Burkin: Estrogens & Progestins Flashcards
(110 cards)
1
Q
List as many of the effects of estrogen as you can think of..
A
helps maintain body temp
helps regulate parts of the brain that prepare the body for sexual & reproductive development
heart & liver: helps regulate liver’s production of cholesterol, decreasing the build-up of plaque in the coronary arteries
ovary: stimulates maturation of the ovaries, start of the menstrual cycle
vagina: stimulates maturation of the vagina, helps maintain a lubricated & thick vaginal lining
breast: stimulates the development of the breasts at puberty & prepares the glands for future milk production
uterus: stimulates the maturation of the uterus
bone: helps preserve bone density
2
Q
What are the primary therapeutic uses for estrogens?
A
contraception
hormone replacement regimens
antiestrogens (for inferility & breast cancers)
3
Q
What does 3-beta hydroxysteroid DH do?
A
converts pregnenolone to progesterone
4
Q
What does 17-beta hydroxysteroid DH do?
A
converts estrone to estradiol
and aldrostendione to testosterone
5
Q
(blank) catalyzes aromatic hydroxylation of the A ring of C19 androgens to form estrogens
A
aromatase
**androstenedione & testosterone to estrone & estradiol
6
Q
What are the three classes of estrogens available for use?
A
natural
synthetic steroidal
synthetic non-steroidal
7
Q
What are the natural estrogen preparations? Are natural estrogens orally active?
A
estradiol
estrone
estriol;
not orally active due to extensive first-pass hepatic metabolism
8
Q
Provide slow, sustained release of estradiol; this route results in lower hepatic exposure and metabolism of the steroid and thus therapeutic levels of estradiol with lower circulating levels of estrone and estriol.
A
transdermal patches (ESTRADERM)
9
Q
What are the estradiol esters? (synthetic steroidal estrogens)
A
estradiol valerate
estradiol cypionate
10
Q
How are synthetic steroidal estrogens administered?
A
dissolved in oil & injected IM
**provide slow, sustained effects
11
Q
What are the conjugated estrogens? (synthetic steroidal estrogens)
A
estrone sulfate
equilin sulfate
12
Q
How are the conjugated estrogens administered?
A
orally, parenterally, topically
13
Q
When are the conjugated estrogens used?
A
for estrogen replacement therapy in menopausal women
IV for emergency treatment of dysfunctional uterine bleeding
14
Q
What are the alkyl estrogens?
What is significant about these?
A
ethinyl estradiol
mestranol (prodrug of ethinyl estradiol);
they are the most potent steroidal estrogens due to increased affinity for the ER receptor
15
Q
When are alkyl estrogens used?
A
widely used in oral contraceptives
16
Q
Non-steroidal estrogen
A potent estrogen that is historically important as it provided a cheap, orally-active estrogen to use in the development of endocrine therapies when natural products were unavailable.
A
diethylstillbestrol (DSB)
17
Q
Many synthetic agents - often polycyclic compounds with a phenolic ring resembling the steroid A ring - have estrogenic or antiestrogenic properties. Name a few dangerous sources of these compounds…
A
pesticides
plasticizers
industrial chemicals
18
Q
This is a natural progestin
Available in an oil solution for IM application, but may cause local irritation
A
P4
19
Q
This is an inactive form of natural progestin
A
17-alpha hydroxyprogesterone
20
Q
What are these?
Medroxyprogesterone (oral) Hydroxyprogesterone caproate (IM)
A
C21 progestins
21
Q
Which progestins, C21 or C19, are more selective for the progesterone receptor? Which ones have more androgenic activity?
A
C21 - more selective for C19
C19 - more androgenic activity
22
Q
What are progestins mainly used for? Minor uses?
A
contraceptives & HRT (in conjunction with estrogen)
minor uses: dysmenorrhea, endometriosis, hirsutism, uterine bleeding
23
Q
How is menopause defined? What is the average age of menopause in the US?
A
12 months after last menstrual period
average age: 51
24
Q
What is perimenopause? When does it begin? What accelerates the menopausal transition by 2 years?
