Mens Health Post Puberty. Nayan Patel PharmD

Transcription

1 Mens Health Post Puberty Nayan Patel PharmD

2 Definition of Androgen Deficiency * Consistently low testosterone * Associated signs/symptoms * Evidence based review of literature * Data is weak at best

3 Definition * A decrease in either of the two major functions of the testes: * sperm production * testosterone production

4 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

5 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

6 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):

7 Treatment of Hypogonadism Depends on the Cause * Primary hypogonadism * Testes failure * Generally permanent * Replace testosterone unless contradindicated * Fertility cannot be regained * Serum Testosterone, FSH & LH * Secondary hypogonadism * Pituitary or hypothalamic failure * Distinguish cause * Evaluate for other hormone deficiencies first * Use testosterone + gonadotropins for fertility * Serum Testosterone, FSH & LH,

8 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

9 Androgen Deficiency Symptoms Sexuality * Sexual desire & activity * Spontaneous erections * 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

10 Androgen Deficiency Symptoms Mood disorder and cognitive function * 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

11 Androgen Deficiency Symptoms Vasomotor and nervous * Hot flushes * Sweating

12 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

13 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

14 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

15 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

16 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)

17 Testosterone for the Following Reasons May be Harmful * To improve strength/athletic performance * For physical appearance * To prevent aging

18 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 * ng/dl

19 Testosterone replacement * Intramuscular preparations * Transdermal patch * Transdermal/Trans- mucosal gel/cream * Oral agent * Testosterone pellet * Buccal testosterone tablets

20 Intramuscular injection * Short- acting: * Testosterone propionate * Intermediate- acting: * Testosterone enanthate * Testosterone cypionate * Long- acting: * Testosterone undecanoate

21 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 mg IM weekly * Or mg IM every other week * Pain at injection site * Excessive erythrocytosis (esp in older pts)

22 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

23 Testosterone Patch * Less increase in hemoglobin than IM shots * Ideal if the patient can tolerate. * Skin irritation/redness/rashes * Patch falls off while exercising

24 Testosterone Pellets * 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

25 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

26 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

27 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

28 Monitor other hormones * No perfect system for testosterone replacement * Either causes increased estradiol levels or * Increase in DHT or * Both.

29 Maintaining Estrogen * Control aromatase enzyme activity * Control the rate of reaction for testosterone converting to estradiol

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31 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.

32 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)

33 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 * 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

34 DHT Blockers * Finasteride * Dutasteride * Saw Palmetto * Stinging Nettle Roots * Pygeum Africanum * Green tea extract (EGCG) * BE CAREFULL! On using DHT blockers.

35 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.

36 Secondary hypogonadal Patient * Low levels of testosterone can be treated with: * HCG 250iu daily for 30days and/or * Clomiphene 25mg caps daily * Combination capsule * Progesterone 25mg * pregnenolone 10mg * DHEA 5mg * 7- Keto DHEA 5mg * anastrozole 0.05mg * Methyl B mg * B6 2mg 40.05mg Per cap daily Add OTC daily or combine with RX capsule

37 Young Male Patient * With previous use of testosterone or related products: * 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

38 * Breast tenderness * Gynecomastia * Compromised fertility * Change in testicle size * Skin reactions * Fluid retention * Acne/oily skin * Increased body hair Side Effects

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40 Andropause Case 1 * Patient: RR * Age: 43 years old Male * Marital Status: Single * Occupation: Social Worker

41 * Allergies: Sulfa, Morphine * Medications, OTC, Vitamins: Ibuprofen 400mg BID prn pain * Medical Conditions: Osteoarthritis

42 * Alcohol: none * Tobacco: none * Caffeine: 3 cups coffee/day

43 * Sexually active: Yes * Exercise: Cardio 4-5 times a week, Weight training * Diet: No dairy, gluten, sugar

44 * Depression 2/10 * Anxiety 2/10 * Irritability 3/10 * Low Libido 9/10 * Fuzzy Thinking 9/10 * Fatigue 5/10

45 * Estradiol 15 * Total Testosterone 432 * Free Testosterone 10 * DHEA- S 200 * Vitamin D3 45

46 Treatment * HCG Inject 200 IU sq daily x 40 days * Pregnenolone/DHEA 25/25mg 1 c po daily

47 Andropause Case 2 * Patient: KR * Age: 56 years old Male * Marital Status: Married * Occupation: Dentist

48 * Allergies: Latex, Ibuprofen, Amoxicillin * Medications, OTC, Vitamins: HCTZ 25mg daily, Aspirin 81mg daily, Vitamin D3 5000IU daily * Medical Conditions: Hypertension

49 * Alcohol: 5 beers/week * Tobacco: none * Caffeine: 1 cup coffee/day

50 * Sexually active: Yes * Exercise: Walk 3x a week * Diet: Overall healthy diet fresh fruits and vegetables; no dairy

51 * Depression 4/10 * Anxiety 3/10 * Irritability 9/10 * Low Libido 10/10 * Fuzzy Thinking 8/10 * Fatigue 5/10

52 * Estradiol 67 pg/ml * Total Testosterone 216 ng/dl * Free Testosterone 4 pg/ml * DHEA- S 40 mcg/dl * Vitamin D3 60 ng/ml

53 Treatment * Testosterone 100mg/ml 1ml skin daily * Pregnenolone/DHEA 25/25mg 1 c po daily

54 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.

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