34 & 35 Pharmacology of Reproductive Hormones Flashcards by Amandaaa Wong

Name the 3 forms of estrogens and how they are formed.

Estradiol
Estrone
Estriol

Estradiol: from testosterone, or by conversion of esterone to estradiol

Estrone: from androstenedione, or by conversion of estradiol to estrone

Estriol: by conversion of estrone to estriol

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What cells are involved in the synthesis of estradiol?

At which organ is it converted to estrone and estriol?

Granulosa cells;

liver

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Where can estrone and estriol be found in the body respectively?

Estrone: placenta, adipose tissue

Estriol: placenta

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Name the 4 synthetic estrogens. What type of synthetic estrogen do they belong to?

Steroidal:
- Mestranol
- Ethinyl estradiol
Non-steroidal
- diethylstilbestrol
- chlorotrianisene

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Where can ER-alpha estrogen receptors be found?

A. Mammary glands
B. Ovaries
C. Vagina 
D. Hypothalamus
E. Pituitary gland 
F. Uterus 
G. Placenta 
H. Vascular smooth muslces
I. Endothelial cells

All except E and G

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There are more ER-beta in ovaries and prostates compared to other organs .
T/F?

True

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How does progesterone and prolactin affect the ER (estrogen receptor) expression in reproductive tract respectively?

Progesterone: decreases the expression

Prolactin: increases ER numbers in mammary gland but NOT in the uterus

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Which of the following option(s) is false concerning the pharmacokinetics of natural estrogens?

A. It can be administered through I.M. injection that produces a sustained release of estrogen
B. It can be administered by I.V. injection
C. It can be administered orally by the form of micronized/conjugated estrogens
D. They are rapidly metabolized in the liver by conjugation
E. There variable amount of enterohepatic cycling
F. They will eventually be excreted in urine only
G. > 97% bound to plasma albumin
H. It can be administered through transdermal patches/ vaginal cream

B
F: also in bile
G: >97% bound to sex-hormone binding globulin (SHBG)

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Other than natural estrogens, what form(s) of steroidal estrogen can be used pharmacologically?
Which of the following is true about it?
A. It is metabolized by CYP450 and conjugated by glucoronidation/ sulphation

B. >99% bound to plasma albumin

C. 50% bioavailability

D. They are rapidly and completely absorbed orally

Mestranol and ethinyl estradiol

All are correct except B: should be >95% bound to plasma albumin

Mestranol undergoes rapid hepatic demethylation to ethinyl estradiol for activities

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Which of the following about progestogens are correct?
A. They are bound to SHBG but not transcortin and albumin
B. They are orally inactive due to rapid metabolism in liver
C. They are excreted in urine after conjugation

B and C only

A: They are bound to transcortin and albumin but not to SHBG

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Which of the following is true about the mechanism of action of progestogens?

A. They have one kind of receptor
B. Presence of adequate receptors requires estrogen priming
C. They act on female reproductive tract, mammary gland, CNS and pituitary

B and C only

A: PR-A and PR-B receptors

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What are the respective fucntions of PR-A and PR-B?

PR-A: acts s a transcriptional inhibitor of other steroid receptors

PR-B: mediates the stimulatory activities

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Which 2 kinds of derivatives are used as progestogens?

When are they used?

Progesterone derivatives
Testosterone derivatives

Progesterone derivatives are used when a selective progestational effect is desired.
It is used in conjunction with estrogens for menopausal hormone replacement therapy.

Testosterone is used in oral contraceptives, with varying degrees of androgenic, estrogenic and antiestrogenic activities.

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Which of the following is false?

