Male Hypogonadism

Male Hypogonadism
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.
Gonadotrope failure
Secondary
Elevated
Testicular failure
Primary
Sperm count
Testosterone
Gonadotropins
Pathology
Hypogonadism
Gonadal Axis
Male Gonadal Function
Male Puberty
Clinical Features
Postpuberty
* Incomplete puberty
* Eunichoidal body habitus*
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
Primary hypogonadism
Elevated
Diagnosis
Gonadotropins (LH/FSH)
Semen analysis
Testosterone

Testosterone Measurements
* Total testosterone (free + protein bound) is almost always an accurate measure of testosterone secretion
* Free testosterone should be measured by equilibrium dialysis; analog methods commonly available give results proportionate to SHBG levels (Vermeulin A JCEM 84:3666)
* Testosterone should be measured in the morning (~ 8 AM) due to diurnal variations in testosterone levels, especially in young men
* Conditions that predispose to low SHBG levels:
o Obesity (BMI > 40)
o Senescence
o Nephrotic syndrome
o Cirrhosis
o Anticonvulsants

Testosterone in Obese Men
Testosterone Secretion: Comparison of Young and Elderly Men
Standard Semen Analysis
* Typically ordered for infertility w/u only
* Normal specimen:
o > 40 million sperm/ejaculate
o > 50% motile; > 25% rapidly motile
o > 50% normal morphology
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

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

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
What is the initial diagnosis?
Primary hypogonadism
What is the next step in work up?
Karyotype: 47 XXY
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 cypionat
Serum testosterone levels after a single 200 mg IM dose of testosterone enanthate.
Transdermal Testosterone
* Patch (Androderm)
* Gels (Androgel, Testim)
Desirable Effects of Testosterone Therapy
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
* Prostate
* Red cell mass
Summary

* Signs and symptoms of hypogonadism depend on when the condition occurs in development
* Initial evaluation focuses on distinguishing between primary and secondary hypogonadism
o Primary: LH elevated, testosterone low
o Secondary: LH low, testosterone low
* Goal of testosterone replacement is physiological testosterone levels and preservation of testosterone-dependent physiological functions

Male Hypogonadism.ppt