The marker “Testost., F+W Bound” stands for Testosterone Free and Weakly Bound. Free and weakly bound testosterone, also referred to as bioavailable testosterone, is thought to reflect an individual’s biologically active, circulating testosterone. It includes free testosterone and testosterone that is bound to albumin. It does not include sex hormone binding globulin-bound testosterone.
What is Free and bioavailable Testosterone?
Most circulating testosterone is bound to sex hormone-binding globulin (SHBG), which, in men, also is called testosterone-binding globulin. A lesser fraction is albumin bound and a small proportion exists as free hormone. Historically, only free testosterone was thought to be the biologically active component. However, testosterone is weakly bound to serum albumin and dissociates freely in the capillary bed, thereby becoming readily available for tissue uptake. All non-SHBG-bound testosterone is therefore considered bioavailable.
Usually, bioavailable and free testosterone levels parallel the total testosterone levels. However, a number of conditions and medications are known to increase or decrease the SHBG (Sex Hormone-Binding Globulin) concentration, which may cause total testosterone concentration to change without necessarily influencing the bioavailable or free testosterone concentration, or vice versa.
Decreased testosterone levels indicate partial or complete hypogonadism. Hypogonadism occurs when your sex glands produce little or no sex hormones.
In hypogonadism, serum testosterone levels are usually below the reference range. The cause is either primary or secondary/tertiary (pituitary/hypothalamic) testicular failure.
Primary testicular failure is associated with increased luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and decreased total, bioavailable, and free testosterone levels.
- Genetic causes (eg, Klinefelter syndrome, XXY males)
- Developmental causes (eg, testicular maldescent)
- Testicular trauma or ischemia (eg, testicular torsion, surgical mishap during hernia operations)
- Infections (eg, mumps)
- Autoimmune diseases (eg, autoimmune polyglandular endocrine failure)
- Metabolic disorders (eg, hemochromatosis, liver failure)
Secondary/tertiary hypogonadism, also known as hypogonadotrophic hypogonadism, shows low testosterone and low, or inappropriately “normal,” LH/FSH levels. Causes include:
- Inherited or developmental disorders of hypothalamus and pituitary (eg, Kallmann syndrome, congenital hypopituitarism)
- Pituitary or hypothalamic tumors
- Hyperprolactinemia of any cause
- Excessive exercise
- Cranial irradiation
- Head trauma
- Medical or recreational drugs (eg, estrogens, gonadotropin releasing hormone [GnRH] analogs, cannabis)
- Drugs, such as androgens other than testosterone, can also decrease testosterone levels.
- Alcoholism in males can decrease testosterone levels.
Decreased testosterone levels may be observed in primary or secondary ovarian failure, analogous to the situation in men, alongside the more prominent changes in female hormone levels. Most women with oophorectomy (=surgical removal of one or both ovaries) have a significant decrease in testosterone levels.
In prepubertal boys, increased levels of testosterone are seen in precocious puberty. Further work-up is necessary to determine the cause of precocious puberty.
In adult men, testicular or adrenal tumors or androgen abuse might be suspected if testosterone levels exceed the upper limit of the normal range by more than 50%.
- In polycystic ovarian syndrome and related conditions, there is often significant insulin resistance, which is associated with low SHBG levels. Consequently, bioavailable or free testosterone levels may be more significantly elevated.
- Congenital adrenal hyperplasia. Non-classical (mild) variants may not present in childhood but during or after puberty. In addition to testosterone, multiple other androgens or androgen precursors, such as 17 hydroxyprogesterone (OHPG / 17-Hydroxyprogesterone, Serum), are elevated, often to a greater degree than testosterone.
- Analogous to males, but at lower levels in prepubertal girls, increased levels of testosterone are seen in precocious (=indicative of early development) puberty.
- Ovarian or adrenal neoplasms. High estrogen values also may be observed and LH and FSH are low or “normal.” Testosterone-producing ovarian or adrenal neoplasms often produce total testosterone values above 200 ng/dL.
- Polycystic ovarian syndrome. Hirsutism, acne, menstrual disturbances, insulin resistance, and, frequently, obesity form part of this syndrome. Total testosterone levels may be normal or mildly elevated and uncommonly exceed 200 ng/dL.
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