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Block 10 Week 3 > Burkin > Androgens, Anti-androgens, & ED > Flashcards

Burkin > Androgens, Anti-androgens, & ED Flashcards

1
Q

what is 5α-reductase?

A

enzyme that converts testosterone to DHT

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2
Q

what is an anabolic steroid?

A

androgen receptor agonist used for anabolic effects

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3
Q

what is hereditary angioedema?

A

genetic dz characterized by C1 esterase inhibitor deficiency

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4
Q

what are the 7 fxns of androgens (it’s long, sorry)

think about what makes a dude a dude

A
  1. conversion of early bipotential gonad into testes
  2. masculinization of male fetus
  3. sperm pdtion
  4. vocal chord enlargement
  5. regulate sex drive & aggression
  6. inhibit fat deposition
  7. increase muscle mass
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5
Q

how many carbons do androgens have?

A

19

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6
Q

what makes 95% of androgens in males?

A

testes!

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7
Q

what cells of the testes make androgens?

A

Leydig cells

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8
Q

what controls androgen production in the testes?

A

LH

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9
Q

if the testes make 95% of androgens in males, what makes the other 5%?

A

adrenal cortex

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10
Q

where are adrenal pro-androgens converted to androgens?

A

in the liver, skin, & fat

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11
Q

what synthesizes androgens in females?

A

ovaries & adrenal cortex

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12
Q

Plasma testosterone conc in males is (__?__) times higher than in females

A

15x

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13
Q

how is 98% of testosterone circulating in blood found?

A

bound to plasma proteins (specifically albumin & sex hormone binding globulin)

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14
Q

in males, what can secrete DHT?

A

testes secrete a little bit

mostly the target cells synthesize DHT from testosterone via 5α-reductase

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15
Q

what are the 5 main types of androgens?

A
  1. testosterone
  2. 5α-dihydrotestosterone (DHT)
  3. dehydroepiandrosterone (DHEA)
  4. androstenedione (andro)
  5. androstenediol
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16
Q

what is DHT a metabolite of?

A

testosterone

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17
Q

which is more potent: DHT or testosterone?

A

DHT

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18
Q

what makes DHT?

A

adrenal cortex

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19
Q

what makes DHEA?

A

adrenal cortex (made from cholesterol)

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20
Q

what is DHEA a precursor to?

A

natural estrogens

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21
Q

what are 2 other names for DHEA?

A

dehydroisoandrosterone
dehydroandrosterone
(DHEA stands for DeHydroEpiAndrosterone)

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22
Q

where is androstenedione produced?

A

testes
adrenal cortex
ovaries

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23
Q

what is andro metabolically converted to?

A

testosterone & other androgens

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24
Q

what are the 2 active metabolites of testosterone?

A

DHT

estradiol

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25
Q

what are the 2 inactive metabolites of testosterone?

A

androsterone

etiocholanolone

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26
Q

what are the 4 effects of testosterone?

A
  1. gonadotropin regulation
  2. spermatogenesis
  3. sexual differentiation
  4. sexual maturity at puberty
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27
Q

what happens once testosterone gets in the cell (7 steps)?

A
  1. 5α-reductase > DHT
  2. DHT binds to AR
  3. the complex dimerizes
  4. the dimer goes into the nucleus
  5. recruits a coactivator (ARA70)
  6. DNA binding at an androgen-response element
  7. target gene activation & biological response
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28
Q

when is sperm production maximal?

A

“adult” > age 17-60

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29
Q

how much testosterone is around when a baby boy is born?

A

NONE

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30
Q

when does testosterone peak in the prenatal period?

A

2nd trimester

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31
Q

what 2 anabolic effects do androgens have?

A
  1. increase skeletal muscle growth

2. simulate erythropoiesis

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32
Q

what are the 5 androgenic effects of androgens (i.e. non-anabolic effects)?

A
  1. male reproductive phenotype
  2. male genitalia growth at puberty
  3. long bone growth & epiphyseal plate closure
  4. male characteristic maintenance
  5. inc libido & aggression
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33
Q

what are 4 reasons you might give a pt androgens?

