TESTOSTERONE

















References [1,2,3]
Primary hypogonadism
Cause Risk factors/Symptoms/Other
Klinefelter's syndrome
  • 1 in 600 births
  • Small, firm testes or undescended testes
  • Underdeveloped genitalia, infertility
  • Reduced body hair, gynecomastia
  • Tall stature, learning disabilities
Undescended testes or ectopic testes
  • Also called cryptorchidism
  • 85% idiopathic
Testicular trauma
  • Blunt trauma
  • Testicular torsion
Orchitis
  • Infections (ex. mumps)
Cancer treatment
  • Alkylating chemotherapeutic agents (ex. cyclophosphamide)
  • Radiation
Varicocele
  • Possible cause
Defects of steroid biosynthesis
  • 17,20 desmolase defect
  • 17β-hydroxysteroid dehydrogenase defect
Y-chromosome defects
  • Microdeletions
  • 46, XX male syndrome (1 in 10,000 - 20,000 births)
  • 47,XYY syndrome (1 in 2,000 births)
Noonan syndrome
  • Cryptorchidism, short stature, short neck
  • Deep philtrum, wide-spaced eyes, heart defects
LH receptor mutations
  • 1 in 20,000 to 1 in 1,000,000 births
  • Leydig cells do not develop


References [1,2,3,28,29]
Secondary hypogonadism
Cause Comments
Unknown
  • Most common
  • Often seen in obese men
  • May be secondary to increased estradiol production in adipose tissue
Hyperprolactinemia
Isolated hypogonadotropic hypogonadism (IHH)
  • GnRH deficiency
Kallmann syndrome
  • 1 in 10,000 to 86,000 births
  • GnRH deficiency and no sense of smell (anosmia)
  • Cryptorchidism, cleft palate, hearing loss
  • Bimanual synkinesis - movements of one hand are mirrored by the other hand
Hypopituitarism
  • Radiation therapy-induced
  • Head trauma
  • Infections (tuberculosis)
  • Infiltrative diseases (hemochromatosis, sarcoidosis, histiocytosis)
  • Vascular insufficiency (stroke)
  • Congenital
Pituitary adenomas
  • Both hormone-secreting and inactive
  • Visual field defects may be present (mass effect)
Prader-Willi syndrome
  • 1 in 10,000 births
  • Congenital disturbance of GnRH
  • Chronic overeating, underdeveloped genitals
  • Mild-to-moderate learning disabilities
Congenital adrenal hypoplasia
with hypogonadotropic hypogonadism
  • 1 in 12,500 births
  • X-chromosome recessive disease
Pasqualini syndrome
  • Isolated LH deficiency
LH or FSH mutations
  • Mutations in the Beta subunit


References [1,2,3]
Combined hypogonadism
Alcoholism
Age-related hypogonadism
Cirrhosis
Corticosteroid treatment
DAX-1 mutation
Hemochromatosis
Sickle cell disease
Thalassemia


References [1,2,3]
Diseases associated with hypogonadism
HIV - particularly in wasting syndrome
End stage kidney disease
COPD, moderate-to-severe
Type 2 diabetes
Obesity



  • Ranges are based on log hormone concentrations since their distribution is skewed
  • Reference [4]
Average age
of sample
Average
testosterone level
∼ 95% CI
Average free
testosterone level
∼ 95% CI
55
(N=1667)
517 ng/dl
(17.9 nmol/l)
167 - 867 ng/dl
(5.8 - 30 nmol/L)
11.5 ng/dl
(0.4 nmol.l)
2.9 - 20.1 ng/dl
(0.10 - 0.70 nmol/l)
62
(N=947)
459 ng/dl
(15.9 nmol/l)
145 - 773 ng/dl
(5.03 - 26.8 nmol/L)
9.3 ng/dl
(0.32 nmol/l)
3.3 - 15.3 ng/dl
(0.11 - 0.53 nmol/l)
68
(N=584)
414 ng/dl
(14.4 nmol/l)
94 - 734 ng/dl
(3.3 - 25.5 nmol/L)
7.1 ng/dl
(0.25 nmol/l)
1.9 - 12.3 ng/dl
(0.066 - 0.43 nmol/l)



  • - To convert ng/dl to nmol/l, multiply ng/dl by 0.0347
  • 1CPL labs, 2LabCorp®, 3PMID 26707506
Total testosterone3 Free testosterone
(calculated)1
Free testosterone
(equilibrium dialysis)2
Bioavailable2
231 - 850 ng/dl
(8 - 29.5 nmol/l)
4.8 - 25 ng/dl 52 - 280 pg/ml
(1.5 - 3.2%)
40 - 250 ng/dl
(9 - 46% of total)


  • References [1,2,27]
Conditions that may DECREASE
SHBG levels
Obesity
Kidney disease (Nephrotic syndrome)
Hypothyroidism
Use of corticosteroids, progestins, and androgenic steroids
Acromegaly (growth hormone tumors)
Diabetes
Conditions that may INCREASE
SHBG levels
Aging
Hyperthyroidism
Use of estrogens
Use of seizure medications
HIV
Liver cirrhosis
Vegan diet



Medications that may cause low testosterone
Anabolic steroids
Antipsychotics
may raise prolactin levels leading to hypogonadism
Corticosteroids
daily doses of ≥ 15 mg
Estrogens
GnRH antagonists
(e.g. degarelix)
GnRH agonists
(e.g. leuprorelin, triptorelin, goserelin)
Ketoconazole
inhibits steroidogenesis
Metoclopramide (Reglan®)
may raise prolactin levels leading to hypogonadism
Opiate pain medication
suppress GnRH synthesis
Progesterones
Seizure and mood stabilizer medications



  • Reference [1,2,3]
Finding Considerations
Delayed or absent sexual development
  • Primary hypogonadism
  • Consider genetic studies for Klinefelter's, etc.
Gynecomastia / galactorrhea
  • Consider hyperprolactinemia
  • Check prolactin
  • MRI to rule out prolactinoma
  • Consider medications that raise prolactin (antipsychotics, metoclopramide, etc.)
Low impact fractures
  • Bone mineral density testing
Visual field defects
  • MRI to look for pituitary mass
Skin hyperpigmentation
  • Consider hemochromatosis
  • Check iron level
  • Diabetes and liver disease are commonly present
Centripetal obesity / moon facies / abdominal striae
  • Consider Cushing's syndrome