A
onset of menopause like symptoms ~4 yrs prior to menopause;
avg age of onset 47;
smoking accelerates the menopausal transition by 2 yrs
**symptoms: fatigue, loss of libido, weight gain, depression, hot flashes, night sweats, mood swings
25
What are some early physiological changes in menopause?
decreased inhibin --> elevated FSH
increased ovarian follicular response
overall higher estrogen levels (can reach a higher concentration than in women younger than 35!!)
26
This is the most common cause of erratic menstrual bleeding
anovulation
27
T/F: Many women in their late 40s do not consider themselves fertile
But often they still have occasional ovulatory cycles
True!
28
Contraception can be discontinued by all women at the age of (blank)
55
29
The risk of endometrial cancer increases to (blank)% in women with abnormal uterine bleeding
10%
30
This is a feature of menopause that affects up to 60% of women
hot flashes
**Estrogen stabilizes the CNS thermoregulatory set point and leads to a normal thermoregulatory response. During menopausal transition, decreased estrogen levels lead to instability of the set point and an altered response to external thermal stimuli. Gradually over time, the set point becomes stable again
31
What are some reasons why decreased estrogen in menopause causes physiologic symptoms?
estrogen withdrawal affects neurotransmitter levels
estrogens modulate adrenergic receptors
alters the sensitivity of the 5HT receptors in the hypothalamus
32
What happens in late menopause?
impaired folliculogenesis
increased anovulation
ovarian follicles undergo an accelerated rate of loss until the supply of follicles is depleted
FSH levels continue to rise
33
Changes in late menopause reflect the reduced quality and capability of aging follicles to secrete (blank)
inhibin
**inhibin inhibits FSH, so less inhibin leads to increased FSH levels
34
What are the symptoms of post menopause?
```
vaginal dryness
weight gain
stress incontinence
UTIs
insomnia
occasional hot flashes
~*~bone loss ~*~
```
35
(blank) is a major indication for hormone replacement therapy in postmenopausal women
osteoporosis
**estrogens prevent bone loss
36
What causes the increased bone loss in menopause?
decreased E2 (which limits RANKL expression on osteoblasts, which ultimately forms mature osteoclasts) --> so less E2 = more osteoclasts --> increased bone resorption
37
Why does the risk of cardiovascular disease increase after menopause?
estrogen helps maintain favorable lipoprotein profiles in women
**Prevention of cardiovascular disease was long considered a benefit from estrogen replacement therapy
38
What are the benefits of using medical hormone therapy (oral contraceptives) in perimenopause?
restores regular cyclicity
protects against ovarian & endometrial cancer
increases bone density
39
(blank) doses of estrogen & progestin are used in postmenopausal women
lower
40
In 2002, there was a turning point for medical hormone therapy. What happened? How has this changed the recommendations for hormone therapy?
a study showed that a combined estrogen-progestin (Prempo) caused increased strokes, heart attacks, breast cancer cases, blood clots, dementia
**Not only did hormone therapy increase the women's risk of breast cancer, it also made tumors harder to detect
**hormone therapy should be used to treat symptoms for the shortest time possible!!!
41
What is one test you can do to confirm that a woman is postmenopausal?
FSH test --> FSH levels will dramatically rise in postmenopause (no inhibin)
42
Where is the alpha estrogen receptor found?
uterus, testes, pituitary, ovary, kidney, epididymis, adrenal gland
43
Where is the beta estrogen receptor found?
prostate, ovary, lung, bladder, brain, uterus, testes
44
What are SERMS?
selective estrogen receptor modulators - block estrogen receptors in the breast, but activate estrogen receptors in the uterus
45
The prototypical SERM, long half life
binds with high affinity to both ERa and ERb.
