Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

nongonadal illness

1st line – treatment of the underlying cause

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ONGOING
|
nongonadal illness
1st line – 

treatment of the underlying cause

Patients with hypogonadism due to a nongonadal illness should have treatment of the underlying cause. For instance, obesity is a common cause of hypogonadism, which may be reversed by lifestyle intervention.

Consider – testosterone therapy

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ONGOING
|
nongonadal illness
Consider – 

testosterone therapy

Treatment recommended for SOME patients in selected patient group

When nongonadal illness cannot be reversed with treatment of the underlying cause, testosterone therapy may be considered.

The therapeutic aim is to achieve physiologic testosterone levels, usually to the mid-normal range, and to reverse hypogonadal symptoms and signs.

The choice of specific type of testosterone and route of testosterone administration should be informed by shared decision-making and guided by efficacy, patient preference, ease of use, and safety.[43]

The adequacy of testosterone therapy is assessed by clinical symptoms and serum hormone levels.[43]

Patients require regular follow-up to ensure compliance, assess effectiveness, adjust dosing, and monitor for side effects. Patients should be reviewed at regular intervals (every 3 to 4 months) during the first year of treatment, and annually thereafter.[28][34]​ Hematocrit should also be checked at these visits. Dose titration may be required to attain adequate circulating testosterone levels.

Topical and transdermal formulations include gels, solution, and transdermal patch (in some countries); these require once-daily application. Testosterone levels can be checked to see if they have reached therapeutic levels after 1 week of using transdermal products. Physiologic serum levels can be achieved with dose adjustment. Testosterone level should be measured 2 to 4 hours after gel application as this gives the peak value.

Transfer of testosterone from patient to partner or child through skin-to-skin contact has been reported in patients using gel or cream preparations, but is extremely rare. This can be avoided by washing hands after application, and covering treated skin areas with clothing.[43]

A long-acting intramuscular formulation (testosterone undecanoate) can be given every 8-12 weeks to maintain testosterone levels within the normal physiologic range. Testosterone levels should be measured immediately prior to an injection (i.e., trough level) to ensure concentration is near the low-normal range.

Short-acting forms of injectable testosterone include esters such as testosterone cypionate and testosterone enanthate. Short-acting injectable formulations are normally administered every 1-4 weeks (depending on the formulation); dose interval may need to be adjusted to achieve therapeutic effect without adverse effects.

Intramuscular dosing may cause intermittent supraphysiologic testosterone levels with resulting fluctuations in mood and sexual behavior, polycythemia, and gynecomastia.

All intramuscular preparations of testosterone should be warmed to body temperature and administered slowly to reduce discomfort. Long-acting intramuscular testosterone undecanoate should be administered over 60 to 90 seconds to reduce injection pain and the risk of pulmonary oil microembolism (POME).

Other formulations or brands of testosterone may be available; consult your local drug formulary for more information.

Primary options

testosterone transdermal: (1% gel) apply 50-100 mg once daily; (1.62% gel) apply 20.25 to 81 mg once daily; (2% gel) apply 10-70 mg once daily; (2% solution) apply 30-120 mg once daily

More

OR

testosterone nasal: (5.5 mg/actuation) 1 actuation in each nostril (11 mg total) three times daily

More

OR

testosterone undecanoate: consult specialist for guidance on dose

More

OR

testosterone cypionate: consult specialist for guidance on dose

More

OR

testosterone enanthate: consult specialist for guidance on dose

More

not desiring fertility currently: primary hypogonadism

1st line – testosterone therapy

Back
ONGOING
|
not desiring fertility currently: primary hypogonadism
1st line – 

testosterone therapy

The therapeutic aim is to achieve physiologic testosterone levels, usually to the mid-normal range, and to reverse hypogonadal symptoms and signs.

The choice of specific type of testosterone and route of testosterone administration should be informed by shared decision making and guided by efficacy, patient preference, ease of use, and safety.[43]

The adequacy of testosterone therapy is assessed by clinical symptoms and serum hormone levels.[43]

Patients require regular follow-up to ensure compliance, assess effectiveness, adjust dosing, and monitor for side effects. Patients should be reviewed at regular intervals (every 3 to 4 months) during the first year of treatment, and annually thereafter.[28][34]​ Hematocrit should also be checked at these visits. Dose titration may be required to attain adequate circulating testosterone levels.

