Low-T

Report
http://www.isitlowt.com
What is [Low-T]?
Definition of Male Hypogonadism
• Hypogonadism in men is a clinical syndrome that
results from failure of the testis to produce
physiological levels of testosterone (androgen
deficiency) and a normal number of spermatozoa
due to disruption of one or more levels of the
hypothalamic-pituitary testicular axis
Endocrine Society clinical practice guideline
Wang C et al. Aging Male 2009;12(1):5– 12
Clinical Diagnosis – H&P
• Symptoms (non-specific)
– Fatigue, decreased libido, erectile dysfunction
– Androgen Deficiency in Aging Males (ADAM) test
http://www.isitlowt.com
Screening test for depression?
Clinical Diagnosis – H&P
• Symptoms (non-specific)
– Fatigue, decreased libido, erectile dysfunction
– Androgen Deficiency in Aging Males (ADAM) test
• Associated disease states
e.g. obesity, COPD, metabolic syndrome, diabetes, etc.
– Is low-T the cause of these diseases?
– Is it a complication of these diseases?
– Is it a co-morbidity?
Clinical Diagnosis – H&P
• Symptoms (non-specific)
– Fatigue, decreased libido, erectile dysfunction
– Androgen Deficiency in Aging Males (ADAM) test
• Associated disease states
e.g. obesity, COPD, metabolic syndrome, diabetes, etc.
– Is low-T the cause of these diseases?
– Is it a complication of these diseases?
– Is it a co-morbidity?
• Signs
– Mostly associated with congenital or developmental
hypogonadism (e.g. Klinefelter’s, undescended testes)
Definition of Male Hypogonadism
Hypogonadism in men is a clinical syndrome that
results from failure of the testis to produce
physiological levels of testosterone (androgen
deficiency) and a normal number of spermatozoa
due to disruption of one or more levels of the
hypothalamic-pituitary testicular axis
Endocrine Society clinical practice guideline
Wang C et al. Aging Male 2009;12(1):5– 12
Lab Diagnosis of Hypogonadism
Total testosterone <300 ng/dl
• Based upon lower limit of total testosterone in young
men (usually quoted normal range of 300-1000 ng/dl)
• No generally accepted lower limit of normal (lower limit
is 220 ng/dl at the Cleveland Clinic)
• Does not necessarily reflect free testosterone levels
• Should 70-yr old men be judged by norms for 30-yr olds?
• 15% of healthy young men will have a testosterone level
below the normal range in any 24 hour period
• Not necessarily indicative of “physiological levels of
testosterone”
Hypogonadism defined as
Total Testosterone <300ng/dl
Definition of Male Hypogonadism
Hypogonadism in men is a clinical syndrome that
results from failure of the testis to produce
physiological levels of testosterone (androgen
deficiency) and a normal number of spermatozoa
due to disruption of one or more levels of the
hypothalamic-pituitary testicular axis
Endocrine Society clinical practice guideline
Wang C et al. Aging Male 2009;12(1):5– 12
Low-T ≠ T-Deficiency
• Low Testosterone levels do NOT necessarily
indicate hypogonadism or testosterone deficiency
– testosterone levels can be low in normal, healthy young
men with normal sperm counts
– lots of false positives with low serum testosterone
levels alone
• Low sperm counts are necessary for the diagnosis
of hypogonadism, but seldom done
Low-T + Oligospermia = Hypogonadism
Work-up of Hypogonadism
• LH/FSH  primary vs. secondary
• If LH/FSH are inappropriately low, need to get
–
–
–
–
TSH
am cortisol level
prolactin level to rule out S.O.L.
