12 - Estrogens & Progestins Flashcards
(75 cards)
1
Q
What are estrogens?
A
Substances capable of inducing estrus or sexual receptivity in females
2
Q
What is estradiol? Where is it produced?
A
- Major natural estrogen
- Produced in ovaries
3
Q
Where are estrone and estriol produced?
A
Liver and other tissues
4
Q
How does the secretion rate of estradiol change during the menstrual cycle, pregnancy, and post menopause?
A
- Menstrual cycle - low during first week of menstrual cycle, peaks during mid cycle and decreases during luteal phase
- Pregnancy - very high
- Post menopause - very low
5
Q
What are the 2 types of estrogen receptors and where are they found?
A
1) Alpha receptors - uterus, ovaries, breast, testes, prostate heart, and brain
2) Beta receptors - more broadly expressed (brain, lungs, bones, blood vessels)
6
Q
What is the function of alpha estrogen receptors?
A
Hormone production in testes and Leydig cells
7
Q
What is the function of beta estrogen receptors?
A
Spermatogenesis in testes and Serotoli cells
8
Q
What are the actions of estrogen?
A
- Promotes synthesis of its own receptors and progesterone
- During puberty, causes changes in reproductive organs, distribution of fat, and shape of body
- Later required for skin texture, bone strength, gut motility, and low LDL/HDL ratio
- Anabolic, weight gain, water and salt retention
9
Q
What are the actions of progesterone in high concentrations?
A
Decrease synthesis, number, and responsiveness to estrogen and progesterone
10
Q
How is estrogen metabolized?
A
Liver produces inactive sulfates and glucuronide derivatives for excretion
11
Q
How is estrogen absorbed?
A
- Through skin and mucous membranes
- Prompt and complete absorption from GI tract
12
Q
What can prevent or slow down metabolism of estrogen?
A
- Esters slow absorption and prolong action
- Micronization slows first pass metabolism
13
Q
Example of a drug that is non-steroidal and estrogenic
A
Diethylstilbesterol
14
Q
Example of a drug that is non-steroidal and anti-estrogenic
A
Clomiphen
15
Q
Example of a drug that is non-steroidal and mixed
A
- Tamoxifen and raloxifene
- Anti-estrogenic or estrogenic depending on tissue
- AKA SERMs (selective estrogen receptor modifiers)
16
Q
What are the uses of estrogen?
A
- Replacement therapy (ovarian failure, surgical removal, menopause)
- Hirsutism, acne
- Neoplastic diseases (anti-estrogen or estrogen)
- Anti-estrogens as fertility drugs
- Contraception
17
Q
What does diane-35 contain? What is its function? How long is tx required?
A
- A progestrogen w/ anti-androgenic properties
- Reduces activity of sebaceous gland, excessive hair growth, and deepening of voice
- Tx = 3-6 months
18
Q
What benefits can estrogen have on menopause side effects?
A
- Decreases post-menopausal sleep disturbances
- Protective effect against CV disease
- Decreases resorption of bone
- Decreases frequency of hip fractures
- Decreases frequency of hot flashes
19
Q
Tx w/ estrogens must begin w/in ____ years of menopause, earlier if possible
A
2-3 years
20
Q
What are some adverse reactions of estrogen use during menopause?
A
- Most frequent = nausea; anorexia, vomiting, and mild diarrhea w/ larger doses
- Bleeding
21
Q
Where is tamoxifen an antagonist and where is it an agonist?
A
- Competitive antagonist in brain and breast tissue
- Agonist in CV system, bone, and uterus
22
Q
Where is raloxifene an antagonist and where is it an agonist?
A
- Competitive antagonist in brain and breast tissue
- Agonist in CV system and bone (no effect in uterus)
23
Q
Which SERM is preferred for osteoporosis?
A
Raloxifene
24
Q
What is the action of clomiphene?
