HYU Benign - Testis

Question 1

How do you diagnose low T?

Answer 1

Two separate early AM total T levels below 300 ng/dL

Question 2

T-Deficiency

Answer 2

Low total T + signs/symptoms

Question 3

History that should prompt consideration of T measurement even in asymptomatic men

Answer 3

Unexplained anemia
Bone density loss
Diabetes
Exposure to chemotherapy
Exposure to testicular radiation
HIV/AIDS
Chronic narcotic use
Male Infertility
Pituitary dysfunction
Chronic corticosteroid use

*Validated questionnaires are not currently recommended for identifying TRT candidates or monitoring response

Question 4

If low T, what other test should you get?

Answer 4

Measure LH

Question 5

Low T and high LH?

Answer 5

Think testicular failure
(lack of negative feedback via estradiol)

Question 6

Low T and low LH?
What else measure?

Answer 6

Suggests a problem in hypothalamus or anterior pituitary

Measure prolactin
- If persistently high prolactin (>80 ng/ml) and idiopathic, get endocrine evaluation. Get pituitary MRI and ophtho consult.

Question 7

Low T + breast symptoms or gynecomastia

Answer 7

measure serum estradiol before TRT

Question 8

T-deficiency and infertility

Answer 8

Get reproductive health evaluation
Don’t start testosterone

Question 9

Labs needed before TRT can be started

Answer 9

Measure hemoglobin and hematocrit
- Discuss risk of polycythemia

Check PSA in a man > 40yo

Question 10

What should you counsel patients on before starting TRT?

Answer 10

• Low T is a risk factor for CVD
• TRT may improve erectile function, low sex drive, anemia, bone mass density, lean body mass, quality of life
• Evidence is inconclusive re: cognitive function, measures of diabetes, energy, fatigue, lipid profiles, quality of life
• Discuss long-term impact of exogenous T on spermatogenesis in those interested in fertility (recovery variable, most within 1-2 years)
• TRT has NOT been shown to increase risk of prostate cancer or venothrombolic events
• T-deficiency + personal history of PCa –> inadequate evidence to quantify risk-benefit ratio of TRT (expert opinion)
• Currently it cannot be definitively determined whether TRT increases or decreases the risk of cardiovascular events
• Lifestyle modifications can be used instead of or in addition to TRT

Question 11

Goal range of TRT therapy

Answer 11

Adjust TRT to achieve total testosterone in the middle tertile of normal reference range (450-600 ng/dL)

Question 12

Don’t prescribe TRT to men trying to concieve

Question 13

How to treat men with low T who desire to maintain fertility?

Answer 13

Aromatase Inhibitors (anastrozole, letrozole)
hCG
SERMs (clomiphene citrate)

A combination

Question 14

How long to wait after cardiovascular event to start TRT?

Answer 14

3-6 months

Question 15

Why don’t we rx alkylated oral testosterone?

Answer 15

High risk of liver toxicity

Question 16

Other TRT pearls

Answer 16

Discuss risk of transference with testosterone gel/creams

Commercially manufactured products should be used over compounded T when available

Question 17

TRT follow-up
- Initial?
- Maintenance?
- If sxs don’t change with normal T?

Answer 17

Measure initial follow-up total testosterone to ensure target level achieved
- 2-4 weeks for gels, patches, intranasal formulations
- After 3-4 cycles for short-acting IM or short acting SQ pellets

Measure testosterone q6-12 months while on therapy

If total T normalizes but symptoms don’t change, discuss cessation of TRT

Question 18

TRT and FDA approval

Answer 18

TRT is only FDA approved for men with low T caused by certain medical conditions
It is not approved in age-related low T

Question 19

Absolute contraindications for TRT

Answer 19

Breast cancer
Polycythemia
PSA >4ng/mL
Nodules on DRE

Question 20

Relative contraindications for TRT

Answer 20

Hct >50%
Desire for fertility
Severe LUTS
Poorly controlled CHF
Untreated OSA
MI or stroke within 6 months

