03 - Andropause.pptx

Mens’ Health “Post Puberty” Nayan Patel PharmD Definition of Androgen Deficiency *  Consistently low testosterone *  Associated signs/symptoms *  Evidence based review of literature *  Data is weak at best Definition
*  A decrease in either of the two major functions of the testes: *  sperm production *  testosterone production
Don’t Screen Every Man for Low T *  Don’t look for low T in men seeking care for unrelated reasons *  Does not meet any criteria for general screening *  No trials of efficacy or cost-­‐effectiveness *  Mortality impact of untreated low T unknown Who to Screen for AD *  Men who ask about it based on symptoms *  Case finding in men with high prevalence clinical disorders *  Even in these groups, data on risk/benefits of T replacement is unavailable-­‐limited The ADAM Questionnaire 1. Do you have a decrease in libido (sex drive)? 2. Do you have a lack of energy? 3. Do you have a decrease in strength and/or endurance? 4. Have you lost height? 5. Have you noticed a decreased "enjoyment of life?" 6. Are you sad and/or grumpy? 7. Are your erections less strong? 8. Have you noticed a recent deterioration in your ability to play sports? 9. Are you falling asleep after dinner? 10. Has there been a recent deterioration in your work performance? If you answered YES to questions 1 or 7 or any 3 other questions, you may have low testosterone. **Adapted from Morley JE, et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism. 2000;49(9):1239-­‐1242. Treatment of Hypogonadism Depends on the Cause *  Primary hypogonadism * 
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Testes failure Generally permanent Replace testosterone unless contradindicated Fertility cannot be regained Serum Testosterone↓, FSH & LH ↑ *  Secondary hypogonadism * 
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Pituitary or hypothalamic failure Distinguish cause Evaluate for other hormone deficiencies first Use testosterone + gonadotropins for fertility Serum Testosterone↓, FSH & LH ↔ , ↓ Androgen Deficiency Symptoms
Musculoskeletal *  Decreased vigour and physical energy *  Diminished muscle bulk & strength *  easily fatigued *  poor exercise tolerance *  diminished strength and muscle mass *  decrease in bone mineral density Androgen Deficiency Symptoms
Sexuality *  ↓ Sexual desire & activity *  ↓ Spontaneous erections * 
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Reduction in frequency of sexual activity Poor erectile function/arousal Loss of nocturnal erections Reduced quality of orgasm Reduced volume of ejaculate *  Breast discomfort, gynecomastia *  ↓ Body hair (axillary & pubic), ↓ shaving *  Very small or shrinking testes (esp < 5 ml) *  Inability to father children, low/zero sperm counts Androgen Deficiency Symptoms
Mood disorder and cognitive function * 
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Irritability & lethargy Decreased sense of well-­‐being Lack of motivation & mood changes Low mental energy Memory impairment Difficulty with short-­‐term memory & reduction in intellectual activity Depression Low self-­‐esteem Insomnia Nervousness & anxiety Poor work performance Androgen Deficiency Symptoms
Vasomotor and nervous *  Hot flushes *  Sweating Goals of Testosterone Therapy *  Improve/maintain secondary sexual characteristics *  Improve libido and erections *  Increase energy and well-­‐being *  Improve muscle mass and strength *  Improve bone mineral density Who Should be Treated with T? *  Men with low T & signs/symptoms of AD *  Men with low testosterone & low libido *  Men with low testosterone & erectile dysfunction *  After evaluation of underlying causes of ED *  And consideration of other treatment for ED Who Else Should be Treated with T? *  Men with low testosterone, HIV infection & weight loss *  Short-­‐term treatment *  For weight-­‐maintenance, lean body mass, & muscle strength *  Men with low testosterone & taking high dose glucocorticoids *  Short-­‐term treatment *  For lean body mass and bone mineral density What About Older Men? *  Caution against offering T to all older men with low T *  Treat men with consistently low T and clinically significant symptoms *  After