Testosterone replacement.  Do you (or your man) need it? I recently attended a medical conference discussing the subject of testosterone deficiency (and replacement!),  risks and benefits.  I’d like to share what I learned…

Direct-to-consumer advertisements.  There are MANY ads to promote the vigor that testosterone gives men.  Of note, the quality of life and vigor from testosterone replacement is the least well-studied part of research.

What should we call this condition?!  One term, testosterone replacement therapy, is not be the most appropriate name in that “replacing” implies a deficit.  Other names for this are androgen deficiency therapy, symptomatic androgen deficiency, pathological androgen deficiency, and testosterone replacement therapy.  It is best called testosterone therapy.  Your physician may medically appropriately diagnose it as late-onset hypogonadism (LOH).  But, the real question is….Is the deficiency of testosterone causing a decrease in quality of life?

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Criteria for LOH.

• total testosterone less than 300 ng/dl.
• Or free testosterone concentration less than 5 mg/dl.
• LH and FSH may be tested, but this is very uncommonly.
• Sexual symptoms:
  • decreased libido,
  • lack of spontaneous erections,
  • erectile dysfunction.

What is NOT LOH criteria?  (what are the MARKETED symptoms…)

• decreased energy, depressive symptoms,
• poor concentration,
• sleep disturbance,
• reduced muscle mass,
• increased body fat,
• decreased physical or work performance.  These MARKETED symptoms are vague and testosterone may be prescribed at some offices WITHOUT ever getting labs.

Prevalence of LOH.  Based on sexual symptoms (the first 3– and only LOH-specific- symptoms) 20-40% prevalence by age 80.  The MARKETED symptoms are prevalent in 40-60% by age 80.  If lab is done, then there is only low testosterone in 6% (!) in those with sexual symptoms.    The prevalence of “low total testosterone” in men with obesity, insulin resistance, metabolic syndrome is 50% and these patients may need a free testosterone to appropriately diagnose LOH.

What % of men across the globe are prescribed testosterone?  Mexico 0.05%.  Denmark 0.1%.  UK 0.3%.  Australia 0.5%.  US  3.5%. Canada 13% (inflated due to internet prescriptions being sent out of the country, read this… sent to the US among other countries).

Marketing of Low testosterone.  There are questionnaires with high sensitivity, but low specificity.  This means that the questionnaire is SO inclusive that almost all men who have low testosterone are included, but also many men who do not have low testosterone are show positive also.  As a provider, I should look at two parameters: sexual symptoms and testosterone level.  Most above questionnaires rely on MARKETING symptoms.

LOH consequences.

• frailty which increases fall risk,
• reduced bone strength.
• cardiovascular disease.
• increased all-cause mortality  (we are unsure about the association versus causation.)  There is minimal evidence that replacement of testosterone decreases all-cause mortality (meaning you may not live longer than without testosterone replacement). Supplementation of testosterone may not decrease all-cause mortality rate by much.

Influences on Testosterone levels.  Testosterone levels vary daily and throughout the day.  So, have more than one testosterone level drawn.  Check on more than one day.  Labs should all be obtained in the morning (as up to 13% lower in the afternoon).  30% of abnormal afternoon tests may be normal in the morning. Should you get a total testosterone or a free testosterone.  60% of testosterone is bound to sex-hormone binding globulin (SHBG), 38% is bound to albumin.  2% is free.  So, if the total testosterone level is low and the patient is obese, then a free testosterone may be helpful, as it may really be at a normal level.

Benefits of testosterone therapy.

• Slightly decreased depressive symptoms.
• Slight increase in 6-minute walking distance.
• Moderate benefit in improved sexual function (BUT this fades over time).
• No change in vitality, overall function, quality of life.
• No benefit to those who take testosterone in their muscle mass versus muscle strength and performance.

The testosterone trials.  https://clinicaltrials.gov/ct2/show/NCT00799617  The largest and longest clinical trial.  They screened 51,000 men to get 790 men to be in the study.  (This was 1.5% of those screened).  Total testosterone level to be in the study was less than 275 ng/dl and men had sexual side effects.  We know that Viagra (or similar medications) is better for erectile dysfunction.  Testosterone benefits waned over time  Increased estradiol levels may occur (especially is obese men who then noted breast development).

Risks of testosterone.

• Mood disorders can occur with testosterone, just like it does with anabolic steroids.
• Liver cancer can occur although this is avoided with transdermal of intramuscular administration of testosterone.
• Increased red blood cells which may increase the risks of making blood clots.
• Gynecomastia–men making breast tissue (from testosterone changing to estrogen within the body).
• Sleep apnea.
• Whereas, prior concerns of testosterone increasing prostate cancer is now disproven, this does not happen.

Benefits of testosterone.

• May lower blood pressure.
• May improve left ventricular heart function.
• May increase blood pressure in obese men,
• lowers good-cholesterol (HDL).
• Increased red blood cells which may increase the risks of blood clots.

Contraindication to testosterone therapy.

• Breast cancer.
• Prostate cancer.
• Severe lower urinary symptoms (like difficulty starting or stopping the stream of urine, getting up at night to urinate).
• Sleep apnea risk increases or may worsens with testosterone.

Testosterone Preparations.

• 85% of prescriptions for testosterone is by gel administration.  Gel 25-50mg/d.
• The least expensive formulation of testosterone is an injection intramuscular

How to monitor testosterone therapy?

• Baseline assessment:
  • Needs a digital prostate exam.
  • PSA lab work should be under 4 ng/ml.
  • Bone density test.
• Monitoring of lab should be done every 3-6 months.
  • Total testosterone should be above 350-400 ng/dl.
  • Patient should fill out a symptom assessment.  If the patient does not FEEL better, then the testosterone may be discontinued.
  • Check red blood cell count.
  • Follow up rectal exam and PSA (if the PSA increases by more than 0.4 ng/ml/year that’s important).
  • Consider re-check bone density.

Overall.  There is no widespread screening recommended to check for testosterone level.  Treatment should be based on LOW testosterone levels ONLY if patients also have sexual symptoms.  Understand that free testosterone lab may be needed with those with obesity or diabetes.   The patient needs to have an informed consent as he needs to know the risks of treatment.  If the patient’s benefits go away, then stop the testosterone.

I hope this helps…