04 Meletis BHRT and Supplements #4 -...

BHRT and Nutraceu/cal Considera/ons

Dr. Chris D. Mele/s Naturopathic Physician DrMele/[email protected] www.DrMele/s.com

Are All Men Created Equal?

vs. vs.

Testosterone –A Varied Journey

Total Testosterone •  Bound testosterone aHaches to sex hormone binding globulin (SHBG).

•  Testosterone not bound up with SHBG is known as free testosterone, and it is in this form that it can exert its powerful anabolic and androgenic effects on the human body.

• 

60% 38% 2%

Bioavailable testosterone

Total testosterone

Free Albumin bound SHBG bound

Select Causes

•  Tes/cular injury (trauma, castra/on, infec/on) •  Radia/on or chemotherapy •  Pituitary tumors or diseases (high levels of prolac/n) •  Systemic diseases (HIV/AIDS, chronic liver and kidney disease)

•  Obesity •  Gene/c condi/ons:

•  Klinefelter syndrome, hemochromatosis, •  Kallmann syndrome, Prader-‐Willi syndrome, and myotonic

dystrophy •  Aging Process

Does 300 Mark the Line in the Sand?

NOT SO QUICK!!!

OK

Needs Help

Okay, So I Stepped Over the Line

A Vicious Catch 22

Low Testosterone Obesity

Chen RY, et al., Diabetes Obes Metab. 2006 Jul;8(4):429-‐35.

Crea/ng a Healthier Ecology

PuCng the Brakes On!!!

•  Men who receive testosterone replacement therapy for hypogonadism experience slower progression from metabolic syndrome to diabetes or cardiovascular disease.

•  Testosterone has beneficial effects on insulin regula/on, lipid profiles, and blood pressure.

•  Higher natural testosterone levels are associated with higher insulin sensi/vity and a reduced risk of developing the metabolic syndrome.

Makhsida N, et al., J Urol. 2005 Sep;174(3):827-‐34. Muller M, et al., J Clin Endocrinol Metab. 2005 May;90(5):2618-‐23.

FaGer = RelaJve Estrogen Surge (beware of replacement in fat guys)

•  Excess aromatase ac/vity decreases testosterone and increases estrogen levels, resul/ng in a host of deleterious body changes for men.

•  Low serum testosterone concentra/ons are closely correlated with high body mass index (BMI), along with elevated ra/os of body fat to lean mass.

Cohen PG. Med Hypotheses. 2008;70(2):358-‐60. Zumoff B. Acta Med Scand Suppl. 1988;723:153-‐60.

Diaz-‐Arjonilla M, Int J Impot Res. 2009 Mar-‐Apr;21(2):89-‐98. Kaplan SA, et al., J Urol. 2006 Oct;176(4 Pt 1):1524-‐7; discussion 27-‐8.

Schubert M, Urologe A. 2010 Jan;49(1):47-‐50.

C-‐ReacJve Protein Joins the Party

•  Declining testosterone levels are also closely linked to a steady rise in markers of inflammaJon such as CRP.

•  Inflamma/on plays a cri/cal role in development of obesity and many of its related condi/ons such as atherosclerosis and cancer.

•  InflammaJon perpetuates insulin resistance and type 2 diabetes.

•  At the same /me, the fat deposited as a result of a testosterone deficiency pumps out increasing levels of inflammatory cytokines.

Dandona P, et al., Curr Mol Med. 2008 Dec;8(8):816-‐28. Traish AM, et al.,. J Androl. 2009 Jan-‐Feb;30(1):23-‐32.

Fat and Now Depressed

Musculoskeletal

Bigger Muscles and Stronger Bones

Building muscle mass and bone density while reducing abdominal fat are well-‐established improvements in body composi/on observed in response to testosterone therapy.

Isidori AM, et al. Clin Endocrinol (Oxf). 2005 Sep;63(3):280-‐93. Moren C, et al. J Endocrinol Invest. 2005;28(3 Suppl):56-‐64. Wang C, et al. J Clin Endocrinol Metab. 2004 May;89(5):2085-‐98.

An Offer too Good to Refuse, Become a Convert!

