Burkin > Androgens, Anti-androgens, & ED Flashcards
(199 cards)
1
Q
what is 5α-reductase?
A
enzyme that converts testosterone to DHT
2
Q
what is an anabolic steroid?
A
androgen receptor agonist used for anabolic effects
3
Q
what is hereditary angioedema?
A
genetic dz characterized by C1 esterase inhibitor deficiency
4
Q
what are the 7 fxns of androgens (it’s long, sorry)
think about what makes a dude a dude
A
- conversion of early bipotential gonad into testes
- masculinization of male fetus
- sperm pdtion
- vocal chord enlargement
- regulate sex drive & aggression
- inhibit fat deposition
- increase muscle mass
5
Q
how many carbons do androgens have?
A
19
6
Q
what makes 95% of androgens in males?
A
testes!
7
Q
what cells of the testes make androgens?
A
Leydig cells
8
Q
what controls androgen production in the testes?
A
LH
9
Q
if the testes make 95% of androgens in males, what makes the other 5%?
A
adrenal cortex
10
Q
where are adrenal pro-androgens converted to androgens?
A
in the liver, skin, & fat
11
Q
what synthesizes androgens in females?
A
ovaries & adrenal cortex
12
Q
Plasma testosterone conc in males is (__?__) times higher than in females
A
15x
13
Q
how is 98% of testosterone circulating in blood found?
A
bound to plasma proteins (specifically albumin & sex hormone binding globulin)
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
15
Q
what are the 5 main types of androgens?
A
- testosterone
- 5α-dihydrotestosterone (DHT)
- dehydroepiandrosterone (DHEA)
- androstenedione (andro)
- androstenediol
16
Q
what is DHT a metabolite of?
A
testosterone
17
Q
which is more potent: DHT or testosterone?
A
DHT
18
Q
what makes DHT?
A
adrenal cortex
19
Q
what makes DHEA?
A
adrenal cortex (made from cholesterol)
20
Q
what is DHEA a precursor to?
A
natural estrogens
21
Q
what are 2 other names for DHEA?
A
dehydroisoandrosterone
dehydroandrosterone
(DHEA stands for DeHydroEpiAndrosterone)
22
Q
where is androstenedione produced?
A
testes
adrenal cortex
ovaries
23
Q
what is andro metabolically converted to?
A
testosterone & other androgens
24
Q
what are the 2 active metabolites of testosterone?
A
DHT
estradiol
25
what are the 2 inactive metabolites of testosterone?
androsterone
| etiocholanolone
26
what are the 4 effects of testosterone?
1. gonadotropin regulation
2. spermatogenesis
3. sexual differentiation
4. sexual maturity at puberty
27
what happens once testosterone gets in the cell (7 steps)?
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
28
when is sperm production maximal?
"adult" > age 17-60
29
how much testosterone is around when a baby boy is born?
NONE
30
when does testosterone peak in the prenatal period?
2nd trimester
31
what 2 anabolic effects do androgens have?
1. increase skeletal muscle growth
| 2. simulate erythropoiesis
32
what are the 5 androgenic effects of androgens (i.e. non-anabolic effects)?
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
33
what are 4 reasons you might give a pt androgens?
1. hypogonadism
2. to reverse negative nitrogen balance in certain catabolic states
3. to stimulate erythropoiesis
4. to stimulate bone growth in kids
34
T/F: you can't misuse or abuse androgens
FALSE
| yes you can
35
what are the sx of prepubertal hypogonadism?
```
infantile genitalia
long arms & legs
poor muscular dvlpmnt
inc body fat
dec peak bone bass
high-pitched voice
sparse male-pattern body hair
```
36
why is the dx of prepubertal hypogonadism rarely missed?
the sx are usu obvious & there is accompanying psychosocial distress
37
how do you treat prepubertal hypogonadism (generally)?
2-3 years of testosterone ester injections with either T ethanate, cypionate, or proprionate
38
what increases the bioavailability of methyltestosterone?