A
  1. hypogonadism
  2. to reverse negative nitrogen balance in certain catabolic states
  3. to stimulate erythropoiesis
  4. to stimulate bone growth in kids
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34
Q

T/F: you can’t misuse or abuse androgens

A

FALSE

yes you can

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35
Q

what are the sx of prepubertal hypogonadism?

A 
infantile genitalia
long arms & legs
poor muscular dvlpmnt
inc body fat
dec peak bone bass
high-pitched voice
sparse male-pattern body hair
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36
Q

why is the dx of prepubertal hypogonadism rarely missed?

A

the sx are usu obvious & there is accompanying psychosocial distress

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37
Q

how do you treat prepubertal hypogonadism (generally)?

A

2-3 years of testosterone ester injections with either T ethanate, cypionate, or proprionate

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38
Q

what increases the bioavailability of methyltestosterone?

A

17 methyl group

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39
Q

which group of men should receive testosterone therapy?

A

men w/ consistent sx of low T
AND
unequivocally low serum T

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40
Q

what does “unequivocally low serum T” mean numerically?

A

total serum T < 8 nmol/L
OR
serum free T < 225 pmol/L

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41
Q

do NOT offer testosterone therapy to older men w/ (__?__) without clinically significant sx of androgen deficiency

A

low T

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42
Q

what are the 3 categories of clinical indications for T therapy?

A

sexual
musculoskeletal
neuropsychological

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43
Q

what are the 2 sexual indications for T therapy?

A
  1. low libido

2. ED

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44
Q

what are the 2 musculoskeletal indications for T therapy?

A
  1. osteoporosis or high risk for fx d/t low bone mineral density (w/ contraindications to osteoporosis drugs)
  2. dec muscle mass or strength in men 65+ yo
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45
Q

what are the neuropsychological indications for T therapy?

A

impaired cognition
irritability
mood changes
declining energy & stamina

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46
Q

T/F: there are oral, injectable, gel, patch, pumps, and subQ formulations of testosterone

A

TRUE

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47
Q

which is more potent: fluoxymesterone or methyltestosterone

A

fluoxymesterone

~5x more potent

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48
Q

what receptor do anabolic steroids use?

A

androgen receptor (they’re agonists)

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49
Q

what aspects of testosterone do anabolic steroids mimic?

A

build muscle tissue

promote muscle repair

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50
Q

what can you treat in females w/ anabolic steroids?

A

breast cancers & endometriosis

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51
Q

to affect skeletal growth, how much anabolic steroid do you need?

A

“large doses”
let’s
get
juiced

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52
Q

name the 3 synthetic anabolic steroids

A

stanozolol
nandrolone
methenolone

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53
Q

what is stanozolol derived from?

A

DHT

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54
Q

even though stanozolol is a synthetic anabolic steroid, it has therapeutic applications. for what?

A

anemia

hereditary angioedema

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55
Q

T/F: anabolic steroids don’t have very many side effects

A

FALSE

there are literally a zillion side effects, steroids are the worst

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56
Q

T/F: anabolic steroids cause reversible masculinization in women

A

FALSE

it’s IRREVERSIBLE!

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57
Q

what age group is experiencing an alarming increase in the use of anabolic steroids?

A

pre-teens & teens

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58
Q

why do people often take several other meds if they take anabolic steroids?

A

to increase performance or to counteract side FX

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59
Q

what 2 sports are particularly known for anabolic steroid misuse?

A 
body building
baseball
bears
beets
battlestar galactica
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60
Q

what sex has higher levels of steroid abuse?

A

men

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61
Q

what is danazol derived from?

A

testosterone

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62
Q

if you are taking danazol for endometriosis, how long do you take it?

A

6 months

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63
Q

how does danazol affect ovulation?

A

it interferes w/ it by creating a high androgen, low estrogen env

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64
Q

what does danazol do to endometrial tissue?

A

atrophy of ectopic endometrial tissue

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65
Q

how effective is danazol?

A

80% of women have pain relief & lesion shrinkage

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66
Q

what % of women have side FX w/ danazol?

