Define male hypogonadism
Clinical syndrome resulting from failure to produce testosterone OR normal amounts of sperm or BOTH
- needs both
What enzyme used to turn testosterone to dihydrotestosterone DHT? What is DHT responsible for? (2)
5a-reductase
Responsible for:
1. External genitalia
- differentiation during gestation
- maturation during puberty
- adult prostatic disease
What enzyme used to turn testosterone to estradiol? What is estradiol responsible for? (2)
CYP19 (aromatase)
Responsible for:
1. Bone
- ephiphyseal closure
- increased density
What is testosterone alone used for without getting converted into anything (4)
Differentiate between primary and secondary hypogonadism
Disease type?
low test + LH/FSH levels?
Fertility?
Primary
- Disease of testes
- LH/FSH levels high
- Fertility cannot be restored, seminiferous tubules damaged
Secondary
- Disease of hypothalamus or pituitary
- LH/FSH levels low or normal
- Fertility CAN be restored, using GnRH therapy
Define late-onset male hypogonadism
What age group would you suspect primary hypogonadism? Secondary?
From 20-50
- likely primary
50+
- more often secondary but primary still occurs
What is the age-related defects that occur at the hypothalamic-pituitary-testicular axis?
Which is likely the main cause of declining androgen levels?
What are the MOST specific symptoms of late-onset hypogonadism? (3)
What are less-specific symptoms of late-onset hypogonadism
What are signs of late-onset hypogonadism
Is there evidence for testosterone treatment to help with decreased muscle mass, higher visceral fat mass, insulin resistance etc..
Low total and Free testosterone levels are weakly associated with multiple adverse outcomes
When should you measure testosterone levels?
Measure in morning between 7 - 11
OR
3 hours after you wake up
How much % of testosterone is bound to serum proteins?
Which protein is testosterone bound to that does not make it bioavailable?
98% is bound to serum proteins
- 44% is bound so SHBG (not bioavailable)
Sex hormone binding globulin increases with aging
When do we measure free testosterone (3)
What conditions and drugs decrease SHBG?
Conditions
- obesity
- diabetes
- hypothyroidism
- nephrotic syndrome
- polymorphisms in SHBG gene
Drugs
- glucocorticoids
- progestins
- androgenic steroids
What conditions and drugs increase SHBG?
Conditions
- Aging
- HIV
- Cirrhosis and hepatitis
- hyperthyroidism
- polymorphisms in the SHBG gene
Drugs
- anticonvulsants
- estrogens
What is the pathogenesis of androgenetic alopeica? (3)
Androgen dependent trait that requires a genetic predisposition.
- Located on the X chromosome
thinning starts in the crown
number of hair follicles and growth steps (cycle) remain constant
- BUT the anagen or growth stage is shorter (length of growth period is shorter)
- causes a shorter and thinner hair shaft
What is are the 3 key pathophysiologic features of alopecia pathogenesis
do males castrated before puberty or patients with androgen insensitivity develop alopecia?
No
Which hormone plays a role in alopecia
Dihydrotestosterone
- binds to androgen receptor activating genes involved in hair follicles
Which enzyme is used in alopecia? What are the 2 isoforms types in scalp hair follicles
5-alpha-reductase
2 isoforms
Type 1 in
- sebaceous glands
- epidermal and follicular keratinocytes
- dermal papillae cells
- sweat glands
Type 2 in (MAIN DRIVER)
- outer sheath of hair follicles
- Plus epididymis, vas deferens, seminal vesciles and prostate
Is it common to have symptoms of BPH before age 50?
No