A
- Increases pituitary secretion of gonadotropins (FSH and LH)
- Interferes w/ estrogen “receptor sites” involved in feedback inhibition by estrogen on secretion of LH and FSH
25
What is the use of clomiphene?
Treating infertility and to induce ovulation
26
What are side effects of clomiphene?
- Common = hot flashes
| - Rare = skin rashes, gastric upset, and visual disturbances (reversible when drug stopped)
27
What are progestins?
Substances that prepare the uterus for reception of fertilized ovum
28
What is the function of progestins?
Increase secretions from endometrial tissue that has been primed w/ estrogen
29
When does withdrawal bleeding occur?
- Aka menstruation
| - When there is no progesterone and estrogen in the blood
30
What is breakthrough bleeding? What normally causes it?
- Any bleeding that occurs despite the presence of steroids
| - Usually due to high levels of progesterone relative to estrogen
31
What are characteristics of the ideal contraceptive method?
- Few side effects
- Full and easy reversibility
- Absolute effectiveness
- Ease of use
32
How is efficacy of contraception assessed?
Measuring the number of pregnancies during use of a specified period
33
What is the pearl index?
- Number of failures per 100 women years of exposure (must follow at least 100 women for at least 12 cycles)
- Pregnancies / total months of use (at least 12) * 1200
34
Why are oral contraceptives considered the best amongst the various methods?
- Easy reversibility
- Ease of use
- Few side effects
35
What are the 3 groups of orally active contraceptive agents?
1) Estrogen/progestin (combination pills)
2) Progestin only (mini pills)
3) Interceptives or post-coital (morning after pill)
36
What is the MOA of oral contraceptives?
- Inhibit synthesis or release of pituitary gonadotropins w/ subsequent suppression of ovulation
- Prevent sperm from entering uterus (progesterone secretes thick mucous)
- Prevent implantation of fertilized ovum
37
What are the predominant actions of estrogen and progesterone?
- Estrogen = inhibit secretion of FSH
| - Progesterone = inhibit release of LH
38
How do large doses of estrogen prevent implantation of the fertilized ovum?
- Alter motility of the oviduct
| - Alter properties of endometrium
39
Does estrogen or progesterone cause the majority of undesirable side effects?
Estrogen, so use a lower dose of estrogen
40
What can very low estrogen cause? What should be done about this?
- Can cause breakthrough bleeding
| - If problem persists beyond 3 months, dose of estrogen should be increased
41
When are progestin only pills recommended?
- Breastfeeding
| - Women w/ family or personal history of clots
42
What is the mechanism of progestin only pills to prevent pregnancy?
Alteration of cervical mucous and endometrium w/o suppressing ovulation
43
How long can subcutaneous implantations of progestin last?
Up to 5 years
44
What is a warning w/ the progestin injection (Depo-provera)?
Possibility to cause permanent infertility
45
What is a possible mechanism for breakthrough bleeding?
- While estrogen promotes the synthesis of progesterone and its own receptors, progesterone inhibits the synthesis of estrogen and its own receptors
- W/o receptors, hormones can't have actions, so bleeding will occur despite the presence of steroids
46
When is breakthrough bleeding likely to occur?
- First 3 months of use
| - More common in smokers
47
What is the tx for breakthrough bleeding?
Short period of estrogen (either ethinyl estradiol or oral forms of estradiol) for 7 days when bleeding is present
48
What is the Yuzpe method?
2 combination pills w/in 72 hours after sexual intercourse and 2 more 12 hours later
49
What is the MOA of Mifeprix (mifepristone misoprostol)?
- Competitive antagonist on progesterone receptor, causing detachment of blastocyst, decreasing hCG
- Increases prostaglandins and uterine motility (misoprostol)
- Causes cervical softening, facilitating expulsion
50
What are side effects of Mifeprix?
Bleeding and abdominal cramps that may last 8-17 days
51
When should oral contraceptives be discontinued?