A

75% :(

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67
Q

T/F: danazol side FX are reversible

A

true

the voice thing might take a few months to go back to normal though

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68
Q

what is hereditary angioedema?

A

inherited disorder d/t C1 esterase inhibitor deficiency

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69
Q

what is C1 esterase?

A

serum inhibitor of the activated first component of compliment

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70
Q

how does danazol work for hereditary angioedema?

A

INC complement protein synthesis in the liver but the mechanism is unk

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71
Q

since the mechanism for danazol on hereditary angioedema is unk, how do we know that it does NOT work?

A

does NOT posses progestogenic activity
does NOT suppress corticotropin release from pituitary
does NOT suppress cortisol release from adrenals

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72
Q

why would you give a hereditary angioedema pt danazol?

A

to prevent attacks

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73
Q

when should you initiate danazol therapy for fibrocystic breast dz?

A

during menstruation

otherwise, make SURE your pt is NOT PREGGO

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74
Q

what happens at high doses of danazol in female pts?

A

irregular menstrual patterns & amenorrhea

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75
Q

what sx does danazol relieve in fibrocystic breast dz?

A

breast pain & tenderness

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76
Q

how long does danazol take to work against fibrocystic breast dz?

A

1 month

best effect in 2-3 mos

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77
Q

how do you eliminate nodularity in fibrocystic breast dz w/ danazol?

A

4-6 mos of uninterrupted therapy

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78
Q

Danazol is pregnancy category (__?__)

A

X

REAL BAD

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79
Q

what is pseudotumor cerebri?

A

a benign intracranial HTN

side effect of danazol

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80
Q

how does pseudotumor cerebri manifest in a pt?

A

papilledema
HA
N/V
visual disturbances

81
Q

what should you do if you have a pt on danazol who has papilledema?

A

discontinue danazol IMMEDIATELY

refer pt to neurologist

82
Q

where is the type II 5α-reductase isozyme primarily found?

A 
prostate
seminal vesicles
epididymides
hair follicles
liver
83
Q

the type II 5α-reductase isozyme is responsible for how much of circulating DHT

84
Q

what is the primary androgen that stimulates the development of prostate tissue?

85
Q

what is propecia for?

A

male pattern baldness (i.e. androgenic alopecia)

86
Q

if you give a pt propecia, where does that pt probably have baldness?

A

vertex & anterior mid-scalp

87
Q

what is the 1st line therapy for prostate cancer?

A

flutamide + leuprolide

88
Q

flutamide is good for prostate cancer, but not other hormonally dependent dz like (__?__)

A

breast cancer

BPH

89
Q

who should you NOT give flutamide to?

A

women

think of alyson hannigan from american pie and how she should not be allowed to have flutes

90
Q

flutamide can cause severe side FX in what organ?

91
Q

to assess side FX of flutamide, what can you measure?

A

serum transaminase conc
prior to treatment
monthly during first 4 mos
then periodically

92
Q

what does sustained leuprolide activity lead to?

A

downregulation of receptor

DEC FSH & LH pdtion

93
Q

what does leuprolide stop in the male?

A

testosterone pdtion in testes

94
Q

what does leuprolide stop in the female?

A

estrogen pdtion in the ovaries

95
Q

what are the 4 main causes of male infertility?

A
  1. lifestyle
  2. pretesticular
  3. testicular
  4. post-testicular
96
Q

what is Kallmann syndrome?

A

gonadotropin deficiency

absence of GnRH

97
Q

how do you achieve virility & fertility in Kallmann syndrome pts?

A

FSH & LH to stimulate testis fxn

98
Q

what 3 syndromes lead to GnRH deficiency?

A
  1. Kallmann
  2. Prader-Willi
  3. Bardet-Biedl
99
Q

what is a “fertile eunuch”?

A

isolated LH def (& low T) w/ normal FSH

100
Q

what are the 3 hypothalamic dzs that lead to male infertility?

A
  1. gonadotropin def (Kallmann)
  2. isolated LH def (fertile eunuch)
  3. isolated FSH def
101
Q

what are LH & T like in isolated FSH def?

