1/7/2016
This information (and any accompanying printed
Aging Healthy with Hormone Balance Nelson Vergel g Director Program for Wellness Restoration (PoWeR) ExcelMale.com DiscountedLabs.com
material) is not intended to replace the attention or advice of a physician or other health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a qualified health care professional.
The Human Glands
Glands/hormones covered today
Steroid Hormone Pathway
Circadian Rhythm: Sleep Effect on Hormones
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Morning time T Level is Higher But Effect is Blunted by Age
Symptoms of Low and High Thyroid Blood Levels
Hypothalamic-Pituitary HypothalamicPituitary-Thyroid Axis
Little to no data are available on thyroid hormones levels in HIV aging!
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Thyroid Blood Tests
Thyroid Medications & Drugs that Interact with Them
Diagnosis of Thyroid Dysfunction
Hormone Treatment for Women
Hormone Levels Pre and Post Menopause Menstrual Cycle
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Hypothalamus
Testosterone and Aging
Signs and Symptoms of Low Testosterone
Loss of muscle mass and strength Loss of libido and erectile dysfunction Depression Lethargy gy (fatigue, ( g , lack of focus)) Bone loss Some regression of secondary sexual characteristics (body hair loss, etc) Low or no sperm count
Tenover JL. Endocrinol Metab Clin North Am. 1998;27:969-987 Petak SM, et al. AACE Clinical Practice Guidelines. Available at: http://www.aace.com/clin/guides/hypogonadism.html
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Hypothalamus GnRH
Production and Regulation of Testosterone Free T 2%
AlbuminAlbuminbound T 38%
Pituitary Testosterone
(binds
LH FSH
testosterone)
Testis SHBG-bound T SHBG60% Testosterone
T = testosterone Only 2% is free testosterone and 98% is bound
Sperm Adapted from Bagatell CJ, Bremner WJ. N Engl J Med. Med. 1996;334:707--715. 1996;334:707
Adapted from Braunstein GD. In: Basic & Clinical Endocrinology. Endocrinology. 5th ed. Stamford, Conn: Appleton & Lange; 1997:4031997:403-433.
Testosterone Deficiency Finasteride
(Hypogonadism) • Normal levels in blood: Men...
Total test. 300-1100 ng/dL, Free test. 5 - 21 ng/dL Women... Total test. 10 10-50 50 ng/dL Free test. 0.10-0.85 ng/dL
• Symptoms of testosterone deficiency: Fatigue, low or lack of sex drive, poor appetite, loss of muscle mass & strength, depression Anastrozole Tamoxifen
What T level is too low? Review of studies (Avg. T levels that increased risks)
Testosterone Replacement Benefits
Mental focus
< 450 ng ng/dl /dl (15.3 nmol nmol/l) /l) - Risk of metabolic syndrome < 400 ng ng/dl /dl (15.3 nmol nmol/l) /l) - Venous leakage (internal penile damage) risk < 350 ng ng/dl /dl (11.9 nmol nmol/l /l ) - All cause death risk and anemia risk < 300 ng/ ng/dL (10.2 (10 2 nmol/L) nmoll/L) - Lowered L d libido,Weight libid W i ht gain i & Di Diabetes b t risk increases < 300 ng ng//dL (10.2 nmol nmol/L) /L) - Quartile risk of fractures (osteoporosis), memory--related issues & depression risk increases memory < 250 ng ng/dl /dl (8.5 nmol nmol/l) /l) - Arterial plaque (arteriosclerosis) & sleep quality affected
Stamina and Bone Strength
Sexual function Lean Body Mass
< 235 ng ng/dl /dl (8.0 nmol nmol/l) /l) - Hardening of arteries (dialysis patients) < 200 ng ng/dl /dl (6.8 nmol nmol/l) /l) - Morning erections decrease < 150 ng ng/dl /dl (5.1 nmol nmol/l) /l)-- Increased inflammation (TNF(TNF-alpha)
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TRT – Time of Onset of Benefits
Testosterone Options
Gels
Buccal
Injections
Armpit lotion
Pellets
Axiron
Compounded Gels
Patch
2 % Gel
Newest Testosterone Products Long Acting First FDA approved for women
To be called Aveed in the US
Most Men on Androgel and Testim Stop Using Them
Included were 15,435 hypogonadal men, from the Thomson Reuters MarketScan® MarketScan® Database, who had an initial topical testosterone prescription in 2009 and who were followed for 12 months.