17 methyl group
39
which group of men should receive testosterone therapy?
men w/ consistent sx of low T
AND
unequivocally low serum T
40
what does "unequivocally low serum T" mean numerically?
total serum T < 8 nmol/L
OR
serum free T < 225 pmol/L
41
do NOT offer testosterone therapy to older men w/ (__?__) without clinically significant sx of androgen deficiency
low T
42
what are the 3 categories of clinical indications for T therapy?
sexual
musculoskeletal
neuropsychological
43
what are the 2 sexual indications for T therapy?
1. low libido
| 2. ED
44
what are the 2 musculoskeletal indications for T therapy?
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
45
what are the neuropsychological indications for T therapy?
impaired cognition
irritability
mood changes
declining energy & stamina
46
T/F: there are oral, injectable, gel, patch, pumps, and subQ formulations of testosterone
TRUE
47
which is more potent: fluoxymesterone or methyltestosterone
fluoxymesterone
| ~5x more potent
48
what receptor do anabolic steroids use?
androgen receptor (they're agonists)
49
what aspects of testosterone do anabolic steroids mimic?
build muscle tissue
| promote muscle repair
50
what can you treat in females w/ anabolic steroids?
breast cancers & endometriosis
51
to affect skeletal growth, how much anabolic steroid do you need?
"large doses"
let's
get
juiced
52
name the 3 synthetic anabolic steroids
stanozolol
nandrolone
methenolone
53
what is stanozolol derived from?
DHT
54
even though stanozolol is a synthetic anabolic steroid, it has therapeutic applications. for what?
anemia
| hereditary angioedema
55
T/F: anabolic steroids don't have very many side effects
FALSE
| there are literally a zillion side effects, steroids are the worst
56
T/F: anabolic steroids cause reversible masculinization in women
FALSE
| it's IRREVERSIBLE!
57
what age group is experiencing an alarming increase in the use of anabolic steroids?
pre-teens & teens
58
why do people often take several other meds if they take anabolic steroids?
to increase performance or to counteract side FX
59
what 2 sports are particularly known for anabolic steroid misuse?
```
body building
baseball
bears
beets
battlestar galactica
```
60
what sex has higher levels of steroid abuse?
men
61
what is danazol derived from?
testosterone
62
if you are taking danazol for endometriosis, how long do you take it?
6 months
63
how does danazol affect ovulation?
it interferes w/ it by creating a high androgen, low estrogen env
64
what does danazol do to endometrial tissue?
atrophy of ectopic endometrial tissue
65
how effective is danazol?
80% of women have pain relief & lesion shrinkage
66
what % of women have side FX w/ danazol?
75% :(
67
T/F: danazol side FX are reversible
true
| the voice thing might take a few months to go back to normal though
68
what is hereditary angioedema?
inherited disorder d/t C1 esterase inhibitor deficiency
69
what is C1 esterase?
serum inhibitor of the activated first component of compliment
70
how does danazol work for hereditary angioedema?
INC complement protein synthesis in the liver but the mechanism is unk
71
since the mechanism for danazol on hereditary angioedema is unk, how do we know that it does NOT work?
does NOT posses progestogenic activity
does NOT suppress corticotropin release from pituitary
does NOT suppress cortisol release from adrenals
72
why would you give a hereditary angioedema pt danazol?
to prevent attacks
73
when should you initiate danazol therapy for fibrocystic breast dz?
during menstruation
| otherwise, make SURE your pt is NOT PREGGO
74
what happens at high doses of danazol in female pts?
irregular menstrual patterns & amenorrhea
75
what sx does danazol relieve in fibrocystic breast dz?
breast pain & tenderness
76
how long does danazol take to work against fibrocystic breast dz?
1 month
| best effect in 2-3 mos
77
how do you eliminate nodularity in fibrocystic breast dz w/ danazol?
4-6 mos of uninterrupted therapy
78
Danazol is pregnancy category (__?__)
X
| REAL BAD
79
what is pseudotumor cerebri?
a benign intracranial HTN
| side effect of danazol
80
how does pseudotumor cerebri manifest in a pt?
papilledema
HA
N/V
visual disturbances
81
what should you do if you have a pt on danazol who has papilledema?
discontinue danazol IMMEDIATELY
| refer pt to neurologist
82
where is the type II 5α-reductase isozyme primarily found?
