Diagnosis and treatment algorithm

A standardized algorithm for the diagnosis and treatment of male hypogonadism is summarized in the Figure 1.1
Figure 1: Practical algorithm for work-up and management of testosterone deficiency
vergrößern Figure 11: Practical algorithm for work-up and management of testosterone deficiency
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Table 1: Symptoms of male hypogonadism
Organ/affected function Onset of hypogonadism before completion of puberty Onset of hypogonadism after completion of puberty
Larynx No voice mutation No change
Hair Horizontal pubic hair line; straight frontal hair line; diminished beard growth Diminished secondary body hair; decreased beard growth
Skin Absent sebum production; lack of acne; pallor; fine skin wrinkling Decreased sebum production; pallor; fine skin wrinkling
Bone Eunuchoid tall stature; osteoporosis Osteoporosis
Haematopoiesis Anaemia Anaemia
Breast Sometimes gynaecomastia Sometimes gynaecomastia
Muscles Underdeveloped Atrophia
Penis Infantile No change/atrophy
Prostate Underdeveloped Atrophy
Testes Small volume; often maldescensus Decrease of volume
Spermatogenesis Not initiated Arrest
Mood Reduced Reduced
Erectile function and libido Not developed Loss
Symptoms typically met in late-onset hypogonadism (LOH)
  • Diminished sexual desire and arousability (libido)
  • Loss of erectile quality and frequency
  • Loss of particularly nocturnal erections
  • Depression, fatigue, lack of vigor, irritability
  • Decreased intellectual activity: cognitive functions, spatial orientation
  • Sleep disturbances
  • Decrease in lean body mass, diminution of muscle volume, and strength
  • Increase in visceral fat
  • Decrease in body hair and skin alterations
  • Osteopenia, osteoporosis, and increased risk of bone fractures
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Table 2: Overview of main disorders with male hypogonadism
Primary hypogonadism Secondary hypogonadism Androgen resistance
  • Anorchia
  • Maldescensus testis Orchitis
  • Klinefelter syndrome; 47,XXY
  • XX-male syndrome
  • Leydig cell tumors
  • LH-receptor defects
  • Chronic disease
  • Testicular trauma
  • Testicular radiation
  • Chemotherapy
  • Idiopathic hypogonadotropic hypogonadism (IHH)
  • Kallmann syndrome
  • Pituitary adenoma
  • Chronic disease
  • Haemochromatosis
  • Central ischaemia
  • Cerebral trauma
  • Radiation of cerebral areas during tumor therapy
  • Cachexia
  • Opioid medication or abuse
  • GnRH-receptor mutations
  • Mutations of the androgen receptor
  • Long androgen receptor gene CAG repeats (> 25 ?)
  • 5-alpha-reductase insufficiency
Mixed primary and secondary hypogonadism Late-onset hypogonadism (LOH)
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Table 3: Absolute and relative contraindications for testosterone substitution
Absolute contraindications Relative contraindications
  • Prostate carcinoma or suspicion thereof
  • Breast carcinoma or suspicion thereof
  • Desired paternity
  • Criminal sexual behaviour
  • Unclear polycythosis
  • Untreated sleep apnea
  • Severe symptoms of lower urinary tract obstruction
  • Severe heart failure
  • Benign prostate hyperplasia
  • Mild polycythosis
  • Acne
  • Competitive sports
  • Unclear liver disease
  • Unclear renal disease
  • Treated sleep apnea
  • Mild symptoms of lower urinary tract obstruction
  • Unclear gynaecomastia
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Table 4: Currently available testosterone preparations
Pathway of application Generic name Trade name Dose
Oral Testosterone
undecanoate
Andriol
Testocaps
2 capsules
2–3 times/d
Transdermal Testosterone patch

Testosterone gel
25 mg or 50 mg

Testosterone gel
25 mg or 50 mg

Testosterone gel
50 mg
Androderm

Testogel


Androtop Gel


Testim
2 × 5 mg/d

50–100 mg/d


50–100 mg/d


50–100 mg/d
Intramuscular Testosterone
enanthate 250 mg

Testosterone
undecanoate
1000 mg
Testosterone
Depot 250

Nebido
1 ampoule every
2–3 weeks

1 ampoule every
10–14 weeks
(see text for loading dose)
Buccal Testosterone 30 mg Striant 1 tablet 2 times/d
Implants Testosterone 200 mg Testosterone Implant 200 mg 3–5 pellets every 4–6 months
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Table 5: Surveillance of testosterone therapy
Surveillance target Measure Interval first year* Interval following years* Threshold (action required)
Blood viscosity Haematocrit Every 3 months 1 or 2 times per year 52 % (dose reduction)
Prostate Size (TRUS)




Palpation



PSA
Every 3 months



Every 3 months


Every 3 months
1 or 2 times per year



1 or 2 times per year


1 or 2 times per year
Symptoms of obstruction (dose reduction and other therapy)

Pathological finding (withdrawal/biopsy)


4 ng/ml or PSA velocity > 0.4 ng/ml/year after 1st year and absolute PSA > 1 ng/ml(withdrawal/biopsy) therapy)
Hair Observation Every 6 months Annually Undesired balding (dose reduction or change of preparation)
Sleep Question or sleep monitoring Every 6 months Annually Sleep apnea (dose reduction and adequate therapy)
Skin Observation Every 3 months Annually Acne/irriation (dose reduction or change of preparation)
Lipids Total cholesterol, triglycerides, HDL-C, LDL-C Every 6 months Annually In case of no favourable effects, consider increment of dose and determination of CAG repeat androgen receptor polymorphism
Bone Densitometry After 1 year Every 2 years In case of no favourable effects, consider increment of dose and determination of CAG repeat androgen receptor polymorphism
Sexuality Question Every 3 months 1 or 2 times per year In case of no favourable effects, consider increment of dose and determination of CAG repeat androgen receptor polymorphism
Mood Question Every 3 months 1 or 2 times per year In case of no favourable effects, consider increment of dose and determination of CAG repeat androgen receptor polymorphism
* In men younger than 40 years, surveillance may be performed at 3 months and 9 months after start of therapy; * only in case of normal findings, otherwise 1st year-intervals apply after change of dose; TRUS = transrectal ultrasound
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References

1. Traish A et al., Testosterone Deficiency, The American J of Medicine (2011) 124:578-587.
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Last updated: 2016
G.GM.MH.04.2015.0334