Hypogonadism Flashcards
Terminology
hypogonadism
primary hypogonadism
secondary
* (Symptomatic) Late onset hypogonadism (S)LOH:
AOH
(P)ADAM
Testosterone deficiency (TD)
- Hypogonadism: a condition resulting from or characterized by abnormally decreased
functional activity of the gonads, with retardation of growth and sexual development. - Primary Hypogonadism: Primary disorder of testicular function
- Secondary Hypogonadism: Disorders of the pituitary or hypothalamus resulting in
inadequate gonadotropin stimulation of the testes. - (Symptomatic) Late onset hypogonadism (S)LOH: A clinical and biochemical syndrome
associated with advancing age and characterized by typical symptoms and deficiency in
serum testosterone levels. First used in guidelines in 2002. - AOH: Adult-onset hypogonadism
- (P)ADAM: (Partial) androgen decline in the aging male
- Andropause (International Society of the Study of the Ageing Male, ISSM): The term
previously used to describe LOH. - Testosterone deficiency (TD) (ISSM, 2015): a clinical and biochemical syndrome
characterized by a deficiency of testosterone, or testosterone action, and relevant
symptoms and signs. TD may affect the function of multiple organ systems, and result in
significant detriment in the quality of life, including alterations in sexual function. - Teststerone Deficiency Syndrome (TDS) (Canadian Guidelines 2015)
- Which term is currently accepted as correct medical terminology?
A. Andropause
B. Low T
C. Manopause
D. Late onset hypogonadism (LOH)
E. Partial androgen decline in the aging male (PADAM)
D. Late onset hypogonadism (LOH)
What does Testosterone Do?
- Fetal masculinization (i.e. become male)
- Pubertal changes (boy to man)
- Sexual function (have sex)
- Sperm production (reproduce)
- …. And so much more
◼ Decreased testicular production
◼ Testes less responsive
◼ Increase in sensitivity of the
hypothalamus
◼ Peripheral conversion to
estrogen
◼ SHBG increases
Classification * Primary
secondary
Primary * Testicular disorders * Testicular insults * Autoimmune syndrome * Secondary * GnRH deficiency * Hyperprolactinemia * Pituitary disorders * Medications
OH is diagnosed by:
A. Patient reported questionnaire
B. Signs
C. Symptoms
D. Testosterone levels
E. Physical appearance, body habitus
B. Signs
C. Symptoms
D. Testosterone levels
Are they symptomatic? So that’s the first thing. You don’t just if someone has no symptoms, they have no complaints about I’m low libido or fatigue or anything like that, then you’re not going to bother working them up. You’re not just searching for a deficiency to treat. They have to have complaints that the deficiency is manifest in signs or symptoms.
Assessment – Signs and Symptoms
signs and symp of LOH
see slide 20`
more specific symp:
less specific symp
signs
Screening Tool - Example
* The ADAM Questionnaire
Do you have a decrease in libido?
* Do you have a lack of energy?
* Do you have a decrease in strength and/or endurance?
* Have you lost height?
* Have you noticed a decreased “enjoyment of life”?
* Are you sad and/or grumpy?
* Are your erections less strong?
* Have you noted a recent deterioration in your ability to play sports?
* Are you falling asleep after dinner?
* Has there been a recent deterioration in your work performance?
* If answered “yes” to question 1 or 7, or at least 3 of the other questions,
the patient may have low testosterone levels
We do not recommend using a screening tool because they have been mostly created by the pharmaceutical industry. So it doesn’t mean necessarily that that’s bad, that that’s evil, but it does mean that there is a bias. And so almost all of the tools that have been developed and used in clinical trials always seem to encourage people to take testosterone
Screening - Questionnaires
Controversial
* Some developed by industry
* Biased toward supplementation
* Evidence – poor sensitivity and specificity
* CPG recommend not relying on these questionnaires
We do not recommend using a screening tool because they have been mostly created by the pharmaceutical industry. So it doesn’t mean necessarily that that’s bad, that that’s evil, but it does mean that there is a bias. And so almost all of the tools that have been developed and used in clinical trials always seem to encourage people to take testosterone
Are you grumpy? Is there less enjoyment in life? Again, like during COVID, we would have diagnosed pretty much every man with hypogonadism then because there was so much else going on. So they’re not very specific. They might tell you that there’s something that the patient needs more assessment for. But it shouldn’t be shouldn’t be used because the patient will end up thinking like, yeah, Now I need testosterone
T Levels - Changes with Age
* Can be measured in:
◼ Between ages 25-75:
◼ T levels decrease 35%
◼ Free T decreases 50-60%
◼ At age 75
◼ 20% of men still have T levels in upper quartile of
values of young men
◼ FT and TT ↓ approx 1%/y starting in the third
decade (mean age 28)
- Can be measured in:
- saliva (not covered by Alberta Health)
- urine (24-h collections)
- blood work
*Ranges for bloodwork
* Total testosterone (TT) >12 nmol/L
* Borderline TT 8-12 nmol/L
* Low TT <8 nmol/L
* Free testosterone (FT) > 150 pmol/L
* approx 2% of TT
Oftentimes, there’s a calculation for free testosterone. It’s about 2% of total. These are the ranges that are generally given in most guidelines. So total testosterone should be greater than 12.
