a memorandum on andropause management dr. claude chauchard paris, france chairman & ceo - la...
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A memorandum on A memorandum on
andropause managementandropause management
Dr. Claude Chauchard
Paris, FRANCE
Chairman & CEO - La Clinique de Paris Group
Former Assistant Professor of
Montpellier University
Anti-aging Medicine World Congress Anti-aging Medicine World Congress
Monte Carlo, MonacoMonte Carlo, Monaco
April 8-10, 2010April 8-10, 2010
© Claude Chauchard La Clinique de Paris 2009 1
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Goal of Anti-Ageing MedicineGoal of Anti-Ageing Medicine
Increase Health Span not just lifespan
Increase lifespan if:
strong and vigorous
happy content creative
spiritually satisfied
No one wants to live longer with
debility or chronic illness or cognitive
impairment© Claude Chauchard La Clinique de Paris 2009
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Balanced hormone replacement therapy
All hormones restored to 25-30 years
old level and monitored by regular
serum levels
Natural (Bioidentical) hormones
Identical molecular structure to hormones
produced by human female or male
Not xeno hormones or horse hormones
Synthetically produced
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Balanced HRT
Human growth hormone
DHEA, Pregnenolone, Melatonin
Testosterone in men and women
Estrogens and Progesterone in
women (Bio-identical hormones)
Not Premarin or Provera (MPA)
Thyroid (T3 and T4, not just T4)
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We age because our hormones decline, our hormones don’t decline because we age
Testosterone replacement therapy is safe and can provide dramatic benefits
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Andropause & Menopause
Breast Cancer Prostate Cancer
Osteoporosis Osteoporosis
Cardiovascular Disease
Cardiovascular Disease
Sexual function Sexual function
Well being Well being
Body Fat Body Fat
Estrogen Testosterone
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Symptoms of Change of LifeSymptoms of Change of Life
© Claude Chauchard La Clinique de Paris 2009
Male Female
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Testosterone & ProstateTestosterone & Prostate
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OverviewOverview
9© Claude Chauchard La Clinique de Paris
ECBUECBU
UIVUIV
Bladder Bladder FullFull
Abdominal Abdominal SonographSonograph
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Male Menopause = AndropauseMale Menopause = Andropause
Less sudden in onset than female
menopause
Just as severe in long term
consequences
The cause …
Decreased bioavailable
TESTOSTERONE
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Male MenopauseMale Menopause
FatigueDepressionIrritabilityReduced libido and potency
◦ Decreased desire and fantasies
◦ Decreased morning erections
◦ Decreased erectile tension
◦ Longer recovery time between orgasms
◦ Decreased intensity of orgasms
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Male MenopauseMale Menopause
Increased aging of heart and circulation
◦Increased MI’s and CVA’s
◦Decreased hemodynamic function
Increased brain aging
◦Decreased memory
◦Decreased intelligence
◦Increased Dementia, Alzheimer’s
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Male MenopauseMale Menopause
Loss of drive and competitive edge
Stiffness and pain in muscles and
joints
Falling level of fitness
Decreased effectiveness of workouts
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Male MenopauseMale Menopause
The cause …
Decreased bioavailable
TESTOSTERONEPlus
◦ Stress
◦ Alcohol
◦ Increased fat especially abdominal fat
◦ Lack of exercise
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Does T decline with age ?Does T decline with age ?
Older studies showed no difference◦ Did not measure free T◦ Did not get AM samples
Total T, Free T, Bioavailable T, E1 and E2 decline with age
T declines 10 ng/dl per yearFree T 1% per yearAll T measures correlated with strength,
BMD body composition, fat mass
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Sex Hormone Binding Globullin (SHBG) binds T > E
◦ 20-60 nmol/l male
◦ 40-120 nmol/l femaleFree Androgen IndexTestosterone x 1000 / SHBGT is tightly bound to SHBG and loosely
bound to albuminFree T is unbound to SHBG or albuminBioavailable T = unbound + loosely bound
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0 0400 0800 1200 1600 2000
Clock Time (Hours)
400
500
600
700
800S
eru
m C
on
cen
trati
on
(n
g/d
l)
Old Men
Young Men
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Hypothalamus
GnRH
AnteriorPituitary
Estrogens
FSH
Aromatase
LH TESTOSTERONE
DHT
5-alpha Reductase
Testes
Leydig cell
Sperm Sertoli cell
Inhibin
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Methods of TRTMethods of TRT
Injections of T enathate or T cypionate
Older method 200 mg q 2 weeks
◦ Roller coaster effect
◦ Suprahysiologic levels followed by low levels
◦ More aromatization to Estradiol
◦ More polycythemia
◦ Less DHT increase thatn transdermal
Weekly dose 100 mg
◦ More physiologic stable levels
◦ Less aromatization to Estradiol
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Oral – Methyltestosterone
◦ Hepatotoxic, contraindicated
Oral – T undecanoate (Andriol)
◦ Lymphatic absorption, no hepatic toxicity
reported
◦ Must use TID
◦ No available in US
Subcutaneous pellets
◦ Minor surgical procedure
◦ Last 2-3 months
Methods of TRT
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TransdermalTransdermal
Well absorbed as proven by serum levels
More DHT since hair follicles contain 5
alpha reductase
Steady state after 24 hours
Scrotal (Testoderm) – shaved scrotum
required, inconvenient, high DHT
Patches (Androderm) – Delivers 5 mg per
day, inconvenient, expensive
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TransdermalTransdermal
Androgel
◦ 1% transdermal gel
◦ Commercially available
◦ 50, 75 or 100 mg packages
Compounding pharmacies
◦ Can custom produce transdermal gel
◦ Can titrate to serum levels by varying
percentage 1-20 and dose
◦ Preferred method in most men
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T gel precautionsT gel precautions
Avoid scrotum (increased DHT)
Avoid getting gel on females and kids
Rub in well over large surface area
Can increase hair growth in area of application but (unfortunately) not on head
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Dihydro TestosteroneDihydro Testosterone
More potent than T (2-5x)
Conversion of T to DHT via 5-alpha-
reductase
Not aromatizeable to Estrogens
Is DHT an important beneficial androgen
or is DHT the evil twin of Testosterone ?