A. Norethisterone and norethynodrel are less selective than progesterone esters
B. Gestodene and norgestimate are orally active with 1-3 days duration
C. Levonorgestrol has higher androgenic activity than norethisterone

C is false.
They have lower androgenic activity compared to norethisterone, norethynodrel and ethynodiol (19-Nor testosterone derivatives)

A is correct: they are 19-nor testosterone derivatives

B is correct: they are levonorgestrel (testosterone derivatives)

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What are the main ingredients of a combined oral contraceptive pill? (COCP)

estrogen
ethinyl estradiol (mestranol)
Progestogen (lowest conc.): levonorgestrel, norethisterone; gestogene, desogestrel, norgestimate

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The effect of combined oral contraceptive pill will be missed if _______ hours late.

What are the effects of combined oral contraceptive pill on the hypothalamus-pituitary axis?

Estrogen upregulates progesterone receptors and enhances sensitivity to progesterone
Estrogens and progesterone provide negative feedback on both the hypothalamus and the pituitary, thus GnRH and FSH, LH levels are suppressed respectively.
Ovulation is therefore prevented with no LH surge.

What are the 3 effects of combined oral contraceptive pills on female reproductive tract?

Overall:
Reduce likelihood of conception and implantation

reduce transportation of sperm and ovum by fallopian tubes
Change in endometrium making it less receptive to implantation
Thicken cervical mucus to reduce sperm penetration

Which of the following are benefits of combined oral contraceptive pills?

A. prevent iron deficiency anaemia
B. reduce osteoporosis and bone loss
C. decrease menstrual cramps (decrease dysmenorrhea)
D. improve existing iron deficiency anaemia
E. reduce risk of pelvic inflammatory diseases
F. protect against ovarian and endometrial cancer
G. decrease benign breast disease and ovarian cysts

All except B

What are the side effects of combined oral contraceptive pill? 
A. Dizziness
B. Nausea 
C. Hypotension
D. Acne, weight gain and hirsutism
E. Amenorrhea 
F. Breast fullness/ tenderness (mastalgia) 
G. Mood changes

All except C

should be high blood pressure

What are the 5 main effects of estrogen on cardiovascular system?

Vasodilation (increase NO production)
Retention of water and salt (lowers osmotic threshold for stimulation of release of ADH)
Increase plasma level of angiotensinogen (stimulatory effect on liver)
Elevate serum triglycerides and reduce total serum cholesterol (increase HDL, decrease LDL > reduce atherosclerosis)
Increase coagulability of blood (significant increase in fribrinogen and blood clotting factors, inhibit antithrombin III formation > increase venous thromboembolism)

Estrogen increases the changes of venous thromboembolism but decreases the changes of atherosclerosis.
T/F?

True

Which of the following about combined oral contraceptive pill is/are true?
A. The chances of venous thromboembolism is related to the dose of estrogen

B. There is a reduced risk of venous thromboembolism with 3rd generation pills

C. They change platelet functions and fibrinolytic system by reducing venous blood flow and increasing coagulability of thrombosis

D. There is high risk of myocardial infarction in all women if taken

A, C

B: in 2nd generation pills only, effects of 3rd generation remains debatable

D: slightly high risk in women who are sedentary and obese, with history of preeclampsia, hypertension, diabetes and hypercholesteremia, is over 35 years old

Combined oral contraceptive pill shall be contraindicated when the patient :
A. Has diabetes
B. Has liver diseases/tumours
C. With hypertension
D. Has blood clotting disorders
E. will undergo major surgery
F. has headaches
G. is a smoker who is over 35 years old 
H. Has history of stroke / ischemic heart disease

All of the above

What are the 2 main drug interactions with combined oral contraceptive pills? Describe briefly.

1. Enzyme inducers - reduce effectiveness by increase estrogen metabolism by CYP450 e. g. rifampicin, barbiturates, anticonvulsants (phenytoin) 2. Antibiotics - reduce effectiveness by decreasing enterohepatic recirculation of steroid hormones through disturbance of bacterial flora of the gut e. g. ampicillin, tetracycline

Which of the following are features of transdermal combined contraceptives (Ortho Eva)? A. They bypass GI tracts B. Side effects include breast discomfort C. Side effects include application-site reactions and dysmenorrhea C. Delivers 150 g norelgestromin and 20 ug of ethinyl estradiol to systemic circulation

All of the above

Progestogen-only contraceptive: Its efficacy is mainly contributed by which 2 actions? What effects can it cause hormonally?

