What is the normal percentage of free testosterone?

From the Guidelines

Normal percent free testosterone typically ranges from 1.5% to 3% of total testosterone in adult males. This range is based on the understanding that free testosterone is the biologically active form of testosterone that can enter cells and activate testosterone receptors, influencing various physiological functions such as muscle growth, bone density, and sex drive 1. The majority of testosterone in the body is bound to proteins like sex hormone-binding globulin (SHBG) and albumin, which makes it unavailable for immediate use.

Factors Influencing Free Testosterone Levels

Several factors can affect percent free testosterone levels, including:

• Age: Testosterone levels naturally decline with age
• Health conditions: Certain medical conditions can impact testosterone production
• Medications: Some medications can alter testosterone levels
• Obesity: Obesity-related decreases in testosterone are frequently attributable to low concentrations of sex hormone-binding globulin, but some individuals with obesity may also have low free testosterone levels due to increased aromatization of testosterone to estradiol in adipose tissue 1

Clinical Evaluation

When evaluating low total testosterone clinically in a man with obesity, the measurement of morning serum free testosterone is essential, as men with obesity and hypogonadism who have low total testosterone due solely to low sex hormone-binding globulin may have normal free testosterone levels 1. The assessment should include a morning total testosterone concentration drawn between 8 AM and 10 AM, as well as a free testosterone level by equilibrium dialysis and a sex hormone-binding globulin level in patients with obesity.

Testosterone Replacement Therapy

In patients with obesity, treatment with testosterone-replacement therapy should be considered when the morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments, and the hypogonadism workup has been completed to rule out an etiology of hypogonadism unrelated to obesity 1. The method of testosterone replacement should be individualized for each patient, with transdermal testosterone preparations suggested for most hypogonadal men because they usually produce normal serum testosterone concentrations and are typically found to be the most convenient by patients.

From the Research

Normal Percent Free Testosterone

• The normal percent free testosterone is not explicitly stated in the provided studies, but we can look at the normal ranges for free testosterone levels.
• According to 2, free testosterone levels are approximately 15-25 times higher in adult men compared to women, and most testosterone circulates tightly bound to sex hormone-binding globulin (SHBG) or weakly bound to albumin.
• A minor amount circulates as free testosterone, and it is believed that this is the metabolically active fraction.
• In the study 3, the mean free testosterone level before treatment was 8.1 pg/ml, and during treatment, it was 20.4 pg/ml.
• However, without a clear definition of the normal percent free testosterone, it is difficult to provide a specific answer to this question.
• It is worth noting that the measurement of free testosterone is important in the diagnosis of many diseases, most importantly disorders of androgen deficiency in men (i.e., hypogonadism) and androgen excess in women (i.e., polycystic ovary syndrome and hirsutism) 2.

Measurement of Free Testosterone

• Many methodologies are available for free testosterone measurement, including the reference methods (equilibrium dialysis and ultrafiltration), analog immunoassay, and calculated free testosterone based on measurement of total testosterone, SHBG, and albumin 2.
• The study 4 suggests that free testosterone levels should be measured in men in whom alterations in binding protein concentrations are suspected or in whom total testosterone levels are only slightly above or slightly below the lower limit of the normal male range for testosterone.
• The choice of method for measuring free testosterone may depend on the specific clinical context and the availability of resources.

Clinical Utility of Free Testosterone Measurement

• Measurement of free testosterone is important in the diagnosis of many diseases, most importantly disorders of androgen deficiency in men (i.e., hypogonadism) and androgen excess in women (i.e., polycystic ovary syndrome and hirsutism) 2.
• The study 3 shows that concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy, and free testosterone levels were measured as part of this study.
• The study 5 compares serum testosterone response and symptom improvement in men with hypogonadism in response to treatment with clomiphene citrate, human chorionic gonadotropin, or a combination of both therapies, and free testosterone levels were not directly measured, but total testosterone levels were measured.