Topical and transdermal formulations include gels, solution, and transdermal patch (in some countries); these require once-daily application. Testosterone levels can be checked to see if they have reached therapeutic levels after 1 week of using transdermal products. Physiologic serum levels can be achieved with dose adjustment. Testosterone level should be measured 2 to 4 hours after gel application as this gives the peak value.

Transfer of testosterone from patient to partner or child through skin-to-skin contact has been reported in patients using gel or cream preparations, but is extremely rare. This can be avoided by washing hands after application, and covering treated skin areas with clothing.[43]

A long-acting intramuscular formulation (testosterone undecanoate) can be given every 8-12 weeks to maintain testosterone levels within the normal physiologic range. Testosterone levels should be measured immediately prior to an injection (i.e., trough level) to ensure concentration is near the low-normal range.

Short-acting forms of injectable testosterone include esters such as testosterone cypionate and testosterone enanthate. Short-acting injectable formulations are normally administered every 1-4 weeks (depending on the formulation); dose interval may need to be adjusted to achieve therapeutic effect without adverse effects.

Intramuscular dosing may cause intermittent supraphysiologic testosterone levels with resulting fluctuations in mood and sexual behavior, polycythemia, and gynecomastia.

All intramuscular preparations of testosterone should be warmed to body temperature and administered slowly to reduce discomfort. Long-acting intramuscular testosterone undecanoate should be administered over 60 to 90 seconds to reduce injection pain and the risk of pulmonary oil microembolism (POME).

Other formulations or brands of testosterone may be available; consult your local drug formulary for more information.

Primary options

testosterone transdermal: (1% gel) apply 50-100 mg once daily; (1.62% gel) apply 20.25 to 81 mg once daily; (2% gel) apply 10-70 mg once daily; (2% solution) apply 30-120 mg once daily

More

OR

testosterone nasal: (5.5 mg/actuation) 1 actuation in each nostril (11 mg total) three times daily

More

OR

testosterone undecanoate: consult specialist for guidance on dose

More

OR

testosterone cypionate: consult specialist for guidance on dose

More

OR

testosterone enanthate: consult specialist for guidance on dose

More

not desiring fertility currently: secondary hypogonadism

1st line – dopamine agonist

Back
ONGOING
|
not desiring fertility currently: secondary hypogonadism
|
due to prolactinoma
1st line – 

dopamine agonist

A dopamine agonist, such as cabergoline or bromocriptine, is first-line treatment.[59]​ Patients should be referred to an endocrinologist for management, which will include magnetic resonance imaging (MRI) of the pituitary gland, and visual field assessment (due to the association with bitemporal hemianopia in prolactin-secreting macroadenomas).

Cabergoline is more potent than bromocriptine, has a better adverse effect profile, and only needs to be taken twice weekly. It is a selective dopamine-2 agonist; bromocriptine is a combined dopamine-1/dopamine-2 agonist.

Testosterone therapy can be initiated to improve symptoms of hypogonadism in the small percentage of patients who do not respond to a dopamine agonist.

Primary options

cabergoline: 0.25 to 1 mg orally twice weekly

Secondary options

bromocriptine: 2.5 to 15 mg orally once daily

Consider – testosterone therapy

Back
ONGOING
|
not desiring fertility currently: secondary hypogonadism
|
due to prolactinoma
Consider – 

testosterone therapy

Treatment recommended for SOME patients in selected patient group

The therapeutic aim is to achieve physiologic testosterone levels, usually to the mid-normal range, and to reverse hypogonadal symptoms and signs.

The choice of specific type of testosterone and route of testosterone administration should be informed by shared decision making and guided by efficacy, patient preference, ease of use, and safety.[43]

The adequacy of testosterone therapy is assessed by clinical symptoms and serum hormone levels.[43]

Patients require regular follow-up to ensure compliance, assess effectiveness, adjust dosing, and monitor for side effects. Patients should be reviewed at regular intervals (every 3 to 4 months) during the first year of treatment, and annually thereafter.[28][34]​ Hematocrit should also be checked at these visits. Dose titration may be required to attain adequate circulating testosterone levels.

