The document discusses the diagnosis and management of hypogonadism. It defines hypogonadism and outlines the key diagnostic steps including medical history, physical exam, and lab tests to distinguish between primary and secondary causes. The primary care management of hypogonadism is also reviewed, including treatment with testosterone and monitoring of side effects.

1. Hosts
The Second Annual CME
Operational Medicine
Conference
4-6 November 2013
1300-1700
7 November 2013
1300-1530
at the
Medical Simulation Training Center (MSTC)
Fort Hood, Texas
The
1st Cavalry Division
Division Surgeon Section (DSS)

2. Non-Disclosure
References
1. Steven M. Petak; American Association of Clinical
Endocrinologists Medical Guidelines for Clinical Practice for the
Evaluation and Treatment of Hypogonadism in Adult Male Patients
2002; Vol 8 No.6; 439-456.
2. Kevin M. Pantalone; Male Hypogonadism: More than Just a
Low Testosterone; Cleveland Clinic Journal of Medicine 2012;
Vol 79 No. 10; 717-724
3. John J McGill; Androgen Deficiency in Older Men: Indications,
Advantages, and Pitfalls; Cleveland Clinic Journal of Medicine
2012; Vol 79 No. 11; 797-806

3. INTRODUCTION
Hypogonadism if defined as “inadequate gonadal function, as manifested by
deficiencies in gametogenesis and /or secretion of gonadal hormones”(1).
Key Points:
Low testosterone by definition is 2 low testosterone levels in 1 month. Low for
our lab (Quest) is less than a total testosterone of 300 ng/dl (1,2,3).
Low testosterone levels need to be drawn at 8am. 8 am values are 30% higher
than the rest of the day (2).
Androgen deficiency in older men is associated with metabolic syndrome, type
2 diabetes, obesity, osteoporosis, renal failure, anemia, acute illness, and
previous treatment with corticosteriods , anabolic steroids, opiates (2-3).
Treatment is discouraged in the absence of clinical symptoms (3).

4. DIAGNOSIS
Progressive loss of muscle mass, loss of libido, impotence, oligospermia or
azoospermia, low volume ejaculate, menopausal-type hot-flashes with acute
onset with hypogonadism, poor ability to concentrate, fatigue.
PHYSICAL EXAMINATION
Beard growth and distribution of body hair, gynecomastia, galactorrhea
(hyperestrogenism) (1)
Adult testes are 20-30ml in volume and 4.5-6.5cm long by 2.8-3.3 cm wide
Peripubertal testes are 4-15ml in volume and more than 2 cm long
Prostate exam- nonpalpable prostate suggests low testosterone levels (1).

5. LABS
1 2 3
Testosterone Testosterone LH
Liver Function Lipids Renal
PSA Albumin Cortisol
Hematocrit (CBC) Prolactin RA, CRP, ANA, RF
TSH, T3/T4 free Estrogen DRE
FSH/LH-3 LH
Iron SHBG (Sex Hormone Binding Globulin)
Testosterone Free, BIO, Total
Testosterone primarily bound: SHBG 30% not Bio available , albumin 68% and weakly
bound, 2% free and active (1).
Increased SHBG assoc with hyperthyroid, liver Dz, severe androgen deficiency, or
estrogen excess. Older men with impotence the interpretation of free and total
testosterone and SHGB is used to determine threshold of therapy goals (1).

6. A low SHBG level can be assoc with hypothyroidism, obesity, or acromegaly.
FSH/LH determine is hypogonadism is primary or secondary, FSH has longer half
life (1). Progressive hypogonadism will have increased FSH well before LH (1).
Secondary: Low or normal FSH/LH- Hypogonadotropic- Hypothalmic-pituitary
Kallmann Syndrome, GnRH receptor mutation, opiods,
corticosteriods, obesity, Type 2 DM, Illness, HIV, Estrogen excess,
alcohol, anorexia, Hyperprolactinemia, surgery, aging, OSA (2).
Primary: Elevated FSH/LH- Hypergonadotropic – Testicular disorder-
Klinefelters, toxic exposure chemotherapy, mumps orchitis,
ketoconazole inhibit biosynthesis, increased temperature
varicocele or large panniculus, impaired sperm production (2).
Ferritin levels : Iron overloads can cause both conditions because of
hemochromatosis- secondary more common (2).