Testosterone not only helps increase the strength and size of each muscle cell, but also influences nearby cells into becoming muscle cells.

Choong K, et al., Asian J Androl. 2008 May;10(3):351-‐63.

Bhasin S, et al. J Gerontol A Biol Sci Med Sci. 2003 Dec;58(12):M1103-‐10.

Osteoporosis Imaging

MicroMRI of Tibia

Control Hypogonadal Man

Benito M, et al., J Clin Endocrinol Metab. 2003; 88: 1497-‐1502

Stronger Structures with

•  Testosterone supplementa/on can also help reverse sarcopenia and osteoporosis.

•  Supplemental testosterone has been shown to increase bone mass of the lumbar spine in elderly men.

•  A 1995 showed testosterone given men aged 64-‐to-‐69 who had low testosterone levels caused a measurable increase in skeletal muscle protein synthesis and strength.

Snyder PJ, et al. J Clin Endo Metab 1999; 84: 1966-‐72. Urban RJ, et al. Am J Physio 1995 Nov; 269(1): 820-‐6.

Journal of Endocrinology and Metabolism

403 healthy men aged 73-‐to-‐94 years, were examined rela/ve to decreases in muscle strength, bone mass, and body composi/on.

Findings: Muscle strength and bone mass were at op/mal levels in men with the highest levels of free testosterone, leading the authors to state that “a number of clinical problems present in older men may be related to androgen [testosterone] deficiency, including reduced muscle mass, changes in body composi/on, and loss of BMD [bone mass density].”

van Den Beld AW, et al. J Clin Endocrinol Metab 2000 Sep; 85(9): 3276-‐82.

“The chief funcJon of the body is to carry the brain around.”

Thomas A. Edison

CogniJve Decline

Keeping the Spark

•  Testosterone is also needed for op/mal brain func/oning.

•  Mul/ple studies have confirmed that men who maintain op/mal testosterone levels as they age have significantly fewer symptoms of senility compared to men with low levels of testosterone.

•  In a hallmark study published in 2002, 407 men aged 50-‐to-‐91 were followed for 10 years and were given mul/ple tests to determine their testosterone levels and cogni/ve func/oning.

Moffat SD, et al. J Clin Endocrinol Metab 2002 Nov; 87(11): 5001-‐7.

“Higher FTI [free testosterone levels] was associated with beGer scores on visual and verbal memory, visuospaJal funcJoning and visuomotor scanning and a reduced rate of longitudinal decline in visual memory.”

Randomized, placebo-‐controlled studies showed that testosterone supplementa/on improved verbal memory, working memory and visuospa/al performance in elderly men.

BarreH-‐Connor E, et al. J Clin Endocrinol Metab 1999 Oct; 84: 3681-‐85. Janowsky JS, et al. Behav Neurosci 1994 Apr; 108: 325-‐32. Cherrier MM, et al. Neurology 2001 Jul 10; 57: 80-‐88.

Janowsky JS, et al. J Cogn Neurosci 2000 May; 12(3): 407-‐14

To Quote the Authors:

T The evidence abounds that lower testosterone

contributes to neurologic decline.

Lu PH, et al. Arch Neurol. 2006 Feb;63(2):177-‐85. Cherrier MM, et al. Psychoneuroendocrinology. 2004 Jan;29(1):65-‐82.

Moffat SD, et al. Neurology. 2004 Jan 27;62(2):188-‐93. Hogervorst E, et al., Neuro Endocrinol LeH. 2003 Jun;24(3-‐4):203-‐8. Moffat SD, et al. J Clin Endocrinol Metab. 2002 Nov;87(11):5001-‐7. Cherrier MM, et al. J Clin Endocrinol Metab. 2002 Jul;87(7):3090-‐6. Gouras GK, et al. Proc Natl Acad Sci USA. 2000 Feb 1;97(3):1202-‐5.

Cardiac Health

72x60x24=103,680

High Prevalence of Prolonged QT Interval in Obese Hypogonadal Males

•  Obese subjects show several electrocardiographic altera/ons, including prolonged QT interval, a marker for fatal cardiac arrhythmias. Prolonged QT interval has recently been linked to low testosterone levels, a frequent occurrence in male obese pa/ents.