```
prostate
seminal vesicles
epididymides
hair follicles
liver
```
83
the type II 5α-reductase isozyme is responsible for how much of circulating DHT
2/3
84
what is the primary androgen that stimulates the development of prostate tissue?
DHT
85
what is propecia for?
male pattern baldness (i.e. androgenic alopecia)
86
if you give a pt propecia, where does that pt probably have baldness?
vertex & anterior mid-scalp
87
what is the 1st line therapy for prostate cancer?
flutamide + leuprolide
88
flutamide is good for prostate cancer, but not other hormonally dependent dz like (__?__)
breast cancer
| BPH
89
who should you NOT give flutamide to?
women
| think of alyson hannigan from american pie and how she should not be allowed to have flutes
90
flutamide can cause severe side FX in what organ?
LIVER
91
to assess side FX of flutamide, what can you measure?
serum transaminase conc
prior to treatment
monthly during first 4 mos
then periodically
92
what does sustained leuprolide activity lead to?
downregulation of receptor
| DEC FSH & LH pdtion
93
what does leuprolide stop in the male?
testosterone pdtion in testes
94
what does leuprolide stop in the female?
estrogen pdtion in the ovaries
95
what are the 4 main causes of male infertility?
1. lifestyle
2. pretesticular
3. testicular
4. post-testicular
96
what is Kallmann syndrome?
gonadotropin deficiency
| absence of GnRH
97
how do you achieve virility & fertility in Kallmann syndrome pts?
FSH & LH to stimulate testis fxn
98
what 3 syndromes lead to GnRH deficiency?
1. Kallmann
2. Prader-Willi
3. Bardet-Biedl
99
what is a "fertile eunuch"?
isolated LH def (& low T) w/ normal FSH
100
what are the 3 hypothalamic dzs that lead to male infertility?
1. gonadotropin def (Kallmann)
2. isolated LH def (fertile eunuch)
3. isolated FSH def
101
what are LH & T like in isolated FSH def?
LH & T levels are normal
102
what happens if you give GnRH to a pt w/ isolated FSH def?
nothing
| FSH levels won't respond to GnRH stimulation
103
what are the 3 types of pituitary dz that can cause male infertility?
1. pituitary insuff
2. hyperprolactinemia
3. exogenous or endogenous hormones
104
what can cause pituitary insuff?
tumors
surgery
radiation
infiltrative or granulomatous processes
105
what causes pituitary insuff (& therefore infertility) in sickle cell anemia?
in sickle cell, pituitary & testicular microinfarcts can cause infertility
106
what is hyperprolactinemia most commonly d/t?
prolactin-secreting pituitary adenoma
107
what hormones does hyperprolactinemia affect?
DEC FSH, LH, & T (> infertility)
108
what are the clinical sx of hyperprolactinemia in men?
loss of libido
impotence
galactorrhea
gynecomastia
109
how does XS estrogen lead to infertility?
XS estrogen > DEC gonadotropins > testis failure
110
what can cause XS estrogen in men, leading to infertility?
Sertoli cell tumor
obesity
hepatic cirrhosis
111
what can cause XS androgens in men, leading to infertility?
anabolic steroids
CAH
adrenal or Leydig cell tumors
112
how do XS glucocorticoids cause male infertility?
XS glucocorticoids > LH secretion > secondary testis failure
113
what can cause XS glucocorticoids in men, leading to infertility?
chronic therapy for ulcerative colitis
asthma
RA
cushing's syndrome
114
why is thyroid balance important in male fertility?
imp for normal hypothalamic hormone secretion & sex hormone binding protein levels that govern the T:E ratio
115
0.5% of infertile men have deficient responses to (__?__) & (__?__) treatment improves semen quality
GH
| GH
116
what are the 8 causes of testicular infertility?
1. chromosomal
2. gonadotoxins
3. systemic dz
4. defective androgen activity
5. testis injury
6. cryptorchidism
7. varicocele
8. idiopathic
117
what are some examples of gonadotoxins?
radiation
| drugs & meds > -azoles, spironolactone, alcohol, cimetidine, recreational drugs
118
which systemic diseases can cause testicular infertility?
