male androgen deficiency a/prof usman malabu mbbs, msc (chem path), fwacp, mrcp, facp, fracp staff...
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Male Androgen Deficiency
A/Prof Usman MalabuMBBS, MSC (Chem Path), FWACP, MRCP, FACP, FRACP
Staff Endocrinologist & Year 6 JCU Academic Coordinator
Department of Diabetes & Endocrinology TTH
MALE ANDROGEN DEFICIENCY
A 70 year-old Caucasian male Low testosterone 7 nmol/l
PMH: Type 2 DM, obesity, dyslipidemia, hypertension, low back pain, osteoarthritis and depression
Meds: Metformin XR 2g, Atorvastatin 40 mg OD, Perindopril 4 mg
OD, Fentanyl patch daily Prednisolone 10 mg OD
O/E: BP 130/80, Wt 110 KG, Ht 1.60, BMI 43 kg/m2.
Invs: A1c 7%, Total cholesterol 3 mmol/l, Total Testosterone 7 nmol/l
Group A
Q1. What further history would you inquire?
Q2. What further examination would you do?
Q3. How would you evaluate this patient?
Q4. What is the next step in work up?
Group D 26 year-old male married 6 months with poor erection
Was sexually abstinent & Libido is “fair to poor”
Puberty 15-17 yrs & Exercise tolerance was “good.”
Testes have always been “small”
Negative head trauma, loss of smell, testicular trauma, testicular surgery, or treatment for cancer
The patient denied chronic illness or taking medication
Family history was unremarkable
Exam: Wt 76 Kg, Height 181 cm
Group D
Q13. What further examination would you do?
Q14. How would you evaluate this patient?
Q15. What is the next step in confirming the diagnosis?
Q16. What would be your long-term plan for this patient?
Group B
Q5. List risk factors for hypogonadism in this subject
Q6. What would you do before starting testosterone Rx?
Q7. What are the side effects of testosterone Rx?
Q8. List absolute/relative contraindications to testosterone Rx
Group C
Q9. What conditions require measuring serum T in males?
Q10. What are pros/cons of mode of T Rx of your choice?
Q11. How are you going to monitor the patient on T Rx?
Q12. When would you consider stopping T Rx?
Androgen DeficiencyAndrogen Deficiency
Androgen deficiency is a condition in which tissues do not have enough exposure to androgens for normal function
One in 200 men under 60 years of age suffer from androgen deficiency
Testosterone levels fall with age
At age 65 years, 10% of men have androgen deficiency and this increases to 20% by 70 years
Testosterone and AgeingTestosterone and Ageing
0
5
10
15
20
25
25-34 35-44 45-54 55-64 65-74 75-84 85-100
Age (years)
Tes
tost
ero
ne
leve
l
Androgen deficiency
1 in 10
Range from about 7% between 40-60 years rising to 25% between 60-80 years
Androgen deficiency: symptoms
Decreased libido
Decreased energy
Loss of muscle mass, sex hair – chronic
Bone loss – chronic
Reduced testicular size & sperm count
Gynaecomastia
Diminished muscle mass
Loss of body hair
Abdominal obesity
Gynaecomastia
Testes frequently normal, occasionally small
Physical Signs
Male hypogonadism
Primary hypogonadism Testes Serum Testosterone↓, FSH & LH ↑
Secondary hypogonadism Pituitary gland or Hypothalamus Serum Testosterone↓, FSH & LH ↔ , ↓
Primary testicular failure
Hypothalamus
Pituitary LHFSH
Testosterone
Testis
Insult
Testosterone LH ( FSH)
Causes – testicular disease Klinefelter’s syndrome
Toxin exposure (cancer chemotherapy or radiotherapy, environmental, toxins)
Idiopathic
Defects of testis development
Orchitis
Orchidectomy (advanced prostate cancer)
Evaluation of Men with Androgen Deficiency
Confirmed low testosterone
Check LH+FSH (SA if infertility)
High gonadotropins – 1o Low/low nl gonadotropins – 2o
Karyotype Prolactin, other pituitary hormones, iron studies, sella MRI
Patient 2
How would you evaluate this patient?
Total testosterone: 2 nmol/l (9-35)
Luteinizing hormone (LH): 66 U/L (1.0-9.0)
What is the initial diagnosis?
Primary hypogonadism
What is the next step in work up?
Karyotype: 47 XXY
Klinefelter’s Syndrome
Incidence ~ 1/1,000 live male births
Extra X chromosome, usually 47 XXY
Manifestations Hypogonadism Gynecomastia Behavioral disorders Bronchiectasis/emphysema/bronchitis Mediastinal germ cell tumors Non-Hodgkin’s lymphoma Diabetes mellitus Lower extremity varicosities
Patient 2
How would you manage this patient?
