Synonym

• Free testosterone
• Bioavailable testosterone
• Total testosterone

Tubes

• Red, tiger, or green top tube
• 5-7 mL of venous blood

Additional information

• Indicate patient's age, sex, and history of hormone therapy on lab request
• Handle sample gently to prevent hemolysis
• Send sample to lab promptly

Info

• The testosterone assay measures the concentration of total testosterone (free and protein bound) in the blood
• Testosterone is the principal androgen secreted by the Leydig cells of testes and adrenal glands in males, and is secreted in smaller amounts by the adrenal glands and ovaries in females
• The production of testosterone is stimulated by luteinizing hormone (LH) produced from the pituitary
• In males, testosterone is responsible for the development of secondary sexual characters, induces puberty, stimulates growth of seminiferous tubules and spermatogenesis
• Testosterone is largely bound to specific steroid hormone-binding globulin (SHBG; 60%) and albumin (38%); with this bound testosterone being physiologically inactive
• Unbound or free testosterone is the physiologically active form and makes up just 2% of all testosterone (the other 98% is bound to SHBG and albumin)

Clinical

• The clinical utility of the testosterone assay includes:
• Assists in the diagnosis and differentiation of male sexual precocity and pseudoprecocious puberty in boys <10 years of age
• Evaluation of impotence, infertility, and other sexual dysfunction in men
• Evaluation of hirsutism, virilization, and irregular menstrual periods in women
• Aids in the diagnosis and differentiation of primary and secondary hypogonadism
• To monitor testosterone replacement therapy
• Hypogonadism in males [low testosterone levels, <5 nmol/L (17 pmol/L)] may clinically present as:
• Weakness
• Eunuchoidal body habitus
• Decreased libido
• Depressed mood
• Small testes
• Impotence
• Gynecomastia
• Lack of secondary sexual characters
• Osteoporosis
• Hirsutism/virilization in females may clinically present as:
• Terminal hairs typically over the face/chin, lower abdomen, arms, legs, and around the areola of the breast
• Clitoral enlargement
• Temporal hair loss
• Breast atrophy
• Deepening of voice
• Total testosterone levels >200 ng/dL (>694 pmol/L) with severe hirsutism in females indicates androgenic tumors of the adrenal gland or ovaries
• Syndromes of androgen resistance (androgen insensitivity syndrome/AIS) is associated with increased testosterone due to abnormality of the androgen receptor or deficiency of 5-alpha-reductase enzyme (responsible for the conversion of testosterone to the active metabolite, dihydrotestosterone)
• Measurement of free testosterone levels is of significance in conditions associated with altered SHBG levels such as liver disease, thyroid disease, androgen or estrogen imbalances, and obesity. It is characterized by increased SHBG, increased total testosterone, and normal free testosterone levels

Additional information

• Testosterone undergoes a circadian rhythm in males with peak levels in early morning and lower levels in the evening
• Females show a cyclic elevation during ovulation with levels decreasing by 30% during the menses
• Normal day to day variation is about 10-20%
• Normal testosterone levels are higher in Blacks than in Whites
• In males, testosterone production begins to increase at the onset of puberty and continues to rise during adulthood. Production begins to taper off at about the age 40 and eventually drops to about 1/5 peak level by 80 years of age.
• In women, testosterone levels increase after menopause
• Dehydroepiandrosterone (DHEA), produced in the adrenal cortex, testes, and ovaries, is the main precursor for serum testosterone in women, and is converted to estradiol, the main sex hormone in females
• Testosterone is tightly bound by SGHB, with this testosterone not being biologically available
• Testosterone bound to albumin, which has a much lower affinity for testosterone than SGHB, is bioavailable. Thus, the free and the albumin bound testosterone is referred to as the biologically available form
• Use of androstenedione by athletes does not raise serum total or free testosterone levels, but increases the estradiol and estrone levels
• Different approaches currently used for measuring testosterone status include:
• Total testosterone
• Automated methods based on immunoassay
• Androgen index calculation (estimation of physiologically active testosterone)
• Free testosterone
• Equilibrium dialysis
• Equilibrium ultrafiltration
• Analog tracer immunoassay
• Bioavailable testosterone (selective precipitation of SHBG by ammonium sulfate)
• Salivary testosterone
• Factors interfering with test results include:
• Delay in separation of serum from cells gives false high levels (serum in contact with RBC for a long interval)
• Radioimmunoassay method overestimates testosterone due to nonspecific cross-reaction with dihydrotestosterone
• Hemolysis due to rough handling of sample
• Factors affecting SHBG levels
• Exogenous hormones (listed below)
• Drugs (Danazol cross-reacts to give false high or low results)
• Related laboratory tests include:
• Dehydroepiandrosterone sulfate (DHEA-S)
• Follicle stimulating hormone (FSH)
• Luteinizing hormone (LH)
• Prolactin
• Urine testosterone

Nl Result

Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

High Result

Conditions associated with elevated levels of testosterone include:

• Total testosterone levels
• In males
• Hyperthyroidism
• Syndromes of androgen resistance
• Precocious puberty
• Adrenal hyperplasia in boys
• Testicular or extragonadal tumors
• In females
• Adrenal neoplasms
• Ovarian tumors, benign or malignant (virilizing)
• Trophoblastic disease during pregnancy
• Idiopathic hirsutism
• Hilar cell tumor
• Pregnancy
• Obesity
• For both males and females
• Adrenocortical tumors
• Cirrhosis
• Fatty meals
• Exercise
• After meals
• Hemoconcentration
• Free testosterone levels
• In females
• Female hirsutism
• Polycystic ovaries
• Virilization
• Drugs
• Anabolic steroids
• Anticonvulsants
• Barbiturates
• Bromocriptine
• Casodex
• Clomiphene
• Danazol
• DHEA (in women)
• Estrogen/progestin (women)
• Flutamide
• Gonadotropin
• Goserelin
• Levonorgestrel
• Mifepristone
• Moclobemide
• Naloxone
• Nilutamide
• Norplant (no longer available in U.S.)
• Oral contraceptives
• Phenytoin
• Rifampin
• Tamoxifen
• Valproic acid

Low Result

Conditions associated with decreased levels of testosterone include

• Total testosterone levels
• In males
• Hypogonadism (primary and secondary)
• Klinefelter's syndrome
• Orchidectomy
• Hypopituitarism (primary and secondary)
• Testicular or prostate cancer
• Cryptorchidism
• Down syndrome
• Myotonic dystrophy
• Delayed puberty
• Stress
• Acute illness
• Immobilization
• Heavy exercise
• Obesity
• Malnutrition
• Uremia
• Hemodialysis
• Hepatic insufficiency
• Blind persons
• In females
• Hypogonadism (primary and secondary)
• Anovulation
• Free testosterone levels
• Hypogonadism
• Elderly men
• Drugs
• Acarbose
• Androgens
• Carbamazepine
• Cimetidine
• Conjugated estrogens
• Cyclophosphamide
• Cyproterone
• Danazol
• Dexamethasone
• Diazoxide
• Diethylstilbestrol
• Digoxin
• D-Trp-6-LHRH
• Ethanol
• Fenoldopam
• Finasteride
• Follicle stimulating hormone
• Gemfibrozil
• Glucocorticoids
• Interleukin
• Ketoconazole
• Letrozole
• Leuprolide
• Licorice
• Magnesium sulfate
• Medroxyprogesterone
• Metformin
• Methylprednisolone
• Nafarelin
• Octreotide
• Oral contraceptives
• Phenothiazines
• Pravastatin
• Prednisone
• Pyridoglutethimide
• Spironolactone
• Stanozolol
• Tetracycline
• THC (Marijuana, Marinol®)
• Thioridazine
• Verapamil

References

• AraujoAB et al.Sex steroids and all-cause and cause-specific mortality in men. Arch Intern Med. 2007 Jun 25;167(12):1252-60.
• ARUP Consult®. Hypogonadism. [Homepage on the internet]©2007. Last reviewed in May 2007. Last accessed on June 28, 2007. Available at URL: http://www.arupconsult.com/Topics/Endocrine_Disease/Hypogonadism.html
• ARUP Laboratories®. Testosterone, Bioavailable & Sex Hormone Binding Globulin (Includes Total Testosterone), Adult Male. [Homepage on the internet]©2007. Last accessed on June 28, 2007. Available at URL: http://www.aruplab.com/guides/ug/tests/0070102.jsp
• ARUP Laboratories®. Testosterone, Bioavailable & Sex Hormone Binding Globulin (Includes Total Testosterone), Females or Children. [Homepage on the internet]©2007. Last accessed on June 28, 2007. Available at URL: http://www.aruplab.com/guides/ug/tests/0081057.jsp
• eMedicine from WebMD®. Hirsutism. [Homepage on the Internet] ©1996-2006. Last updated on May 12, 2006. Last accessed on June 28, 2007. Available at URL: http://www.emedicine.com/med/topic1017.htm
• eMedicine from WebMD®. Hypogonadism. [Homepage on the Internet] ©1996-2006. Last updated on April 26, 2006. Last accessed on June 28, 2007. Available at URL: http://www.emedicine.com/ped/topic1118.htm
• Handelsman DJ et al. Testosterone: use, misuse and abuse. Med J Aust. 2006 Oct 16;185(8):436-9.
• Laboratory Corporation of America®. Testosterone: Free T or not Free T. [Homepage on the internet]©2007. Last accessed on June 28, 2007. Available at URL: http://www.labcorp.com/pdf/Testosterone_Article_for_Web.pdf
• Laboratory Corporation of America®. Testosterone, Free and Weakly Bound. [Homepage on the internet]©2007. Last accessed on June 28, 2007. Available at URL: http://www.labcorp.com/datasets/labcorp/html/chapter/mono/sr016000.htm
• Makinen JI et al. Endogenous testosterone and serum lipids in middle-aged men. Atherosclerosis. 2007 Jun 21; [Epub ahead of print]
• Miner MM et al. Evolving issues in male hypogonadism: evaluation, management, and related comorbidities. Cleve Clin J Med. 2007 May;74 Suppl 3:S38-46.
• WisniewskiAB et al. Hypothalamic-pituitary-gonadal function in men and women using heroin and cocaine, stratified by HIV status. Gend Med. 2007 Mar;4(1):35-44.