Conclusion: •  Obese hypogonadal men show a greater prevalence of

prolonged QT interval compared with their eugonadal counterparts.

•  It appears therefore that low levels of testosterone in obese men may contribute to the arrhythmogenic profile of these pa/ents, a heretofore unknown link which warrants further clinical aHen/on.

Pecori Giraldi F, et al., Obesity 2011 Feb 24.

Keeping the Spring in

One’s Step!!!

•  Adequate levels of testosterone are important for maintaining cardiac health.

•  RoHerdam Study examined the associa/on between testosterone levels and cardiac health in 504 men aged 67-‐to-‐75.

•  Showed that men with higher levels of testosterone had lower levels of coronary artery disease.

•  As the authors of the study stated, “we found an independent, inverse associaJon between levels of endogenous testosterone and severe aorJc atherosclerosis and progression of aorJc atherosclerosis in men.”

Hak AE, et al. J Clin Endocrinol Metab 2002 Aug; 87(8): 3632-‐9.

Inflamm-‐Aging (once again C-‐RP at Play)

Low testosterone contributes to the degenera/ve diseases of aging such as chronic inflamma/on.

Tang YJ, et al. J Endocrinol Invest. 2007 Jun;30(6):451-‐8. Maggio M, et al. J Endocrinol Invest. 2005;28(11) Suppl Proceedings):116-‐9.

Laaksonen DE, et al. Eur J Endocrinol. 2003 Dec;149(6):601-‐8. Cutolo M, et al. Ann NY Acad Sci. 2002 Jun;966:131-‐42.

Low T EQUALS Increased Risk for Atherosclerosis

Gooren L. J Steroid Biochem Mol Biol. 2003 Jun;85(2-‐5):349-‐55. Debing E, et al. Int Angiol. 2008 Apr;27(2):135-‐41. Khaw KT, Circula/on. 2007 Dec 4;116(23):2694-‐701.

Muller M, et al. Circula/on. 2004 May 4;109(17):2074-‐9. Zmuda JM, et al. Am J Epidemiol. 1997 Oct 15;146(8):609-‐17. Hak AE, et al. J Clin Endocrinol Metab. 2002 Aug;87(8):3632-‐9.

Journal of American College of Cardiology

Journal of the American College of Cardiology Vol. 54, No. 10, 2009

What to Do?

Is it a Pill Deficiency?

Conserva/ve Es/mate Report 12%

Time to Dial in the NOS •  The nitric oxide (NO) pathway is criJcal for iniJaJon and maintenance of erecJve funcJon.

•  NO and NO synthase in the corpus cavernosum is regulated by androgens.

•  NOS ac/va/on is markedly decreased in castrated animals. Testosterone restores the erec/le response and normalized NOS protein expression and ac/vity.

RelaJonship between Androgens and Peyronie's Disease: A Case Control Study

“Our findings suggest that decreased levels of adrenal androgens may be implicated in the pathogenesis of PD. The mechanism and clinical relevance of this observa/on remain to be established.”

J Sex Med 2010;7:4011–4017.

Shedding Some Light on Clinical Approaches

Increased DHT

Low Testosterone

Estrogens

Obesity

A Fine Balance Indeed!

Anemia

•  In male pa/ents suffering from chronic pain, opioid administraJon induces severe hypogonadism, leading to impaired physical and psychological condiJons such as faJgue, anemia and depression.

Reprod Biol Endocrinol. 2011 Feb 18;9:26.

The Role of Sleep and Oxygen

CorrelaJon between Testosterone Levels and Severity of ObstrucJve Sleep Apnea?

Serum testosterone levels were nega/vely correlated with BMI and the severity of OSA. Measuring testosterone level may be an addi/onal helpful indicator in diagnosis of severity and in follow-‐up of OSA.

Arch Ital Urol Androl. 2010 Dec;82(4):143-‐7.

Sleep Loss Lowers Testosterone in Healthy Young Men

•  Cunng back on sleep dras/cally reduces a healthy young man's testosterone levels, according to a study published in the June 1, 2011 issue of the Journal of the American Medical Associa/on (JAMA).