T Levels
- Challenges with FT
- Should be fasting morning level
- Ideally between 7-11 AM
there is a circadian rhythms, so the norms are established based on peaks in the morning. So that’s pretty big window 7-11. So make sure if you’re testing or assessing a patient, they have had their lab tests done correctly. - May be some variability by racial group
- Some variability may be due to BMI and distribution of fat
- Experts encouraging more research across populations for TT and FT
- Refer to laboratory cut-points
- Netcare = 10.3 – 29.5 nmol/L for AM TT
- T measurement
- fasting morning sample
- May be repeated if the level is low
- Borderline results may be clarified by the assessment of FT
- Free T measurement challenges
- The gold standard equilibrium dialysis methods are too complex for use in routine
clinical laboratories, assays are not harmonized and consequently there are no
common reference intervals to aid result interpretation. - FT - algorithms derived for calculation may not be accurate based on models related to
SHBG variability - FT calculations have not been validated on some patient populations
Risk Factors - Medical
interfering factors w T level
see slide 28
see slide 30
pretty much every medical condition increases the risk for hypogonadism if it’s not managed.
And we could put COVID under inflammatory.
Obesity is TOP concern
Obesity is always problematic. For testosterone. It lowers total lowers free. Obesity is one of the greatest risks that we have.
f that patient has a vegetarian diet for a long period of time that can lower free testosterone, it’s thought that possibly fiber might, they maybe eat more fiber so that interferes with some absorption of steroids, re-absorption through the biliary tract
short intense exercise increases testosterone
t’s usually, it should be done in the morning, fasting, they get up, skipped breakfast, Go get your testosterone level done, eat your breakfast and then exercise later.
Smking increases T
someone may say they’re having symptoms and yet their testosterone level might be still within the normal range. But if they’re smoking, that can be problematic.
Alcohol abuse
Poorly managed chronic disease (any one cal lead to lower T)
Risk Factors – COVID
- Mechanisms for ED
- Endothelial dysfunction
- Psychological distress
- Impaired pulmonary hemodynamics
- Exacerbation of CV disease
- Impact on T levels
- Sensory loss (anosmia, ageusia)
- Italian study (n=100)
- ED 28% vs 9.3% (p=0.027)
the inflammation throughout the body has just been established as just being just a storm of inflammation. And so the damage to the testes, it has now left some men severely hypogonadism. There’ll be on, it looks like chronic life-long testosterone supplementation
here are cases where young men, um, are now unable to have children there infertile
COVID
- Observations post-mortem
- Testicular tissue has reduced Leydig cells, edema, inflammation
- ACE-2 is expressed in testis and plays a role in spermatogenesis
So this highlights that for testosterone, it’s so much more than just a sexual hormone. It’s also involved in other protection, other development of other organ systems. So pulmonary function, cardiovascular function
Medication Risk Factors
for Low T
Decreased T production Alcohol
Ketoconazole
LHRH agonists
T antagonists/Antiandrogens Spironolactone
Cimetidine
Flutamide
estrogens
Increased prolactin Phenothiazines
dopapmine blockers (metoclopramide, domperidone)
centrally-acting antihypertensive agents (methyldopa,
reserpine)
Increased SHBG Barbiturates
Anticonvulsants (e.g. carbamazepine)
Decreased DHT levels 5-alpha reductase inhibitors
saw palmetto
Others Antineoplastic drugs (e.g. cyclophosphamide,
chlorambucil)
(?) statins
Opioids (GnRH secretion)
ClassificationClassification
see slide 36