Topical and transdermal formulations include gels, solution, and transdermal patch (in some countries); these require once-daily application. Testosterone levels can be checked to see if they have reached therapeutic levels after 1 week of using transdermal products. Physiologic serum levels can be achieved with dose adjustment. Testosterone level should be measured 2 to 4 hours after gel application as this gives the peak value.

Transfer of testosterone from patient to partner or child through skin-to-skin contact has been reported in patients using gel or cream preparations, but is extremely rare. This can be avoided by washing hands after application, and covering treated skin areas with clothing.[43]

A long-acting intramuscular formulation (testosterone undecanoate) can be given every 8-12 weeks to maintain testosterone levels within the normal physiologic range. Testosterone levels should be measured immediately prior to an injection (i.e., trough level) to ensure concentration is near the low-normal range.

Short-acting forms of injectable testosterone include esters such as testosterone cypionate and testosterone enanthate. Short-acting injectable formulations are normally administered every 1-4 weeks (depending on the formulation); dose interval may need to be adjusted to achieve therapeutic effect without adverse effects.

Intramuscular dosing may cause intermittent supraphysiologic testosterone levels with resulting fluctuations in mood and sexual behavior, polycythemia, and gynecomastia.

All intramuscular preparations of testosterone should be warmed to body temperature and administered slowly to reduce discomfort. Long-acting intramuscular testosterone undecanoate should be administered over 60 to 90 seconds to reduce injection pain and the risk of pulmonary oil microembolism (POME).

Other formulations or brands of testosterone may be available; consult your local drug formulary for more information.

Primary options

testosterone transdermal: (1% gel) apply 50-100 mg once daily; (1.62% gel) apply 20.25 to 81 mg once daily; (2% gel) apply 10-70 mg once daily; (2% solution) apply 30-120 mg once daily

More

OR

testosterone nasal: (5.5 mg/actuation) 1 actuation in each nostril (11 mg total) three times daily

More

OR

testosterone undecanoate: consult specialist for guidance on dose

More

OR

testosterone cypionate: consult specialist for guidance on dose

More

OR

testosterone enanthate: consult specialist for guidance on dose

More

Consider – surgery

Back
ONGOING
|
not desiring fertility currently: secondary hypogonadism
|
due to prolactinoma
Consider – 

surgery

Treatment recommended for SOME patients in selected patient group

Surgery is considered when the patient is resistant to, or intolerant of, dopamine agonists, or has recurrent tumor after dopamine agonist withdrawal. Preferred surgical candidates include those patients with enclosed microadenoma.[60] Surgery is less preferred for patients with an invasive prolactinoma because postoperative remission rates are less favorable.[61] Surgery itself may cause damage to normal pituitary tissue; the decision to perform surgery should take into account surgeon experience and possibility of complications. Surgery, as with dopamine agonist therapy, may lead to some reversal of the hypogonadism.

1st line – testosterone therapy

Back
ONGOING
|
not desiring fertility currently: secondary hypogonadism
|
isolated hypogonadotropic hypogonadism
1st line – 

testosterone therapy

The therapeutic aim is to achieve physiologic testosterone levels, usually to the mid-normal range, and to reverse hypogonadal symptoms and signs.

The choice of specific type of testosterone and route of testosterone administration should be informed by shared decision making and guided by efficacy, patient preference, ease of use, and safety.[43]

The adequacy of testosterone therapy is assessed by clinical symptoms and serum hormone levels.[43]

Patients require regular follow-up to ensure compliance, assess effectiveness, adjust dosing, and monitor for side effects. Patients should be reviewed at regular intervals (every 3 to 4 months) during the first year of treatment, and annually thereafter.[28][34]​ Hematocrit should also be checked at these visits. Dose titration may be required to attain adequate circulating testosterone levels.

