Abraham Morgentaler, M.D. Discusses 9 Resolutions Representing Expert Consensus and State of the Art in Testosterone
Jeff Morris
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On Friday, May 13, at the 20th Clinical Applications for Age Management Medicine Conference in Orlando, FL, Dr. Abraham Morgentaler of Harvard Medical School presented nine resolutions addressing key issues in testosterone. These resolutions were the result of consensus among experts gathered for a conference in Prague on October 1, 2015, chaired by Dr. Morgentaler, for the express purpose of finding common ground among them in addressing the large amount of misinformation in media and medical journals regarding T deficiency and its treatment. Participating in the conference were 18 individuals from 11 countries on 4 continents. The FDA and European Medicines Agency were invited; the EMA participated. Specialties among those present included internal medicine, urology, endocrinology, diabetology, and basic science research, all with extensive clinical or research experience with T. The E-Journal would like to share these resolutions.
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RESOLUTION 1
Testosterone deficiency is a well-established, significant medical condition that negatively affects male sexuality, reproduction, general health, and quality of life.
Testosterone deficiency:
- May predict increased risk of developing diabetes, metabolic syndrome
- Contributes to decreased bone mineral density
- Is associated with increased all-cause and cardiovascular mortality
- Negatively impact general health and quality of life
RESOLUTION 2
- Symptoms and signs of TD occur in healthy volunteers or patients who undergo androgen deprivation therapy: these symptoms and signs resolve with T normalization
- Historically recognized causes of TD are rare (e.g., anorchia craniopharyngioma, pituitary tumor), recently termed “classical hypogonadism.” These conditions are rare
- TD occurs frequently with conditions other than “classical” causes
- No evidence supports restriction of T therapy only to men with known underlying etiology
RESOLUTION 3
- Prevalence rates in adult men range from 2% to 38% in studies from Asia, Europe, North America, and South America
- Variation in prevalence rates explained by differences in operative definition of TD and biochemical thresholds
- US study estimates additional $190-525 billion in health care expenditures over 20 years due to TD
RESOLUTION 4
Testosterone therapy for men with TD is effective, rational, and evidence-based
High-level evidence shows T therapy effectively:
- Increases sexual desire (libido),and erectile and orgasmic function,
- Increases lean body mass n Decreases fat mass
- Improves bone mineral density
- Strongly suggestive evidence for improvement in mood, energy
RESOLUTION 5
There is no T concentration threshold that reliably distinguishes those who will respond to treatment from those who will not
No study has revealed a single testosterone threshold that reliably separates those who experience signs and symptoms of TD from those who do not, nor who will likely to respond to treatment
Interpretation of total T concentrations confounded by:
- Inter-individual variation
- Variation in serum SHBGc (binds tightly to T, theoretically removing it from the bioavailable pool)
- Genetic variation in androgen sensitivity due to ARd gene polymorphisms (number of CAGe repeats)
- Free testosterone can be useful indicator of androgen status
RESOLUTION 6
There is no scientific basis for any age-specific recommendations against the use of T therapy in adult men
- “Age-related hypogonadism” is of questionable validity, since the decline in mean serum T with age is minor and attributable to comorbidities, especially obesity
- Older men respond well to T therapy, as do younger men
- Increased risk of erythrocytosis in older men requires monitoring, but does not merit withholding T therapy if indicated
- It is illogical to single out TD as the one medical condition among many (eg, diabetes, hypertension, heart disease, cancer, arthritis) that does not merit treatment because it becomes more prevalent with age
RESOLUTION 7
The evidence does not support increased risks of cardiovascular events with T therapy
- Media focused on 2 observational studies that reported increased CV risks. Both had major flaws/limitations
- Low serum T is associated with increased atherosclerosis, coronary artery disease, obesity, diabetes, and mortality
- Several RCTs in men with known heart disease (angina, heart failure) showed greater benefits with T vs placebo (greater time to ischemia, greater exercise capacity)
- Largest meta-analysis showed no increased risk with T therapy: reduced risk noted in men with metabolic conditions
- No increased risk of veno-thrombotic events with T therapy
RESOLUTION 8
The evidence does not support increased risk of prostate cancer with T therapy
- Serum androgen concentrations are not associated with increased risk of PCa nor aggressive disease
- T therapy shows no greater risk of PCa than placebo
- Aggressive/high-grade PCa associated with low serum T levels
- Early data suggests no increased risk of recurrence/progression with T therapy in men previously treated for PCa
RESOLUTION 9
The evidence supports a major research initiative to explore possible benefits of T therapy for cardiometabolic disease, including diabetes
- Large body of evidence suggests lower serum T concentrations associated with increased CV risk: higher levels are protective
- T therapy reliably increases lean mass, decreases fat mass, and may improve glycemic control
- Mortality rates reduced by half in men with TD who received T therapy compared with untreated men- observational studies
- Among men who received T therapy, those with normalized T had reduced rate CV events/mortality vs men with persistently low T
Return to May 2016 e-Journal 
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