1. renal failure
2. liver cirrhosis
3. sickle cell dz
119
how does sickle cell dz lead to testicular infertility?
microinfarcts can damage testes &/or pituitary
120
what are the 2 defects in androgen activity that can lead to testicular infertility?
1. 5α-reductase def
| 2. androgen receptor def
121
what are 3 types of testis injury that can cause testicular infertility?
1. orchitis
2. torsion
3. trauma
122
what % of boys are affected by cryptorchidism at 1 yo?
0.8%
123
what does cryptorchidism increase the risk of?
infertility & cancer
124
how do you treat cryptorchidism?
prophylactic orchidopexy by 2 yo
125
what is a varicocele?
dilated & tortuous scrotal veins
126
how do you treat varicocele?
surgery
127
what is the prevalence of varicocele?
15% of all men
| 40% of infertility pts
128
what % of testicular infertility is idiopathic?
25-50%
129
what are the 3 broad categories of post-testicular infertility?
1. reproductive tract obstruction
2. disorders of sperm fxn or motility
3. disorders of coitus
130
what are the 3 types of reproductive tract obstruction?
1. congenital blockage
2. acquired blockage
3. functional blockage
131
what is CAVD?
congenital absent vas deferens > vas deferens, seminal vesicles, & ejaculatory ducts are atrophic or absent > obstruction
132
80% of CAVD pts harbor what kind of mutation?
a detectable CF mutation
133
what % of infertility cases are d/t CAVD?
1-2%
134
name 4 congenital blockages besides CAVD that can cause post-testicular infertility
1. young syndrome
2. idiopathic epididymal obstruction
3. APKD
4. blockage of ejaculatory ducts
135
what happens in Young syndrome?
abnormally viscous mucous
136
what are 3 types of acquired blockages that cause post-testicular infertility?
1. vasectomy
2. groin/hernia surgery
3. E. coli or chlamydia
137
what can cause a functional blockage & result in post-testicular infertility?
nerve injury or meds > impair contractility of seminal vesicle or vasal musculature
138
what are the 4 types of disorders of sperm fxn/motility that can result in post-testicular infertility?
1. immotile cilia syndromes
2. maturation defects
3. immunologic infertility
4. infxn
139
what are the 2 characteristics of immotile cilia syndromes?
1. abn motor apparatus or axoneme of sperm & other ciliated cells
2. nonmotile but viable sperm in normal #s
140
when can sperm maturation defects happen?
after vasectomy reversal
141
why do pts get sperm maturation defects?
elevated epididymal intratubular pressure & epididymal dysfxn
142
how does a sperm maturation defect impact sperm count?
normal sperm count
| sperm do not regain usual maturation & motility capabilities
143
what % of infertile couples can attribute that problem to immunologic infertility?
10%
144
what are the top 2 bacterial & viral infxns that can cause post-testicular infertility?
N. gonorrheae
Chlamydia trachomatis
CMV
Herpes simplex II
145
what are the 2 types of coital disorders that can cause post-testicular infertility?
1. impotence
| 2. penile abnormalities
146
what is impotence?
low libido or ED
147
how can you start to work up impotence?
hormonal eval
148
how do you treat situational impotence?
counseling + oral PDE inhibitors
149
what is the most important penile abnormality that can cause infertility?
hypospadias
150
why do penile abnormalities cause infertility?
result in placement of the semen too far from the cervix
151
what are the 3 penile abnormalities that can cause post-testicular infertility?
1. HYPOSPADIAS
2. phimosis
3. abn curvature
152
what is pyospermia?
INC leukocytes in semen
153
what 3 things is pyospermia assoc w/?
1. subclinical genital tract infxn
2. elevated ROS
3. poor sperm fxn & infertility
154
how do you treat pyospermia?
broad spectrum abx for both partners
155
what is involved in coital therapy?
counseling on issues of coital timing, frequency, & gonadotoxin avoidance
(& probably some lube)
156
how do you treat immunologic infertility?
suppress the immune system w/ corticosteroids
| IVF & ICSI
157
how do you treat hyperprolactinemia?
bromocriptine
158
what is congenital adrenal hyperplasia (a deficiency of...)?
21-hydroxylase deficiency
159
what happens in congenital adrenal hyperplasia?
