What are the normal values of direct and total testosterone?

From the Guidelines

Normal testosterone values in adult males typically range from 300 to 1,000 ng/dL for total testosterone and 5 to 21 ng/dL for direct or free testosterone. In adult females, total testosterone is much lower, typically 15 to 70 ng/dL, with free testosterone around 0.3 to 1.9 ng/dL 1. These values decrease naturally with age, particularly in men after age 30. Testosterone levels follow a diurnal pattern, with highest levels in the morning, which is why testing is typically recommended before 10 AM.

Some key points to consider when evaluating testosterone levels include:

• The diagnosis of low testosterone should be made only after two total testosterone measurements are taken on separate occasions with both conducted in an early morning fashion 1.
• Clinicians should use a total testosterone level below 300 ng/dL as a reasonable cut-off in support of the diagnosis of low testosterone 1.
• The clinical diagnosis of testosterone deficiency is only made when patients have low total testosterone levels combined with symptoms and/or signs 1.
• Laboratory reference ranges may vary slightly between different testing methods and facilities, and abnormal testosterone levels can indicate various conditions including hypogonadism, polycystic ovary syndrome, or certain tumors, so results should always be interpreted in the clinical context by a healthcare provider 1.

It's also important to note that the role of testosterone treatment in managing age-related low testosterone is controversial, and the U.S. Food and Drug Administration (FDA) requires the pharmaceutical industry to label all testosterone medications to clearly state that their products are approved for use only in persons with low testosterone levels due to known causes 1.

From the FDA Drug Label

The primary endpoint was the percentage of patients with Cavg within the normal range of 300 ng/dL to 1000 ng/dL on Day 112. The patient's daily dose was titrated up or down in 20.25 mg increments if the predose serum testosterone value was outside the range of 350 ng/dL to 750 ng/dL.

The normal values of total testosterone are between 300 ng/dL and 1000 ng/dL.

• The lower limit is 300 ng/dL.
• The upper limit is 1000 ng/dL. There is no information about direct testosterone in the provided drug label 2.

From the Research

Normal Values of Direct and Total Testosterone

The normal values of direct and total testosterone can vary depending on several factors, including age and laboratory methods.

• The mean lower reference value of total testosterone was 231 ± 46 ng/dl, with a range of 160 to 300 ng/dl, and the mean upper limit was 850 ± 141 ng/dl, with a range of 726 to 1,130 ng/dl 3.
• For young men, age-specific middle tertile levels were 409-558 ng/dL (20-24 years old), 413-575 ng/dL (25-29 years old), 359-498 ng/dL (30-34 years old), 352-478 ng/dL (35-39 years old), and 350-473 ng/dL (40-44 years old) 4.
• Average posttreatment testosterone was 573 ng/dL in the clomiphene citrate group and 553 ng/dL in the testosterone gel replacement therapy group 5.

Variability in Reference Ranges

Reference ranges for testosterone assays can vary significantly among laboratories, and are often defined by limited population studies of men with unknown medical and reproductive histories 3.

• Only 9% of laboratories that performed in-house total testosterone testing created a reference range unique to their region, while others validated the instrument-recommended reference values in a small number of internal test samples 3.
• The use of different laboratory methods, such as equilibrium dialysis and liquid chromatography with mass spectrometry, can also affect the reference ranges for free testosterone 3.

Clinical Implications

The variability in reference ranges can affect how clinicians determine treatment for hypogonadism, and highlights the need for age-specific normative values and cutoffs 4.

• The diagnosis of testosterone deficiency has traditionally been performed in an age-indiscriminate manner, but young men have different testosterone reference ranges than older men 4.
• Alternatives to testosterone replacement therapy, such as clomiphene citrate and human chorionic gonadotropin, have been shown to increase endogenous testosterone production and may be considered for young hypogonadal patients who desire future fertility 6, 7.