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MALE
HYPOGONADISM
Definition
Male hypogonadism is a clinical syndrome
caused by androgen deficiency which may
adversely affect multiple organ functions and
quality of life.
Sources:
Guidelines on Male Hypogonadism. European Association of Urology 2015.
Nieschlag E, et al. Andrology: male reproductive health and dysfunction. 3rd edn.
Springer-Verlag Berlin Heidelberg 2010 ISBN 978-3-540-78354-1
SECONDARY
HYPOGONADISM
RABI’ATUL ‘ADAWIYAH BINTI MOHAMAD
10-6-76
KALLMANN
SYNDROME.
GnRH deficiency
with anosmia
PITUITARY
DISORDERS
hyperprolactinemia
INFLAMMATORY
DISEASE
Sarcoidosis,
Histiocytosis and
Tuberculosis
HIV/AIDS
MEDICATIONS
OBESITY
NORMAL AGING
CONCURRENT
ILLNESS
PATHOGENESIS
Dhamirah Sakinah Binti Makmon
10-6-75
CLINICAL PICTURE
AHMAD NAUFAL B NORDEEN 10-6-16
SITI AISYAH BT AHMAD FAIZAL 10-6-85
SITI KHADIJAH BT MANSOR 10-6-89
SITI ZULAIKHA BT SAIAN 10-6-90
Primary hypogonadism Secondary hypogonadism
Genetic: Klinefelter’s syndrome
(common)
Congenital: anorchia
Kallman Syndrome
Pituitary gland tumor
Klinefelter’s syndrome
• Muscle mass is decreased,
• muscle strength is diminished
Increase BMI and body
fat percentage
Erectile dysfunction
• Small testis
• lack scrotal pigmentation
• Small penis (< 8 cm long in adults).
• Loss of pubic hair
• axillary hair
• terminal hair growth along the midline
towards the umbilicus.
Infertility related to low sperm count
Reduced libido and activity
Gynecomastia
• Bilateral enlargement of
male mamillary gland and fat
Depression
INVESTIGATIONS
Siti Suhaila binti Mohaad Sariff 10-6-91
Siti Aisyah binti Rusman 10-6-92
Siti Najwa binti Khamsul 10-6-94
Siti Nurul Afiqah binti Johari 10-6-95
Siti Baizury binti Hassan 10-6-96
Investigations
To determine testosterone deficiency we must consider:
- Clinical signs and symptoms (already mentioned)
- Laboratory values
Physical examination
Hormonal Assays
1. Early morning serum testosterone levels
2. Early morning FSH and LH levels
3. Prolactin level, if increase suggesting more
investigations on pituitary gland
4. PSA assay
 Prepubertal (either 1ry or 2ry)
Differentiate by measuring early morning LH and FSH
levels (8-10 AM)
 1ry hypogonadism: low level of testosterone, high-normal
or high levels of LH and FSH
 2ry hypogonadism: low level of testosterone, normal to low
levels of LH and FSH
*If both physical examination and serum chemistry tests
are normal, constitutional pubertal delay must be
considered
 Postpubertal (S&S include loss of libido, erectile
dysfunction, depression, osteoporosis, regression 2ry
sexual characteristics)
 1ry gonadal failure: low testosterone, increase FSH and
LH. FSH measurement important because of longer half
life & > sensitive than LH
 Hypothalamic-pituitary disorders (2ry): low testosterone
and low to normal FSH and LH
Karyotyping
 To diagnose any chromosomal abnormalities –
Klinefelter’s syndrome, Noonan’s syndrome
Radiological Imaging
1. Magnetic Resonance Imaging (MRI)
 To screen for hypothalamic or pituitary disease
 Undescended testis
2. Dual Energy X-ray Absorptiometry (DEXA)
- Bone mineral density
Other assessment
 Formal assessment of intellectual changes, mood, and
cognitive changes
 Assessment of prostate by DRE
MANAGEMENT OF MALE
HYPOGONADISM
GOAL THERAPY MALE
HYPOGONADISM
 SHAFIRA BINTI SHAHAMEN (10-6-104)
GOAL THERAPY
The goal of hormone replacement therapy in
these men is to restore hormone levels to the
normal range and to alleviate symptoms
suggestive of hormone deficiency.