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Role of Estradiol
Side Effect: Gynecomastia (breast enlargement in men)
Treatment: Estrogen Blocker Medications or surgery (in worst cases)
Factors that Increase Estradiol
Age Obesity Efavirenz Alcohol overoverconsumption p ((incl incl HOPS in beer!) Liver Disease Zinc deficiency (50mg Zn/2mg Cu QD) Vitamin C deficiency
Excessive DHEA supplementation (100mg QD)
Symptoms of Symptoms of Estradiol Estradiol Excess • • •
Xenoestrogens g (incl Vinyl IV bags!) --Lavender, -Lavender, Tea Tree Oil Soy Flax seed
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Anastrozole (Arimidex Arimidex) ) To Control To Control Estradiol Estradiol Levels in Testosterone Treatment • •
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Breast cancer drug used off label in men to control E2 levels Anastrozole is the best single, reliable way to control E2 levels. o Other supplements Zinc 50mg/Copper 2‐3 mg, Chrysin 1000mg, work well in some patients but not as reliable as the gold standard of anastrozole. Compounded anastrozole available Compounded anastrozole available o 1 mg capsules o Dose range – 0.5 to 1.5 mg per week in men with over E2 of 50 pg/mL at 6 week follow up. Adjust dose based on second follow up o Many men may not need anastrazole treatment o Patients can be instructed to take PRN if sensitivity develops in the chest and/or nipples.
Nipple sensitivity Fluid retention Elevation of blood pressure Decreased libido Decreased libido Can educate patient to take extra dose of anastrozole Can educate patient to take extra dose of anastrozole if nipple tenderness/sensitivity occur.. if nipple tenderness/sensitivity occur Prescribe anastrazole Prescribe anastrazole is is estradiol estradiol by ultrasensitive test is over 50 pg/mL test is over 50 pg/ mL at follow up. 1 mg/week is a good starting dose to be readjusted at second follow up visit
Anastrozole in Testosterone in Testosterone Treatment Treatment •
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Emphasize to patients the goal of testosterone treatment is to optimize T levels and control estradiol levels and control estradiol levels between 20 and 50 levels between 20 and 50. . It is recommend to not let It is recommend to not let estradiol estradiol levels fall below 20 pg/ levels fall below 20 pg/mL. mL. This may be linked to low bone density, higher fat content and lower sex drive. Estradiol may also have a role in cognitive function. Usually, higher fat mass will Usually, higher fat mass will increase incidence of high increase incidence of high estradiol estradiol. . Many Many men can taper down dosage of anastrozole after a period of men can taper down dosage of anastrozole men can taper down dosage of anastrozole after a period of time during after a period of time during time during treatment due to fat loss. Less fat means less treatment due to fat loss. Less fat means less aromatization aromatization of of testosterone to estradiol testosterone to estradiol.. A major mistake in testosterone treatment commonly made by many A major mistake in testosterone treatment commonly made by many physicians is to forget to monitor physicians is to forget to monitor estradiol estradiol.. Insurance doesn’t cover Insurance doesn’t cover anastrozole anastrozole for a male indication as it is gender for a male indication as it is gender specific for women with breast cancer. Compounding pharmacies sell it specific for women with breast cancer. Compounding pharmacies sell it cheaply. High estradiol High estradiol may not only cause may not only cause gynecomastia gynecomastia but could also increase cardiovascular risks.
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Side Effect: Increased number of red blood cells (polycythemia)
Watch out for hematocrit over 52 !
Solution: Donate blood or therapeutic phlebotomy (4-5 units every 3-4 months)
Testosterone and Cardiovascular Disease
Low testosterone has been linked to increase cardiovascular death Two recent studies that got a lot media attention concluded that TRT increased cardiovascular risks. Patients were not monitored for hematocrit or estradiol and most were not retested for dose adjustment. Most were under dosed or stopped therapy.
FDA Statement on Testosterone and Cardiovascular Risks
“ There is insufficient evidence of a causal link between testosterone therapy and adverse cardiovascular outcomes” The Agency determined that each study had significant limitations. A Placebo Controlled Study is Enrolling to Provide Better Data.
