Sex Hormones Flashcards
1
Q
Leuprolide class
A
long-acting gonadotropin-releasing hormone agonist
2
Q
GnRH Agonist MOA
A
(GnRH agonists are Leuprolide & goserelin)
continuous administration of this long-acting GnRH agonist causes initial surge, then ultimate inhibition of gonadotropin release
3
Q
GnRH agonists: Indications/Therapeutic effects
A
- reduces androgen production in prostate CA
- treats precocious puberty
- stops endogenous LH surge when stimulating with exogenous gonadotropins for ART
- tx endometriosis, polycystic ovarian dz and uterine leiomyomas (fibroids)
4
Q
goserelin (Zoladex) class
A
GnRH Agonist
5
Q
Leuprolide (Lupron) class
A
GnRH agonist
6
Q
Cetrorelix class
A
GnRH Antagonist
7
Q
Ganirelix class
A
GnRH Antagonist
8
Q
GnRH antagonist MOA
A
suppresses LH at lower doses
& FSH at higher doses
9
Q
GnRH antagonist indications/therapeutic effects (2)
A
- suppress endogenous & FSH for Assisted Reproductive Technologies (ART)-only takes 4-5 days (leuprolide takes 3 weeks)
- tx endometriosis & uterine fibroids
10
Q
Side Effects of long-acting GnRH agonists and GnRH antagonists
A
WOMEN: menopausal sxs
hot flashes, amenorrhea
decreased bone density (osteoporosis w/ long term use)
MEN: testicular atrophy
11
Q
Follicle Stimulating Hormone physiology (3), pharm preps
A
- stimulates development of ovarian follicles & estrogen synthesis
- stimulates spermatogenesis
- secretion is increased in post-menopausal women
multiple pharm preps are available
12
Q
hMG class
A
human menopausal gonadotropin
13
Q
Pergonal
A
human menopausal gonadotropin
14
Q
Menotropins
A
human menopausal gonadotropin
15
Q
Human menopausal gonadotropin: origin, contents, use
A
isolated from urine of post-menopausal women
contains both FSH & LH; isolated from urine of post-menopausal women
used for FSH properties only
16
Q
Luteinizing Hormone (LH): when is it secreted, what does it do (females, males)
A
LH secreted just before ovulation, stimulates ovulation & luteinization of ruptured follicle
required for PROGESTERONE synthesis in corpus luteum
stimulates TESTOSTERONE production in testes
17
Q
human Chorionic Gonadotropin (hCG):
use
MOA
pharmokinetics
A
- the typical LH agonist used, extracted from urine of pregnant women
- binds to LH receptor
- longer half-life than LH
18
Q
Gonadotropin indications (3)
A
- pituitary or hypothalamic hypogonadism with infertility
- Induce spermatogenesis in hypogonadotropic hypogonadal men (hCG & hMG is given for up to 1 year, >50% men become fertile
- infertility in women w/functional ovaries who have not responded to other txs (hMG[FSH] then LH [hCG] are given in sequence)
19
Q
hMG class
A
gonadotropin mixture
20
Q
Menotropins class
A
gonadotropin mixture
21
Q
Urofollitropin class
A
Follicle stimulating hormone (FSH)
22
Q
Human chorionic gonadotropin class
A
luteinizing hormone
23
Q
Adverse Effects of gonadotropins
A
- uncomplicated ovarian enlargement
- ovarian hyperstimulation syndrome (rapid accum. of fluid in peritoneal, pleural & pericardial cavities, hypovolemia, fever, shock)
- multiple births (~20%)
- Gynecomastia sometimes occurs in males
- HA, depression, edema, precocious puberty
24
Q
Gonadotropin contraindications/precautions
A
sex steroid-dependent neoplasia
25
3 major natural estrogens
1. Estradiol
2. Estrone
3. Estriol
26
production of estradiol: location, regulated by
ovary of non-pregnant, premenopausal women
| regulated by LH & FSH and is cyclical
27
Estrogen production location in pregnant women
fetal-placental unit
28
Estrone and estriol locations of formation
liver, kidney, adipose tissue, skeletal muscle, brain and testes
29
Estrogens MOA
act on nuclear protein receptors, which interact w/DNA
| increases mRNA synthesis and protein synthesis
30
Estrogen metabolism
estrogens are metabolized by the liver and undergo enterohepatic circulation
31
Naturally occurring estrogen oral activity
not orally active, so synthetic compounds have been developed for therapeutic use