Consider MRI
Diagnosis of Low-T generally made without
sperm counts or LH/FSH levels
Diagnosis of Low-T is made without ANY
blood work in 20% of cases
Classification of Hypogonadism
Primary Hypogonadism
• Testicular etiology
• Causes:
Undescended testes
Klinefleter’s syndrome
Hemochromatosis
Mumps orchitis
Injury to testes (e.g. cancer therapy)
Classification of Hypogonadism
Secondary Hypogonadism
• Extra-testicular etiology
• Causes:
Hypothalamic disorders (e.g. Kallmann syndrome)
Pituitary disorders (e.g. tumor, surgery, radiation)
Inflammatory disorders (e.g. TB, sarcoidosis)
Medications (especially opioids)
Obesity
HIV
Testosterone Declines Age
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/male-hypogonadism/
Late-Onset Male Hypogonadism
“Late onset hypogonadism (LOH, also referred
to as age-associated testosterone deficiency,
TDS) is a clinical and biochemical syndrome
associated with advancing age and
characterized by symptoms and a deficiency in
serum testosterone levels (below the young
healthy male reference range)”
ISA, ISSAM, EAU, EAA and ASA recommendations (2009)
Bhasin S et al. J Clin Endocrinol Metab 2010;95(6):2536–2559
Late-Onset Hypogonadism (LOH)
Alternate Terminology
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Testosterone-Deficiency Syndrome (TDS)
Age-Related Testosterone Deficiency
Andropause
Androgen Deficiency of the Aging Male (ADAM)
Partial Androgen Deficiency of the Aging Male
(PADAM)
LOH = Low-T
(+ oligospermia)
OK, Testosterone declines with age …
But is LOH a deficiency syndrome?
or a degenerative syndrome?
DEFICIENCY
DEGENERATIVE
Pathological
Normal in the context
of Aging?
Completely Reversible
Not Readily Reversed
No Side Effects if in
Physiological Range
Side Effects Possible
(No Therapeutic
Target Range)
If Low-T were a deficiency …
Artwork from: http://www.sci-news.com/medicine/science-low-testosterone-heart-problems-01418.html
then the syndrome should be
completely reversible
Artwork from: http://www.sci-news.com/medicine/science-low-testosterone-heart-problems-01418.html
If Low-T were degenerative …
Artwork from: http://www.sci-news.com/medicine/science-low-testosterone-heart-problems-01418.html
then the syndrome is not so reversible
Artwork from: http://www.sci-news.com/medicine/science-low-testosterone-heart-problems-01418.html
Reversing Effects of Low-T ?
Effects Attributed to Testosterone
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Sex drive
Erectile function
Well-being & energy
Builds muscle mass
Sperm production
Promotes heart health
Anti-obesity/diabetes
Prevents Alzheimer’s
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Maintains bone density
Supports collagen
Face/body hair
Male-pattern baldness
Aggressiveness
Promotes prostate growth
Red blood cell production
Reversing Effects of Low-T ?
Effects Attributed to Testosterone
•
•
•
•
•
•
•
•
Sex drive
Erectile function
Well-being & energy
Builds muscle mass
Sperm production
Promotes heart health
Anti-obesity/diabetes
Prevents Alzheimer’s
•
•
•
•
•
•
•
Maintains bone density
Supports collagen
Face/body hair
Male-pattern baldness
Aggressiveness
Promotes prostate growth
Red blood cell production
Risks of Treating Low T
Possible adverse effects of treatment
• BPH / elevation of PSA
• Acceleration of prostate CA / breast CA
• Mortality, MI and stroke*
• DVT
• Worsening of OSA
• Polycythemia
No physiological target range
*Vigen et al. JAMA 2013 Nov 6;310(17):1829-36; Basaria et al. NEJM 2010 Jul 8;363(2):109-22
Originator of “Low-T”
• Dr. Abraham Morgentaler
claims to have coined the term
“years ago”
– Founder of Men’s Health Boston
– Author of “Testosterone for Life”
– associate clinical professor of urology at Harvard
Medical School
– On Speaker Bureaus for Watson, Abbott (Abbvie),
Auxillium, Endo (not up to date)
– Industry funded research/investigator for GSK (not up
to date)
Claims testosterone does NOT cause prostate cancer
Is it a deficiency syndrome or a triumph of marketing?
