MALE HYPOGONADISM

DefinitionMale 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 MOHAMAD10-6-76

KALLMANN SYNDROME. 

GnRH deficiency with anosmia

PITUITARY DISORDERS

hyperprolactinemia

INFLAMMATORY DISEASE

Sarcoidosis, Histiocytosis and

Tuberculosis

HIV/AIDSMEDICATIONS

OBESITYNORMAL AGINGCONCURRENT

ILLNESS

PATHOGENESISDhamirah Sakinah Binti Makmon

10-6-75

CLINICAL PICTURE AHMAD NAUFAL B NORDEEN 10-6-16SITI AISYAH BT AHMAD FAIZAL 10-6-85

SITI KHADIJAH BT MANSOR 10-6-89SITI ZULAIKHA BT SAIAN 10-6-90

Primary hypogonadism Secondary hypogonadism

Genetic: Klinefelter’s syndrome (common)Congenital: anorchia

Kallman SyndromePituitary 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

INVESTIGATIONSSiti Suhaila binti Mohaad Sariff 10-6-91

Siti Aisyah binti Rusman 10-6-92Siti Najwa binti Khamsul 10-6-94

Siti Nurul Afiqah binti Johari 10-6-95Siti Baizury binti Hassan 10-6-96

InvestigationsTo determine testosterone deficiency we must consider:- Clinical signs and symptoms (already mentioned)

- Laboratory values

Physical examination

Hormonal Assays1. 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

KaryotypingTo diagnose any chromosomal abnormalities –

Klinefelter’s syndrome, Noonan’s syndrome

Radiological Imaging 1. Magnetic Resonance Imaging (MRI)

To screen for hypothalamic or pituitary diseaseUndescended testis

2. Dual Energy X-ray Absorptiometry (DEXA)- Bone mineral density

Other assessmentFormal 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 THERAPYThe 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 THERAPYRestore Sexual Function, Libido, Well-Being, and

BehaviorProduce and Maintain VirilizationOptimize Bone Density and Prevent OsteoporosisPossibly Normalize Growth Hormone Levels in Elderly

MenPotentially Affect the Risk of Cardiovascular DiseaseRestore Fertility in Cases of Hypogonadotropic

Hypogonadism

CONTRAINDICATIONS TO TESTOSTERONE

THERAPYSHAHIZAN 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 blood2.Insulin or any oral drugs for diabetes3.Propranolol (Inderal)4.Oxyphenbutazone5.Imipramine6.Any kind of corticosteroid drug7.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 reactionsGel

Androgel, testim, axiron, fortesta Avoid skin to skin contact before the gel

is completely dry.

Gum and cheek (buccal cavity)Striant

Implantable pelletsTestopel : surgically implanted under the skinNeed 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 stimulationin hypogonadotropic

hypogonadism

By : SITI NUR JANNAH SHAARI10-6-97

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 .