Androgel 5 g topically QD
Counseling regarding infertility and extragonadal manifestations of Klinefelter’s syndrome
Make patient aware of Klinefelter’s support groups
LHFSH
Secondary testicular failure
Hypothalamus
Pituitary
Testosterone
Testis
Insult
TestosteroneLH ( FSH)
Hypothalamic-pituitary Diseases
Pituitary tumour/therapy (surgery, radiation)
Haemochromatosis
Craniopharyngioma
Idiopathic hypogonadotropic hypogonadism, Kallmann’s syndrome
Hyperprolactinemia
Causes of “Male Menopause”
Pituitary/testes decline Excessive alcohol consumption Obesity Smoking Hypertension Medications Poor diet Lack of exercise Poor circulation Psychological problems - depression
These issues are seen in metabolic syndrome & other medical problems
These issues are seen in metabolic syndrome & other medical problems
Look for co-morbidities in non-responders to PDE-5 inhibitors
Depending on co-morbidities:
Hypogonadism 50% Diabetes mellitus 35% LUTS / BPS 22%
Hypertension 23% Hyperlipidaemia Obesity
Yassin et al. IJIR Vol. 14, Suppl. 3, 9/2002
Diagnostic Testing for Androgen Deficiency
Who to test? Only men with consistent symptoms and signs
of unequivocally low serum testosterone levels
Screening in the general population is not recommended
Screening Questionnaires
Androgen Deficiency in the Aging Male Questionnaire
Massachusetts Male Aging Study questionnaire
Both have fair sensitivity (80-90%) but poor specificity (50-60%)
Not generally recommended
Bhasin, S. et al. J Clin Endocrinol Metab 2006;91:1995-2010
Laboratory evaluation
Testosterone and LH levels
>2 early morning samples
Free testosterone – requires validation
Protein binding – Sex hormone binding globulin (SHBG)
Free androgen index T / SHBG Poor empirical validation
35
Circulating Testosterone
SHBG-bound T (tight)
44%
Albumin-bound T (weak)54%
Free T2%
Bioavailable T
Total T
36
Common Alterations in SHBG
Affect Total and Free T Levels
• Estrogens• HIV
• Anabolic steroids• Acromegaly
• Anticonvulsants• Glucocorticoids
• Hyperthyroidism• Hypothyroidism
• Hepatitis, cirrhosis• Low protein (nephrotic)• Aging• Moderate obesity
SHBG Total T
SHBG Total T
St Louis ADAM questionnaireAndrogen Deficiency in Ageing Males
1. Decrease in sex drive
2. Lack of energy
3. Decrease in strength &/or endurance
4. Lost height
5. Decreased enjoyment of life
6. Sad &/or grumpy
7. Erections less strong
8. Deterioration in sports ability
9. Falling asleep after dinner
10. Decreased work performance
Answering yes to questions 1 or 7, or any other 3 questions indicates a high likelihood of having a low testosterone level.
Beware that depression may result in a high score
Beware that depression may result in a high score
Equilibrium dialysis (gold standard) is very expensive and not readily obtainable
Analog free testosterone is inaccurate and should NOT be used
Calculate bioavailable testosterone using derived formula
Diagnostic Testing for Androgen Deficiency
www.issam.ch/freetesto.htm
Variation in serum total testosterone concentrations
Bremner, WJ, Vitiello, V, Prinz, PN, J Clin Endocrinol Metab 1983; 56:1278
PBS criteria for testosterone therapy
Established pituitary/testicular disorder
Male 40y, no established disorder Not due to aging 2 early am samples, different mornings Testosterone level
< 8 nmol/l 8-15 nmol/l plus LH > 1.5 x upper limit
Micropenis, delayed puberty < 18y
42
Testosterone Formulations
Intramuscular T Extensive experience, inexpensive High-normal T, mood swings or libido, pain
T Patch Low-normal T, skin irritation, expensive
T Gel Low- to high-normal T, flexibility, no irritation Contact transfer, expensive
Buccal T Twice daily, altered taste, gum irritation
Choice often left up to patient
Monitoring: When to refer to Urologist
PSA > 4 ng/ml
Increase in PSA > 1.4 ng/dl within 12 months Rx
Abnormal DRE
Increase in IPSS prostate symptom score > 19
Bhasin, S. et al. J Clin Endocrinol Metab 2006;91:1995-2010
46
Summary: Diagnosis of Male Hypogonadism
Symptoms/signs of androgen deficiency− Sex (erections)− Brain (libido, mood, memory, hot flush/sweats)− Body (muscle, bone, breast and hair)
Consistently low T level x 2
Free or bioavailable T, if suspect SHBG
R/o reversible illness, drugs, nutritional deficiency
LH and FSH 1O vs 2O hypogonadism
47
Conclusions: Hypogonadism in Older Men
Common disorder
Nonspecific clinical findings affected by age, severity and duration of T and co-morbidities
Diagnosis confirmed by repeated T Accurate free T, if SHBG suspected R/O reversible causes
LH and FSH 1o vs 2o hypogonadism
T treatment if benefits > risks
Injectable, patch, gels, buccal T available
Thank You
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