MALE ALLERGY PATIENTS WITH HYPOTESTOSTERONEMIA:

LONG-TERM TREATMENT RESULTS

Steven F. Hotze, M.D.

9225 Katy Freeway, Suite 210

Houston, Texas 77024

(281)579-3600


  1. Introduction
    1. Testosterone1
    1. Produced by the Leydig cells in the testes in response to luteinizing hormone (LH) from the pituitary gland
    2. Predominant male androgen
    3. Average daily production in males 20-29 years old – 10 mg.
    4. Synthesized from cholesterol via pregnenolone
    1. Progesterone pathway
    2. Dehydroepiandrosterone (DHEA) pathway
    1. 19-carbon steroid


      2. OH

      O

    2. 97-99% bound to sex hormone-binding globulin (SHBG) and albumin
    1. SHBG produced by the liver
    2. SHBG increased by Estrogens
    1. 2-4% not bound to protein – Free Testosterone


      2. a. Biologically active fraction of testosterone

    2. Free Testosterone peaks in males at approximately age 20
    3. Free Testosterone declines 1.2%/year over lifetime2


      4. Age Range

    20-29 19-41
    30-39 18-39
    40-49 16-33
    50-59 13-31
    >60 9-26

     
     
     
     
     
     
     
     
     
     
     
  1. Release controlled by diurnal rhythm of luteinizing hormone (LH) secreted by pituitary gland
    1. LH regulated by gonadotrophic release hormone (GRH) from the hypothalamus
B. Actions of Testosterone
    1. Localizes at receptors in the cell nucleus of every cell in the body
    2. Some testosterone converted to dihydrotestosterone (DHT) in the cytoplasm
    3. Receptors have affinity for both DHT and Testosterone
    4. Testosterone/DHT receptor complex activates specific genes
    5. Protein products of these genes mediate the effects of the hormones
    1. Effects of Testosterone
    1. Sexual differentiation
    2. Spermatogenesis – initiation of sperm production by sertoli cells in testes
    3. Development of male internal and external genitalia
    4. Anabolic metabolism – increase in muscle mass, strength and tone3
    5. Decrease in body fat4
    6. Stimulation of osteoblastic activity and increase in calcitonin concentration increasing bone mass5
    7. Stimulates erythropoiesis – increasing RBC production
    8. Enhances sexual behavior, libido and potency6
    9. Increases metabolism by enhancing the conversion of T4 to T3
    10. Brain stimulated to initiate male pattern behavior
    1. Initiative
    2. Assertiveness
    3. Sense of well-being
    4. Self confidence
    5. Elevated moods
    6. Decisiveness
    7. Goal orientation
    8. Abstract thinking
    9. Mathematical ability
    1. Reverses adverse effects of glucocorticoid therapy (i.e., asthmatics)7
    1. Andropause – the gradual decline in the production of testosterone
    2. Hypogonadism – subnormal production of testosterone
    3. Symptoms and Signs of Low Testosterone
    1. Failure of secondary sex characteristics to develop
    2. Low sperm count8
    3. Reduced axillary, pubic and facial hair
    4. Decreased muscle mass and strength
    5. Small testicles and penis
    6. Gynecomastia – enlarged breasts
    7. Osteoporosis9
    8. Decreased hemoglobin and hematocrit
    9. Decreased libido10,11
    10. Erectile dysfunction12
    11. Fatigue
    12. Depressed moods
    13. Lack of motivation and drive for life
    14. Decreased cognitive function
    15. Irritability
    16. Lack of goals
    17. Poor sense of well being
    18. Passivity
    19. Loss of initiative
F. Causes of Hypotestosteronemia
    1. Natural decline in testicular function
    2. Petrochemicals – xenoestrogens (Bisphenol – A, Nonyphenols, alkylphenols, organochlorines)13,14
    1. Mimic effect of estrogen hormones
    2. Antagonize the effect of endogenous hormones
    3. Disrupt the synthesis and metabolism of endogenous hormones
    4. Disrupt the synthesis and metabolism of hormone receptors
    5. Effects
    1. Decreased sperm production (50% decrease in male sperm count since 1960)15
    2. Increase in testicular cancer
    3. Increase in cryptorchidism (undescended testicle)
    4. Increase in breast cancer
    5. Increase in thyroid binding globulin (TBG) causing functional hypothyroidism
    1. Primary Testicular Dysfunction – Klinefelter Syndrome (47xxy)


