HYU Benign - Testis Flashcards
How do you diagnose low T?
Two separate early AM total T levels below 300 ng/dL
T-Deficiency
Low total T + signs/symptoms
History that should prompt consideration of T measurement even in asymptomatic men
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
If low T, what other test should you get?
Measure LH
Low T and high LH?
Think testicular failure
(lack of negative feedback via estradiol)
Low T and low LH?
What else measure?
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.
Low T + breast symptoms or gynecomastia
measure serum estradiol before TRT
T-deficiency and infertility
Get reproductive health evaluation
Don’t start testosterone
Labs needed before TRT can be started
Measure hemoglobin and hematocrit
- Discuss risk of polycythemia
Check PSA in a man > 40yo
What should you counsel patients on before starting TRT?
- 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
Goal range of TRT therapy
Adjust TRT to achieve total testosterone in the middle tertile of normal reference range (450-600 ng/dL)
Don’t prescribe TRT to men trying to concieve
How to treat men with low T who desire to maintain fertility?
Aromatase Inhibitors (anastrozole, letrozole)
hCG
SERMs (clomiphene citrate)
A combination
How long to wait after cardiovascular event to start TRT?
3-6 months
Why don’t we rx alkylated oral testosterone?
High risk of liver toxicity
Other TRT pearls
Discuss risk of transference with testosterone gel/creams
Commercially manufactured products should be used over compounded T when available
TRT follow-up
- Initial?
- Maintenance?
- If sxs don’t change with normal T?
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
TRT and FDA approval
TRT is only FDA approved for men with low T caused by certain medical conditions
It is not approved in age-related low T
Absolute contraindications for TRT
Breast cancer
Polycythemia
PSA >4ng/mL
Nodules on DRE
Relative contraindications for TRT
Hct >50%
Desire for fertility
Severe LUTS
Poorly controlled CHF
Untreated OSA
MI or stroke within 6 months
TRT and red blood cell overproduction
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
Serum Hormone Binding Globulin (SHBG)
Protein made in the liver that transports hormones in the blood in a bio-inactive state (~60% of T in physiologic state)
Medical conditions that increase SHBG and decrease bioavailable T
Hyperparathyroidism/thyrotoxicosis
Estrogen
Medical conditions that decrease SHBG and increase bioavailable T
Progestins
Hypothyroidism
Insulin
Glucocorticoid excess
Hepatic disease
Nephrotic syndrome
Obesity effect on SHBG
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
Routes of TRT administration
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
5-alpha-reductase (5AR)
- MOA?
- Types?
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
5AR deficiency
- Inheritance?
- Outcomes?
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
Chronic opioid effects on T
75% of chronic opioid users have low T
Opioids inhibit GnRH secretion from hypothalamus
T production and physiology
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
Testosterone Actions
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