This can be accomplished in a variety of ways,
although most commonly testosterone
replacement therapy (TRT) is employed.
GOAL THERAPY
 Restore Sexual Function, Libido, Well-Being, and Behavior
 Produce and Maintain Virilization
 Optimize Bone Density and Prevent Osteoporosis
 Possibly Normalize Growth Hormone Levels in Elderly Men
 Potentially Affect the Risk of Cardiovascular Disease
 Restore Fertility in Cases of Hypogonadotropic
Hypogonadism
CONTRAINDICATIONS TO
TESTOSTERONE
THERAPY
SHAHIZAN BINTI MOHD RASID
10-6-102
1.Breast carcinoma (history or presence)
2.Prostate carcinoma (history or presence)
3. benign prostatic hyperplasia
4.Abnormal digital rectal examinations
5.Elevated levels of prostate-specific antigen
6.Age (no limit established; possibly older than 80 years)
7.Psychopathology
8.Sleep apnea (potential for worsening)
9.Hypercoagulable states
10.Polycythemia (hematocrit >51%)
Conditions that contraindicate of testosterone therapy:
Some other chronic diseases:
-Diabetes
-Heart Disease
-Liver or kidney disease
Drug interactions with testosterone
-Testosterone may interfere with the action of
certain drugs.
-Examples:
1.Warfarin (Coumadin) for thinning blood
2.Insulin or any oral drugs for diabetes
3.Propranolol (Inderal)
4.Oxyphenbutazone
5.Imipramine
6.Any kind of corticosteroid drug
7.Some herbal products
Testosterone therapy in
adult male hypogonadism
 For hypogonadism caused by testicular failure, male
hormone replacement (testosterone replacement
therapy, or TRT) is used.
 TRT can restore sexual function and muscle strength
and prevent bone loss.
 In addition, men receiving TRT often experience an
increase in energy, sex drive and sense of well-being.
 Testosterone therapy should provide physiologic range
of :
 serum testosterone levels (generally between 280 and 800
ng/dL)
 dihydrotestosterone and estradiol levels.
These would allow optimal virilization and normal sexual
function.
 In late teenage male patients with delayed puberty,
testicular size should be monitored for evidence of onset
of puberty.
Types of testosterone replacement
therapy
 Injections
 IM injections
 Are safe and effective
 eg : Testosterone undecanoate
 Androderm Patch
 Applied each night to the back, abdomen, upper
arm or thigh
 The site of application is rotated to lessen skin
reactions
 Gel
 Androgel, testim, axiron, fortesta
 Avoid skin to skin contact before the gel is
completely dry.
 Gum and cheek (buccal cavity)
 Striant
 Implantable pellets
 Testopel : surgically implanted under the skin
 Need to be replaced every 3 to 6 months
SIDE EFFECTS OF TRT
• Stimulation of prostate tissue, with perhaps
some increased urination symptoms such as a
decreased stream or frequency
• Increased risk of developing prostate cancer
• Gynecomastia
• Increased risk of blood clots
• Worsening of sleep apnea
• Decreased testicular size
• Increased aggression and mood swings
• May increase risk of heart attack and stroke
MONITORING TRT
Gonadal stimulation
in hypogonadotropic
hypogonadism
By : SITI NUR JANNAH SHAARI
10-6-97
 Gonadotropin /GNRH therapy- only for
hypogonadotrophic hypogonadism
 Uses :
-to induce puberty in boys
-treat androgen defic in hypo. hypogonadism
-initiate& maintain spermatogenesis in hypogonadotropic
men who wants fertility
Gonadotropin therapy to induce
puberty
 How? hCG binds to Leydig cell LH receptors and stimulates
the production of testosterone.
 Peripubertal boys with hypogonadotropic
hypogonadism and delayed puberty can be treated with
hCG instead of testosterone to induce pubertal
development.
 The initial regimen of hCG is usually 1,000 to 2,000 IU
administered intramuscularly 2-3 times a week
 The clinical response is monitored, and testosterone levels
are measured about every 2 to 3 months.
