Male Hypogonadism

Male Hypogonadism
Presentation lecture by:Michael Jakoby, MD/MA
Clinical Associate Professor of Medicine
Chief, Division of Endocrinology


Case study
Definition
Decrease in one or both of the two major functions of the testes.
Low/low nl
Gonadotrope failure
Secondary
Elevated
Testicular failure
Primary Sperm count
Testosterone
Gonadotropins
Pathology
Hypogonadism
Gonadal Axis
Male Gonadal Function
Male Puberty
Clinical Features
Postpuberty
Prepuberty
Micropenis
3rd trimester
Incomplete virilization
1st trimester
Effects
Age
Screening for Androgen Deficiency

* Infertility
* Sellar mass, radiation, or surgery
* Osteoporosis or low trauma fracture
* HIV-associated weight loss
* ESRD
* COPD (moderate to severe)
* Type 2 diabetes mellitus
* Medications that effect testosterone production
o Glucocorticoids
o Opiates
o Ketoconazle
The Endocrine Society recommends against screening for androgen deficiency in the general population
History

* Symptoms onset
* Testicular size
* Breast enlargement
* Behavioral abnormalities
* Chemotherapy or radiation therapy
* Alcoholism
* Visual field defects
* Medications

Examination

* Testicular size
* Pubic hair
* Gynecomastia
* Muscle mass
* Body proportions
* Fundoscopy & visual fields screening

Laboratory Testing
Secondary hypogonadism
Low sperm ct
Primary hypogonadism
Elevated
Low sperm ct
Low/low nl
Diagnosis
Gonadotropins (LH/FSH)
Semen analysis
Testosterone
Testosterone Measurements
Testosterone in Obese Men
Testosterone Secretion:
Comparison of Young and Elderly Men
Standard Semen Analysis
DDx: Primary Hypogonadism

* Klinefelter’s syndrome
* Gonadotropin receptor mutations
* Cryptorchidism
* Androgen biosynthesis disorders
* Varicocele
* Congenital anorchia
* Mumps orchitis
* Radiation
* Antineoplastic drugs
* Ketoconazole
* Glucocorticoid excess
* Trauma
* Testicular torsion
* Autoimmune orchitis
* Cirrhosis
* Chronic renal failure
* HIV infection
* Idiopathic
Congenital
Acquired
DDx: Secondary Hypogonadism

* Isolated hypogonadotropic hypogonadism
* Kallman’s syndrome
* DAX1 mutation
* GPR 54 mutation
* Leptin or leptin receptor mutations
* Gonadotrope receptor mutations
* Hypopituitarism
* Hyperprolactinemia
* Androgen therapy
* GnRH analog therapy
* Glucocorticoid therapy
* Critical illness
* Chronic illness
* Diabetes mellitus
* Opiates
* Pituitary mass lesions
* Infiltrative diseases
* Sellar surgery
* Sellar radiation
Evaluation of Men with Androgen Deficiency

Confirmed low testosterone
Check LH+FSH (SA if infertility)
High gonadotropins – 1o
Low/low nl gonadotropins – 2o
Karyotype
Prolactin, other pituitary hormones, iron studies, sella MRI
Klinefelter’s Syndrome
Gonadal Manifestations of Klinefelter’s Syndrome
Decreased penis length
Decreased axillary hair
Gynecomastia
Decreased sexual function
Increased gonadotropins
Decreased facial hair
Low testosterone
Azoospermia
Decreased testicular length
Abnormal testicular histology
Frequency (%)
Abnormality

Testosterone Replacement
* Primary goal is to restore testosterone levels to the laboratory reference range
* Prescribe only for patients with confirmed hypogonadism
* Role in “treating” decline in testosterone levels with aging uncertain
* Multiple preparations
o Oral
o Intramuscular
o Transdermal
o Buccal
Oral Testosterone Preparations

* Alkylated testosterone more slowly metabolized by liver than native testosterone
* May not induce virilization in adolescents
* Untoward effects
+ Cholestatic jaundice
+ Peliosis hepatis
+ Hepatocellular carcinoma

Intramuscular Testosterone

* Enanthate and cypionate esters of testosterone
* Lipophilic, leading to sustained release from muscle depots
* Side effects related to dosing or administration
* Regimens of 100 mg q wk to 300 mg q 3 wks acceptable
* Goal is a mid-cycle level near the middle of the laboratory reference range

Transdermal Testosterone

* Patch (Androderm)
o Apply to skin of upper arms and torso
o Delivers 5 mg testosterone/24 hr in continuous manner
o Approximately 1/3 of patients develop significant contact dermatitis
* Gels (Androgel, Testim)
o Apply to skin of upper arms and torso
o Usually dosed as 5.0 g or 10.0 g of gel to deliver 50 mg or 100 mg testosterone, respectively in a continuous manner
o Reports of contact dermatitis and gel odor uncommon

Desirable Effects of Testosterone Therapy
* Virilization (incompletely virilized men)
* Increased libido and energy
* Improved erectile function?
* Increased muscle mass and strength (8-10 wks)
* Increased bone mass (full effect ~ 24 mo)

Untoward Effects of Testosterone Therapy

* Pain at injection site (IM preparations)
* Contact dermatitis (patch >> gel)
* Acne or oily skin
* Gynecomastia
* Aggressive behavior (adolescents)
* Short stature (adolescents)
* Increased prostate volume/PSA
* Urinary retention (BPH exacerbation)
* Sleep apnea
* Erythrocytosis

Contraindications to Testosterone Therapy

* Very high risk of adverse outcomes
o Prostate cancer
o Breast cancer
* High risk of adverse outcomes
o Undiagnosed prostate nodule
o Unexplained PSA elevation
o BPH with severe urinary retention
o Erythrocytosis
o NYHA Class III or IV heart failure
Pre-treatment Screening

* Digital rectal exam
* History of urinary retention (urodynamic studies, bladder US PRN)
* History of sleep apnea symptoms (polysomnography PRN)
* PSA (urology referral if > 4 ng/mL)
* CBC

Treatment Monitoring

* Serum testosterone
o IM testosterone: midpoint between injections, level near middle of reference range
o Patch: 3-12 hrs after applying new patch
o Gel: timing not critical
o Buccal pellet: immediately before or after new pellet
* Prostate
o DRE @ 3 months, then annually
o PSA @ 3 months, then annually
o Prostate biopsy if PSA > 4 ng/mL, PSA increases by > 1.4 ng/mL in 12 months, or PSA velocity > 0.4 ng/mL/yr
* Red cell mass
o CBC at 3 months, then annually
o If Hct > 54%, stop therapy, monitor for return to reference range, then resume therapy at a lower dose

Summary
Male Hypogonadism.ppt