•  The effects of sleep loss on testosterone levels were apparent awer just one week of short sleep.

•  Five hours of sleep decreased their testosterone levels by 10 percent to 15 percent.

•  Testosterone levels in men decline by 1 percent to 2 percent a year as they age.

Decreased Pituitary-‐Gonadal SecreJon

in Men with ObstrucJve Sleep Apnea

•  Decreased libido is frequently reported in male pa/ents with obstruc/ve sleep apnea (OSA).

•  The mean levels and area under the curve of LH and testosterone were significantly lower in OSA pa/ents.

•  “Our findings suggest that OSA in men is associated with dysfuncJon of the pituitary-‐gonadal axis.”

•  The rela/on between LH-‐testosterone profiles and the severity of OSA suggests that sleep fragmenta/on and, to a lesser extent, hypoxia in addi/on to the degree of obesity and aging may be responsible for the central suppression of testosterone in these pa/ents.

J Clin Endocrinol Metab. 2002 Jul;87(7):3394-‐8.

Are His Grapes Turning into Raisins?

Toxic Triggers à HypoGonadism

•  In baby boys: Environmental exposure to dioxins and polychlorinated biphenyls reduce levels of gonadal hormones in newborns

(Cao Y, Interna/onal Journal Hyg Environ Health, March 2008)

•  In adult men: Lower serum testosterone associated with elevated polychlorinated biphenyl concentra/ons

(Goncharov A, Environ Health Perspect, September 2009).

Environmental Toxins Affect Testosterone •  Scien/sts in Britain have done research in rats on the estrogen-‐mimicking chemical HPTE, which is a metabolite of the commonly used pes/cide methoxychlor.

•  These scien/sts have shown that HPTE causes a decrease in testosterone producJon from Leydig cells.

•  Other compounds, such as those found in plas/c boHles that hold everything from boHled water to laundry detergent, are man-‐made mimics of estrogen.

Akingbemi BT, et al. Popula/on Briefs, Popula/on Council 1999; 5(4): 31-‐2. Kuiper GG, et al. Endocrinology 1998 Oct; 139(10: 4252-‐63.

Undescended Testes/Late Descent

About 5 out of 100 baby boys are born with an undescended tes/cle.

It is most common in babies who were born before their due date or who were very small at birth.

Undescended TesJcle Triggers

•  Environmental risk factors may include exposure: •  Regular alcohol consump/on during pregnancy (5 or more drinks per week, associated with a 3x increase in cryptorchidism when compared to non-‐drinking mothers)

•  Exposure to pes/cides •  Gesta/onal diabetes •  Being a twin •  Being born to pregnant women who drinks caffeine (at least 3 drinks per day).

www.sciencenews.org/ar/cles/20070106/food.asp www.medscape.com/viewar/cle/570489?src=mpnews

Mother’s Health Factors NSAIDS and Acetaminophen

•  More than half of pregnant women in the Western world report intake of mild analgesics.

•  An/-‐androgens is suspected to contribute to the recent increase in male reproduc/ve problems, and many of the anJ-‐androgenic compounds are like the mild analgesics potent inhibitors of prostaglandin synthesis.

•  In the Danish birth cohort, the use of mild analgesics was dose-‐dependently associated With congenital cryptorchidism.

•  In par/cular, use during the second trimester increased the risk. This risk was further increased awer the simultaneous use of different analgesics.

Human Reproduc/on, Vol.0, No.0 pp. 1–10, 2010

Total and Free

Liberating Ones

Potential

Adrenal Buffer for

Andropausal PaJents?

When Pregnenolone & DHEA Go South

Andosteronedione

Pregnenolone

DHEA

Testosterone

Replacement vs. RestoraJon

•  Besides a decline in testosterone levels, there is also a decline seen in dehydroepiandrosterone (DHEA) in aging males.

•  Several studies have shown that restoring DHEA to youthful levels in older adults increases both physical and mental well being.

•  In a randomized, placebo-‐controlled trial of 50 mg of DHEA given every night for six months, both male and female paJents (aged 40-‐to-‐70) who took DHEA had staJsJcally significant improvements in their energy levels, quality of sleep, mood, and ability to handle stress.

