Testosterone Guidelines

Question 1

What is the lower limit of a normal testosterone?

Answer 1

Guideline 1: A total testosterone level below 300 ng/dL is a reasonable cut-off in support of the diagnosis of low testosterone

Question 2

When should you measure testosterone?

Answer 2

Guideline 1: testosterone levels should be measured conducted in an early morning fashion (peak between 3-8 AM)

Question 3

How many low testosterones should be measured to diagnose low testosterone?

Answer 3

Guideline 2: TWO total testosterone measurements that are taken on separate occasions

Question 4

How do you diagnose testosterone deficiency (not just low testosterone levels)?

Answer 4

Guideline 3: The clinical diagnosis of testosterone deficiency is only made when patients have low total testosterone levels combined with symptoms and/or signs

Question 5

In whom should you consider measuring testosterone in even in the absence of symptoms or signs associated with testosterone deficiency?

Answer 5

Guideline 4: Clinicians should consider measuring total testosterone in patients with a history of unexplained anemia, bone density loss, diabetes, exposure to chemotherapy, exposure to testicular radiation, HIV/AIDS, chronic narcotic use, male infertility, pituitary dysfunction, and chronic corticosteroid use

Question 6

Should you use a validated questionnaire to define patients who are candidates for T replacement?

Answer 6

Guideline 5: The use of validated questionnaires is not currently recommended to either define which patients are candidates for testosterone therapy or monitor symptom response in patients on testosterone therapy.

but you can still use them to supplement your thorough history. One such sample questionnaire is the Aging Male Survey (AMS)

Question 7

Once a person has a diagnosis of low testosterone, what is your next blood work?

Answer 7

Guideline 6: serum luteinizing hormone levels (LH)

Question 8

If someone has low testosterone levels combined with low or low/normal luteinizing hormone levels, what other test should you order?

Answer 8

Guideline 7: serum prolactin level

Guideline 11: (prior to starting treatment) measure hemoglobin and hematocrit (and warn men of the increased risk of polycythemia)

Guideline 12: (prior to starting treatment) PSA should be measured in men over 40 years of age

Question 9

What causes hyperprolactinemia?

Answer 9

Medications, most commonly dopamine antagonists (but also anti-psychotics, anti-emetics, proton pump inhibitors, calcium channel blockers, opiates, and selective serotonin reuptake inhibitors) may cause hyperprolactinemia.

Chronic medical conditions, such as hypothyroidism, renal failure, and cirrhosis are associated with hyperprolactinemia as well.

Question 10

Who should you refer to an endocrinologist?

Answer 10

Patients with persistently high prolactin levels of unknown etiology should undergo evaluation for endocrine disorders

Question 11

What should you measure in a testosterone deficient patients who present with breast symptoms or gynecomastia prior to the commencement of testosterone therapy

Answer 11

Guideline 9: Serum Estadiol

Question 12

What should a testosterone deficient man who is interested in fertility have done and be warned of?

Answer 12

Guideline 10: Men with testosterone deficiency who are interested in fertility should have a reproductive health evaluation performed prior to treatment.

Guideline 16: The long-term impact of exogenous testosterone on spermatogenesis should be discussed with patients who are interested in future fertility

Question 13

What should clinicians should inform testosterone deficient patients about their heart?

Answer 13

Guideline 13: That low testosterone is a risk factor for cardiovascular disease

Question 14

Patients should be informed that testosterone therapy may result in improvements in what?

Answer 14

Guideline 14: erectile function, low sex drive, anemia, bone mineral density, lean body mass, and/or depressive symptoms

Question 15

Patients should be informed that the evidence is inconclusive whether testosterone therapy does what?

Answer 15

Guideline 15: improves cognitive function, measures of diabetes, energy, fatigue, lipid profiles, and quality of life measures

Question 16

What should clinicians say about prostate cancer and testosterone therapy?

Answer 16

Guideline 17: Clinicians should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer

Guideline 18: Patients with testosterone deficiency and a history of prostate cancer should be informed that there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy.

Question 17

What should clinicians say about venothrombolic events and testosterone therapy?

Answer 17

Guideline 19: Patients should be informed that there is no definitive evidence linking testosterone therapy to a higher incidence of venothrombolic events

Question 18

What should clinicians say about cardiovascular events and testosterone therapy?

Answer 18

Guideline 20: Prior to initiating treatment, clinicians should counsel patients that, at this time, it cannot be stated definitively whether testosterone therapy increases or decreases the risk of cardiovascular events (e.g., myocardial infarction, stroke, cardiovascular-related death, all-cause mortality)

Question 19

What is one thing all testosterone deficient men who are overweight or physically inactive should be counseled on as far as one treatment any man should do?

Answer 19

Guideline 21: All men with testosterone deficiency should be counseled regarding lifestyle modifications as a treatment strategy (weight loss and exercise will naturally boost testosterone in these men)

Question 20

When supplementing testosterone, what testosterone level should you try to achieve?

Answer 20

Guideline 22: Clinicians should adjust testosterone therapy dosing to achieve a total testosterone level in the middle tertile of the normal reference range (450-600)

Question 21

What should you not prescribe men who are currently trying to conceive?

Answer 21

Guideline 23: Exogenous testosterone therapy should not be prescribed to men who are currently trying to conceive

Guideline 27: Clinicians may use aromatase inhibitors, human chorionic gonadotropin, selective estrogen receptor modulators, or a combination thereof in men with testosterone deficiency desiring to maintain fertility

Question 22

How long should you wait to start testosterone therapy in a person with a history of cardiovascular events?