Earliest sign of thrombo-embolic disorders, visual defects, or severe headache of unknown etiology
52
What are some beneficial effects of oral contraceptives?
- Less benign breast diseases
- Less rheumatoid arthritis
- Increased bone density
- Dysfunctional bleeding
- Less reports of ovarian cysts
53
What are some side effects of oral contraceptives?
- Common SE = N/V, headache, breast discomfort, weight gain
- Depression (progestin)
- Hypertension (related to age, duration of use, and concentration of estrogen)
- Thromboembolism (risk decreased w/ low dose estrogen)
- MI
- Cerebrovascular diseases
- Neoplastic diseases
- Amenorrhea
- Glucose intolerance (diabetes in women w/ family history)
- Breakthrough bleeding
54
What is the tx for hypertension caused by oral contraceptives?
Discontinue oral contraceptive and BP should return to normal
55
Oral contraceptives should be discontinued _____ before and after major surgery to avoid risk of _____
4-6 weeks; thromboembolism
56
Which drugs reduce the efficacy of oral contraceptives and increase incidence of breakthrough bleeding?
- Barbiturates
- Rifampicin
- Phenylbutazone
- Phenytoin
57
What are some absolute contraindications for oral contraceptives?
- Acute liver disease or impaired liver function
- Carcinoma of breast
- Known or suspected estrogen-dependent neoplasia
- Undiagnosed genital bleeding
- Suspected or known pregnancy
- Past history of cerebrovascular disease, thromboembolic disease, or conditions predisposing to these disorders
58
What are some relative contraindications for oral contraceptives?
- Subjects over 40 y/o
- Migraine headaches
- Hypertension
- Smoking
59
____ is the major androgen
Testosterone
60
What is testosterone responsible for in women?
Libido and growth
61
What is the relationship between testosterone and LH?
Testosterone causes feedback inhibition of LH production
62
What are androgens responsible for in males?
Development of male characteristics during puberty
63
The active form of testosterone is _______
Dihydrotestosterone
64
What are the therapeutic uses of testosterone?
- Replacement therapy (hypogonadism in youth or andropause)
- Endometriosis
- Growth stimulation
- Prevention of osteoporosis
65
What is the tx for hypogonadism in youth?
- Large doses of testosterone IM until maturation is complete
- Long acting preparations given biweekly
66
What is andropause/ADAM?
- ADAM = androgen decline in aging male
- Deficiency in serum androgen levels w/ or w/o genomic sensitivity
- Causes significant alterations in QOL
67
What is a contraindication for testosterone tx for andropause?
Men w/ severe bladder outlet obstruction due to benign prostate (b/c androgens stimulate prostate growth)
68
What are the sx of andropause/ADAM?
- Loss of sexual desire and erectile function
- Decrease in bone mineral density leading to osteoporosis
- Altered mood
- Loss of muscle strength and body hair
69
What is the criteria for diagnosis of andropause?
Testosterone level of less than 0.255 nM between 8-11 am
70
What is the tx for andropause?
- Oral (taken w/ meals in the morning)
| - Transdermal preparations
71
What are some adverse reactions from testosterone therapy for andropause?
- Prostate cancer (must monitor prostate specific antigen levels)
- Liver tumours and jaundice (rare w/ transdermal)
- Mood changes
- RBC mass and hemoglobin levels may increase
72
What is the tx for endometriosis?
Mild androgen
73
What are some adverse effects of anabolic steroids?
- Masculinization of females, even w/ very low doses
- Hepatic dysfunction, hepatocellular carcinoma
- CNS effects (aggressiveness, anger)
- Impotence and decreased sperm count w/ higher concentration
- Increased LDL/HDL ratio
74
Which drugs are androgen receptor blockers? What are they used for?
- Cyproterone acetate
- Flutamide
- Used for prostatic cancer and hirsutism
75
Which drug is a 5-alpha reductase blocker? What is its use?
- Finasteride
| - May be useful in prostatic cancer