Morales AJ, et al. J Clin Endo Metab 1994 Jan; 78(6): 1360-‐67.

DHEA May Increase MoJon

Another study measured DHEA levels in 36 men aged 90 to 103 and found that pa/ents who had the highest levels of DHEA had the highest levels of normal daily ac/vi/es.

Ravaglia G, et al. J Clin Endo Metab 1996; 81(3): 1173-‐78.

Low Serum DHEA Sulfate Predicts All-‐Cause and Cardiovascular Mortality

MAIN OUTCOME MEASURES: •  All-‐cause and CVD mortality by serum DHEA(-‐S) levels. •  The associa/on between low DHEA-‐S and CVD death remained awer adjustment for C-‐reac/ve protein and circula/ng estradiol and testosterone levels.

CONCLUSIONS: •  Low serum levels of DHEA(-‐S) predict death from all causes, CVD, and ischemic heart disease in older men.

J Clin Endocrinol Metab. 2010 Sep;95(9):4406-‐14. Epub 2010 Jul 7

DHEA Therapy

•  Star/ng Doses 10 mg to 25 mg •  Common Maintenance Dose 25 to 75 mg •  High Dosages 100 to 200 mg

Monitor: (Before, 6 to 8 weeks awer ini/al TX, then 3 to 6 months, then q 6 months) •  DRE, DHEA, DHEA Sulfate, Testosterone, Estradiol, SHBG, PSA, CBC with Diff, Ferri/n

HydrostaJc Pressure

•  Israeli team measured hydrosta/c pressure, prostate volume, and PSA scores on 72 men with prostate cancer.

•  All 72 men had incompetent veins (higher pressure), Their PSA levels averaged 8.89 ng/ml. Their prostate volumes averaged 65.3 ml.

•  The team reasoned that cunng out the collateral circula/on might help the situa/on. They performed highly technical sclerosing (closing veins with scarring substances) therapy to the veins in the scrotal cavity elimina/ng back flow to the men's prostate glands.

Andrologia, 41, 2009. 305·∙315. Journal of Andrology, vol. 29, no. 2, March/April 2008.

Prevent the Back Flow

•  The results confirmed their theory. Six months awer treatment, PSA levels declined to an average of 5.95 ng/ml and prostate volume shrank to an average of 36 ml.

•  With varicocele the small amount of testosterone your body sJll produces in spite of these hormone blockers manages to arrive at your prostate at a concentraJon of five Jmes the normal serum level.

•  Block ''back door" entry of massive amounts of free testosterone into the vulnerable gland.

•  CorrecJon of the venous problem reduces the free testosterone in the afflicted glands by 99.25%. Compare that to the only 80% reducJon with chemical castraJon.

StaJns Reduce the Androgen SensiJvity and Cell ProliferaJon by Decreasing the Androgen Receptor Protein in Prostate Cancer Cells

BACKGROUND: •  Epidemiological studies suggest that sta/ns reduce serum prostate-‐specific an/gen (PSA) levels and decrease the risk of prostate cancer.

•  In the present study, we determined the molecular mechanisms related to the regula/on of PSA, androgen receptor (AR), and cell prolifera/on in prostate cancer cell lines by sta/ns.

Prostate. 2011 Feb 15;71(3):298-‐304.

Food as Medicine

Coffee May Reduce Risk of Lethal Prostate Cancer

•  Boston, MA – Men who regularly drink coffee appear to have a lower risk of developing a lethal form of prostate cancer, according to a new study led by Harvard School of Public Health (HSPH) researchers.

•  What's more, the lower risk was evident among men who drank either regular or decaffeinated coffee

•  Men who consumed the most coffee (six or more cups daily) had nearly a 20% lower risk of developing any form of prostate cancer.

•  The inverse associa/on with coffee was even stronger for aggressive prostate cancer. Men who drank the most coffee had a 60% lower risk of developing lethal prostate cancer.

Wilson K., et al., Journal of the Na/onal Cancer Ins/tute, online May 17, 2011.