 The advantages of hCG over testosterone
-the stimulation of testicular growth,
-greater stability of testosterone levels and fewer
fluctuations in hypogonadal symptoms
-stimulating enough intratesticular testosterone to allow
the initiation of spermatogenesis.
 The disadvantages of hCG : the need for more frequent
injections & the greater cost.
Gonadotropin therapy
 Male patients with onset of hypogonadotropic hypogonadism
before completion of pubertal development may have testes
generally smaller than 5 mL. These patients usually require
therapy with both hCG and human menopausal gonadotropin (or
FSH) to induce spermatogenesis. Men with partial gonadotropin
deficiency or who have previously (peripubertally) been stimulated
with hCG may initiate and maintain production of sperm with hCG
therapy only. Men with postpubertal acquired hypogonadotropic
hypogonadism and who have previously had normal production of
sperm can also generally initiate and maintain spermatogenesis
with hCG treatment only . Fertility may be possible at sperm
counts much lower than what would otherwise be considered
fertile. Counts of less than 1 million/mL may be associated with
pregnancies under these circumstances.
 Therapy with hCG is generally begun at 1,000 to 2,000
IU intramuscularly two to three times a week, and
testosterone levels should be monitored monthly
 It may take 2 to 3 months to achieve normal levels of
testosterone.
 When normal levels of testosterone are produced,
examinations should be conducted monthly to
determine whether any testicular growth has occurred.
Sperm counts should also be assessed monthly during
a 1-year period.
 In general, the response to hCG can be predicted on
the basis of the initial testicular volume
 If spermatogenesis has not been initiated by the end of
6 to 12 months of therapy with hCG or LH,
administration of an FSH-containing preparation is
initiated in a dosage of 75 IU intramuscularly three
times a week along with the hCG injections.
GnRH Therapy
 In patients with an otherwise intact pituitary gland and hypogonadotropic
hypogonadism, synthetic GnRH can be given in a pulsatile fashion
subcutaneously through a pump every 2 hours.
 GnRH therapy is monitored by measuring LH, FSH, and testosterone levels
every 2 weeks until levels are in the normal range, at which point monitoring
can be adjusted to every 2 months. GnRH can be used to initiate pubertal
development, maintain virilization and sexual function, and initiate and
maintain spermatogenesis.
 In most patients, these effects may take from 3 to 15 months to achieve
sperm production . As with gonadotropin therapy, fertility can be achieved with
very low sperm counts—often in the range of 1 million/mL.
 GnRH may be more effective than gonadotropin stimulation in increasing
testicular size and initiating spermatogenesis in many patients with
hypogonadotropic hypogonadism .
Male Hypogonadism

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Male Hypogonadism

  • 2. Definition Male hypogonadism is a clinical syndrome caused by androgen deficiency which may adversely affect multiple organ functions and quality of life. Sources: Guidelines on Male Hypogonadism. European Association of Urology 2015. Nieschlag E, et al. Andrology: male reproductive health and dysfunction. 3rd edn. Springer-Verlag Berlin Heidelberg 2010 ISBN 978-3-540-78354-1
  • 3.
  • 4.
  • 5.
  • 9.
  • 10. CLINICAL PICTURE AHMAD NAUFAL B NORDEEN 10-6-16 SITI AISYAH BT AHMAD FAIZAL 10-6-85 SITI KHADIJAH BT MANSOR 10-6-89 SITI ZULAIKHA BT SAIAN 10-6-90
  • 11. Primary hypogonadism Secondary hypogonadism Genetic: Klinefelter’s syndrome (common) Congenital: anorchia Kallman Syndrome Pituitary gland tumor
  • 12. Klinefelter’s syndrome • Muscle mass is decreased, • muscle strength is diminished Increase BMI and body fat percentage
  • 13. Erectile dysfunction • Small testis • lack scrotal pigmentation • Small penis (< 8 cm long in adults). • Loss of pubic hair • axillary hair • terminal hair growth along the midline towards the umbilicus.
