Hypogonadism

Management decisions should not be taken on an isolated testosterone level. Borderline levels should be interpreted in the light of SHBG and albumin to calculate a free androgen index.

If there is any doubt, consider dynamic function testing to confirm isolated nature of hypogonadism.

With isolated hypogonadotropic hypogonadism, the pituitary is likely to be structurally normal. If this is confirmed on MRI scanning, no further imaging need be undertaken in the future.

Documented low bone mineral density will inform decision whether to initiate treatment.

This should be discussed at, or soon after, diagnosis. Semen analysis, counselling, and referral to a fertility clinic for consideration of spermatogenesis induction, should be offered if appropriate.

Discuss whether treatment is actually required in each individual case. Also discuss the different testosterone preparations available, for example daily topical gel, patch, or regular or depot injections.

It is appropriate to start treatment at the usual adult dose in patients with adult onset hypogonadism.

Peak and trough testosterone levels are useful initially to guide the dosage of injectable testosterone esters. Random levels are used to guide dosage on patch and depot preparations.

After the dose has been optimised, annual random levels are sufficient in most cases, with pre dose levels also required in patients on testosterone ester injections. Digital rectal examination, prostate specific antigen, full blood count and liver function tests should also be performed annually with dose reduction and or onward referral if abnormalities arise.

Specialist follow up is not usually required long term.

If there is any doubt that hypogonadotropic hypogonadism may not be isolated, consider dynamic function testing.

Late onset isolated hypogonadotropic hypogonadism is uncommon in females requiring thorough investigation for other causes.

Documented low bone mineral density will inform decision as whether to initiate treatment, and whether other agents should be considered, for example bisphosphonates and vitamin D.

This should be discussed at, or soon after, diagnosis and counselling or referral offered if appropriate.

Cyclical estrogen and progesterone replacement therapy should be considered in all patients.

The combined oral contraceptive pill is a convenient preparation and may be more socially acceptable at diagnosis, and in young patients, though this will not offer sufficient bony protection unless taken continuously.

Hormone replacement therapy is more appropriate and should be tailored to suit the individual, for example by offering topical, depot or oral preparations, and according to age, presence or absence of a uterus, a history or family history of breast or endometrial cancer, or of cardiovascular or thromboembolic disease. 

Estrogen replacement therapy should be continued until the time of the natural menopause - typically to age 50.

Topical estrogen applied as a gel may help vaginal dryness for sexual intercourse.

Management decisions should not be taken on an isolated testosterone level. Borderline levels should be interpreted in the light of SHBG and albumin to calculate a free androgen index.

If there is any doubt about the aetiology of gonadal failure, imaging should be performed and further investigation undertaken, for example with tumour markers (alpha feto protein and human chorionic gonadotropin) and urology referral. 

Primary gonadal failure may be associated with other organ specific auto-immune diseases and so such patients should be screened and monitored for their development.

Primary gonadal failure may be associated with other organ specific auto-immune diseases and so such patients should be screened and monitored for their development.

Documented low bone mineral density will inform decision whether to initiate treatment, and whether other agents such as calcium and vitamin D are required.

This should be discussed at or soon after diagnosis. Semen analysis, counselling and referral to a fertility clinic should be offered if appropriate.

Discuss whether treatment is actually required and the different testosterone preparations available, for example topical gel, patch, regular or depot injections.

Treatment is usually started at standard adult doses in patients with adult onset hypogonadism.

Peak and trough testosterone levels are useful initially to guide dosage of injectable testosterone esters.

Random levels are sufficient to guide dosage on patch and depot preparations.

After initial dose optimisation, annual random levels are sufficient in most cases, with pre dose levels for those taking regular injectable preparations.

Digital rectal examination, prostate specific antigen, full blood count and liver function tests should also be performed annually with dose reduction and or onward referral if abnormalities arise.

B12, 9am cortisol, TSH and free thyroxine should be assessed annually where the cause is presumed to be auto-immune.

Specialist follow up is not usually required long term.

Primary ovarian failure is associated with other organ specific auto-immune diseases and so such patients should be screened and monitored for their development.

Primary ovarian failure is associated with other organ specific autoimmune diseases and so such patients should be screened and monitored for their development.

Documented low bone mineral density will inform decision whether to initiate treatment, and whether other agents should be considered, for example bisphosphonates and vitamin D.

