Hypogonadism Flashcards
Hypogonadism
Low testosterone levels combined with symptoms or signs that are associated with low serum total testosterone
Hypogonadism pathophysiology: Primary vs. Secondary
● Primary Hypogonadism
○ Under performing testicles
■ Leydig cells
● Secondary Hypogonadism
○ Disease of the Hypothalamic-Pituitary-Gonadal
axis (HPG)
Hypogonadism pathophysiology: testosterone
● Testosterone (steroid) - most abundant
○ Synthesized from cholesterol in Leydig cells
○ Dihydrotestosterone (DHT) active metabolite
→ binds to same intracellular receptors in
target cells but more stable than testosterone
● Androstenedione and
dehydroepiandrosterone (DHEA) can
enter circulation but predominantly form
testosterone
Bioavailable testosterone vs. Tightly bound testosterone
In the bloodstream,
testosterone exists unbound or loosely bound to plasma proteins such as albumin (33%)
● Tightly bound testosterone – The other 65% bound to SHBG (sex hormone binding globulin)
____ % of circulating testosterone is free and can
enter the cell and exert its metabolic effects
(responsible for male characteristics)
~ 2
Testosterone is essential to the development of _____
primary and secondary male sex characteristics during puberty and the duration of adult life
Sex drive/libido are driven more by ____ than ____
testosterone than DHT
____ regulates the Leydig cells in the testicle
which produce testosterone
LH
Explain how Circulating gonadotropic hormones are regulated in a negative feedback mechanism
Low testosterone levels will not single
the pituitary and hypothalamus to
“turn off,” so you will see continued
secretion of LH to increase the
testosterone until the testosterone
levels are high enough to produce
negative feedback on the pathway
Hypergonadotropic Hypogonadism
“Primary Hypogonadism”
○ Testis does not produce sufficient testosterone to suppress LH
(and FSH) secretion
■ Low testosterone and High FSH/LH
Hypogonadotropic Hypogonadism
“Secondary Hypogonadism”
○ Failure of the hypothalamus, or pituitary gland, to responded to low testosterone
■ Low testosterone and low FSH/LH
Etiology of Primary Hypogonadism – From the Testicle
● Aging
○ Increase SHBG levels
● Testicular trauma
○ Orchiectomy
● Cryptorchidism
● Klinefelter Syndrome (XXY)
Etiology of Secondary Hypogonadism – From the Pituitary
● Aging
● Obesity
● Alcohol
● Sleep apnea
● Chronic illness/malnourishment
● Drugs – Estrogen, opiates, marijuana,
ketoconazole, spironolactone
Klinefelter Syndrome features
Clinical manifestations of a male with an extra “X” chromosome (XXY)
Variability of Klinefelter syndrome phenotype
● Micropenis/macroorchidism
● Hypospadias
● Cryptorchidism
● Delayed puberty
● Reduced body hair
● Gynecomastia
● Long legs (4-8 cm longer than average) due
to delayed epiphyseal closure
● Infertility – oligo/azoospermia
● Low testosterone
Clinical Presentation - Hypogonadism
● Decreased libido
● Erectile dysfunction
● Depression
● Fatigue
● Loss of muscle mass
● Weight gain
○ Central
● Infertility
● Gynecomastia
What is an important PMH question for hypogonadism workup?
● Medication use
○ Hx of past testosterone use
Physical Exam - hypogonadism
● Evaluate Testes
○ Relative size
○ Cryptorchidism
● Evaluate genitalia
○ Hypospadias
● Decreased body hair
● Gynecomastia
● Lean muscle loss
● Central obesity
Diagnostic labs - Hypogonadism
● Total Testosterone (morning)
○ <300 ng/dL
○ Two separate readings
○ Signs and symptoms of “Low T”
● Luteinizing Hormone – (FSH/LH): Once low testosterone has been established
● Prolactin: If LH is low or low/normal
● Estradiol: Especially for gynecomastia and for baseline
● Hematocrit
● PSA
Optional Labs
● Sex Hormone Binding Globulin
● Bioavailable Testosterone
Even without signs or symptoms, consider measuring total testosterone in patients with 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
Hypogonadism Managment
Testosterone Replacement Therapy (TRT) – Androgen
● Testosterone Therapy also includes Aromatase inhibitors, Human Chorionic
gonadotropin (bHCG), and Selective Estrogen Receptor Modulator (SERM)
Benefits of TRT
● Mood
● Libido
● Erectile function
● Energy
● Exercise endurance
TRT side effects
● Nausea, vomiting, diarrhea
● Edema - Mild mineralocorticoid effect
● Worsening of BPH
● Acne
● Skin irritation/contact dermatitis - Gel
● Emotional lability
TRT Side Effects (Major)
● Worsening of sleep apnea
● Increased risk of MI or Stroke*
● Stimulation of prostate cancer growth
Contraindications for hypogonadism
● Prostate cancer
○ Androgens stimulate prostate
gland and tumor growth
● Men with breast cancer
Black Box Warning for TRT
Women and children should avoid exposure to testosterone gel or gel application sites
Testosterone Replacement Therapy (TRT) Management and dosing - IM/SC
TRT – Intramuscular/Subcutaneous
Dosing
● IM – every 1-4 weeks (buttock or thigh)
● SQ – 2-3x/week (abdominal or thigh)
Testosterone Replacement Therapy (TRT) Management and dosing - Topical
TRT – Topicals – Patch Dosing
● Applied to skin and changed
every 24 hours
Disadvantages of IM/SC TRT
● Injections (fear of needles)
● Fluctuating levels, with “peak
and trough”
Disadvantages of Topical - Gel/creams/solutions TRT
● Skin irritation
● Transference – Black Box Warning
Hypogonadism TRT – Intranasal dosing
● 2 pumps (one in each nostril)
three times a day
TRT – Pellets/implants Dosing
● Small pellets placed under the skin
Hypogonadism monitoring
● Recheck levels every 6-12 months
○ Every 6 weeks with dose changes
● Check hemoglobin and hematocrit at baseline, 3-6 months after starting
● Check PSA yearly while on replacement ● If no improvement in Sx after 3-6, even if levels have improved, consider TRT cessation
Hypogonadism considerations - family planning
● Exogenous testosterone therapy should not be prescribed to men who are currently trying to conceive
● Consider using the following
○ HCG
○ Aromatase Inhibitors (AI)
○ Selective estrogen receptor modulators (SERM)