  • 14. Infertility related to low sperm count Reduced libido and activity Gynecomastia • Bilateral enlargement of male mamillary gland and fat Depression
  • 15. INVESTIGATIONS Siti Suhaila binti Mohaad Sariff 10-6-91 Siti Aisyah binti Rusman 10-6-92 Siti Najwa binti Khamsul 10-6-94 Siti Nurul Afiqah binti Johari 10-6-95 Siti Baizury binti Hassan 10-6-96
  • 16. Investigations To determine testosterone deficiency we must consider: - Clinical signs and symptoms (already mentioned) - Laboratory values
  • 18. Hormonal Assays 1. Early morning serum testosterone levels 2. Early morning FSH and LH levels 3. Prolactin level, if increase suggesting more investigations on pituitary gland 4. PSA assay
  • 19.  Prepubertal (either 1ry or 2ry) Differentiate by measuring early morning LH and FSH levels (8-10 AM)  1ry hypogonadism: low level of testosterone, high-normal or high levels of LH and FSH  2ry hypogonadism: low level of testosterone, normal to low levels of LH and FSH *If both physical examination and serum chemistry tests are normal, constitutional pubertal delay must be considered
  • 20.  Postpubertal (S&S include loss of libido, erectile dysfunction, depression, osteoporosis, regression 2ry sexual characteristics)  1ry gonadal failure: low testosterone, increase FSH and LH. FSH measurement important because of longer half life & > sensitive than LH  Hypothalamic-pituitary disorders (2ry): low testosterone and low to normal FSH and LH
  • 21.
  • 22. Karyotyping  To diagnose any chromosomal abnormalities – Klinefelter’s syndrome, Noonan’s syndrome
  • 23. Radiological Imaging 1. Magnetic Resonance Imaging (MRI)  To screen for hypothalamic or pituitary disease  Undescended testis
  • 24. 2. Dual Energy X-ray Absorptiometry (DEXA) - Bone mineral density
  • 25. Other assessment  Formal assessment of intellectual changes, mood, and cognitive changes  Assessment of prostate by DRE
  • 27. GOAL THERAPY MALE HYPOGONADISM  SHAFIRA BINTI SHAHAMEN (10-6-104)
  • 28. GOAL THERAPY The goal of hormone replacement therapy in these men is to restore hormone levels to the normal range and to alleviate symptoms suggestive of hormone deficiency. This can be accomplished in a variety of ways, although most commonly testosterone replacement therapy (TRT) is employed.
  • 29. GOAL THERAPY  Restore Sexual Function, Libido, Well-Being, and Behavior  Produce and Maintain Virilization  Optimize Bone Density and Prevent Osteoporosis  Possibly Normalize Growth Hormone Levels in Elderly Men  Potentially Affect the Risk of Cardiovascular Disease  Restore Fertility in Cases of Hypogonadotropic Hypogonadism
  • 31. 1.Breast carcinoma (history or presence) 2.Prostate carcinoma (history or presence) 3. benign prostatic hyperplasia 4.Abnormal digital rectal examinations 5.Elevated levels of prostate-specific antigen 6.Age (no limit established; possibly older than 80 years) 7.Psychopathology 8.Sleep apnea (potential for worsening) 9.Hypercoagulable states 10.Polycythemia (hematocrit >51%) Conditions that contraindicate of testosterone therapy:
  • 32. Some other chronic diseases: -Diabetes -Heart Disease -Liver or kidney disease
  • 33. Drug interactions with testosterone -Testosterone may interfere with the action of certain drugs. -Examples: 1.Warfarin (Coumadin) for thinning blood 2.Insulin or any oral drugs for diabetes 3.Propranolol (Inderal) 4.Oxyphenbutazone 5.Imipramine 6.Any kind of corticosteroid drug 7.Some herbal products
  • 34. Testosterone therapy in adult male hypogonadism
  • 35.  For hypogonadism caused by testicular failure, male hormone replacement (testosterone replacement therapy, or TRT) is used.  TRT can restore sexual function and muscle strength and prevent bone loss.  In addition, men receiving TRT often experience an increase in energy, sex drive and sense of well-being.
  • 36.  Testosterone therapy should provide physiologic range of :  serum testosterone levels (generally between 280 and 800 ng/dL)  dihydrotestosterone and estradiol levels. These would allow optimal virilization and normal sexual function.  In late teenage male patients with delayed puberty, testicular size should be monitored for evidence of onset of puberty.
