Low T: A Pathologist’s Perspective

Low testosterone (low T), a term that has become commonplace, is heard everywhere. You have probably seen the commercials. It is one of the biggest stories in men’s health. With it has come a lot of debate on the risks and benefits.

Now a new study links borderline low T and depression.


Published online, researchers at the George Washington University found that men referred for evaluation of borderline low testosterone frequently suffered from depression. What is unique about this study is that it is one of the first to examine men with borderline low testosterone. Another surprising finding was that 25% of patients were using an antidepressant. The patients had high incidences of obesity and physical inactivity. They also commonly reported symptoms of sexual dysfunction, sleep disturbances and low energy.

Low T has become big business. In 2013, 2.3 million prescriptions were written, up from 1.3 million in 2010. Yearly US sales were $2.4 billion in 2013 and are expected to rise to $3.8 billion in 2018. Marketing was at $152 million in 2013, a 2,800% rise since 2009. Let’s break it down from a pathologist’s perspective

What is low T?

Testosterone normally peaks in a man’s 20s then falls 1-2% per year thereafter. Testosterone is produced by the testicles and is an important male sex hormone. It serves numerous functions, including maintenance of sperm production, sex drive and bone health. Low testosterone contributes to a loss of muscle mass, diminished sex drive, low sperm count, hair loss, weak bones, depression, breast tenderness and an increase in body fat.

Low testosterone can occur though normal aging and many diseases. About 2.4 million 40-49 year old men have low T levels, even higher in those over 50. An estimated 481,000 new diagnoses are made each year with a prevalence of about 13 million American men.

Lab testing

Testosterone levels can vary in an individual patient, based on time of day and underlying illness. The level is highest in the morning. Values can vary from lab to lab depending on the instruments used, making it important that the same lab is used for your testing.

Testing for testosterone, in addition to all blood tests, is performed in the lab and is overseen by pathologists. A blood sample is spun down in a centrifuge, heard here.  

Next it is analyzed on an automated instrument where many different tests are resulted, heard here.

The diagnosis of low T requires signs and symptoms plus a low testosterone lab value. The testosterone level may be repeated in order to establish a baseline value. Depending on the level, additional testing may be done for other hormones and related markers, i.e. free testosterone, bioavailable testosterone, sex hormone binding globulin (SHBG), FSH and LH. Your doctor will continue to monitor levels throughout treatment, as well as PSA.

There are algorithms used for the diagnosis and replacement of low T. However, there is no consensus on the definition of low T. Lab values must be evaluated in the appropriate clinical context. Efforts are underway to standardize testing and reporting.


There are reports of an increased risk of heart disease, diabetes, obesity, osteoporosis, sleep apnea, blood clots, stroke and prostate problems both benign and cancer, with testosterone treatment. As such, one must be careful to select a doctor with experience in treating Low T. Be wary of the many “low T clinics” that have sprung up. As such, many may be inappropriately treated. The FDA warns that many patients do not meet criteria for treatment, not even having been tested for testosterone. They recently rejected a proposal to issue a warning regarding cardiovascular disease. Clearly more studies need to be done.

What you can do?

Know the signs and symptoms of low T. Talk with your doctor about the risks and benefits. Make sure your doctor checks your testosterone if you are experiencing any of these symptoms. See a urologist or another doctor with experience in the diagnosis and treatment of low T. Make sure guidelines are followed, such as those issued by The American Urological Association.  Follow a healthy lifestyle. One can boost natural testosterone through weight loss and building muscle through exercise.

This also offers an opportunity to meet your pathologist. Make sure the lab doing your testing is accredited by a regulatory agency, such as the College of American Pathologists, which assures accuracy, precision and quality control in lab testing. Take control of your health.



Dr. Michael Misialek currently serves as Associate Chair of Pathology at Newton-Wellesley Hospital, Newton, MA. He is the Medical Director of the Vernon Cancer Center, Chemistry Laboratory and Point of Care Testing. He practices in all areas of pathology in a busy community hospital. Holding an academic appointment at Tufts University School of Medicine as a clinical assistant professor of pathology, he regularly instructs medical students and pathology residents. Dr. Misialek is a strong advocate for pathology and is very active in the College of American Pathologists (CAP), serving on the Personalized Healthcare Committee, the political action committee PathPAC, the CAP Foundation and as chair of the Massachusetts delegation in the CAP House of Delegates. He is an inspector with the CAP and has conducted several domestic and international hospital laboratory inspections.

He received his MD from the University of Massachusetts, did an internship in internal medicine at Boston Medical Center and completed his residency in anatomic and clinical pathology at the University of Massachusetts Medical Center. He did a fellowship in general surgical pathology at the University of Florida and is board certified in Anatomic and Clinical Pathology.