A

LH & T levels are normal

102
Q

what happens if you give GnRH to a pt w/ isolated FSH def?

A

nothing

FSH levels won’t respond to GnRH stimulation

103
Q

what are the 3 types of pituitary dz that can cause male infertility?

A
  1. pituitary insuff
  2. hyperprolactinemia
  3. exogenous or endogenous hormones
104
Q

what can cause pituitary insuff?

A

tumors
surgery
radiation
infiltrative or granulomatous processes

105
Q

what causes pituitary insuff (& therefore infertility) in sickle cell anemia?

A

in sickle cell, pituitary & testicular microinfarcts can cause infertility

106
Q

what is hyperprolactinemia most commonly d/t?

A

prolactin-secreting pituitary adenoma

107
Q

what hormones does hyperprolactinemia affect?

A

DEC FSH, LH, & T (> infertility)

108
Q

what are the clinical sx of hyperprolactinemia in men?

A

loss of libido
impotence
galactorrhea
gynecomastia

109
Q

how does XS estrogen lead to infertility?

A

XS estrogen > DEC gonadotropins > testis failure

110
Q

what can cause XS estrogen in men, leading to infertility?

A

Sertoli cell tumor
obesity
hepatic cirrhosis

111
Q

what can cause XS androgens in men, leading to infertility?

A

anabolic steroids
CAH
adrenal or Leydig cell tumors

112
Q

how do XS glucocorticoids cause male infertility?

A

XS glucocorticoids > LH secretion > secondary testis failure

113
Q

what can cause XS glucocorticoids in men, leading to infertility?

A

chronic therapy for ulcerative colitis
asthma
RA
cushing’s syndrome

114
Q

why is thyroid balance important in male fertility?

A

imp for normal hypothalamic hormone secretion & sex hormone binding protein levels that govern the T:E ratio

115
Q

0.5% of infertile men have deficient responses to (__?__) & (__?__) treatment improves semen quality

116
Q

what are the 8 causes of testicular infertility?

A
  1. chromosomal
  2. gonadotoxins
  3. systemic dz
  4. defective androgen activity
  5. testis injury
  6. cryptorchidism
  7. varicocele
  8. idiopathic
117
Q

what are some examples of gonadotoxins?

A

radiation

drugs & meds > -azoles, spironolactone, alcohol, cimetidine, recreational drugs

118
Q

which systemic diseases can cause testicular infertility?

A
  1. renal failure
  2. liver cirrhosis
  3. sickle cell dz
119
Q

how does sickle cell dz lead to testicular infertility?

A

microinfarcts can damage testes &/or pituitary

120
Q

what are the 2 defects in androgen activity that can lead to testicular infertility?

A
  1. 5α-reductase def

2. androgen receptor def

121
Q

what are 3 types of testis injury that can cause testicular infertility?

A
  1. orchitis
  2. torsion
  3. trauma
122
Q

what % of boys are affected by cryptorchidism at 1 yo?

123
Q

what does cryptorchidism increase the risk of?

A

infertility & cancer

124
Q

how do you treat cryptorchidism?

A

prophylactic orchidopexy by 2 yo

125
Q

what is a varicocele?

A

dilated & tortuous scrotal veins

126
Q

how do you treat varicocele?

127
Q

what is the prevalence of varicocele?

A

15% of all men

40% of infertility pts

128
Q

what % of testicular infertility is idiopathic?

129
Q

what are the 3 broad categories of post-testicular infertility?

A
  1. reproductive tract obstruction
  2. disorders of sperm fxn or motility
  3. disorders of coitus
130
Q

what are the 3 types of reproductive tract obstruction?

A
  1. congenital blockage
  2. acquired blockage
  3. functional blockage
131
Q

what is CAVD?

A

congenital absent vas deferens > vas deferens, seminal vesicles, & ejaculatory ducts are atrophic or absent > obstruction

132
Q

80% of CAVD pts harbor what kind of mutation?

A

a detectable CF mutation

133
Q

what % of infertility cases are d/t CAVD?