Side Effect: Testicular Shrinkage (atrophy)
Human Chorionic Gonadotropin •
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Treatment:
Human Chorionic Gonadotropin (hCG)
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Produced by human placenta, sterile product derived from urine of Produced by human placenta, sterile product derived from urine of pregnant females.. pregnant females In men HCG mimics LH from pituitary to stimulate Leydig In men HCG mimics LH from pituitary to stimulate Leydig cells of testes to produce testosterone. It can add to TRT increases in estradiol It can add to TRT increases in estradiol, , hematocrit hematocrit and/or acne Normal Normal lyophilized vial contains 11,000 units l lyophilized vial contains 11,000 units HCG by compounding l hl d l 11 000 HCG by compounding CG b d pharmacies (commercial products cost 3X compounding) Used by fertility specialists to induce ovulation to harvest eggs, etc Used by fertility specialists to induce ovulation to harvest eggs, etc.. Latest data show that men on TRT + HCG were able to remain fertile. Usual recommended dose 350‐‐500 IU two times a week for Usual recommended dose 350 prevention/reversal of testicular atrophy. Anecdotal effect on raising sex drive
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HCG Use in Males •
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Exogenous form of testosterone can shut down testicles (negative feedback loop) and testes can atrophy. HCG acts as a Leydig cell stimulator and cell volumizer. Testicles under regain size but do not grown beyond baseline size. Continuous testosterone can reduce fertility in over 50% of TRT users and testicular size by 10‐30 % . Noticeable testicular size reduction can be a more common complaints in men y p with smaller testicular size at baseline. May not be important to some older men or men not worried about fertility. Explain this to patients and give option to patients for use since it requires high adherence of added injection frequency. May be used in patients for 6‐8 weeks who have abused steroids to reset the natural production of testosterone. May be used in younger males as sole method of testosterone treatment with secondary hypogonadism. All men respond differently to HCG in ability to boost T production by testes. HCG may not work well with men who have primary hypogonadism, i.e. dysfunction of the Leydig cells in the testes.
Does Testosterone Cause Prostate Cancer?
Side Effect : Increased prostate size (benign prostatic hypertrophy)
Prevention:
Digital Rectal Exam (DRE) Prostatic Specific Antigen (PSA) blood test
TRT After Prostate Cancer
Meta Analysis of Studies from 19501950-2006: “This historical perspective reveals that there is not now — nor has there ever been — a scientific basis for the belief that testosterone causes prostate to grow.” – Abraham Morgentaler. MD.
Side Effect: Acne
Treatment: Nizoral shampoo, Bezoyl Peroxide, salicilic acid lotions, showering after exercising, 20 min of sun a day, Zinc supplements
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TRT Patient Monitoring
Blood Test Ranges
Initial Blood Test – New Patient – – – – – – –
Testosterone, Free & Total, if under 150 ng ng//dL test for prolactin prolactin.. PSA LH & FSH Lipids CBC CMP TSH, free T3 (if high TSH, test for thyroid antibodies)
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6wk Follow up – 6wks after initial RX – – – – –
CBC CMP Testosterone, Free & Total Estradiol TSH
(1)
Lowest Cost Blood Tests Online:
6 Month Follow up – 6 months after initial RX – – – – – – –
* X (2)
Testosterone, Free & Total PSA LH & FSH Lipids CBC CMP Estradiol
Annual Blood Test – Same as 6 months
Growth Hormone and GHRH For HIV-Related Fat Accumulation
Potential Interventions for Decreasing Abdominal Fat (visceral adipose tissuetissue-VAT) Diet- Lower carbohydrate diets, Mediterranean diet DietExercise-- cardiovascular and resistance trainingExercise training- Some pilot
data with good results
Anti--diabetic drugs: Metformin (Glucophage) Anti Glucophage)- conflicting
and inconclusive data Testosterone gelgel- subcutaneous fat loss only Anabolic steroidssteroids- Oxandrin Oxandrin,, nandrolone? nandrolone?- limited VAT data
Human Growth Hormone Human Growth Hormone Releasing Hormone Hormone-- Sermorelin and Tesamorelin Tesamorelin-- Approved for the treatment of HIV
related visceral fat accumulation Surgery-- Liposuction of visceral fat very difficult and risky Surgery
Growth Hormone Effect on Fat Accumulation in HIV
Growth Hormone Releasing Hormone: Tesamorelin (Egrifta) Egrifta) Effect on Fat Mass
Approval not granted by the FDA due to high blood glucose
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Egrifta:: Responders Vs Non Egrifta Non--Responders
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