explicit discussion of pros and cons *  Always consider their active/inactive lifestyle before offering such therapy Contraindications to Testosterone Therapy *  Breast or prostate cancer *  Lump/hardness on prostate exam by DRE *  PSA >3 ng/ml that has not been evaluated for prostate cancer *  Severe untreated BPH (AUA/IPSS >19) *  Erythrocytosis (hematocrit >50%) *  Hyperviscosity *  Untreated obstructive sleep apnea *  Severe heart failure (class III or IV) Testosterone for the Following Reasons May be Harmful *  To improve strength/athletic performance *  For physical appearance *  To prevent aging How Do You Give Testosterone? *  Start at standard dose *  Check levels *  Therapeutic target *  Serum testosterone in mid-­‐normal range for healthy, young men *  Target in older men *  Considerable disagreement among experts *  Total T in the lower part of the normal range for younger men *  400-­‐500 ng/dl Testosterone replacement
*  Intramuscular preparations *  Transdermal patch *  Transdermal/Trans-­‐mucosal gel/cream *  Oral agent *  Testosterone pellet *  Buccal testosterone tablets
Intramuscular injection
*  Short-­‐acting: *  Testosterone propionate *  Intermediate-­‐acting: *  Testosterone enanthate *  Testosterone cypionate *  Long-­‐acting: *  Testosterone undecanoate Testosterone Enanthate or Cypionate Injections (IM) *  T levels are supraphysiologic, then gradually drop to hypogonadal range *  Peaks and valleys *  Fluctuation of mood or libido *  Relatively inexpensive if self-­‐administered *  Start at 75-­‐100 mg IM weekly *  Or 150-­‐200 mg IM every other week *  Pain at injection site *  Excessive erythrocytosis (esp in older pts) Testosterone Blends *  Testosterone Cyp/Enan (80:20) *  Most commonly prescribed *  Testosterone Cyp/Enan/Prop (40:40:20) *  Painful at injection site because of propionate. *  Perfect combination for immediate, intermediate and long acting testosterone. *  Always ordered in prefilled syringes *  Avoid wastage *  Patient specific dose eliminate over/under usage Testosterone Patch *  Less increase in hemoglobin than IM shots *  Ideal if the patient can tolerate. *  Skin irritation/redness/rashes *  Patch falls off while exercising Testosterone Pellets *  4-­‐6 200-­‐mg pellets implanted subQ *  Serum T peaks at 1 month and then is sustained in normal range for 4-­‐6 months *  Requires surgical incision for insertion *  Infection risk *  Pellets may spontaneously extrude Buccal, Bioadhesive T Tablet *  Normalizes T and DHT *  30 mg to buccal mucosa twice daily q12h *  Gum-­‐related adverse events in 16% *  Gum irritation *  Examine gums and oral mucosa for irritation *  Alteration in taste Testosterone Gel *  Starting dose 5-­‐10 grams daily *  Skin tolerates it well *  Potential transfer to others by skin contact *  Cover the application site *  Wash hands with soap and water after application *  Wash skin before skin-­‐to-­‐skin contact with others *  T levels maintained when skin washed 4-­‐6 hours after application Testosterone Gel *  Trans-­‐mucosal application of a very low dose testosterone gel/cream *  Apply on anal mucosal area *  Highly absorbed & fast *  Less fear of skin to skin transfer to someone else *  Generally requires 10% to 15% of the full topical dose only Monitor other hormones *  No perfect system for testosterone replacement *  Either causes increased estradiol levels or *  Increase in DHT or *  Both. Maintaining Estrogen *  Control aromatase enzyme activity *  Control the rate of reaction for testosterone converting to estradiol Aromatase Aromatase found in the liver, fat and skin. Zinc deficiency increases aromatase activity. High insulin level increases the aromatase activity Zinc found in oysters, red meat and nuts. Zinc (and magnesium) depleted by alcohol. Aromatase production also increase with age (we don’t know why). *  Drugs: Aromatase inhibitors – Anastrazole (Arimidex®), Letrozole (Femara®), Exemestane (Aromasin®) *  Chyrsin is a natural aromatase blocker. * 