This should be discussed at, or soon after, diagnosis and counselling or referral offered if appropriate.

Cyclical estrogen and progesterone replacement therapy should be considered in all patients.

The combined oral contraceptive pill is a convenient preparation and may be more socially acceptable at diagnosis and in young patients. However, this will not offer sufficient bony protection unless taken continuously.

Hormone replacement therapy is more appropriate in the long term, and should be tailored to suit the individual, for example by offering topical, depot or oral preparations. Choice will also depend on the age of the patient, presence or absence of a uterus, and history or family history of breast or endometrial cancer. A history of, or strong risk factors for cardiovascular or thromboembolic disease will also need to be considered. 

Estrogen replacement therapy should be continued until the time of the natural menopause - typically to age 50. Vaginal dryness may be ameliorated by topical estrogen gels.

Estrogen replacement therapy requires no routine monitoring unless the patient is symptomatic, for example menstrual irregularity or hot flushes.

Annual monitoring of TSH, free thyroxine, 9am cortisol and vitamin B12 level should be initiated to screen for the development of other associated conditions.

Specialist follow up may not be required long term.

Treatment aims to replicate the natural process of puberty and should occur over approximately the same timescale - approximately two to three years.

Adult patients should be warned that accelerating the process may have adverse long term psychological and physical consequences, for example poor breast development.

If appropriate, fertility should be discussed early with the patient and their family.

Patients need to understand that successful pubertal induction will not affect or restore fertility, although appropriate uterine development is necessary prior to possible future pregnancies.

Adult patients with absent puberty require karyotype analysis to differentiate between different causes, for example Klinefelter's syndrome, androgen insensitivity or Turner's syndrome.

If there is any doubt that hypogonadotropic hypogonadism may not be isolated, consider dynamic function testing.

If karyotype is normal, and cause of hypogonadotropic hypogonadism is uncertain, thorough investigation for other causes should be performed.

Delayed bone age supports the diagnosis of absent puberty.

Initiate very low dose estrogen replacement therapy.

Typical starting dose in an estrogen naive patient is 1.25mcg ethinylestradiol. Increase dose to 2.5mcg, then by 2.5mcg increments every six months to 10mcg. The dose may then increase to 15mcg.

Consider pelvic ultrasound scan to assess uterine size at this stage.

Once the patient experiences vaginal bleeding or if the patient has tolerated 15mcg, consider adding cyclical progesterone.

The combined oral contraceptive pill is a convenient preparation and may be more socially acceptable in young patients, for example Loestrin 20.

However, these do not provide sufficient bony protection unless used continuously and HRT is more appropriate long term.

Topical, depot and oral preparations should be offered and treatment tailored according to the individual. Topical estrogen gel may also be used to aleviate vaginal dryness.

Continue sex hormone replacement therapy until the time of the natural menopause - typically to age 50.

Offer life long follow up to all patients.

Consider periodic monitoring of bone densitometry and of pituitary function where indicated.

Patients with Turner’s syndrome, Klinefelter’s, Kallmann’s or underlying pituitary disease will require specific follow up.

Initiate very low dose testosterone therapy, and warn patient of expected psychological and physical effects.

Typical starting dose in a testosterone naive patient is approximately 20% of the usual adult dose. This has traditionally been given as 50mg testosterone ester as an intramuscular injection, monthly.

Monthly testosterone treatment is then typically increased by a further 50mg every six months according to clinical response.

Alternatives include low dose depot testosterone, or topical gel using the same dosing schedule.

Routine monitoring of serum testosterone levels is not necessary until the expected adult dose is reached.

Peak and trough levels may be useful to guide dose adjustment with monthly testosterone. Random levels are sufficient with other forms of testosterone replacement therapy.

Once patient is virilised appropriately and established on full adult dose, offer switching to alternative preparation, for example daily gel or depot preparation.

Optimise final dose according to symptoms and serum levels.

Annual random levels are sufficient in patients on topical and depot preparations. Annual pre dose levels are required in those on injectable testosterone esters. 

Digital rectal examination, prostate specific antigen, full blood count and liver function tests should also be performed annually with dose reduction and onward referral if abnormalities arise.

Offer life long follow up to all patients.

Consider periodic monitoring of bone densitometry and of pituitary function where indicated.

Patients with Turner’s syndrome, Klinefelter’s, Kallmann’s or underlying pituitary disease will require specific follow up.