LM 6.2: Testerone Overview Flashcards
what is andropause?
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
what are the general symptoms of andropause?
- symptoms include diminished sense of well being
- decreased libido
- fatigue
- erectile dysfunction
- metabolic syndrome
- sarcopenia
- decreased bone density
what is male hypogonadism?
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
what is primary hypogonadism?
testicular failure
conditions that cause this include:
1. Klinefelter’s
- undescended testicles
- varicocele
- iatrogenic
- trauma
- infant hernia/hydrocele repair
- post pubertal mumps orchitis
what is seoncdary hypogonadism?
hypogonadotrophic
things that cause thing:
1. pituitary adenoma
- prolactinoma
- chronic narcotic use
- hemochromatosis
what are some of the reasons behind increased rates of testosterone testing and prescriptions?
- direct-to-consumer advertising
- clinical centers for men’s health no run by MDs
- anti-aging industry
what stimulates testosterone secretion?
most of it is from Leydig cells due to stimulation form LH
a minor fraction of testosterone comes from the adrenals
how does testosterone get into the blood?
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).
what can circulating testosterone do? what can it be turned into?
- circulating testosterone is converted to estradiol (E2) in adipose cells using enzyme aromatase
estradiole inhibits lH release from pituitary in response to GnRH
- circulating testosterone inhibits hypothalamic release of GnRH
- testosterone is converted to active form DHT (dihydrotestosterone) by enzyme 5 alpha reductase in prostate, scalp etc
how reliable is it to measure free testosterone levels?
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
how do you diagnose testosterone deficiency?
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
if a patient isn’t having symptoms of low testosterone, when would you still check the levels?
if there is 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
- chronic corticosteroid use
check if these are unexplained even in the absence of symptoms or signs associated with testosterone deficiency
what do you do next if there is low testosterone?
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
when would you check serum estradiol levels in testosterone deficient patients?
if they present with breast symptoms or gynecomastia prior to the commencement of testosterone therapy
what is a clinical consideration when prescribing testosterone therapy?
clinicians should measure hemoglobin and hematocrit and inform patients regarding the increased risk of polycythemia
what are the complications associated with low testosterone?
- cardiovascular disease
what are the benefits of testosterone replacement therapy?
helps to improve:
1. ED
- labido
- anemia
- bone mineral density
- lean body mass
- depressive symptoms
inconclusive whether testosterone therapy improves cognitive function, measures of diabetes, energy, fatigue, lipid profiles, and quality of life measures
what are some of the long term effects of testosterone replacement therapy?
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
how would you treat testosterone deficiency based on their family planning?
- if there family is completed –> exogenous TRT
- 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
- may need varicocelectomy
how do you treat men with testosterone deficiency that want to maintain their fertility?
- aromatase inhibitors
- hCG
- selective estrogen receptor modulators
when should you not start TRT?
it is not be commenced for a period of three to six months in patients with a history of a cardiovascular events
how do you followup with testosterone replacement therapy?
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
what are the benefits of TRT in hypogonadal males?
- increased lean body mass
- decreased fat mass
- improved boen mineral dnesity
- improved libido
- improved morning erections
- improved erectile function
- improves fasting glucose, A1C, and insulin sensitivity so helps with DM
- improves TG and total cholesterols
- improves mood
what are the adverse effects of TRT in hypogonadal males?
- helps cardiac perfusion, ischemic threshold, exercise threshold, and CO
- increased sebum production
- increased acne
- increased hair loss
- increased Hct
- increased DVT
- exogenous testosterone used alone results in reduced spermatogenesis
- hypothetical increased risk of gynecomastia and breast caner
- early worsening of sleep apnea in patients with severe baseline symptoms
no increased risk of prostate cancer or worsening urinary symptoms or flow
how does TRT effect muscle?
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
how does TRT effect spermatogenesis?
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
why does TRT sometimes cause gynecomastia?
peripheral aromatization of testosterone to estradiol (E2)
how does TRT effect prostate cancer?
significant progression of disease following exogenous T administration in locally advanced or metastatic prostate cancer
what are the contraindications to TRT?
- existing prostate/breast cancer
- Hct > 54%
- increases OSA
- untreated severe congestive heart failure
how do you diagnose hypogonadism?
- AM testosterone levels, LH.
- 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
- hypothalamic/pituitary disorder suspected
- check prolactin, brain MRI
