LM 6.2: Testerone Overview

Question 1

what is andropause?

Answer 1

there isn’t a measurable/observable event like menopause

it’s just a normal decline in testosterone production after the 5th decade after 4 years old

usually associated with a rise in LH indicating end organ unresponsiveness

a better term would be ADAM: androgen deficiency in aging male

Question 2

what are the general symptoms of andropause?

Answer 2

1. symptoms include diminished sense of well being
2. decreased libido
3. fatigue
4. erectile dysfunction
5. metabolic syndrome
6. sarcopenia
7. decreased bone density

Question 3

what is male hypogonadism?

Answer 3

a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone (T) and sperm due to disruption of one or more levels of the hypothalamic-pituitary-testicular axis

the term “testosterone deficiency” may be used to refer specifically to the syndrome of low serum testosterone without regard to spermatogenic potential

Question 4

what is primary hypogonadism?

Answer 4

testicular failure

conditions that cause this include:
1. Klinefelter’s

2. undescended testicles
3. varicocele
4. iatrogenic
5. trauma
6. infant hernia/hydrocele repair
7. post pubertal mumps orchitis

Question 5

what is seoncdary hypogonadism?

Answer 5

hypogonadotrophic

things that cause thing:
1. pituitary adenoma

2. prolactinoma
3. chronic narcotic use
4. hemochromatosis

Question 6

what are some of the reasons behind increased rates of testosterone testing and prescriptions?

Answer 6

1. direct-to-consumer advertising
2. clinical centers for men’s health no run by MDs
3. anti-aging industry

Question 7

what stimulates testosterone secretion?

Answer 7

most of it is from Leydig cells due to stimulation form LH

a minor fraction of testosterone comes from the adrenals

Question 8

how does testosterone get into the blood?

Answer 8

intratesticular testosterone is 500-1000 times higher than circulating T levels

it diffuses into the capillaries into circulation

it’s bound by proteins like pre-albumin and sex hormone binding globulin (SHBG).

Question 9

what can circulating testosterone do? what can it be turned into?

Answer 9

1. circulating testosterone is converted to estradiol (E2) in adipose cells using enzyme aromatase

estradiole inhibits lH release from pituitary in response to GnRH

2. circulating testosterone inhibits hypothalamic release of GnRH
3. testosterone is converted to active form DHT (dihydrotestosterone) by enzyme 5 alpha reductase in prostate, scalp etc

Question 10

how reliable is it to measure free testosterone levels?

Answer 10

it’s very unreliable to measure free testosterone levels

calculated bioavailable T levels are the closest assay to free T assay

SHBG increases with age and can make isolated T level check inaccurate in patients above age 65 yrs

Question 11

how do you diagnose testosterone deficiency?

Answer 11

total testosterone level below 300 ng/dL - reasonable cut-off in support of the diagnosis of low testosterone

two low levels of testosterone on separate occasions to confirm – make sure to do early morning draws as testosterone has circadian rhythm

clinical diagnosis of testosterone deficiency is only made when patients have low total testosterone levels AND symptoms and/or signs of low T

Question 12

if a patient isn’t having symptoms of low testosterone, when would you still check the levels?

Answer 12

if there is a history of unexplained:

1. anemia
2. bone density loss
3. diabetes
4. exposure to chemotherapy
5. exposure to testicular radiation
6. HIV/AIDS, chronic narcotic use
7. male infertility
8. pituitary dysfunction
9. chronic corticosteroid use

check if these are unexplained even in the absence of symptoms or signs associated with testosterone deficiency

Question 13

what do you do next if there is low testosterone?

Answer 13

if low testosterone confirmed – next step is to measure serum luteinizing hormone levels

if low T and low/normal LH then check serum prolactin levels

persistently high prolactin levels of unknown etiology should undergo evaluation for endocrine disorders via MRI/CT brain

Question 14

when would you check serum estradiol levels in testosterone deficient patients?

Answer 14

if they present with breast symptoms or gynecomastia prior to the commencement of testosterone therapy

Question 15

what is a clinical consideration when prescribing testosterone therapy?

Answer 15

clinicians should measure hemoglobin and hematocrit and inform patients regarding the increased risk of polycythemia

Question 16

what are the complications associated with low testosterone?