      2. a. Occurrence – one (1) in one thousand (1000) newborn males

    2. Pituitary dysfunction
    3. Hypothalamic dysfunction
    1. Diagnosis
    1. Clinical History – question the patient and listen
    2. Free Testosterone Level16
    3. Luteinizing hormone (LH) & follicular stimulating hormone (FSH) levels
    1. Treatment of Hypotestosteronemia17
    1. Testosterone Cypionate (TC) or Ethanate (TE) intramuscularly
    1. Esterification prevents metabolic inactivation prolonging biological effects18
    2. Injection Vehicle – TC – cottonseed oil, TE – sesame oil
    1. Alkylated Androgens
    1. Methyltestosterone (Estratest, Testred, Virilon)
    2. Fluoxylmesterone (Halotestin)
    3. Several Side Effects
    1. Increases low density lipoproteins (LDL)
    2. Decreases high density lipoproteins (HDL)
    3. Hepatic adenomas
    4. Hepatic carcinoma
    5. Peliosis hepatitis
    6. Cholestatic hepatitis and jaundice
    1. Transdermal Testosterone
    1. Scrotal patch (Testoderm) – scrotal skin is 5x more permeable
    1. High levels of DHT due to 5a-reductase in scrotal skin
    1. Skin patch – (Androderm) – applied nightly
(1) 50% incidence of erythema at application site
    1. Testosterone Slow Release Capsules
    1. Methocel E4M 12 hour time released base for slow release in small intestine
    2. Therapeutic serum levels are difficult to obtain
    1. Treatment of Hypotestosteronemia at Hotze Health & Wellness Center
    1. Testosterone Cypionate 200 mg./cc – produced by compounding pharmacy
    1. Physiologic replacement dose
    1. Initially Testosterone Cypionate 300 mg. (1 ½ cc) I.M.
    2. Testosterone Cypionate 200 mg. (1 cc) I.M. weekly for 4 weeks19
    3. Maintenance Dose – Testosterone Cypionate 100 mg. (1/2 cc) I.M. weekly
    4. Ideal range of Free Testosterone – 30-40 pg/ml
    1. Saw Palmetto 160 mg. – 2x/day – decreases the conversion of testosterone to DHT – DHT causes Benign Prostatic Hyperplasia20
    1. Side Effects of Supraphysiological doses of Testosterone21
    1. Acne
    2. Weight gain – due to increased muscle mass
    3. Excessive stimulation of libido
    4. Polycythemia
    5. Gynecomastia and/or breast nipple tenderness
    1. Due to peripheral aromitization of testosterone to estradiol
    1. Decreased sperm production in 50% of males22,23
    2. Treatment – reduce dosage of testosterone
    3. No major adverse side effects of testosterone supplementation24
    4. No significant increase in PSA25
    1. Original Study January 1, 1998 – December 31, 1998
    1. 125 male allergy patients were studied
    2. 117 (94%) of these patients were diagnosed with Hypotestosteronemia
    1. Long-Term Treatment Results
    1. 87 (74%) of those men responded
    2. 61 (70%) men responded who were taking testosterone cypionate injections as prescribed
    3. The average Free Testosterone level of 117 men with Hypotestosteronemia was 14.86 pg/ml
    4. The average Free Testosterone level of 61 men in the study group was 15.0 pg/ml
    5. The average age of 117 men with Hypotestosteronemia


      6. a. 42.6 years old

    6. Average age of 61 men in study group
    1. 43.7 years old
    1. Age Composition of Patients in Study
    No. of Pts. Age in Years Average Testosterone Level
    5 20-29 15.38 pg/ml
    20 30-39 16.43 pg/ml
    20 40-49 14.93 pg/ml
    11 50-59 12.73 pg/ml
    5 60 + 13.74 pg/ml
  1. Average length of treatment
    1. 5.4 months
    1. 23 (38%) established patients in this study
    2. 38 (62%) NPAL (first time patients) in this study
    3. Comparison of New Patients vs. Established Patients – Symptomatic response to treatment (presenting symptoms for each patient differed – not all patients had each of the following symptoms)
Percentage of Improvement and/or Resolution of Symptoms

of Patients in Study Taking Testosterone
Symptom New Patients  Established Patients
Fatigue 79% (30/38) 78% (18/23)
Mental Sharpness 81% (29/36) 74% (17/23)
Memory 65% (24/37) 65% (15/23)
Abstract Thinking 69% (25/36) 71% (15/21)
Mathematical Ability 61% (22/36) 55% (12/22)
Goal Setting 66% (23/35) 77% (17/22)
Initiative 86% (31/36) 65% (15/23) 
Assertiveness 78% (29/37) 68% (15/22)
Decisiveness 78% (29/37) 70% (16/23)
Sense of Well Being 84% (32/38) 78% (18/23)
Self Confidence 76% (29/30) 78% (18/23)
Depressed Moods 71% (25/35) 71% (15/21)
Anxiety 67% (22/33) 65% (13/20)
Irritability 69% (22/32) 65% (13/20)
Insomnia 55% (17/31) 29% (4/14)
Muscle Pain 39% (13/33) 53% (9/17)
Muscle Strength 59% (20/34) 73% (16/22)
Libido 65% (22/34) 77% (17/22)

 
    1. Conclusion
The results demonstrate that testosterone supplementation, when indicated in patients with allergic disorders, provides significant improvement in the patient’s overall health, well-being and energy level. An overwhelming number of male patients who were treated for their allergies in combination with testosterone supplementation, when indicated, reported a marked improvement in their original symptoms.