Cranking Up “T” Au Naturel

The BIG QUESTION Does A Man With Low “T”

Need a Handout or a Hand-‐Up?

Exercise to the Rescue

•  In both the younger and older groups, there was a sta/s/cally significant increase in testosterone levels awer exercise.

•  Strength training in middle-‐aged men (44-‐to-‐48) caused an increase in their levels of free testosterone.

Izquierdo M, et al. J App Physiol 2001; 90(4): 1497-‐1507.

Exerciseà Testosterone

•  Regular high-‐intensity exercise has been shown in mul/ple studies to contribute to keeping a man’s testosterone at op/mal levels.

•  A study published in 1999 examined how heavy resistance training in both young (23-‐to-‐35 year old) and older (58-‐to-‐65 year old) men affected their testosterone levels.

Kraemer WJ, et al. J App Physiol 1999 Sep; 87(3): 982-‐92.

Weightlising and Protein

Many middle-‐aged and elderly men aren’t genng enough protein in their diet to maintain muscle mass and stave off sarcopenia.

Campbell WW, et al. J Gero A Biol Sci Med Sci 2001; 56(6): M373-‐80.

Low Protein Can Increase SHBG

“…diets low in protein in elderly men [40-‐to-‐70 years old] may lead to elevated SHBG levels and decreased testosterone availability.”

Longcope C, et al. J Clin Endocrinol Metab 2000 Jan; 85(1): 293-‐96.

Soy Keep Estrogen and SHBG in Check

Aging Men owen experience an increase in SHBG and estrogen via ac/vity of the aromatase enzyme, both of which can lead to a decrease in testosterone levels. A study of 97 men, 49-‐to-‐72 years of age showed that men who had high levels of soy intake had lower levels of estradiol when compared to men with lower levels of soy intake. They postulated that this beneficial inverse relaJonship could be due to inhibiJon of the aromatase enzyme by soy and soy-‐based food products.

Nagata C, et al.. Nutr Cancer 2000; 36(1): 14-‐18.

Something Fishy •  Essen/al faHy acids EPA and DHA impact on SHBG levels in men 43-‐to-‐88 years of age.

•  Awer controlling for other variables, the researchers came to the conclusion that both EPA and DHA decreased levels of SHBG in middle-‐aged and elderly men.

Nagata C, et al. Nutr Cancer 2000; 38(2): 163-‐67.

Balancing Act

Internal Risk Factors

External Risk

Factors

The Key is Balance & Determines UlJmate

SuscepJbility!!!

Things to Watch For With “T” Therapy

•  Acne •  Apnea •  Carcinoma (See Being Debated) •  Decrease in HDL to LDL (good to

bad cholesterol) ra/o (Controversial)

•  Depression (Can Help as well) •  Edema due to fluid and

electrolytes reten/on •  Increased or decreased libido

•  Insomnia •  Liver cell tumors •  Male paHern baldness •  Nausea/Vomi/ng •  Bladder irritability •  Gynecomas/a •  Increased frequency of erec/on •  Inhibi/on of tes/cular func/on •  Tes/cular atrophy

Prescribing Trends

Pro’s and Con’s

Individualizing Clinical Analysis and Care

Beware of Dosing the Family, Friends, and Colleagues

Each Man Needs a Different Dosing,

The Key is Nudging not Shoving.

Treat the Adrenals First!!!

DiagnosJc and Monitoring TesJng for Androgen Deficiency

•  When/How to test? –  Morning as near to 8 AM as possible (prior to 10 AM)

•  What to Test: –  Total Testosterone and Free Testosterone –  SHBG –  Estradiol –  DHT –  Total and Free PSA

•  To Confirm or Not, Test Results?