134
Q

name 4 congenital blockages besides CAVD that can cause post-testicular infertility

A
  1. young syndrome
  2. idiopathic epididymal obstruction
  3. APKD
  4. blockage of ejaculatory ducts
135
Q

what happens in Young syndrome?

A

abnormally viscous mucous

136
Q

what are 3 types of acquired blockages that cause post-testicular infertility?

A
  1. vasectomy
  2. groin/hernia surgery
  3. E. coli or chlamydia
137
Q

what can cause a functional blockage & result in post-testicular infertility?

A

nerve injury or meds > impair contractility of seminal vesicle or vasal musculature

138
Q

what are the 4 types of disorders of sperm fxn/motility that can result in post-testicular infertility?

A
  1. immotile cilia syndromes
  2. maturation defects
  3. immunologic infertility
  4. infxn
139
Q

what are the 2 characteristics of immotile cilia syndromes?

A
  1. abn motor apparatus or axoneme of sperm & other ciliated cells
  2. nonmotile but viable sperm in normal #s
140
Q

when can sperm maturation defects happen?

A

after vasectomy reversal

141
Q

why do pts get sperm maturation defects?

A

elevated epididymal intratubular pressure & epididymal dysfxn

142
Q

how does a sperm maturation defect impact sperm count?

A

normal sperm count

sperm do not regain usual maturation & motility capabilities

143
Q

what % of infertile couples can attribute that problem to immunologic infertility?

144
Q

what are the top 2 bacterial & viral infxns that can cause post-testicular infertility?

A

N. gonorrheae
Chlamydia trachomatis

CMV
Herpes simplex II

145
Q

what are the 2 types of coital disorders that can cause post-testicular infertility?

A
  1. impotence

2. penile abnormalities

146
Q

what is impotence?

A

low libido or ED

147
Q

how can you start to work up impotence?

A

hormonal eval

148
Q

how do you treat situational impotence?

A

counseling + oral PDE inhibitors

149
Q

what is the most important penile abnormality that can cause infertility?

A

hypospadias

150
Q

why do penile abnormalities cause infertility?

A

result in placement of the semen too far from the cervix

151
Q

what are the 3 penile abnormalities that can cause post-testicular infertility?

A
  1. HYPOSPADIAS
  2. phimosis
  3. abn curvature
152
Q

what is pyospermia?

A

INC leukocytes in semen

153
Q

what 3 things is pyospermia assoc w/?

A
  1. subclinical genital tract infxn
  2. elevated ROS
  3. poor sperm fxn & infertility
154
Q

how do you treat pyospermia?

A

broad spectrum abx for both partners

155
Q

what is involved in coital therapy?

A

counseling on issues of coital timing, frequency, & gonadotoxin avoidance
(& probably some lube)

156
Q

how do you treat immunologic infertility?

A

suppress the immune system w/ corticosteroids

IVF & ICSI

157
Q

how do you treat hyperprolactinemia?

A

bromocriptine

158
Q

what is congenital adrenal hyperplasia (a deficiency of…)?

A

21-hydroxylase deficiency

159
Q

what happens in congenital adrenal hyperplasia?

A

XS androgen levels > DEC GnRH

precocious puberty

160
Q

how do you treat congenital adrenal hyperplasia?

A

corticosteroids

161
Q

how do you treat testosterone XS?

A

GnRH replacement in a pulsatile manner via portable infusion pump

162
Q

how do you treat testosterone def?

A

“jump start” the testes w/ hCG (LH) & FSH

163
Q

what are the 3 empiric medical therapies for men with idiopathic infertility?

A
  1. clomiphene citrate
  2. antioxidant therapy
  3. GH
164
Q

what can you use to treat oligospermia?

165
Q

why would you use antioxidant therapy for infertile men?

A

40% of infertile men have increased ROS levels in their reproductive tract

166
Q

what is clomiphene citrate?

A

a synthetic nonsteroidal drug that acts as an antiestrogen

167
Q

why do you give clomiphene citrate?

A

idiopathic low sperm w/ low-normal LH, FSH, & T

168
Q

how does clomiphene citrate work?

