Testosterone Levels are helpful in evaluating abnormalities with sex characteristics. Testosterone Levels are also helpful in diagnosing precocious puberty, virilizing syndromes in the female, and infertility in the male. Testosterone Levels may also be used as a tumor marker for rare tumors of the ovary and testicle.
Androgens include Dehydroepiandrosterone (DHEA), androstenedione, and testosterone. In the adrenal glands, DHEA is produced in the process of making cortisol and aldosterone. DHEA is also produced de novo by the testes or the ovaries. DHEA is the precursor of androstenedione, which is the precursor of testosterone (and estrogen).
Testosterone levels vary by stage of maturity (indicated by Tanner Stage). Serum concentrations of testosterone in both sexes during the first week of life average about 25 ng/dL. In male infants, values increase sharply in the second week to a maximum (mean about 175 ng/dL) at about two months, which lasts until about 6 months of age. In female infants, values decrease in the first week and remain low throughout early childhood. Levels increase during puberty to adult values.
In the male most of the testosterone is made by the Leydig cells in the testicle; this accounts for 95% of the circulating testosterone in men. In the female about half of the testosterone is made by the conversion of DHEA to testosterone in the peripheral fat tissue. Another 30% is made by the same conversion of DHEA in the adrenal gland, and 20% is made directly by the ovaries.
Approximately 60% of circulating testosterone binds strongly to sex hormone–binding globulin (SHBG), which is also called testosterone-binding globulin. Most of the remaining testosterone is bound loosely to albumin, and approximately 2% is free or unbound. The unbound portion is the active component. Most assays for testosterone measure the total testosterone (i.e., bound and unbound portions). The free testosterone can be measured where the testosterone binding proteins may be altered (obesity, cirrhosis, thyroid disorders). Free testosterone is estimated in this panel by an indirect method, equilibrium ultrafiltration. It can be reported as a percentage of total testosterone, or as an absolute number.
In males a biofeedback mechanism exists that starts in the hypothalamus. Gonadotropin-releasing hormone (GnRH) induces the pituitary to produce Luteinizing Hormone (LH) (called interstitial cell–stimulating hormone in the male) and follicle-stimulating hormone (FSH). LH stimulates the Leydig cells to produce testosterone. FSH stimulates the Sertoli cells to produce sperm. Testosterone then acts to inhibit further secretion of GnRH.
Physiologically, testosterone stimulates spermatogenesis and influences the development of male secondary sexual characteristics. Overproduction of this hormone in the young male may cause precocious puberty. This can be caused by testicular, adrenal, or pituitary tumors. Overproduction of this hormone in females causes masculinization, which is manifested as amenorrhea and excessive growth of body hair (hirsutism). Ovarian and adrenal tumors/hyperplasia and medications (e.g., danazol) are all potential causes of masculinization in the female. Reduced levels of testosterone in the male suggest hypogonadism or Klinefelter syndrome.
There are several testosterone stimulation tests that can be performed to more accurately evaluate hypogonadism. Human chorionic gonadotropin, clomiphene, and GnRH can be used to stimulate testosterone secretion.
Methods used for the measurement of testosterone include radioimmunoassay and extraction chromatography. There is a slight diurnal variation in the secretion of testosterone. Levels are maximal around 7 am and minimal around 8 pm.
Normal Testosterone Levels
Free Testosterone: Between 0.3 and 2 pg/mL.
Percentage of Free Testosterone: Between 0.1% and 0.3%.
Normal Total Testosterone Levels
Tanner Stage I (Between 7 months and 9 Years):
Males and Females: Less than 30 ng/dL.
Tanner Stage II (Between 10 Years and 13 Years):
Males: Less than 300 ng/dL.
Females: Less than 40 ng/dL.
Tanner Stage III (Between 14 Years and 15 Years):
Males: Between 170 and 540 ng/dL.
Females: Less than 60 ng/dL.
Tanner Stages IV and V (Between 16 months and 19 Years):
Males Between 250 and 910 ng/dL.