7. Hyperprolactinemia can be caused by dopamine, antagonists, antipsychotics, reglan,
pituitary adenomas, microadenomas less 10mm, no stalk compression, benign (2).
Stalk compression can cause prolactin elevation, this disrupts pulsatile release of GnRH
from hypothalamus, which is required for normal LH and FSH secretion.
Prolactin can cause reduced libido if high, MRI of pituitary (1).
Estrogen excess: from exogenous estrogen-containing contrceptives and creams,
testicular and very rarly adrenal estrogen secreating tumors, steroids (2).

8. Aging
SHBG levels increase probably due to increased estradiol levels from adipose
tissue (1).
Symptomatic hypogonadism total testosterone less than 200 ng/dL (1).
Resulting intervention can occur at 319 ng/dL. 30% of men older than 75 would
have a level below this.
Untreated men score high on depression, fatigue, and confusion scales (1).
Erectile dysfunction may not improve after adequate treatment (1).

9. PRIMARY CARE MANAGEMENT
Total testosterone between 280-800 ng/dL and normal estradiol levels.
UpToDate: value should be well within the normal range 400 to 700 ng/dL.
Fortesta, 8 am level check and 6 am application
Testosterone Cypionate 200mg/ml. 50mg every 7 days till in range goal, check
levels on day 3 after injection, slow decline over 1-2 weeks or 100-150mg every
2 weeks (1). Treatment to ensure a consistent clinical response. 22Gx 1 ½ min.
Levels should be in the range of 250-300 ng/do before next injection (1).
Side effects should be monitored every 3-4 months once stable dose
determined. PSA, Gynecomastia (aromatization) and changes in SHBG,
hematocrit causing hyperviscosity above 50% (1). Sleep apnea relative
contraindication
Oral, increase LDL and lower HDL and increased cardiovascular risk (1).

10. SIDE EFFECTS
HCG binds to Leydig cell LH receptors and stimulates production of
testosterone.
Dosage of HCG is 1-2000 IU TID week for 2 weeks following testosterone
treatment (1). 500IU weekly for 16 weeks during treatment. Half life is long.
HCG treatment stimulates intra-testicular testosterone to allow initiation of
spermatogensis and testicular growth.
Increased Estrogen levels during treatment.
Estrogen Males: 40-115 pg/mL
Estradiol Males: 11.6-57.5 pg/mL

11. SIDE EFFECTS
Antiestrogen in Oligospermia
Long term use of low dose clomiphene citrate 25mg daily to increase pituitary
stimulation of testicular function (1).
Tamoxifen: Has been used similarly. Bone weakness and osteoporosis 2x that
of other meds.
Anastrozole: 1mg weekly. Aromatase-inhibiting terminal binding. Reduce
estradiol. TX benign prostatic hyperplasia, gynecomastia, and symptoms of
hypogonadism, emotional, water retention.

12. Testosterone in Women
Testosterone, an essential precursor of estrogen in women, made in ovaries and
adrenal glands. Steady decline in testosterone from the 20s through
menopause.
No clear limit of testosterone established, however less than 15ng/dL is
commonly used as low . Marked decrease in sexual desire occurs at levels of 0-
10ng/dL.

13. Goals
Increased lean muscle
Improved: mood, well being, erectile dysfunction, bone density, muscle
strength.
Risks
Benign prostatic hyperplasia: No clear evidence
Cardiovascular: No clear effect
Liver toxicity: Not at therapeutic doses
Polycythemia: High dose only
Virilization, alopecia, hirsutism, acne: Dose and duration related

14. Summary
The major objective of the initial assessment for hypogonadism are to
distinguish between primary and secondary hypogonadism gonadal failure (1).
History and physical exam to determine major medical problems, medications,
toxic exposure developmental milestones (1).
Major symptoms low libido, impotence, fatigue, impaired concentration, and
sexual dysfunction (1).
Clear lab values that support hypogonadism
MRI essential along with a compliant patient
Accurately timed and trendable testosterone levels