Acts as an agonist in bone and cardiovascular system
increases bone density, decreases fractures, decreases total cholesterol
acts as an antagonist in the breast and uterus
50+% decrease in overall cancer incidence
Raloxifene
46
What is Raloxifene FDA approved to treat?
osteoporosis
| reducing risk of invasive breast cancer
47
What is unique about Raloxifene in terms of its agonist/antagonist profile?
provides the same benefits as estrogen on bone density and lipoproteins, WITHOUT the adverse effects of the uterus and breast tissue (doesn't increase risk of uterine or breast cancer)
48
Side effects of Raloxifene? Contraindications?
hot flashes
leg cramps
blood clots
Don't use during pregnancy or breastfeeding, premenopause, history of thromboembolic events, smoking
49
Brand name Osphena
Used to treat dyspareunia (painful intercourse)
SERM with estrogenic effects on vaginal epithelium
Can be taken orally
Ospemifene
50
Side effects of Ospemifene? Contraindications?
Side effects: vaginal discharge, hot flashes, diaphoresis, endometrial cancer
Contraindications: undiagnosed vaginal bleeding; estrogen-dependent neoplasia; history of thrombosis; pulmonary embolism, pregnancy, hepatic impairment
51
Which is preferred, conventional hormone therapy or compounded hormone therapy?
conventional
**there is insufficient evidence to support superiority claims of compounded bioidentical hormones
52
Substances found in plant-based foods that have weak estrogenic effects
may help lower cholesterol, relieve hot flashes
phytoestrogens
53
May help with short term treatment of hot flashes and vaginal dryness
Black cohosh
54
Natural phytoestrogen
Weak estrogen (higher affinity for ERb)
Stimulates bone formation, inhibits bone resorption, and prevents bone loss
lowering LDL cholesterol and triglycerides
may help relieve hot flashes
Lower doses inhibit prostate, cervical, brain, colon and breast cancers
However, high doses can increase rate of growth of some ER-dependent breast cancers
reduces efficacy of tamoxifen and aromatase inhibitors
depress thyroid function and cause infertility
Genistein
55
How do antiestrogens work?
competitive antagonists for estrogen receptors
| inhibitors of estrogen synthesis
56
Chemically similar drugs that act as partial estrogen agonists or antagonists depending on the tissue examined
Clomiphene
| Tamoxifen
57
Anti-estrogen given orally for female infertility
Induces ovulation
Increases FSH & LH production by blocking inhibitory action of E2
Less active as antiestrogen in the periphery
Clomiphene Citrate
58
What are the side effects of Clomiphene citrate?
hot flashes
ovarian cysts
multiple births
59
Antiestrogen that is the treatment of choice in postmenopausal women with breast cancer
Often used in conjunction with surgical and or chemotherapeutic options
Not thought to alter lipid profiles or accelerate osteoporosis
Less active as an antiestrogen at the pituitary
Now thought to be beneficial for the prevention of breast cancer in women at risk
Tamoxifen
60
Tamoxifen can increase the risk of (blank) cancer
endometrial
61
Side effects of Tamoxifen?
hot flashes, nausea, vomiting
62
This estrogen synthesis inhibitor binds reversibly to aromatase and blocks estrogen production by competitive inhibition
Preferred as adjuvant treatment for postmenopausal women with localized or metastatic ER+ breast cancer
Aminoglutethimide or anastrozole
63
What is the MOA of anastrozole?
binds reversibly to aromatase & blocks estrogen production by competitive inhibition
64
Binds aromatase irreversibly
indicated for treatment of ER+ breast cancer in postmenopausal women whose disease has progressed following 2-3 years on tamoxifen
(2011) progression-free survival improved if combined with the mTOR inhibitor everolimus (Afinitor)
Exemestane
65
Prevents aromatase from producing estrogens by competitive, reversible binding to the heme of its cytochrome P450 subunit
Approved for the treatment of local or metastatic breast cancer that is ER+ or of unknown hormonal status in postmenopausal women.