Females Less than 70 ng/dL.
Adults 20 years and over:
Males: Between 280 and 1080 ng/dL.
Females: Less than 70 ng/dL .
Drugs that Affect Testosterone Levels
- Drugs that may cause High Testosterone Levels include Alcohol, Anticonvulsants, Barbiturates, Estrogens, and Oral Contraceptives.
- Drugs that may cause Low Testosterone Levels include alcohol, Androgens, Dexamethasone, Diethylstilbestrol, Digoxin, Ketoconazole, Phenothiazine, Spironolactone, and Steroids.
Causes of High Testosterone Levels in Males
- Idiopathic Sexual Precocity: This is usually because of oversecretion of Luteinizing Hormone, which stimulates the testicles to produce testosterone.
- Pinealoma: This is a hypothalamic tumor that produces an increased quantity of GnRH, which stimulates the pituitary to produce Luteinizing Hormone, which in turn stimulates the testicles to produce testosterone.
- Encephalitis: This viral infection of the CNS can stimulate the hypothalamus to produce an increased quantity of Gonadotropin-releasing hormone (GnRH), which stimulates the pituitary to produce LH, which in turn stimulates the testicles to produce testosterone.
- Congenital Adrenal Hyperplasia: An enzyme deficiency in the production of cortisol causes an accumulation of large amounts of Dehydroepiandrosterone (DHEA). DHEA is a precursor of androstenedione, which is a precursor of testosterone.
- Adrenocortical Tumor: Neoplasm involving the adrenal gland can produce large amounts of testosterone or DHEA. DHEA is a precursor of androstenedione, which is a precursor of testosterone.
- Testicular or Extragonadal tumor: Leydig cell tumors can produce testosterone, which can cause precocious puberty in males. However, no spermatogenesis occurs because gonadotropin hormones are not produced and are, in fact, inhibited.
- Hyperthyroidism: These patients have elevated bound testosterone because of elevated SHBG proteins. This causes elevation of the total testosterone levels.
- Testosterone Resistance Syndromes: These patients resist the effect of testosterone on tissue. In response, higher levels of testosterone are secreted.
Causes of Low Testosterone Levels in Males
- Klinefelter syndrome: These patients have an extra X chromosome (XXY). This syndrome is associated with primary testicular failure.
- Cryptorchidism: These patients usually have normal testosterone levels, but occasionally testicles that fail to descend into the scrotum can be atrophic.
- Primary and secondary hypogonadism: Infection, tumor, or congenital abnormalities are all possible causes of primary (testicular) or secondary (pituitary) failure.
- Down Syndrome (Trisomy 21): The pathophysiology of this genetic defect is not defined.
- Orchiectomy: The testicles must both be removed. Surgical removal of just one testicle does not cause deficient testosterone levels.
- Hepatic cirrhosis: These patients have reduced proteins and therefore have reduced amounts of bound testosterone, which makes up most of the total testosterone that is measured.
Causes of High Testosterone Levels in Females
- Ovarian tumor: Arrhenoblastoma is an uncommon ovarian tumor that can produce testosterone.
- Adrenal Tumor: Neoplasms involving the adrenal gland can produce large amounts of testosterone or DHEA. DHEA is a precursor of androstenedione, which is a precursor of testosterone. Hirsutism in females is common with these tumors.
- Congenital Adrenocortical hyperplasia: An enzyme deficiency in the production of cortisol causes an accumulation of large amounts of DHEA. DHEA is a precursor of androstenedione, which is a precursor of testosterone. In females this can result in pseudohermaphroditism (ambiguous genitalia).
- Trophoblastic Tumor: These tumors (hydatidiform mole, choriocarcinoma) produce hCG, which can stimulate the production of testosterone.
- Polycystic Ovaries: This syndrome is associated with obesity, hirsutism, and amenorrhea. Patients have increased testosterone levels. The pathophysiology is not well defined.
- Idiopathic Hirsutism: The pathophysiology of this observation is not known.