A

blocks estrogen on male axis

increases GnRH, FSH, LH > inc T & spermatogenesis

169
Q

T/F: clomiphene citrate is indicated for treatment of male infertility

A

FALSE

it’s “off-label” technically

170
Q

what classes of meds (4) are assoc w/ impaired ejaculation?

A
  1. anti-HTN agents
  2. α-adrenergic blockers
  3. antipsychotics
  4. SSRIs
171
Q

how does an erection happen?

A

stimulation > info to nerve centers (primary fibers connect to penis to regulate blood flow) > NO release > smooth muscle relaxation > INC blood flow > veins compress (no outflow)

172
Q

what happens when penile smooth muscle relaxes?

A

blood flow dramatically increases

173
Q

what happens to the veins of the penis as the erectile tissue fills w/ blood?

A

they are compressed, blocking outflow

174
Q

what happens to abolish an erection?

A

cessation of nervous impulses to the penis or sympathetic vasoconstrictor impulses
(or recite the pledge)

175
Q

where can you find nitric oxide synthase?

A 
cavernous nerve
endothelial cells (deep penile arteries)
176
Q

what does the cavernous nerve innervate?

A

smooth muscle surrounding penile arteries

177
Q

what is the rxn to create NO?

A

arginine + O2 –> citrulline + NO

178
Q

how does NO cause muscle relaxation & vasodilation (long, sorry)?

A
  1. NO diffuses across SMC membrane
  2. activate guanylyl cyclase
  3. GTP > cyclic GMP
  4. cGMP activates a protein kinase
  5. ER Ca uptake
  6. low cytoplasmic Ca causes relaxation
  7. relaxation causes vasodilation
179
Q

when does ED occur?

A

when a man can no longer get or keep an erection firm enough for sexual intercourse

180
Q

what % of men suffer from ED?

181
Q

what % of men have minimal, moderate, & complete ED?

A 
minimal = 17%
moderate = 25%
complete = 10%
182
Q

what are the physical causes of ED?

A

literally anything > any dz, any drug, booze, even prolonged biking

183
Q

what are 6 psych causes of ED?

A
  1. depression
  2. anxiety
  3. stress
  4. mental health conditions
  5. relationship probs
  6. combo of physical & psych probs
184
Q

what terminates the erection signal?

A

cGMP –> GMP via PDE V in corpus cavernosum

185
Q

what are the 4 ED drugs?

A
  1. sildenafil (viagra)
  2. vardenafil (levitra)
  3. tadalafil (cialis)
  4. avanafil (stendra)
186
Q

how do the ED drugs work?

A

PDE V inhibitors > inc blood flow to penis

187
Q

how does viagra cause blindness?

A

inhibition of PDE6, which is the PDE used in signal transduction of light signals in the retina

188
Q

T/F: priapism is common

189
Q

what is priapism?

A

prolonged erection in the absence of sexual arousal

190
Q

what are the 2 types of priapism?

A
  1. non-ischemic

2. ischemic

191
Q

T/F: priapism is a medical emergency

192
Q

what causes non-ischemic priapism?

A

injury to penis or perineum

193
Q

what is the treatment for non-ischemic priapism?

A

usu clears up on its own, or use an ice pack

194
Q

what is ischemic priapism?

A

blood flows into penis but does not flow out

195
Q

what happens in ischemic priapism d/t loss of circulation?

A

corpora cavernosa doesn’t get any oxygen > damages erectile tissue, causes scarring, can lead to permanent loss of fxn

196
Q

what is “therapeutic aspiration” & how well does it work?

A

urologist draws blood directly from the cavernosa (RX for ischemic priapism)
only resolves ~30% of cases

197
Q

what is the best way to treat ischemic priapism?

A

injecting a sympathomimetic agent > usu PHENYLEPHRINE (or epi, or metaraminol)

198
Q

how effective is injecting a sympathomimetic to treat ischemic priapism?

A

resolves 77% of cases

199
Q

what happens if ischemic priapism is resistant to both aspiration & drug injections?

A

surgeon must perform a surgical shunt

Block 10 Week 3 (7 decks)

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