Answer 22

Guideline 24: Testosterone therapy should not be commenced for a period of three to six months in patients with a history of cardiovascular events.

Question 23

What type of testosterone should you not prescribe?

Answer 23

Guideline 25: Clinicians should not prescribe alkylated oral testosterone. (due to their liver toxicity)

You can prescribe testopils, gels, creams, liquids, sublinquial, IM, etc

Question 24

Clinicians should discuss the risk of transference with patients using testosterone gels/creams. How do you prevent this?

Answer 24

Use an alternative therapy.

Wash hands well after applying

cover the area with clothing after drying

Wash skin prior to skin to skin contact

Wash clothes that touched testosterone separately

Question 25

should you prescribe testosterone products that are compounded?

Answer 25

Guideline 28: Commercially manufactured testosterone products should be prescribed rather than compounded testosterone, when possible

Question 26

When should men measure their total testerone level after starting testosterone therapy?

Answer 26

guideline 29: Clinicians should measure an initial follow-up total testosterone level after an appropriate interval to ensure that target testosterone levels have been achieved.

generally 2-4 weeks for gels, liquids and creams
short-acting IM or short-acting SQ pellets (testosterone cypionate or enanthate) mid-cycle after ~ 4 cycles
long-acting IM testosterone (testosterone undecanoate) ~ 15 weeks
anastrozole, clomiphene citrate, and hCG > 4 weeks after starting
long-acting SQ pellets (2-4 weeks to see if number of testopels is appropriate and then 10-12 weeks)

Question 27

Once a patient is on a stable dose of testosterone therapy, how often should you check their testosterone?

Answer 27

Guideline 30 Testosterone levels should be measured every 6-12 months while on testosterone therapy. (Also check their H/H!)

Question 28

Describe testosterone regulation in the body:

Answer 28

GnRH released from hypothalamus acts on anterior pituitary to stimulate release of LH and FSH (both act on testes)

FSH → Sertoli Cells → spermatogenesis

LH → Leydig cells → testosterone

Negative feedback to hypothalamus and anterior pituitary by both testosterone and through aromatase (estradiol)

Question 29

What forms is testosterone found in the body:

Answer 29

60% bound to SHBG (not bioavailable, can measure in elderly or obese men)

Bioavailable:
1-2% free and remainder bound loosely to albumin

AR binds to testosterone and DHT (higher affinity)

Question 30

What aspects of history are important in assessment of testosterone deficiency?

Answer 30

hypothyroid (similar sxs, measure TSH)
low libido
tiredness
mood altrations (irritability)
fogginess
decreased strength/stamina
loss of muscle mass
central obesity
opioids
corticosteroids
surgeries testis or head
torsion, trauma, orchitis
chemo or radiation
HbA1C, glucose control
PSA (over 40)

Question 31

Labs to consider with low T

Answer 31

SHBG (older or obese)
TSH
PRL (severely low)
LH
HCT
PSA
HbA1C

Question 32

Types of hypogonadism:

Answer 32

1. Hypergonadotropic hypogonadism (primary) → testicular failure; low T, elevated LH
   
   1. Examples: gonadotoxin (chemo, RT), congenital (UDT, Kleinfelter’s), testicular insults (torsion, trauma, testis cancer), meds (spironolactone, ketoconazole)
2. Hypogonadotropic hypogonadism (secondary) → low LH, low T (hypothalamus or pituitary problem)
   
   1. Examples: genetics (Kallmann, Prader-Willi), trauma (pituitary tumor, prolactinoma, RT, infarct), substances/neg feedback (opioids, steroids, marijuana), metabolic dz (DM, OSA, ESRD, malnutrition, obesity)
3. Mixed (compensated hypogonadism) → low T normal/borderline low LH (adult onset)

Question 33

Benefits of treating hypogonadism:

Answer 33

Sexual function (libido, erections, response to PDE5i)

Body composition (bone mineral, decreased fat, increase skeletal musc)

Psychologic (improved depression)

Cognitive (decreased memory loss, greater attention span)

Comorbidity mgmt. (improved glucose/lipid)

Question 34

Risk of T treatment:

Answer 34

Impaired spermatogenesis (decreased T production in testis)

Erythrocytosis (higher with IM), keep <54%

Gynecomastia (aromatase)

OSA worsened??

CV risk, controversial

Question 35

Contraindications to T replacement:

Answer 35

No absolute contraindications

Not ideal for fertility

recommended to avoid prostate cancer, breast cancer, severe OSA, Hct > 50%, severe LUTs, PSA . 4, male infertility

NONE of above are absolute contraindication

Question 36

Other treatment options besides T for low T:

Answer 36

Not FDA Approved

SERMs: attenuating negative feedback of estrogen on hypothalamus and pituitary → increase LH (less likely to work with testis failure)

CLOMIPHENE CITRATE

Aromatase inhibitor: inhibit conversion of T → E

ANASTRAZOLE (LETROZOLE)

HCG: stimulate Leydig cell production of T (oral and generic)

Question 37

what do you do if your patient on T therapy has Hct >54%

Answer 37

Men with significant polycythemia (Hct >54%) may require dose adjustment, periodic phlebotomy, or temporary/permanent T discontinuation.