32
Synthetic estrogens found only in:
combination oral contraceptives
| are very potent estrogens
33
Ethinyl estradiol is a:
synthetic estrogen compound found in combination oral contraceptives
34
Mestranol
synthetic estrogen compound found in combination oral contraceptives
35
Conjugates estrogens indication
post-menopausal hormone replacement therapy, oral contraceptives, primary hypogonadism (given to estrogen-deficient patients age 11-13 to stimulate development of puberty and growth), decrease dysfxnal uterine bleeding in absence of organic pathology, suppress ovulation, tx androgen dependent CAs (i.e. prostate)
36
Conjugate estrogens pharmokinetics
metabolized by the liver, undergo enterohepatic circulation
| vaginal, transdermal or injected forms sometimes used to avoid these affects
37
Major adverse effects of conjugate estrogens (3)
1. migraine headaches
2. thromboembolism
3. accelerated blood clotting
38
2 major Conjugate estrogens contraindications/precautions
1. estrogen dependent neoplasms
| 2. history of thromboembolic disorders
39
Tamoxifen MOA
selective estrogen receptor modulator (SERM)
AGONIST IN UTERUS & BONE (prevents bone loss)
ANTAGONIST IN BREAST
40
Tamoxifen Therapeutic Effects
Tx of estrogen-dependent breast CA
pos. prophylactic prevention of breast CA
prevents bone loss
DOES NOT RELIEVE HOT FLASHES
41
Tamoxifen Adverse Effects
Increased risk of uterine CA
may decrease HDL
hot flashes, N/V
42
Toremifene: class & effects
SERM (selective estrogen receptor modulator)
| similar to Tamoxifen but increases HDL
43
Raloxifene: class & MOA
SERM
ANTAGONIST IN BREAST & UTERUS
AGONIST IN BONE and liver
44
Raloxifene indications
postemenopausal osteoporosis
| lowers total and LDL cholesterol in post-menpause
45
Adverse effects of Roloxifene
hot flashes, DVT, leg cramps
46
Clomiphene indication
DOC for infertility in women w/intact HPG axis
| stimulates secretion of LH & FSH (by inhibiting negative feedback)
47
Clomiphene adverse effects
```
Multiple pregnancies (5010%)
hot flashes, HA, constipation, allergic rxns & hair loss
enlarges ovaries
```
48
Fulvestrant MOA
pure estrogen receptor antagonist
| effective in some pts w/ tamoxifen-resistant tumors
49
Fulvestrant AEs
hot flashes, GI sxs, HA, back pain, pharyngitis
50
Aromatase inhibitors MOA, indications
inhibit estrogen synthesis, do not inhibit other steroid synthesis
used to tx breast CA in post-menopause
51
Anastrozole class
nonsteroidal competitive inhibitor of aromatase (final step in estrogen synthesis)
DO NOT INHIBIT ADRENAL STEROID SYNTHESIS
52
Letrozole class
nonsteroidal competitive inhibitor of aromatase (final step in estrogen synthesis)
DON'T INHIBIT ADRENAL STEROID SYNTHESIS
53
Exemestane class
irreversible aromatase inhibitor
54
Exemestane Indication
DOC: tx of breast CA in post-menopause
| 2nd line tx for advances breast CA whose dz progressed during tamoxifen therapy
55
Exemestane adverse effects
Menopausal sxs, even in post-menopausal women
| diarrhea, abd. pain, N/C, bone fractures, joint pain, hypercholesterolemia
56
Exemestane contraindications
premenopausal women
| if used, will need ovarian ablation first to make women post-menopausal
57
Progesterone synthesis & secretion:
a. occurs where
b. is stimulated by
synth and secretion by CORPUS LUTEUM
| stimulated by LH & later in pregnancy by hCG
58
Progesterone MOA
acts on nuclear protein receptors, which interact w/DNA->inc. mRNA synthesis & protein synthesis
59
Progesterone effects on (4) target tissues
1. Uterus: converts endometrium to secretory state needed to maintain pregnancy. Suppresses uterine contractility, especially during pregnancy
2. Endocervical glands: regulates composition of cervical mucus
3. Breasts: lobuloalveolar development in pregnancy & puberty
4. Thermogenic action increases body temp
60
Why do we use semi-synthetic progestin compounds instead of naturally occurring progestins?
