm production, so fertility impairment does not mirror serum testosterone perfectly.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Sexual symptom cluster

Low desire, reduced morning erections, erectile difficulty and infertility together increase suspicion, while isolated fatigue or low mood has many non-gonadal explanations.

Primary testicular failure

Small firm testes, reduced body hair, gynaecomastia or infertility with low testosterone and raised gonadotrophins suggests Klinefelter syndrome, prior orchitis, torsion, trauma, chemotherapy or genetic testicular disease.

Central hypogonadism

Low testosterone with low or inappropriately normal LH and FSH suggests congenital GnRH deficiency, hyperprolactinaemia, pituitary mass, infiltrative disease, haemochromatosis or functional suppression.

Pituitary mass effectRed flag

Headache, visual field loss, diplopia, galactorrhoea, polyuria, adrenal or thyroid deficit and severe central biochemistry needs prompt pituitary investigation.

Pituitary apoplexyRed flag

Thunderclap headache, visual loss, ophthalmoplegia, vomiting, hypotension or impaired consciousness is an endocrine and neurosurgical emergency with possible acute cortisol deficiency.

Functional suppression

Higher weight, sleep apnoea, systemic illness, undernutrition, excessive exercise, opioids or glucocorticoids may suppress the axis reversibly; testing during instability can mislabel chronic disease.

Anabolic steroid withdrawal

Muscular appearance does not exclude profound central suppression. Infertility, low mood, reduced libido and small testes after stopping non-prescribed androgens require non-judgemental specialist care.

Bone consequence

Low-trauma fracture, height loss or low bone density may reveal long-standing sex-steroid deficiency and should trigger calcium, vitamin D and secondary osteoporosis assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Two early-morning total testosterone measurementsFirst step
Why
Confirm persistent biochemical deficiency under standardised conditions.
Interpretation and limitations
Sample on separate stable mornings using the local laboratory protocol, ideally fasting where required. Defer routine diagnosis during acute illness and interpret against assay-specific reference ranges rather than one universal threshold.
02
Sex hormone-binding globulin and calculated free testosterone
Why
Clarify borderline or discordant total testosterone when binding protein is abnormal.
Interpretation and limitations
Use a validated calculation with albumin where required. Low SHBG in obesity can lower total testosterone without equivalent free deficiency, while high SHBG can conceal it.
03
LH and FSH
Why
Separate primary testicular failure from central or functional hypogonadism.
Interpretation and limitations
Raised gonadotrophins support primary failure; low or inappropriately normal values suggest central suppression. A mixed or borderline picture should be repeated and interpreted with fertility and testicular findings.
04
Prolactin, thyroid function and morning cortisol pathway
Why
Identify pituitary or systemic endocrine contributors to central hypogonadism.
Interpretation and limitations
Repeat prolactin after reviewing stress and medicines and assess macroprolactin per the laboratory. Suspected cortisol deficiency is assessed urgently and treated before thyroid hormone if clinically unstable.
05
Full blood count and haematocrit
Why
Establish baseline erythrocytosis risk and monitor testosterone safety.
Interpretation and limitations
An elevated haematocrit requires investigation and may preclude or alter treatment; sleep apnoea, smoking, lung disease and product peaks can contribute.
06
PSA and prostate assessment
Why
Establish prostate safety before and during treatment in the population for whom screening is appropriate.
Interpretation and limitations
Use age, symptoms, examination and shared decision-making under current prostate guidance. A suspicious result needs urology assessment and should not be obscured by starting testosterone.
07
Semen analysis
Why
Assess spermatogenesis when fertility is current or future priority.
Interpretation and limitations
Obtain through the current NICE NG257 pathway and repeat abnormal results as specified. Testosterone concentration does not predict sperm presence, and exogenous testosterone can suppress the count.
08
Pituitary MRI and visual fields
Why
Detect a sellar lesion when severe central deficiency, raised prolactin or mass-effect symptoms are present.
Interpretation and limitations
Image under endocrine triage after assessing adrenal safety; sudden headache or visual change is an emergency, not an outpatient MRI request.
09
Bone density and secondary bone profile
Why
Assess skeletal consequence in prolonged deficiency, fracture or high-risk disease.
Interpretation and limitations
Interpret DXA with age-appropriate metrics and check calcium, phosphate, vitamin D, renal, thyroid and coeliac or other secondary factors as indicated.
10
Karyotype or targeted genetic testing
Why
Confirm Klinefelter syndrome or congenital central hypogonadism when the phenotype supports it.
Interpretation and limitations
Arrange through endocrine, andrology or genetics services with counselling; anosmia suggests congenital GnRH deficiency and very small testes with high gonadotrophins may suggest sex-chromosome disease.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Vascular erectile dysfunction

Preserved libido and spontaneous erections with vascular risk or situation-specific erectile difficulty may indicate a non-endocrine sexual disorder.