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DHT Gel 70mg Vs. PlaceboDHT Gel 70mg Vs. Placebo
Men > 60 yo, T < 15 nMol/l = 428 ng/dlDecreased LDL, no change HDL Increased Hemoglobin/HematocritDecreased Fat MassKnee strength increased not other muscles No change QOLNo change PSA or prostate volume Ly LP et al. Randomized Clinical Trial of Transdermal
Dihydrotestosterone Gel on Muscular Strength, Mobility and Quality of Life in Older Men with Partial Androgen Deficiency
J Clin Endocrinol Metab 2001 88:4078-4088
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DHT RT Reduces Prostate SizeDHT RT Reduces Prostate Size
1.8 year study
BPH requires both DHT and E2
De Lignieres B Transdermal
dihydrotestosterone treatment of
‘andropause’
◦Ann Med 1993 Jun; 25(3):235-41
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DHT For AndropauseDHT For Andropause
DHT gel 125-250 mg/day vs Placebo x 6 months
Improved erections and morning erectionsDecreased LH, FSH, E2, T and SHBGNo change lipids or hepatic functionHg/Hct increasedNo change in prostate weight or PSA
Kunelius P et al. The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. J Clin Endocrinol Metab 2002 Apr; 57(4):1457-72
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HCG InjectionsHCG Injections
Human Chorionic Gonadotropin (HCG)
Polypeptide hormone produced by the
human placenta
Alpha and beta sub-unit
Alpha sub-unit is essentially identical to
the alpha sub-units of LH and FSH
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HCGHCG
If there is no Leydig cell failure can treat hypogonadism with HCG injections
2000-5000 units per weekNo decrease in testicular size or sperm
countCan use as TRT (measure free T to confirm
success) or cycle with TRT every 6 months
Zilzmann M Hormone substitution in male hypogonadiam Mol Cell Endocrinol 2000 Mar 30; 161(1-2):73-88
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Improved with patch and gel◦ Sexual function
◦ Mood
◦ Muscle strength, leg > arm
◦ Subjects did not exercise
With gel but not patch◦ Improved lean body mass and fat mass
◦ Correlated with serum level of T obtained
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No change in lipid profile including HDL Skin Irritation
◦ 5.5% gel, 66% patchHg/Hct increase in 100 mg gel group
◦ Mean 1.3/4.1PSA
◦ Small increase with gel but not patch◦ Correlated with serum T◦ Remained within normal range◦ Stabilized on day 90◦ 50 mg 0.17 increase 100 mg 0.2
increaseProstate symptom score : no change
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S e xS e x
Improved◦ Enjoyment with partner
◦ Erection firmness
◦ Sexual performance
◦ Sexual desire
Not related to dose or method of delivery or serum T obtained
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T and Erectile FunctionT and Erectile Function
T > Placebo
Transdermal (81%) > Oral (51%) or IM
(53%)
All statis. Significant
Jain P et al. TESTOSTERONE
SUPPLEMENTATION FOR ERECTILE
DYSFUNCTION: RESULTS OF A META-
ANALYSIS : J Urol 2000 Aug; 164(2):371-375
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T and MemoryT and Memory
T supplementation increased working memory in men
No similar charge with estrogen in women
Janowsky J et al. Sex Steroids modify working memory J Cogn Neurosci 2000 May; 12(3):407-14
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T and Mood (and Erections)T and Mood (and Erections)
Effective when psych drugs do not work
in pts with low T Cooper MA. Testosterone Replacement Therapy for Anxlety Am J
Psychiatry 157:1884, Novermber 2000
TRT increases nocturnal and
spontaneous erections and improves
mood. Burris A et al. A long-term, prospective study of the physiologic and
behavioral effects of hormone replacement in untreated hypogonadal
men. J Androl 1993 Jul-Aug; 13(4):297-304.
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Does TRT increase angry Does TRT increase angry behavior ?behavior ?
No
Tricker R et al. The effects of
supraphysiological doses of testosterone
on angry behavior in healthy eugonadal
men- a clinical research center study
J Clin Endocrinol Metab 1996 Oct; 81(10):3754-8
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Adverse EffectsAdverse Effects
Fluid retention (rare)
Does TRT accelerate male pattern
hair loss ? No Info.
Possible increase in sleep apnea
Possible decrease in testicular size
Decreased sperm count
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Testosterone Replacement in Testosterone Replacement in men improves:men improves:
LibidoErectile FunctionMoodMemoryAnginaType 2 diabetesMuscle massFat
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Testosterone Replacement in Testosterone Replacement in men may prevent:men may prevent:
Heart DiseaseDiabetesInsulin ResistanceAlzheimer Osteoporosis
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SexySexy
Increased libido
Increased sexual pleasure and
performance
Improved body image
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This is how much the male This is how much the male hormone replacement can keep hormone replacement can keep
you youngeryou younger
All my wishes to youAll my wishes to [email protected]
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