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 * 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,
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 * 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 * 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.
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 * 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: * 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
* Breast tenderness * Gynecomastia * Compromised fertility * Change in testicle size * Skin reactions * Fluid retention * Acne/oily skin * Increased body hair Side Effects
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 2/10 * Anxiety 2/10 * Irritability 3/10 * Low Libido 9/10 * Fuzzy Thinking 9/10 * Fatigue 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 4/10 * Anxiety 3/10 * Irritability 9/10 * Low Libido 10/10 * Fuzzy Thinking 8/10 * Fatigue 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.