- Prevent ovulation in 60%-80% of the cycles - Contributed by: 1. Thickening of cervical mucus, decreased sperm penetration 2. Endometrial alterations that impair implantations - Slow down the frequency of GnRH pulse and blunting LH surge

Which of the following are true for Progestogen-only contraceptives? A. They can be taken in the form of minipills orally B. They contain high doses of progestogens C. They can cause side effects like erratic uterine bleeding and ectopic pregnancy D. Missed if 3 hours late (short safety interval) E. They can be in the form of I.V F. They can be in the form of subdermal slow-release implant, which is removable at anytime

All except B,E B: Low dose of progestogens - E.g. 350 ug northisterone or 75 ug of norgestrel E: Intramuscular: increase LDL/HDL ratio and decrease bone density F: correct, cause local irritation, headache, weight gain and mood changes

Which of the following is correct about morning after pills (emergency postcoital contraceptive)? A. They contain high doses of oral contraceptive B. Their main action is preventing ovulation C. Side effects include nausea and vomiting

All except B A: - 2X [Ethinyloestradiol (50μg) and levonorgestrel (0.25 mg)] e.g. Preven Levonorgestrel (0.75 mg), e.g. Plan B B: Reduced fallopian tube mobility and a direct effect on endometrium

Name 2 non-contraceptive therapeutic uses of female sex steroids. List examples.

1. Menstrual problems - Premenstrual problems - Dysmenorrhea - Menorrhagia 2. Replacement therapy - young patients: hypogonadism/ hypopituitarism > estroge deficiency - adult patients: menopaused > symptoms due to reduced estrogen levels

Name the 3 main categories of female sex steroids antagonists. Name their respective drugs.

1. SERM (specific estrogen receptor modulators) - Tamoxifen - Toremifene - Raloxifene 2. Antiestrogens - Clomiphene 3. Antiprogestogens - Mifepristone

Which of the followings are true about Tamoxifen? A. It is always anti-estrogenic B. It causes side effects like nausea, hot flashes and vomiting C. It is for palliative treatment of estrogen dependent brest cancer D. It can prevent postmenstrual osteoporosis E. Orally active with initial half life of 7-14 hours F. Daily oral dose of 10-20 mg twice a day

All except A and D A: - Anti-estrogenic: mammary tissue - Estrogenic: plasma lipids, endometrium and bone - Estrogenic activity stimulate proliferation of endometrial cells > increase risk of endometrial cancer D: Raloxifene, not Tamoxifen

Which of the followings are true about Raloxifene? A. It can be both anti-estrogenic and estrogenic B. It has no action on endometrial , thus will not increase risk of endometrial cancer C. It does not have side effects D. It prevents postmenstrual osteoporosis E. It cannot help stopping proliferation of ER positive breast tumours F: It decreases risks of deep vein thrombosis

All except C, E and F C: Common side effects: hot flashes and leg cramps E: Anti-proliferation of ER positive breast tumours F: increases risks of deep vein thrombosis

Which of the followings are true about Clomiphene? A. It is an antiestrogen B. It is a full agonist of estrogen receptors, and therefore impairs the synthesis of ER > estrogen insensitivity C. It causes increase in GnRH pulse D. It is used for treating infertility that is due to the lack of ovulation

All except B | B: partial agonist

Which of the followings are true about Mifepristone? A. It is an anti progestogen B. It is a full agonist at progesterone receptors C. It is used for terminating pregnancy after 3 months D. It is used for postcoital contraceptive to prevent implantation E. It sensitizes the uterus to cause contractile action of prostaglandins F. It stimulates glucocorticoid and androgen receptors.

All except B, C and F B: partial agonist C: terminate pregnancy within 49 days (7 weeks) F: inhibits glucocorticoid and androgen receptors