Depression or sleep deprivation

Fatigue, low motivation and reduced libido overlap strongly, but repeated valid testosterone and gonadotrophin patterns support endocrine deficiency.

Medicine effect

Opioids and other medicines can suppress central signalling or sexual function; timing and reversibility help distinguish them from structural pituitary disease.

Hyperprolactinaemia

Raised prolactin suppresses gonadotrophin release and may accompany galactorrhoea, headache or visual symptoms that redirect assessment to the pituitary.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ConfirmSymptoms with low testosteroneFirst stepCompatible sexual, reproductive, pubertal or skeletal features and an initial low result.

1Review timing, fasting, acute illness, sleep, alcohol, obesity, medicines, opioid or anabolic exposure and repeat an early-morning total testosterone under standardised stable conditions.
2Add SHBG and calculated free testosterone when total values are borderline or binding protein may be abnormal, using the laboratory's validated method.
3Measure LH and FSH to localise the axis, then prolactin and targeted pituitary, thyroid, iron or genetic tests according to the pattern.
4Do not start replacement until symptoms, repeated biochemistry, cause, fertility intention and baseline safety have been reconciled, unless specialist emergency care directs otherwise.

02CentralLow gonadotrophins or pituitary cluesLow testosterone with low or inappropriately normal LH and FSH, severe deficiency or another pituitary feature.

1Assess headache, vision, polyuria, galactorrhoea, adrenal symptoms and other pituitary axes; sudden mass-effect features trigger the apoplexy emergency pathway.
2Repeat prolactin appropriately, review medicines and obtain morning cortisol and thyroid assessment with endocrine advice before imaging or hormone sequencing.
3Arrange pituitary MRI and visual fields when indicated and treat the cause, including prolactinoma, haemochromatosis, infiltrative disease or functional suppression.
4Choose testosterone replacement only if fertility is not sought; for fertility, use specialist GnRH or gonadotrophin induction and preserve testicular stimulation.

03ReplaceEstablished hypogonadism without fertility goalPersistent symptoms and confirmed biochemical deficiency after cause and contraindications are assessed.

1Discuss gel and injectable options, transfer or injection risks, reversibility, monitoring, fertility suppression, expected benefits and uncertain or non-responsive symptoms.
2Record baseline testosterone timing, full blood count or haematocrit, blood pressure, prostate assessment where appropriate, sleep apnoea and cardiovascular stability.
3Start the licensed product at its standard regimen, measure testosterone at the formulation-specific time and adjust through the specialist or shared-care protocol.
4Review symptom benefit, haematocrit, PSA or prostate status and adverse effects; pause, reduce or switch when thresholds, absent benefit or preference require it.

04FertilityHypogonadism with desired spermatogenesisCurrent or near-future biological parenthood is a priority in primary or secondary hypogonadism.

1Obtain semen analysis, fertility history and reproductive-partner assessment in parallel, and discuss sperm cryopreservation when gonadotoxic treatment or progressive testicular failure is possible.
2Avoid exogenous testosterone because it suppresses gonadotrophins and intratesticular testosterone; stop non-prescribed anabolic agents with specialist recovery support.
3For hypogonadotrophic hypogonadism, refer for pulsatile GnRH or gonadotrophin therapy under NICE NG257 and andrology monitoring; response may take many months.
4For primary testicular failure, discuss surgical sperm retrieval, donor conception or assisted reproduction according to semen, genetics and local HFEA-licensed service options.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Provides adjustable physiological replacement and allows rapid cessation if adverse effects or fertility plans change.

Transdermal testosterone gel

Apply the licensed daily starting amount to the specified clean dry skin and titrate from timed levels.

Prevent transfer to partners or children by washing hands, covering the site and following product contact instructions. Monitor haematocrit, testosterone and prostate safety; skin irritation and adherence affect exposure.

Provides infrequent replacement for confirmed hypogonadism when stable long-acting therapy is preferred.