Topical and transdermal formulations include gels, solution, and transdermal patch (in some countries); these require once-daily application. Testosterone levels can be checked to see if they have reached therapeutic levels after 1 week of using transdermal products. Physiologic serum levels can be achieved with dose adjustment. Testosterone level should be measured 2 to 4 hours after gel application as this gives the peak value.

Transfer of testosterone from patient to partner or child through skin-to-skin contact has been reported in patients using gel or cream preparations, but is extremely rare. This can be avoided by washing hands after application, and covering treated skin areas with clothing.[43]

A long-acting intramuscular formulation (testosterone undecanoate) can be given every 8-12 weeks to maintain testosterone levels within the normal physiologic range. Testosterone levels should be measured immediately prior to an injection (i.e., trough level) to ensure concentration is near the low-normal range.

Short-acting forms of injectable testosterone include esters such as testosterone cypionate and testosterone enanthate. Short-acting injectable formulations are normally administered every 1-4 weeks (depending on the formulation); dose interval may need to be adjusted to achieve therapeutic effect without adverse effects.

Intramuscular dosing may cause intermittent supraphysiologic testosterone levels with resulting fluctuations in mood and sexual behavior, polycythemia, and gynecomastia.

All intramuscular preparations of testosterone should be warmed to body temperature and administered slowly to reduce discomfort. Long-acting intramuscular testosterone undecanoate should be administered over 60 to 90 seconds to reduce injection pain and the risk of pulmonary oil microembolism (POME).

Other formulations or brands of testosterone may be available; consult your local drug formulary for more information.

Primary options

testosterone transdermal: (1% gel) apply 50-100 mg once daily; (1.62% gel) apply 20.25 to 81 mg once daily; (2% gel) apply 10-70 mg once daily; (2% solution) apply 30-120 mg once daily

More

OR

testosterone nasal: (5.5 mg/actuation) 1 actuation in each nostril (11 mg total) three times daily

More

OR

testosterone undecanoate: consult specialist for guidance on dose

More

OR

testosterone cypionate: consult specialist for guidance on dose

More

OR

testosterone enanthate: consult specialist for guidance on dose

More

1st line – testosterone therapy

Back
ONGOING
|
not desiring fertility currently: secondary hypogonadism
|
combined pituitary hormone deficiency
1st line – 

testosterone therapy

The therapeutic aim is to achieve physiologic testosterone levels, usually to the mid-normal range, and to reverse hypogonadal symptoms and signs.

The choice of specific type of testosterone and route of testosterone administration should be informed by shared decision making and guided by efficacy, patient preference, ease of use, and safety.[43]

The adequacy of testosterone therapy is assessed by clinical symptoms and serum hormone levels.[43]

Patients require regular follow-up to ensure compliance, assess effectiveness, adjust dosing, and monitor for side effects. Patients should be reviewed at regular intervals (every 3 to 4 months) during the first year of treatment, and annually thereafter.[28][34]​ Hematocrit should also be checked at these visits. Dose titration may be required to attain adequate circulating testosterone levels.

Topical and transdermal formulations include gels, solution, and transdermal patch (in some countries); these require once-daily application. Testosterone levels can be checked to see if they have reached therapeutic levels after 1 week of using transdermal products. Physiologic serum levels can be achieved with dose adjustment. Testosterone level should be measured 2 to 4 hours after gel application as this gives the peak value.

Transfer of testosterone from patient to partner or child through skin-to-skin contact has been reported in patients using gel or cream preparations, but is extremely rare. This can be avoided by washing hands after application, and covering treated skin areas with clothing.[43]

A long-acting intramuscular formulation (testosterone undecanoate) can be given every 8-12 weeks to maintain testosterone levels within the normal physiologic range. Testosterone levels should be measured immediately prior to an injection (i.e., trough level) to ensure concentration is near the low-normal range.

Short-acting forms of injectable testosterone include esters such as testosterone cypionate and testosterone enanthate. Short-acting injectable formulations are normally administered every 1-4 weeks (depending on the formulation); dose interval may need to be adjusted to achieve therapeutic effect without adverse effects.

Intramuscular dosing may cause intermittent supraphysiologic testosterone levels with resulting fluctuations in mood and sexual behavior, polycythemia, and gynecomastia.