  • 37. Types of testosterone replacement therapy  Injections  IM injections  Are safe and effective  eg : Testosterone undecanoate  Androderm Patch  Applied each night to the back, abdomen, upper arm or thigh  The site of application is rotated to lessen skin reactions  Gel  Androgel, testim, axiron, fortesta  Avoid skin to skin contact before the gel is completely dry.
  • 38.  Gum and cheek (buccal cavity)  Striant  Implantable pellets  Testopel : surgically implanted under the skin  Need to be replaced every 3 to 6 months
  • 39.
  • 40. SIDE EFFECTS OF TRT • Stimulation of prostate tissue, with perhaps some increased urination symptoms such as a decreased stream or frequency • Increased risk of developing prostate cancer • Gynecomastia • Increased risk of blood clots • Worsening of sleep apnea • Decreased testicular size • Increased aggression and mood swings • May increase risk of heart attack and stroke
  • 43.  Gonadotropin /GNRH therapy- only for hypogonadotrophic hypogonadism  Uses : -to induce puberty in boys -treat androgen defic in hypo. hypogonadism -initiate& maintain spermatogenesis in hypogonadotropic men who wants fertility
  • 44. Gonadotropin therapy to induce puberty  How? hCG binds to Leydig cell LH receptors and stimulates the production of testosterone.  Peripubertal boys with hypogonadotropic hypogonadism and delayed puberty can be treated with hCG instead of testosterone to induce pubertal development.  The initial regimen of hCG is usually 1,000 to 2,000 IU administered intramuscularly 2-3 times a week  The clinical response is monitored, and testosterone levels are measured about every 2 to 3 months.
  • 45.  The advantages of hCG over testosterone -the stimulation of testicular growth, -greater stability of testosterone levels and fewer fluctuations in hypogonadal symptoms -stimulating enough intratesticular testosterone to allow the initiation of spermatogenesis.  The disadvantages of hCG : the need for more frequent injections & the greater cost.
  • 46. Gonadotropin therapy  Male patients with onset of hypogonadotropic hypogonadism before completion of pubertal development may have testes generally smaller than 5 mL. These patients usually require therapy with both hCG and human menopausal gonadotropin (or FSH) to induce spermatogenesis. Men with partial gonadotropin deficiency or who have previously (peripubertally) been stimulated with hCG may initiate and maintain production of sperm with hCG therapy only. Men with postpubertal acquired hypogonadotropic hypogonadism and who have previously had normal production of sperm can also generally initiate and maintain spermatogenesis with hCG treatment only . Fertility may be possible at sperm counts much lower than what would otherwise be considered fertile. Counts of less than 1 million/mL may be associated with pregnancies under these circumstances.
  • 47.  Therapy with hCG is generally begun at 1,000 to 2,000 IU intramuscularly two to three times a week, and testosterone levels should be monitored monthly  It may take 2 to 3 months to achieve normal levels of testosterone.  When normal levels of testosterone are produced, examinations should be conducted monthly to determine whether any testicular growth has occurred. Sperm counts should also be assessed monthly during a 1-year period.
  • 48.  In general, the response to hCG can be predicted on the basis of the initial testicular volume  If spermatogenesis has not been initiated by the end of 6 to 12 months of therapy with hCG or LH, administration of an FSH-containing preparation is initiated in a dosage of 75 IU intramuscularly three times a week along with the hCG injections.
  • 49. GnRH Therapy  In patients with an otherwise intact pituitary gland and hypogonadotropic hypogonadism, synthetic GnRH can be given in a pulsatile fashion subcutaneously through a pump every 2 hours.  GnRH therapy is monitored by measuring LH, FSH, and testosterone levels every 2 weeks until levels are in the normal range, at which point monitoring can be adjusted to every 2 months. GnRH can be used to initiate pubertal development, maintain virilization and sexual function, and initiate and maintain spermatogenesis.  In most patients, these effects may take from 3 to 15 months to achieve sperm production . As with gonadotropin therapy, fertility can be achieved with very low sperm counts—often in the range of 1 million/mL.  GnRH may be more effective than gonadotropin stimulation in increasing testicular size and initiating spermatogenesis in many patients with hypogonadotropic hypogonadism .