Question 21

TRT and red blood cell overproduction

Answer 21

Hypoxia –> HIF-1a –> increased transcription of erythropoietin and increase in VEGF

Testosterone and angiotensin II also induce erythrocytosis but not as much as hypoxia

Acquired polycythemia is Hct >52%
- Can be caused by hypoxia, high altitude, polycythemia vera, paraneoplastic syndromes, and TRT
- Highest risk with intramuscular > pellets > gels

Therapeutic phlebotomy indications: Hct > or = 54% with low/normal T and Free T while on TRT

Question 22

Serum Hormone Binding Globulin (SHBG)

Answer 22

Protein made in the liver that transports hormones in the blood in a bio-inactive state (~60% of T in physiologic state)

Question 23

Medical conditions that increase SHBG and decrease bioavailable T

Answer 23

Hyperparathyroidism/thyrotoxicosis
Estrogen

Question 24

Medical conditions that decrease SHBG and increase bioavailable T

Answer 24

Progestins
Hypothyroidism
Insulin
Glucocorticoid excess
Hepatic disease
Nephrotic syndrome

Question 25

Obesity effect on SHBG

Answer 25

Obesity of a/w reduced SHBG and decreased overall T but unchanged free T

Excess aromatase activity in visceral fat –> greater T breakdown into estradiol, which further lowers T and elevates estradiol

LH typically normal even with low T due to elevated estradiol

Question 26

Routes of TRT administration

Answer 26

IV, gels, subcutaneous, intranasal, intramuscular, oral

IV (ethanate or cypionate): significant peaks/valleys which can result in mood swings and changes in libido and potency

IM: Most likely to have side effect of erythrocytosis and risk of thrombotic events

Alkylated oral androgens (fluoxymesterone, methyltestosterone): serious liver toxicity and adverse effects on serum lipids –> should not be used

Question 27

5-alpha-reductase (5AR)
- MOA?
- Types?

Answer 27

5AR converts T to DHT
- DHT is the most potent receptor binder

5ARI’s (like finasteride) INCREASE intraprostatic (decrease conversion of T to SHT) and serum T (decreased negative feedback from DHT on pituitary)

5ARIs work on type II 5AR
Type I 5AR continues to function in the skin and liver

Question 28

5AR deficiency
- Inheritance?
- Outcomes?

Answer 28

Autosomal recessive, incomplete penetrance

Mullerian structures absent at birth because testes are present and produce mullerian inhibiting factor

Wolffian structures present at birth because testosterone is present –> ambiguous genitalia to variable degree because DHT not present
At puberty DHT is low and so cannot feedback to inhibit LH production –> increased LH, increased T, and increased T:DHT ratio –> virilization occurs at puberty

Question 29

Chronic opioid effects on T

Answer 29

75% of chronic opioid users have low T

Opioids inhibit GnRH secretion from hypothalamus

Question 30

T production and physiology

Answer 30

90% of circulating T is synthesized from Leydig cells in the testis with roughly 10% coming from the adrenal glands
Testicular synthesis of T is stimulated by luteinizing hormone (LH), which is produced in the anterior pituitary gland by the gonadotropic basophil cells
LH production is, in turn, stimulated by secretion of gonadotropin-releasing- hormone (GnRH) from the hypothalamus
T, as well as its metabolite estradiol, inhibit GnRH and LH secretion via negative feedback at the level of both the hypothalamus and the pituitary

Question 31

Testosterone Actions

Answer 31

T acts directly or via its primary metabolites, dihydrotestosterone (DHT) and estradiol (E2)

It is converted to DHT via the enzyme 5-alpha reductase, and to estradiol via the enzyme aromatase

T is critical for development of the male phenotype and drives male puberty

T and/or its metabolites have important normal physiological contributions to muscle, bone, skin, spermatogenesis, sexual function, brain, peripheral nerves, and hematopoiesis. Deficiency of T has been associated with abnormalities in all of these organ systems