Long-acting testosterone undecanoate injection

Administer the licensed deep intramuscular loading and maintenance schedule by trained staff with timed monitoring.

Observe product-specific post-injection precautions and avoid casual initiation because reversal is slow. Peaks, erythrocytosis, prostate concerns and changing fertility plans require review.

Offers lower-cost replacement with greater reversibility than a long-acting depot.

Shorter-acting testosterone injection

Use the licensed intramuscular schedule and adjust interval through specialist monitoring of symptoms and trough or timed levels.

Peak–trough fluctuation can affect mood, symptoms and haematocrit. Prescribe by exact brand and strength, avoid dosing errors and do not use for fertility induction.

Replaces LH-like and FSH stimulation to induce intratesticular testosterone and spermatogenesis in hypogonadotrophic hypogonadism.

Gonadotrophin fertility therapy

Use the specialist reproductive-endocrine regimen with serial testosterone, testicular and semen response monitoring.

Treatment is specialist led, prolonged and distinct from testosterone replacement; monitor gynaecomastia, erythrocytosis, testicular response and fertility outcomes with the reproductive service.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Infertility

Reduced intratesticular androgen action or primary seminiferous damage impairs sperm production, and exogenous testosterone can suppress it further.

Low bone density

Chronic androgen and oestrogen deficiency increases bone loss and fragility-fracture risk, particularly when onset is early or prolonged.

Anaemia and muscle loss

Reduced androgen action lowers erythropoietic and anabolic support, contributing to anaemia, reduced muscle mass and impaired physical function.

Psychosexual distress

Low libido, erectile difficulty, infertility and body-composition change can affect confidence, relationships, mood and overall quality of life.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Measure testosterone at the formulation-specific time after initiation and dose change, using the current Society for Endocrinology, BNF and local shared-care protocol.
Check full blood count and haematocrit at baseline and the recommended early and annual intervals, acting on erythrocytosis rather than repeatedly renewing unchanged treatment.
Review PSA, prostate symptoms and examination in the relevant age and risk group, with prompt urology referral for concerning change.
Assess libido, erections, energy, muscle function, mood and bone symptoms against the original treatment goals; normalising a number without benefit is not sufficient.
Ask about fertility intentions, testicular size and anabolic exposure repeatedly because priorities can change and testosterone suppresses spermatogenesis.
Monitor blood pressure, oedema, sleep apnoea, acne, breast symptoms and cardiovascular events, adjusting formulation or stopping through the specialist plan when harm emerges.
For osteoporosis or delayed puberty, follow bone density, vitamin D, growth or pubertal progression in the appropriate endocrine service.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Illness lowers testosterone

Acute inflammation and poor intake suppress the gonadal axis. Testing during admission can create a false chronic diagnosis that disappears with recovery.

Symptoms must match biochemistry

Fatigue with one borderline result is not enough, and a low value without relevant symptoms does not automatically justify lifelong controlled-drug treatment.

SHBG changes the story

Low binding protein can make total testosterone appear low in obesity, while high binding protein can mask deficient free hormone. Use validated calculation rather than intuition.

Testosterone is contraceptive to sperm

Replacement can improve libido while suppressing semen profoundly. A fertility conversation belongs before the first prescription, not after azoospermia is discovered.

Primary and secondary differ

High gonadotrophins point towards testicular failure and genetic implications; low values redirect attention to pituitary disease, medicines, nutrition and functional suppression.

Gel transfer is clinical harm

Secondary exposure can virilise a partner or child. Application site, covering, washing and contact timing must be taught and revisited.

Recovery from anabolic use varies

Gonadotrophin and sperm recovery may take months and is not guaranteed. Non-judgemental endocrine, fertility and mental-health support improves disclosure and safety.

Replacement is a monitored trial

Established irreversible disease often needs long-term therapy, but formulation and dose should still be reviewed when symptoms fail to improve or risks rise.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing hypogonadism from one afternoon testosterone result.
02
Testing during acute illness and treating the transient suppression as permanent.
03
Ignoring SHBG when total testosterone and clinical features conflict.
04
Starting testosterone before asking about fertility.
05
Missing pituitary disease in severe central hypogonadism.
06
Treating nonspecific ageing symptoms with testosterone despite normal repeat biochemistry.
07
Failing to monitor haematocrit and prostate safety.
08
Allowing gel transfer to a child or partner through incomplete counselling.