XS androgen levels > DEC GnRH
| precocious puberty
160
how do you treat congenital adrenal hyperplasia?
corticosteroids
161
how do you treat testosterone XS?
GnRH replacement in a pulsatile manner via portable infusion pump
162
how do you treat testosterone def?
"jump start" the testes w/ hCG (LH) & FSH
163
what are the 3 empiric medical therapies for men with idiopathic infertility?
1. clomiphene citrate
2. antioxidant therapy
3. GH
164
what can you use to treat oligospermia?
GH
165
why would you use antioxidant therapy for infertile men?
40% of infertile men have increased ROS levels in their reproductive tract
166
what is clomiphene citrate?
a synthetic nonsteroidal drug that acts as an antiestrogen
167
why do you give clomiphene citrate?
idiopathic low sperm w/ low-normal LH, FSH, & T
168
how does clomiphene citrate work?
blocks estrogen on male axis
| increases GnRH, FSH, LH > inc T & spermatogenesis
169
T/F: clomiphene citrate is indicated for treatment of male infertility
FALSE
| it's "off-label" technically
170
what classes of meds (4) are assoc w/ impaired ejaculation?
1. anti-HTN agents
2. α-adrenergic blockers
3. antipsychotics
4. SSRIs
171
how does an erection happen?
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
what happens when penile smooth muscle relaxes?
blood flow dramatically increases
173
what happens to the veins of the penis as the erectile tissue fills w/ blood?
they are compressed, blocking outflow
174
what happens to abolish an erection?
cessation of nervous impulses to the penis or sympathetic vasoconstrictor impulses
(or recite the pledge)
175
where can you find nitric oxide synthase?
```
cavernous nerve
endothelial cells (deep penile arteries)
```
176
what does the cavernous nerve innervate?
smooth muscle surrounding penile arteries
177
what is the rxn to create NO?
arginine + O2 --> citrulline + NO
178
how does NO cause muscle relaxation & vasodilation (long, sorry)?
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
when does ED occur?
when a man can no longer get or keep an erection firm enough for sexual intercourse
180
what % of men suffer from ED?
52%
181
what % of men have minimal, moderate, & complete ED?
```
minimal = 17%
moderate = 25%
complete = 10%
```
182
what are the physical causes of ED?
literally anything > any dz, any drug, booze, even prolonged biking
183
what are 6 psych causes of ED?
1. depression
2. anxiety
3. stress
4. mental health conditions
5. relationship probs
6. combo of physical & psych probs
184
what terminates the erection signal?
cGMP --> GMP via PDE V in corpus cavernosum
185
what are the 4 ED drugs?
1. sildenafil (viagra)
2. vardenafil (levitra)
3. tadalafil (cialis)
4. avanafil (stendra)
186
how do the ED drugs work?
PDE V inhibitors > inc blood flow to penis
187
how does viagra cause blindness?
inhibition of PDE6, which is the PDE used in signal transduction of light signals in the retina
188
T/F: priapism is common
FALSE
189
what is priapism?
prolonged erection in the absence of sexual arousal
190
what are the 2 types of priapism?
1. non-ischemic
| 2. ischemic
191
T/F: priapism is a medical emergency
TRUE
192
what causes non-ischemic priapism?
injury to penis or perineum
193
what is the treatment for non-ischemic priapism?
usu clears up on its own, or use an ice pack
194
what is ischemic priapism?
blood flows into penis but does not flow out
195
what happens in ischemic priapism d/t loss of circulation?
corpora cavernosa doesn't get any oxygen > damages erectile tissue, causes scarring, can lead to permanent loss of fxn
196
what is "therapeutic aspiration" & how well does it work?
urologist draws blood directly from the cavernosa (RX for ischemic priapism)
only resolves ~30% of cases
197
what is the best way to treat ischemic priapism?
injecting a sympathomimetic agent > usu PHENYLEPHRINE (or epi, or metaraminol)
198
how effective is injecting a sympathomimetic to treat ischemic priapism?
resolves 77% of cases
199
what happens if ischemic priapism is resistant to both aspiration & drug injections?
surgeon must perform a surgical shunt