Bhasin, S. et al. J Clin Endocrinol Metab 2006;91:1995-‐2010

www.issam.ch/freetesto.htm

“J Clin Endocrinol Metab 84:3666-‐3672, 1999 – A cri/cal evalua/on of simple methods for the es/ma/on of free testosterone in serum”

Treat The Man In Front of You

Monitoring of Testosterone Therapy Follow Up Visit One Month

–  Blood Pressure –  Cardiac Review/Exam and Lipids –  ROS of Male Reproduc/ve System –  ROS of Mood and Breast Tenderness –  Draw Total and Free Testosterone and PSA

Follow Up Visit 3rd Month (Post Treatment Ini/a/on) –  Comp Metabolic /CBC with Diff (with same ROS as 1st Month F/U) –  Ferri/n and Lipids –  PSA and Free PSA

Every 6 Months –  Comp Metabolic/CBC with Diff (with same ROS as 1st Month F/U) –  Ferri/n and Lipids –  Total and Free Testosterone, SHBG, Estradiol, DHT –  PSA/DRE

Monitor DHT and Estradiol ProducJon

•  DHT-‐ 5-‐alpha reductase (TàDHT)

•  Estradiol-‐ aroma/za/on (TàE)

“Control the downstream dris effect”

Estradiol

HO

OH

Estrone

HO

O

Androstenedione

O

O

Testosterone

OH

O

DiHydroTestosterone

OH

O

CH3

CH3

NutraceuJcals

Supplemen/ng a Good Diet and Lifestyle; Hence they are called Supplements not Subs/tutes!

Effects of Micronutrients on Androgen Deficiency

– Par/al androgen deficiency in the aging male (PADAM) is a kind of syndrome which affects the aging males health.

– “Some studies have shown that quite a few nutrients, especially vitamin A, vitamin E, zinc and selenium are favorably related to androgen deficiency and sperm producJon.”

Zhonghua Nan Ke Xue. 2005 Oct;11(10):784-‐6.

Eurycoma Longifolia in Aged Orchidectomised Rats

•  In this study, Eurycoma longifolia (EL), a plant with androgenic effects, was supplemented to an androgen-‐deficient osteoporo/c aged rat as alterna/ve to testosterone.

•  Both testosterone replacement and EL supplementa/on to orchidectomised rats were able to maintain the bone calcium level, with the former showing beHer effects.

Aging Male. 2010 Sep 28

SJnging NeGles (1000 mg QD –BID Freeze Dried)

RESULT: •  A marked benefit in terms of quality of life, measured by IPSS

score, uroflow, residual urine and nocturia, was observed in the treated group compared to controls.

CONCLUSIONS: •  The new phytotherapeu/c combina/on evaluated in the

present study would seem to be highly effec/ve for the treatment of LUTS in BPH pa/ents and does not have nega/ve side effects. Its use could therefore be strongly advocated in this senng.

Urologia. 2010 Jul-‐Sep;77(3):180-‐6.

Tes/cular Pain, Apnea, Hypogonadism

39 year old male—Highly Stressed, 20 pound weight gain in 2 years, Adrenal Fa/gue, Tes/cular Pain, Low Total and Free T, Urina/ng 3 to 5 /mes a night.

Prostate Exam and PSA; Tes/cular Exam All Normal

Dx: Sleep Apnea-‐ O2 Desatura/on down to 65% Treatment: Auto-‐PAP; Weight Loss; Pregnenolone 75 mg; DHEA 50 mg; Adrenal Support –Ashwaghanda/Ginseng Combina/on

Zinc–EssenJal for Sexual Health (Zinc 30 to 60 mg QD with Food –Remember Copper)

•  There have been mul/ple studies on the effec/veness of zinc in trea/ng male infer/lity due to low testosterone levels.

•  In a study of 37 infer/le men with decreased testosterone levels and associated low sperm counts. The men were given 60 mg of zinc daily for 45 to 50 days.

•  In 22 pa/ents, testosterone levels significantly increased and mean sperm count rose from 8 to 20 million

Tikkiwal M, et al. Ind J Phys Pharm 1987 Jan-‐Mar; 31(1):30-‐34. Takihara H, et al. Urology 1987 Jun; 29(6): 638-‐641. NeHer A, et al. Arch Androl 1981; 7(11): 69-‐73.

Influence of Zinc and Selenium on Cadmium Induced Tes/cular Pathophysiology

The combined treatment of Cd-‐exposed animals with Se and Zn assured a more significant decrease in plasma and tesJcular Cd concentraJons and a more efficient protec/on against the observed tes/cular damage as evidenced by the total preven/on of both Se and Zn depriva/on and by the en/re restora/on of the sperm mo/lity and the tes/cular an/oxidant status.

