Hypogonadism Flashcards
T functions (4)
Fetal masculinization (ex- becomes male)
Pubertal changes (boy to men)
Sexual function (have sex)
Sperm production (reproduce)
what happens with testosterone with age?
↓ testicular production (testes less responsive)
↑ in sensitivity of the hypothalamus
Peripheral conversion to estrogen
SHBG ↑
a condition resulting from or characterized by abnormally↓ functional activity of the gonads, with retardation of growth and sexual function
hypogonadism
disorders of the pituitary or hypothalamus resulting in inadequate gonadotropin stimulation of the testes
secondary hypogonadism
primary disorder of testicular function
primary hypogonadism
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 2022
(Symptomatic) late onset hypogonadism (S)LOH
what is the correct medical terminology for hypogonadism
(Symptomatic) late onset hypogonadism (S)LOH
what does (P)DAAM stand for
(partial) androgen decline in the aging male
the term previously used to describe LOH
andropause
a clinical and biochemical syndrome characterized by a deficiency of testosterone, or testosterone action, and relevant s/s
testosterone deficiency
3 specific sx of hypogonadism
↓ libido
ED
↓ freq of morning erections
signs of hypogonadism
↓ body/ facial hair
Central obesity
↓ testicular volume
↓ muscle mass, ↑ body fat
Gynecomastia
Osteoporosis
higher BMI = _____ testosterone
lower
are screening tools for hypogonadism recommended? why or why not
not recommended -mostly been made by the pharmaceutical industry (bias)
poor sensitivity/ specificity- most sx listed are less specific + may encourage pts to take testosterone
how does T change from 25-75
T ↓ 35%, free T ↓ 50-60%
FT and TT decreases ___/yr starting around ~28yrs old
1%
there may be some variability in testosterone decreased by _________
racial group
T can be measured in (3)
urine, saliva, blood work
free T is ~___% of of total T
2%
ideal time to measure T is
fasting morning level, between 7-11am
what are some difficulties with measuring free T
cold standard equilibrium dialysis methods are too complex
no common RR to aid result interpretation
equations for free T may not be accurate due to SHBG variability + pt population
genetics are responsible for ___% of T variability
30%
how does exercise impact T levels
short, intense exercise increase T (~30%)
how does smoking imapct T levels
5-15% higher T
how does substance and alcohol use impact T levels
lower T
how does diet impact T
vegetarians have lower T
how do chronic diseases impact T
poor disease control generally associated with lower T and/or FT
COVID mechs for ED
endothelial dysfunction, psychological distress, impaired pulmonary hemodynamics, exacerbation of CV disease, impact on T levels, sensory loss (anosmia, ageusia)
before starting T therapy, what should be done?
address chronic conditions (obesity, increase exercise, osteoporosis, sleep apnea)
discontinue meds that interfere with T
what is classified as late onset hypogonadism
> 30ysr old
what is the goal for prepubertal hypogonadism
goal to stimulate long bone growth and induce mild virilization- do not interfere with spontaneous pubertal onset
when should tx for prepubertal hypogonadism be started
age 14 (withhold tx until then)
T therapy is recommended in hypogonadal men to induce and maintain
secondary sex characteristics
what are some consistent findings of T trials in hypogonadal men
increased lean body mass and BMD + decreased fat in those with low serum T levels (but not in those with normal)
overall increased QoL
T or F: T consistently decreases fat mass and increases BMD even in men that are not deficient
F- consistency only found in deficient men
T derm effects
↑ in hair growth (beard, pubic, axillary)
T CNS effects
improvement in fatigue (3-6mths), small improvement in depressive mood (1mth max benefit may take longer to show)
T genitourinary effects
improvement in libido (1mth), ED (6-12mths)
T endocrine effects
improvement in T levels, insulin sensitivity (few days) and glycemic control (3-12mths)
T CV effects
↑ in fat free mass + lean mass (6-12mths), ↓ waist circ, ↓ in total cholesterol and LDL (1mth), improvement in HF and exercise capacity improvement in ECG ST segment depression due to exercise
T trials that are typically not adequately powered to assess ____ or ____ events
CV or prostate cancer
hematologic T effects
↑ hematocrit in anemic men (3-6mths)
T effect MSK
improvement in BMD (6mths), ↓ fracture risk, ↑ muscle strength, slowed progression of mobility limitations
AEs of T (with evidence of association) (5)
Erythrocytosis
Acne and oily skin
Detection of subclinical prostate cancer
Growth of metastatic prostate cancer
↓ sperm production and fertility (less endogenous production = shuts down spermatogenesis)
Uncommon AEs for which there is weak evidence of association with T admin:
Gynecomastia
Male pattern hair loss
Growth of breast cancer
Induction or worsening of OSA
IM T specific AEs
Fluctuations in mood or libido
Pain at injection site
Coughing episodes immediately after injection
transdermal T gels and solutions specific AEs
Potential risk for T transfer to partner or another person who is in close contact
Skin irritation, odor at application site
Stickiness, slow drying, dripping
are oral T tablets recommended for hypogonadism?
no- effects on liver and cholesterol
T nasal gel SEs
Rhinorrhea, epistaxis, nasal discomfort, nasal congestion, parosmia
which of the following is a formulation specific AE for IM testosterone
1. irritation of gums
2. parosmia
3. coughing episodes immediately after administration
4. effects on liver and cholesterol after admin
3
testosterone increases risk of _________, _________ , ______ compared to placebo
(CV RF)
total CV events
atherosclerotic events
major adverse CV events
____ suppression is often used for prostate cancer tx
testosterone suppression
men with hx of _____ often have low T and sx
prostate cancer
can you use T supplementation if pt has hx of prostate cancer, resulting in hypogonadism
may consider if 1yr of cure psot cancer tx
avoid if mod-high risk prostate cancer or still under active surveillance
oral T issues
hepatotoxicity, erratic absorption, cholesterol raising, high first pass effect
transdermal T reaches SS in
2-3d
transdermal T characteristic includes
1. reach SS in 4-5 d
2. be applied to the scrotum
3. wait to shower or swim after application
4. have hepatotoxicity
3
where should TD T not be applied
scrotum
which T inj contains cottonseed oil
Testosterone cypionate (depot-testosterone)
which T inj contains sesame oil
Testosterone enanthate (Delatestryl)
T distribution depends on
SHBG, albumin (small amount bound to albumin, mostly SHBG)
T si metabolized by ___________ to ___, _____
5 alpha reductase to DHT, estradiol
T interacts with
Warfarin (↑ INR)
Insulin / hypoglycemics (T ↓ glucose)
Cyclosporin (↑ levels, nephrotoxicity)
is DHEA recommended for hypogonadism
no but may still be used
DHEA production peaks in _________ and decliens ________
peaks in early adulthood
declines over time
what is the evidence behind CAM for hypogonadism
some evidence that T can be normalized
clomiphene MOA in hypogonadism
Competes with estrogen at receptors at hypothalamus and pituitary negative feedback leads to ↑ FSH and LH from anterior pituitary leads to ↑ T production
clomiphene class
SERM
GnRH MOA in hypogonadism
GnRH stimulatesLH and FSH from anterior pituitary, leading to T production
hCG is an analog of
LH
aromatase inhibitors MOA in hypogonadism
inhibit peripheral conversion of T to estradiol lower feedback from reduced estradiol levels on HPA ↑ gonadotropins
what are 3 classes of investigational tx for hypogonadism
SERM
gonadotrophins
aromatase inhibitors