Off label uses: ovarian stimulation (in place of clomiphene), gynecomastia in men, endometriosis
Letrozole
66
When are aromatase inhibitors contraindicated? What are their adverse effects?
contraindicated in women who are premenopausal, during pregnancy, & lactation
ASE: hot flashes, arthalgia, fatigue, long term use --> osteoporosis
67
What are the most common components of oral contraceptives?
ethinyl estradiol & mestranol + a 19-nortestosterone
68
What is the primary mechanism of action of combination birth control pills?
suppress the secretion of FSH & LH through negative feedback
prevent the rise in FSH that initiates follicle development
prevent the LH surge that triggers ovulation
likely to decrease pituitary responsiveness to GnRH
progestin causes the cervix to produce a thick viscous mucus to reduce sperm penetration
the endometrium becomes unreceptive to implantation
69
What is the difference between monophasic vs biphasic/triphasic vs extended cycle pills?
monophasic: fixed amount of hormones - 21 days on, 7 days off
biphasic: reduces the total amount of steroids administered, more closely approximates menstrual cycle
extended cycle pills: allow women to have fewer menstrual periods
70
What do the extended cycle pills contain?
ethinyl estradiol & levanorgestrel
**Seasonale, Seasonique, Lybrel - make it possible to have like 4 periods a year!
71
This is responsible for generating the plasma estrogen levels necessary for contraception
enterohepatic cycling
**estrogens are conjugated in the liver --> pass from the liver to the GI tract --> get broken down to release free estrogen
72
(blank) can interrupt enterohepatic cycling and diminish OC efficacy
antibiotics
73
What is contained in the BC patch that is applied weekly?
Ethinyl estradiol and norelgestromin
74
What are some estrogen driven side effects of BC?
```
HTN
thromboembolic disorders
gall bladder disease
nausea
vomiting
breast tenderness
headache
edema
```
75
What are some progesterone driven side effects of BC?
```
weight gain
hirsutism
depression
acne
irregular bleeding
```
76
OCs decrease incidence of these cancers
50% decrease in endometrial cancer
| decrease in ovarian cancer, too
77
What are the major risks associated with combined oral contraceptives?
increased risk of stroke of MI in smokers 35+yo
| venous thromboembolism!!!
78
Are combined OCs associated with increased breast cancer rates?
nooo!
79
How does the NuvaRing work?
it is a combined hormonal vaginal contraceptive
flexible plastic ring that releases low doses of ethinyl estradiol and progestin over 3 weeks
then you take it out for one week
**efficacy is reduced if the ring is removed or accidentally taken out for more than 3hrs!
80
Marketed as a "newer Progestin” closer to the natural progesterone
Approved by the FDA to treat moderate acne and premenstrual dysphmorphic disorder
Mean decrease in weight, no significant change in lipid profiles
Drosperinone
81
What are some negative effects of Drosperinone?
increases risk of developing thromboembolism (6-7x)
| risk of hyperkalemia - esp in pts taking other drugs that increase K+
82
What was the big deal about Yaz? Like what negative effects was it causing?
hyperkalemia which could lead to heart attacks, stroke, PE, DVT, or sudden cardiac death :(
83
This is one progestin only pill
Keeps natural estrogen levels normal
Highly efficacious, probably due largely to thickening of cervical mucus
Endometrial alterations impair embryo implantation
Not dependent on gut bacteria for absorption so they aren't affected by antibiotics!!
Desogestrel (Cerazette)
84
Is there evidence of increased cardiovascular disease in pts taking progestin only pills?
no!!
85
What is Depo-Provera? How do you administer it?
depot medroxyprogesterone acetate
| FDA approved injection (in the arm or butt) given every 3 months for contraception and endometriosis pain management
86
How does Depo-Provera (depot medroxyprogesterone acetate) protect against pregnancy & endometrial pain/hyperplasia?
effectiveness largely due to a thickening of cervical mucus
| endometrial lining becomes thin & atrophic
87
(FDA) recommends that Depo-Provera not be used for longer than 2 years, unless there is no viable alternative method of contraception, due to concerns over (blank)
bone loss
88
This is a silicone capsule filled with levonorgestrel that is implanted subdermally in the upper arm. It is effective for five yrs, but was discontinued in the US due to lawsuits
Norplant
89
What are the IUD names? What is the active component in them?
Mirena or Skyla;
| contain levonorgestrel
90
What are IUDs used for?
contraception
prevent/treat endometriosis & dysmennhorea
**side effects include bleeding pattern alterations, vulvovaginitis, abdominal/pelvic pain, acne/seborrhea, ovarian cyst and headache
91
What can happen if BC pills are used during pregnancy accidentally? What are the guidelines?
if used in 2-9 weeks after fertilization, can act as teratogens :(
guidelines: stop oral contraceptives as soon as pregnancy is detected!!