Food Chem Toxicol. 2010 Oct;48(10):2759-‐65.

Zinc Therapy and Level of Sex Hormones

BACKGROUND: •  It is demonstrated that the zinc level is significantly lower in the

hemodialysis pa/ents. OBJECTIVE: •  In this clinical trial, we inves/gate the effect of zinc supplement therapy on

the serum levels of sexual hormones in hemodialysis male pa/ents. PATIENTS AND METHODS: •  The pa/ents received zinc supplement (zinc sulfate, 250 mg/day) for 6

weeks, and sex hormones and zinc plasma level were checked again. RESULTS: •  Serum level of FSH and prolac/n did not have any significant changes

before and awer interven/on, but serum level of testosterone, LH, and zinc increased significantly.

Ren Fail. 2010 May;32(4):417-‐9.

VITAMIN D

Vitamin D and Testosterone

•  The male reproduc/ve tract is a target /ssue for vitamin D.

•  200 Healthy overweight nondiabe/c men undergoing a weight reduc/on program.

•  Par/cipants received either 83 micrograms (3,332 IU) vitamin D daily for 1 year (n=31) or placebo (n=23).

Vitamin D Impact—on Low T With Vitamin D use it was noted:

Significant increase in total testosterone levels Ø  (from 10.7±3.9 nmol/l to 13.4±4.7 nmol/l; p<0.001)

Increase of bioac/ve testosterone Ø  (from 5.21±1.87 nmol/l to 6.25±2.01 nmol/l; p=0.001)

Increase of free testosterone levels Ø  (from 0.222±0.080 nmol/l to 0.267±0.087 nmol/l; p=0.001)

By contrast, there was no significant change in any testosterone measure in the placebo group.

E. ZiHermann Hormone and Metabolic Research, Dec 10, 2010

AssociaJon of Vitamin D Status with Serum

Androgen Levels in Men •  Men with sufficient 25(OH)D levels (> or =30 microg/l) had

significantly higher levels of testosterone and FAI and significantly lower levels of SHBG.

CONCLUSION: •  Androgen levels and 25(OH)D levels are associated in men

and reveal a concordant seasonal varia/on.

Clin Endocrinol (Oxf). 2010 Aug;73(2):243-‐8.

Testosterone Cream Case •  52 year old male; Total T 242; Free T (Low Normal); Estradiol (mid range), DHT (high normal)

•  Pa/ent very depressed, Achilles tendon injury, ED, Thin and formerly very fit

•  Started Pt. on 1% Testosterone transdermal •  Started Pt. on Zinc picolinate 30 mg per day; NeHles 500 mg BID; Saw PalmeHo 300 mg BID; Chrysin 500 mg per day

•  Pt. applied “T” Cream q.o.d. to inner forearm and Achilles tendon.

•  Result: Mood Improved, ED Improved, 18 month injured Achilles healed rapidly.

Select Overview Modulator 5 Alpha Reductase

InhibiJon Aromatase InhibiJon

SHBG Lowering

Saw PalmeGo (85-‐95% FaHty Acids)

320 mg QD to BID

Astaxanthin 4 mg QD to BID

Black Cohosh standardized to 2.5% triterpene glycosides

40 to 80 mg QD to BID

QuerciJn 1000 mg QD to BID

Chrysin (w/Bioperine) 500 to 1000 mg QD to BID

Green Tea Extract (98% polyphenols, 80% catechins, 50% EGCG (leaves)

500 -‐1000 mg QD to BID

Boron 10 mg QD

NeGles (o.8% sterols)

500 to 1000 mg BID

Summary of Approaches

•  Improve Lean Body Mass •  Exercise and Sleep •  Remove Toxic Burdens •  Support Adrenal Glands-‐

–  DHEA and Pregnenolone –  Adaptogens

•  Testosterone Replacement/Restora/on •  Control Downstream Metabolism of All Sources of “T” •  Produc/on Support

–  Botanical /Nutrients

BoHom Line!

Biological vs. Chronological Age

04 Meletis BHRT and Supplements #4 -...

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