All intramuscular preparations of testosterone should be warmed to body temperature and administered slowly to reduce discomfort. Long-acting intramuscular testosterone undecanoate should be administered over 60 to 90 seconds to reduce injection pain and the risk of pulmonary oil microembolism (POME).

Other formulations or brands of testosterone may be available; consult your local drug formulary for more information.

Primary options

testosterone transdermal: (1% gel) apply 50-100 mg once daily; (1.62% gel) apply 20.25 to 81 mg once daily; (2% gel) apply 10-70 mg once daily; (2% solution) apply 30-120 mg once daily

More

OR

testosterone nasal: (5.5 mg/actuation) 1 actuation in each nostril (11 mg total) three times daily

More

OR

testosterone undecanoate: consult specialist for guidance on dose

More

OR

testosterone cypionate: consult specialist for guidance on dose

More

OR

testosterone enanthate: consult specialist for guidance on dose

More

Plus – treatment of associated pituitary hormone deficiencies

Back
ONGOING
|
not desiring fertility currently: secondary hypogonadism
|
combined pituitary hormone deficiency
Plus – 

treatment of associated pituitary hormone deficiencies

Treatment recommended for ALL patients in selected patient group

Confirmation of the diagnosis of secondary (also known as central or hypogonadotropic) hypogonadism requires a full pituitary evaluation to rule out other anterior and/or posterior pituitary hormone dysfunction, and treatment of any deficiencies.

desiring fertility currently: primary hypogonadism

1st line – assisted reproductive technology (ART)

Back
ONGOING
|
desiring fertility currently: primary hypogonadism
1st line – 

assisted reproductive technology (ART)

Assisted reproductive technologies such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) involve the administration of hormonal treatment to the female partner to stimulate ovarian follicle growth. Eggs are collected, fertilized, then reimplanted in the uterus.

desiring fertility currently: secondary hypogonadism

1st line – gonadotropin therapy or selective estrogen receptor modulator or aromatase inhibitor

Back
ONGOING
|
desiring fertility currently: secondary hypogonadism
1st line – 

gonadotropin therapy or selective estrogen receptor modulator or aromatase inhibitor

Human chorionic gonadotropin, alone or in combination with follicle stimulating hormone (FSH, e.g., urofollitropin, follitropin alfa, follitropin beta), helps to stimulate spermatogenesis in the testes and secretion of endogenous testosterone.[63] Pulsatile gonadotropin-releasing hormone therapy is seldom available outside the research setting.

Exogenous testosterone therapy will suppress luteinizing hormone and FSH, and temporarily inhibits spermatogenesis. However, prior testosterone therapy does not significantly impair future semen quality in men with hypogonadism.[62]

Patients should be reassured that testosterone therapy is suitable and safe for men to take until they are approximately 1-2 years from wanting to conceive with their partner. Once men want to conceive, they may be switched from testosterone to human chorionic gonadotropin treatment.

A selective estrogen receptor modulator (SERM) such as clomiphene or tamoxifen, or an aromatase inhibitor such as anastrozole, are off-label alternatives to gonadotropins that may be considered by a specialist. They are only suitable when pituitary function is intact.[64]

Primary options

chorionic gonadotropin: consult specialist for guidance on dose

OR

chorionic gonadotropin: consult specialist for guidance on dose

-- AND --

urofollitropin: consult specialist for guidance on dose

or

follitropin alfa: consult specialist for guidance on dose

or

follitropin beta: consult specialist for guidance on dose

Secondary options

clomiphene: consult specialist for guidance on dose

OR

tamoxifen: consult specialist for guidance on dose

OR

anastrozole: consult specialist for guidance on dose

Consider – assisted reproductive technology (ART)

Back
ONGOING
|
desiring fertility currently: secondary hypogonadism
Consider – 

assisted reproductive technology (ART)

Treatment recommended for SOME patients in selected patient group

Assisted reproductive technologies such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) involve the administration of hormonal treatment to the female partner to stimulate ovarian follicle growth. Eggs are collected, fertilized, then reimplanted in the uterus.

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer