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Instalab ResearchTestosterone is the primary male sex hormone, produced mainly in the testes, and to a lesser extent in the adrenal glands. It plays a critical role in a wide range of physiological functions including:
While testosterone is often discussed in the context of sexual health, its impact reaches far beyond libido. Low levels can influence everything from insulin sensitivity to cardiovascular health, making it vital to monitor and understand.
Testosterone levels begin to decline gradually starting in a man's 30s, with a more noticeable drop by age 40 to 50. Clinical studies have shown that total testosterone levels decline approximately 1% per year after the age of 30. This decline is exacerbated by increases in SHBG, which binds testosterone and makes it unavailable to tissues.
A large population-based study involving over 2,500 men aged 70 and older found significant associations between age and reduced levels of both total and free testosterone. This same study also demonstrated that increases in SHBG were a primary factor in reduced testosterone bioavailability, independent of total testosterone concentration. Such findings highlight the importance of assessing multiple testosterone markers, not just total testosterone.
Total testosterone includes all testosterone circulating in the blood, whether it is free or bound to proteins such as SHBG and albumin. It is typically the first marker tested in routine hormone assessments. While total testosterone offers a general overview of hormonal status, it does not distinguish between active and inactive forms of the hormone.
In clinical practice, relying solely on total testosterone can be misleading. Conditions like aging, liver disease, and thyroid dysfunction can alter SHBG levels, leading to misleading total testosterone readings. In a study evaluating the biochemical profiles of aging men, researchers found that men with clinically normal total testosterone levels often had symptoms of androgen deficiency due to elevated SHBG and reduced free testosterone.
Free testosterone represents the fraction of testosterone not bound to proteins and is considered the most biologically active form. Although it comprises only about 2% of the total testosterone in circulation, it is the portion that can enter cells and activate androgen receptors.
Multiple studies have shown that free testosterone levels are more strongly correlated with symptoms of hypogonadism than total testosterone. For example, a clinical investigation comparing hematologic markers and testosterone levels found that free testosterone had a stronger association with erythropoietic activity than total testosterone, suggesting its greater physiological relevance.
Because direct measurement of free testosterone is technically complex and subject to variability, many clinicians use calculated free testosterone, which incorporates measurements of total testosterone, SHBG, and albumin. Research indicates that calculated values closely reflect biologically available testosterone and correlate well with symptoms in older men.
Sex hormone-binding globulin is a glycoprotein produced by the liver that binds tightly to sex hormones, including testosterone and estradiol. SHBG plays a critical role in regulating the amount of free testosterone available to body tissues. When SHBG levels are elevated, more testosterone is bound and rendered biologically inactive.
SHBG levels tend to increase with age and can also be influenced by several factors such as thyroid function, liver health, and body mass index. A pivotal study involving elderly men found that low SHBG levels were a stronger predictor of metabolic syndrome than low total or free testosterone. This suggests SHBG not only modulates testosterone availability but may also serve as a marker of broader metabolic health.
Albumin is the most abundant protein in blood plasma and binds to testosterone with lower affinity than SHBG. Because this bond is weak and easily reversible, albumin-bound testosterone is considered bioavailable, meaning it can dissociate and become active when needed.
While often overlooked, albumin plays a vital role in testosterone transport and bioavailability. Studies comparing the clinical utility of various testosterone fractions have shown that measuring or calculating bioavailable testosterone, which includes both free and albumin-bound forms, provides a more accurate representation of androgen status than total testosterone alone, particularly in men with borderline hormone levels.