92
What is Plan B? What does it contain? What are its side effects?
```
plan B (L-norgestrel) is an emergency contraceptive, only to be used when other means of contraception have failed!!
contains higher dose estrogens or progestins alone or in combo
side effects: nausea, vomiting, abdominal pain, fatigue, headache, breast tenderness
```
93
This is an anti-progestin
It is a derivative of norethindrone
Acts at progesterone & glucocorticoids receptors as an antagonist
Blocks progesterone's effects in early pregnancy
Causes decidual breakdown & detachment of the bastocyst
Also decreases hCG produced by the corpus luteum
Leads to increased sensitivity of the uterus to prostaglandin F2alpha, contraction & expulsion of the embryo
Can be used as a post-coital contraceptive
RU 486, Mifepristone
94
What is infertility? What is primary infertility vs secondary infertility?
inability to conceive after 1 yr of unprotected intercourse;
primary - no prior pregnancies
secondary - infertility following at least one prior conception
95
What are some lifestyle factors that can contribute to infertility?
smoking
alcohol/caffeine
obese or underweight
elicit drugs or toxins
96
What are some ways in which you can assess ovulation?
regular menstrual patter
cyclic menses at an interval of 25-35 days w/ 3-7 days of bleeding
basal body temp
sonography to look at ovaries
midluteal serum progesterone levels (taken 7 days after ovulation)
97
What are some aquired disorders that can lead to ovulatory dysfunction?
excessive exercise
eating disorders
stress
98
What are some other hormonal diseases that can lead to ovulatory dysfunction?
thyroid disease
hyperprolactinemia
hypothalamic hypogonadism (Kallmann syndrome)
99
What are some inherited anatomic disorders of the female GU system?
distal outflow tract obstruction: imperforate hymen, a transverse vaginal septum, isolated atresia of the vagina
mullerian defects
100
In utero exposure to (blank) is linked to malformations of uterine development
small, T-shaped uterus
increased risk for vaginal adenosis.
diethylstillbestrol (DES)
101
This disease is characterized by intrauterine adhesions crossing the lining of the uterus
Asherman syndrome
102
This abnormality is characterized by benign smooth muscle tumors
Leiomyomas
103
Loss of oocytes and the surrounding support cells prior to age 40 years.
ovarian function is decreased or absent (hypogonadism)
FSH levels are high (hypergonadotropic).
primary dysfunction at the level of the ovary
Affects 1:1000 women under 30 & 1:100 women under 40
hypergonadotropic hypogonadism
104
Other terms for hypergonadotropic hypogonadism?
premature ovarian failure
105
What are some other causes for premature ovarian failure?
heavy smoking
ovarian surgery
chemo
pelvic irradiation
106
Primary abnormality lies in the hypothalamic-pituitary axis
LH and FSH levels are low or even undetectable
viewed as a continuum
Inherited or aquired
hypogonadotropic hypogonadism
107
What are some ways in which you can acquire hypothalamic dysfunction?
```
eating disorders
exercise induced
stress
hypothalamic tumors, trauma, radiation
pseudocyesis
```
108
Inherited abnormalities of the pituitary gland?
LH, FSHbeta, GnRH-R mutations
| kisspeptin-1 & its receptor GPR54
109
What are some ways in which you can get chronic sex-steroid secretion, which interferes with normal feedback b/w the ovary and the HPA axis?
PCOS --> too much LH, too much androgen production
congenital adrenal hyperplasia (21 hydroxylase deficiency)
ovarian tumor
hyperprolactinemia & hypothyroidism
110
Given orally for female infertility
induces ovulation
binds to the estrogen receptor in the pituitary and hypothalamus
estrogen's negative feedback is interrupted
Increases FSH and LH production
This leads to maturation of multiple follicles.
long half- life (~5 to 7 days)
Side effects: hot flashes, ovarian cysts, multiple births
Clomiphene citrate