Answer 16

1. cardiovascular disease

Question 17

what are the benefits of testosterone replacement therapy?

Answer 17

helps to improve:
1. ED

2. labido
3. anemia
4. bone mineral density
5. lean body mass
6. depressive symptoms

inconclusive whether testosterone therapy improves cognitive function, measures of diabetes, energy, fatigue, lipid profiles, and quality of life measures

Question 18

what are some of the long term effects of testosterone replacement therapy?

Answer 18

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

however, there is no evidence linking testosterone therapy to the development of prostate cancer or higher incidence of venothrombolic events

Question 19

how would you treat testosterone deficiency based on their family planning?

Answer 19

1. if there family is completed –> exogenous TRT
2. if they want to preserve fertility -> refer to male reproductive urology

TRT is not to be prescribed to men who are currently trying to conceive

3. may need varicocelectomy

Question 20

how do you treat men with testosterone deficiency that want to maintain their fertility?

Answer 20

1. aromatase inhibitors
2. hCG
3. selective estrogen receptor modulators

Question 21

when should you not start TRT?

Answer 21

it is not be commenced for a period of three to six months in patients with a history of a cardiovascular events

Question 22

how do you followup with testosterone replacement therapy?

Answer 22

Initial follow-up total testosterone level after an appropriate interval to ensure that target testosterone levels have been achieved

measured every 6-12 months while on testosterone therapy

stop TRT three to six months after commencement of treatment in patients who experience normalization of total testosterone levels but fail to achieve symptom or sign improvement

Question 23

what are the benefits of TRT in hypogonadal males?

Answer 23

1. increased lean body mass
2. decreased fat mass
3. improved boen mineral dnesity
4. improved libido
5. improved morning erections
6. improved erectile function
7. improves fasting glucose, A1C, and insulin sensitivity so helps with DM
8. improves TG and total cholesterols
9. improves mood

Question 24

what are the adverse effects of TRT in hypogonadal males?

Answer 24

1. helps cardiac perfusion, ischemic threshold, exercise threshold, and CO
2. increased sebum production
3. increased acne
4. increased hair loss
5. increased Hct
6. increased DVT
7. exogenous testosterone used alone results in reduced spermatogenesis
8. hypothetical increased risk of gynecomastia and breast caner
9. early worsening of sleep apnea in patients with severe baseline symptoms

no increased risk of prostate cancer or worsening urinary symptoms or flow

Question 25

how does TRT effect muscle?

Answer 25

T results in hypertrophy of type-I and II skeletal muscle fibers, and preferential differentiation of progenitor cells into muscle over adipose tissue

dose-dependent beneficial effects of T replacement for increasing muscle and strength, while decreasing fat mass

meta-analyses of RCTs evaluating T replacement in hypogonadal males demonstrate significant increases in lean muscle (2.7 kg) and reductions in fat mass (2.0 kg) without change in overall body weight, BMI, or waist circumference

Question 26

how does TRT effect spermatogenesis?

Answer 26

exogenous T supplementation results in decreased gonadotropin secretion by feedback inhibition at the level of the hypothalamus and pituitary

this leads to impairment in spermatogenesis by suppression of follicle stimulating hormone (FSH)

TRT with HCG and TRT with Anastrazole – preserved spermatogenesis

weightlifters using supra-therapeutic dosages for periods up to five years have demonstrated a return to spermatogenesis and fertility following discontinuation

Question 27

why does TRT sometimes cause gynecomastia?

Answer 27

peripheral aromatization of testosterone to estradiol (E2)

Question 28

how does TRT effect prostate cancer?

Answer 28

significant progression of disease following exogenous T administration in locally advanced or metastatic prostate cancer

Question 29

what are the contraindications to TRT?

Answer 29

1. existing prostate/breast cancer
2. Hct > 54%
3. increases OSA
4. untreated severe congestive heart failure

Question 30

how do you diagnose hypogonadism?

Answer 30

1. AM testosterone levels, LH.
2. repeat Free and total testosterone

range of normal 300-1000 ng/dl (lab dependent)

if low LH and low T:
1. ask about h/o exogenous testoerone abuse or supplementation

2. hypothalamic/pituitary disorder suspected
3. check prolactin, brain MRI