Natural-occurring progestins are not orally active
61
Progesterone class
derivative of progestin nucleus
| varying levels of androgenic activity
62
Medroxyprogesterone class
derivative of progestin nucleus
| varying levels of androgenic activity
63
Megestrol acetate class
derivative of progestin nucleus
| varying levels of androgenic activity
64
Norethindrone class
19-nortestosterone
| has progestin & androgenic activity
65
Norgestrel class
19-nortestosterone
| has progestin & androgenic activity
66
Levonorgestrel class
19-nortestosterone
progestin & androgenic activity
(aka Plan B)
67
Norgestimate
19-nortestosterone
| progestin & androgenic activity
68
19-nortestosterone Indications (3)
1. Oral contraceptives
2. prevention of endometrial hyperplasia in HRT
3. dysmenorrhea, endometriosus, hirsutism & bleeding when estrogens are contraindicated
69
progesterone derivative indications
1. Oral contraceptives
2. prevention of endometrial hyperplasia in HRT
3. dysmenorrhea, endometriosus, hirsutism & bleeding when estrogens are contraindicated
70
19-nortestosterone & progesterone derivative indications
possible increase in BP
| high dose progestin therapy may reduce plasma HDL levels, esp the estranes
71
Mifepristone MOA
blocks progestin binding to the PROGESTERONE receptor
(aka RU 486)
also ANTAGONIZES GLUCOCORTICOID RECEPTOR
72
Mifepristone indications/therapeutic effects
pregnancy termination
| prevent implantation if administered w/in 72 hours after intercourse
73
Mifepristone adverse effects
GI-vomiting, diarrhea, abdominal or pelvic pain, vaginal bleeding
74
Mifepristone contraindications
pregnancy or breastfeeding
| ppl on glucocorticoids
75
Danazol MOA
weak progestin androgen & glucocorticoid that suppresses ovarian fxn
76
Danazol indication
endometriosis
77
Danazole adverse effects
weight gain, edema, acne & oily skin, hirsutism, deepening voice, HA, flush libido changes, cramps
(C) but (U) fairly mild
78
Danazole contraindications
liver dysfunction
| pregnant of breast feeding (possibly teratogenic)
79
Combination Oral Contraceptive contents
| & the name of the exception
estrogen & progestin in various amounts
| exception is Drospirenon/ethinyl estradiol
80
Adverse effects of combination oral contraceptives
increased breakthrough bleeding esp. during 1st year
| hard to tell if you are pregnant
81
Yasmin composition and advantages
ethinyl estradiol & drospirenone (mineralcorticoid antagonist)
adv: less water retention-FDA approved for PMDD
very little androgenic properties
82
Natazia MOA
uses estradiol valerate to produce E2 in vivo->bioidentical hormones (uses dienogest as progestin, weird 4 cycle regimen)
83
NuvaRing, what is this thing?
a vaginal ring containing a 3-week supply of etonogesterel & ethinyl estradiol
84
Progestin-only pills use
87-98% effective for birth control
| used for adolescents & breast feeding
85
Depo-Provera
3-month depot injection of medroxyprogesterone
| progestin-only contraceptive
86
Implanon
single silastic tube implanted in arm
| >99% effective-3 years, progestin-only
87
Mirena
Intrauterine contraceptive containing levonorgesterel
| 99.9% effective-up to 5 years
88
Plan P
levonorgestrel-only pill
take w/in 72 hours of intercourse, earlier is better
available without a prescription 18yos & up
89
Mifepristone
aka RU-486, Mifeprix
| can be used to prevent implantation if administered w/in 72 hours after intercourse
90
(C) adverse effects of combo oral contraceptives
```
weight gain
nausea
edema
depression
breakthrough bleeding (progestin alone or too little estrogen)
---try different combos
```
91
other adverse effect of combo oral contraceptives
cardio: clotting (esp >35yo smokers), mild HTN, migraine, MI/stroke
Cholestatic jaundice & gallbladder dz
teratogenesis
fertility (can be suppressed for 3+ mos)
92
Combo Oral Contraceptive Benefits
effective contraception
| dec. risk of ovarian & endometrial CA, ovarian cysts, benign breast dz, ectopic pregnancy, iron deficienct, RA, PMS
93
ABSOLUTE contraindications of combo oral contraceptives
```
thrombophlebitis
THROMBOEMOLIC PHENOMENA
cardiovascular dos
ESTROGEN-DEPENDENT NEOPLASMS
pregnancy
```
94
RELATIVE contraindications of combo oral contraceptives
LIVER DISEASE, pre-epiphyseal closure, asthma, eczema, migraine, HTN, DM, optic neuritis, retrobular neuritis, seizure dos, >35yos smokers
95
What decreases the effectiveness of oral contraceptives
```
P450 inducers (phenytoin, rifamipin, carbamazepine, etc.)
Antibiotics reduce effectiveness of (stop enterohepatic circulation
```
96
Oral contraceptives decrease effectiveness of:
anticoagulants, anticonvulsants, TCAs, guanethidine, oral hypoglycemics
97
Menopause endocrine changes
↓ovarian response to gonadotropins
↓ovarian steroids
↑gonadotropins
98
Menopause sxs:
Vasomotor, GU, Ostoporosis Hrt Dz
99
Advantages of HRT
menopausal symptoms
osteoporosis
heart disease
100
HRT concerns
breast CA
| strokes
101
General guidelines for HRT
10 years after menopause=HRT is not so great
102
Androgens physiological effects (3 categories)
1. Virilizing (androgenic effects): spermatogenesis, sexual development
2. Anabolic effects: ↑bone density, ↑AA incorporation into muscle, ↑RBC mass, antagonize catabolic effect of glucocorticoids
3. Puberty: development of 2ndary sexual characteristics in males
103
Androgen uses (4)
1. Men: testicular deficiency
2. Women: female hypopituitarism (estrogens & androgens)
3. both sexes: hypoproteinemia of nephrosis
4. negative nitrogen balance patients