Excerpt from Abstract:
In the absence of any new indications, off-label
testosterone prescribing has increased in most countries
in 2000–2011, especially over the last half of the period …
… By eliminating the fundamental distinction between
pathological and functional androgen deficiency, these
guidelines tacitly promote increased testosterone
prescribing, bypassing the requirement for high-quality
clinical evidence of safety and efficacy and creating
dramatic increases in prescription of testosterone
products.
Handelsman DJ. Med J Aust. 2013 Oct 21;199(8):548-51
Low “T” as in “Template”
How to Sell Disease
Schwartz and Woloshin, JAMA Intern Med. 2013;173(15):1460-1462
Three strategies:
1. Lower the bar – broaden the criteria for
definition to include more people
2. Raise the stakes – “It is one thing to tell men
that Low T can make them grumpy; it is
another to say that it can kill them.”
3. Spin the evidence – list symptoms/conditions
associated with low endogenous testosterone;
implication problems reversed with restoration
exogenous testosterone
For baby-boomers, it’s all about
SEX!
You know it’s really working
when …
A man on TV is selling me
a miracle cure that will
keep me young forever.
It’s called Androgel…for
treating something called
Low T, a pharmaceutical
company–recognized
condition affecting
millions of men with low
testosterone, previously
known as getting older.
The Colbert Report, December 2012
Direct to Consumer Advertising from
Abbvie (formally Abbott)
(makers of Androgel)
Are our memories really that short?
Remember
What?
Women are Clearly Smarter than Men
Hello …?
Women are Clearly Smarter than Men
Remember
Premarin?
Published in 1964
Dr. Robert Wilson
“… menopause is a
Hormone deficiency
and totally
preventable”
Today, it would
be called:
[Low-E]
Purported Benefits of Premarin
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Prevents hot flushes
Prevents osteoporosis
Prevents vaginal atrophy
Keeps skin young by maintaining collagen
Reduce risks of heart attacks & strokes
Prevents Alzheimer’s
Prevents age-related macular degeneration
Reduce colon cancer risk
Help prevent diabetes, Parkinson’s, tooth loss, etc.
http://www.hotzehwc.com/en-US/Resource-Center/Articles/Broken-Promises--The-History-of-HRT.aspx
Data Actually Showed …
• 1997: meta-analysis of 51 epidemiological studies
 increased risk of breast cancer
• 1998: Heart Estrogen/Progestin Replacement Study (HERS)
 no heart benefit, higher rates of cardiovascular disease
• 2002: Women’s Health Initiative (WHI)
 halted 3 years early due to risks of breast cancer and
DVT/PE
• 2003: further analysis of WHI showed increased risks of
breast CA and cardiovascular events
• 2013: estrogen might not increase cardiovascular toxicity
in early menopause
Estrogen safe in early menopause?
- Comparing Menopause & Andropause
Diagnosis of menopause is very specific, but diagnosis
of LOH is plagued by false positives
Menopause = Low-E
Low-T ≠ Andropause
Menopause is abrupt; andropause is gradual
what is early andropause?
Ok to treat flushing, osteoporosis, not as a
hormone to restore youth
SAFETY OF TESTOSTERONE THERAPY
CANNOT BE INFERED FROM WHI
Bottom Line:
Testosterone replacement therapy is
probably not warranted at this time and
should not be recommended until and
unless long-term studies demonstrate
benefits outweigh risks of therapy
MEDICALIZATION
MEDICALIZATION
Medicalization is a social process through
which a previously normal human condition
(behavioral, physiological or emotional)
becomes a medical problem in need of
treatment under the jurisdiction of medical
professionals.
Examples of Medicalization
Less Controversial
• Low-T
• Menopause
• ED
• Mammary hypoplasia
• Micrognathia
• Overbite/underbite
• Acne
• Circumcision
More Controversial
• Nutritional deficiency
• Precocious puberty
• Psychiatric diagnoses
(e.g. social anxiety,
ADHD, bipolar disorder)
• Hyperlipidemia
• Pain
• Abnormal test results
(e.g. Pap smears, PSA)
Did I lose anyone?
QUESTIONS?
Email:
[email protected]

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