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Progesterone in Men *  Progesterone stimulates the leydig cell to secrete testosterone *  Progesterone and 17-­‐OH progesterone induce a depolarizing effect on the leydig cell plasma membrane , where DHEA-­‐S, estradiol, testosterone, and cortisol do not. *  Leydig cells are able to synthesize testosterone from progesterone and pregnenolone. *  Progesterone may be useful in benign prostatic hypertrophy (BPH) *  Progesterone is a 5 alpha reductase inhibitor *  Progesterone reduces PSA *  Progesterone has an inhibitory effect on luteinizing hormone (LH) Progesterone in Men References *  Marco, R, et al. Identification of functional binding sites for progesterone in rat Leydig cell plasma membrane. Steroids 64, 1–2, January–February 1999, Pages 168–175 *  Chen, GCC, et al. The aging leydig cell II: Two distinct populations of leydig cells and the possible site of defective steroidogenesis. Steroids 37,1 Jan 1981 *  Shilpa, NK, et al. Novel actions of progesterone: what we know today and what will be the scenario in the future? Journal of Pharmacy and Pharmacology 64. Jan 2012, Pages 1040-­‐106. DHT Blockers *  Finasteride *  Dutasteride *  Saw Palmetto *  Stinging Nettle Roots *  Pygeum Africanum *  Green tea extract (EGCG) *  BE CAREFULL! On using DHT blockers. Typical Rx for Andropause *  Testosterone/P4 (9:1) 5mg to 15mg gel from QD to BID to be applied to anal mucosal area *  Other Testosterone/P4 (9:1) option is 5% to 10% topical gel QD to BID *  Pregnenolone/DHEA 25/25mg to 50/50mg SR caps daily *  Chrysin/zinc 250/30mg to 250/50mg caps QD *  DHT blocker like saw palmetto w/nettle root and pygeum 320mg QD (Rarely) *  Anastrazole 0.1mg to 0.25mg QD is added if chrysin/Zinc is not effective. Secondary hypogonadal Patient *  Low levels of testosterone can be treated with: *  HCG 250iu daily for 30days and/or *  Clomiphene 25mg caps daily *  Combination capsule * 
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Progesterone 25mg pregnenolone 10mg DHEA 5mg 7-­‐Keto DHEA 5mg anastrozole 0.05mg Methyl B-­‐12 0.5mg B6 2mg 40.05mg Per cap daily Add OTC daily or combine with RX capsule Young Male Patient *  With previous use of testosterone or related products: * 
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HCG 2500iu QOD for 16days Clomiphene 50mg daily for 30days Tamoxifen 20mg daily for 45 days Re-­‐evaluate the need of testosterone after 60 days Side Effects *  Breast tenderness *  Gynecomastia *  Compromised fertility *  Change in testicle size *  Skin reactions *  Fluid retention *  Acne/oily skin *  Increased body hair Andropause Case 1 *  Patient: RR *  Age: 43 years old – Male *  Marital Status: Single *  Occupation: Social Worker *  Allergies: Sulfa, Morphine *  Medications, OTC, Vitamins: Ibuprofen 400mg BID prn pain *  Medical Conditions: Osteoarthritis *  Alcohol: none *  Tobacco: none *  Caffeine: 3 cups coffee/day *  Sexually active: Yes *  Exercise: Cardio 4-­‐5 times a week, Weight training *  Diet: No dairy, gluten, sugar *  Depression *  Anxiety *  Irritability *  Low Libido *  Fuzzy Thinking *  Fatigue 2/10 2/10 3/10 9/10 9/10 5/10 *  Estradiol 15 *  Total Testosterone 432 *  Free Testosterone 10 *  DHEA-­‐S
200 *  Vitamin D3 45
Treatment *  HCG – Inject 200 IU sq daily x 40 days *  Pregnenolone/DHEA 25/25mg – 1 c po daily Andropause Case 2 *  Patient: KR *  Age: 56 years old – Male *  Marital Status: Married *  Occupation: Dentist *  Allergies: Latex, Ibuprofen, Amoxicillin *  Medications, OTC, Vitamins: HCTZ 25mg daily, Aspirin 81mg daily, Vitamin D3 5000IU daily *  Medical Conditions: Hypertension *  Alcohol: 5 beers/week *  Tobacco: none *  Caffeine: 1 cup coffee/day *  Sexually active: Yes *  Exercise: Walk 3x a week *  Diet: Overall healthy diet – fresh fruits and vegetables; no dairy *  Depression *  Anxiety *  Irritability *  Low Libido *  Fuzzy Thinking *  Fatigue 4/10 3/10 9/10 10/10 8/10 5/10 *  Estradiol 67 pg/ml *  Total Testosterone 216 ng/dl *  Free Testosterone 4 pg/ml *  DHEA-­‐S
40 mcg/dl *  Vitamin D3 60 ng/ml
Treatment *  Testosterone 100mg/ml – 1ml skin daily *  Pregnenolone/DHEA 25/25mg – 1 c po daily Conclusion *  Control Insulin levels to obtain the best results from your testosterone therapy. *  Androgen therapy can be great benefit to your patients as long as they are closely monitored for all the side effects of the therapy.