Low Serum Testosterone

Low serum testosterone, also known as hypogonadism (HG) or andropause, is a condition that affects roughly 40% over the age of 45. If left untreated, androgen deficiency can have serious heath consequences (osteoporosis, loss of muscle mass/function, impaired sexual function/libido, and increased fat mass). Unfortunately, it is my impression that testosterone replacement therapy (TRT) is over prescribed because there is no generally accepted lower limit of normal. Furthermore, there have been no studies to define any age-specific norms. The US FDA has accepted a total testosterone (TT) of 300 ng/ml as the lower limit of normal; however, others have challenged this level, citing a variety of reasons as to why a level of 300 ng/ml is not a true reflection of HG.  Despite this uncertainty, there appears to be some consensus that TT levels above 346 ng/ml do not need TRT and levels below 231 ng/ml require TRT.  Interestingly, testosterone levels vary throughout the day (circadian rhythm), and the levels are the highest in the AM.  Therefore, a PM blood draw could be artificially low.  As a result, testosterone levels should be obtained from 7AM to 11AM.

According to the Endocrine Society, the diagnosis of low T should only be made in men with consistent signs and symptoms and unequivocally low serum T levels. Both the clinical picture and biochemical evidence (lab values) should exist prior to initiating TRT.

Testosterone is bound very tightly to a protein called Sexual Hormone Binding Globulin (SHBG). The rest of the testosterone is free. It is the free fraction that actually interacts with the body to produce its effects. As a result, in clinical conditions that increase SHBG levels, TT levels may underestimate the degree of testosterone deficiency (increased SHBG will increase the TT, but decrease the free T). In these patients, a direct measurement of the free T will unmask the problem.

SHBG levels are elevated in older men, hyperthyroidism, acromegaly, liver disease, Kleinfelter’s disease, HIV, and other chronic diseases. As men age, the increase in SHBG is at least partly responsible for androgen deficiency in the aging male.

A Great Example of SHBG and Its Relationship to Total and Free T:

55 year old male with HIV had symptoms of low T. His TT was 700ng/ml. His free T was 5 nmol/L. His SHBG was 150 (normal is 10-20). In this case, if we only examined his TT, we would not have made a diagnosis of low T. Because the SHGB was extremely elevated, his free T became very low and the patient became symptomatic. This patient was started on TRT despite a TT of 700ng/ml and did very well.

A Few Interesting Facts About Low T:

  • According to the Massachusetts Aging Study (MMAS), decreased sexual desire and activity did not have a high correlation with low levels of TT. Therefore, a high index of suspicion is the key to the diagnosis.
  • In the 15 year MMAS longitudinal follow-up, more than 505 of those men diagnosed with symptomatic TT deficiency had spontaneous remission over time.
  • Only 8-10% of men presenting with erectile dysfunction have low TT. Testosterone regulates mainly libido (sexual drive), and TRT will not always improve sexual function.
  • TRT does not improve sexual function in men with normal TT.


As experts with low T, we do offer all forms of TRT. We offer injection therapy (tesosterone cypionate), gel therapy (Androgel, Testim, Axiron, Fortesta), patch therapy (Androderm), and pellet therapy (Testopel). Essentially, we work with our patients to design a treatment protocol that is well tolerated and accomplishes our goals.