reproductive pharmacology

Question 1

Describe the pathway from hypothalamus to its effects on the reproductive tract

mention

• GnRH
• anterior pituitary
• FSH and LH
• oestrogen and progesterone

Answer 1

mention

-

Question 2

a surge of what hormone occurs immediately after ovulation?

Answer 2

LH - ruptures the follicle

Question 3

How does estrogen influence fertility control?

Answer 3

influences ovum maturation/development of the ovum/follicular unit

• it controls the timing of the follicular phase

Question 4

How does estrogen effect the uterus?

Answer 4

prepares the uterus for implantation

–proliferation/vascularisation of endometrial cells

–induction of progesterone receptors to allow progesterone response during luteal phase

Question 5

How does estrogen levels effect FSH and the anterior pituitary?

Answer 5

Inhibit FSH release, negative feedback on AP

Question 6

what is the metabolic action of estrogen? effect on lipids? bones? skin?

what is the classical mechanism of action of estrogen?

Answer 6

acts on ERalpha and ER beta (estrogen response element) which are in different locations around the body - they induce/repress gene transcription intracellularly

•Metabolic action

–Mineralocorticoid-like - retention of Na+ and water

•Lipids

–Increase [HDL] in plasma

–Decrease [LDL], [cholesterol]

•Increase coagulability of blood

–Increases a number of clotting factors

•Maintains bone density and elasticity of skin & blood vessels

Question 7

what is the non-classical MOA of estrogen?

Answer 7

recently discovered are membrane receptors - that are responsible for the rapid estrogen effects and mediate non-genomic mechanism of signaling

Question 8

why do we use synthetic versions of estrogens?

Answer 8

mestranol, stilbestrol and ethinylestradiol

synthetic versions are used more often b/c they are degraded less rapidly by the liver -

Question 9

estrogen is almost alwys administerd with what?

Answer 9

with a progestogen

given always unless to woemn with historectomy

b/c unopposed estrogen can have an effect on endometrial cancers

Question 11

Under what circumstances do we give estrogen?

Answer 11

contraception

estrogen replacement therapy (ovarian failure, or menopause)

Question 12

what are some side effects of estrogen?

Answer 12

• nausea/vomiting
• retention of salt and water
• risk of thromboembolism
• risk for uterine cancer
• in males - feminisation

Question 13

what are some contraindications of estrogen therapy?

Answer 13

• estrogen dependent tumours
• undiagnosed genital bleeding
• liver disease - liver metabolises estrogen - so woman will be exposed to a much higher dose of estrogen
• history of thromboembolic disorder
• best avoided by heavy smokers - increased risk factors particularly in over 40 years of age

Question 14

what are anti - estrogens?

Answer 14

they compete with endogenous estrogen to bind to recpetors in the body and thereby block estrogen effects

Question 15

what are some examples of anti-estrogens?

Answer 15

Tamoxifen - estrogen antagonist (SERM- selective estrogen receptor modulator) - treat estrogen receptor positive breast cancer and has mild estrogen agonist effects in other tissues like bone, endometrium, and plasma lipids

clomifene - is an SERM as well and induces ovulation (infertility treatment) - by binding in anterior pituitary blocking the normal negative feedback loop - this may be enough to induce FSH and LH to stimulate ovaries in infertility

Question 16

what is the effect of progestogens?

Answer 16

hormonal effects = maturation of endometrium and supports gestation and embryogenesis

other effects = increase basal insulin and insulin response to glucose - increases body temp (has a depressant effect)

Question 17

traditional progesterone pills are derivatives of what?

Answer 17

they are testosterone derivatives so they can be taken orally without risk of first pass metabolism

the only downside to this is that they have slight androgenic activity which is not ideal for women (ex. Norgestrel)

the newer ones

“desogestral” used for contraception has less adverse effects but a higher risk of thromboembolism

Question 18

what are some clinical uses of progestogens?

Answer 18

contraception, HRT, endometriosis, and endometrial cancer

Question 19

What is Mifepristone?

Answer 19

works in the presence of progesterone as a competitive receptor antagonist - so you block the effect of progesterone causing termination of a pregnancy up to 7 weeks

used alone or in combination with prostaglandin E1 analogue - which induces uterine contractions and causes expulsion of the fetus - this is the most effective means.

Question 20

what is the approx. life of egg after ovulation?

Answer 20

12-24 hours

Question 21

what is the life of sperm after ejaculation in the reproductive tract?

Answer 21

up to 3-5 days

Question 22

what is the mechanism of action of the combined estrogen/progestogen oral contraceptive pill?

Question 23

Describe the MOA of a progestogen only pill

Answer 23

MOA = makes cervical mucus inhospitable to sperm, hinders implanation, inhibit LH release and prevents ovulation -

99% reliable if compliant - must be taken within 3 hours of same time everyday

side effects= ovarian cysts potential, irregular menstruation or amenorrhoea

used mostly when estrogen pills are contraindicated

ie.) raised blood pressure with estrogen, history of venous thromboembolism, smokers over 35, and can be used by nursing mothers

Question 24

does prevention of ovulation delay menopause?

Answer 24

• no, you cannot ‘save’ up eggs- there is no evidence that there is protective effect from menopause this way -

Question 25

what are some potential drug interactions with oral contraceptives?

Answer 25

any diarrhea, or vomitting between 2-3 hours after taking the pill will prevent the effectivenes of the drug -

the cytochrome P450 in the liver metabolises both estrogen and progeston- so anything hindering that enzyme will effect the effectiveness of the pill

ex) rifampicin and rifabutin antibiotics, St John’s Wort

Question 26

Describe the progestogen only injectable contraceptive

Answer 26

progestogen-only injectables given intramuscularly every 3 months

slowly released into the systemic circulation following intramuscular injection

• some women report menstrual irregularities on it
• increased risk in osteoporosis and therefore should not be used longterm (no longer than 2 years of continuous use)
• works by suppressing ovulation and cervical mucous thickening

Question 27

describe the progestogen only subdermal implant

Answer 27

implanted subcutaneously - non-biodegradable capsules

releases over 3 years, removed no later than end of 3rd year, irregular bleeding/headaches

suppress ovulation and cervical mucus is thickened, prevent sperm penetration

Question 28

Describe the emergency contraception pill

Answer 28

not 100% effective - they work by delaying or inhibiting ovulation and modifying cervical mucous - they have slightly different effects dependent on what time in the cycle you might use

if ovulation has already taken place - it delays the movement of the egg in the fallopian tube and produces mucuous to try to prevent egg/sperm introduction

*note if the pregnancy is already established it will not disrupt it- generally it has no effect on the fertilized egg*

Question 29

describe the progestin-only emergency contraceptive pill

Answer 29

• must be taken within 72 hours (efficacy decreases with time)
• nausea and vomiting is common
• weight will effect the efficacy (not as efective in women who are obese)

*ex) levonelle or NorLevo, or Plan B

Question 30

Describe the ellaOne emergency contraceptive pill

Answer 30

• used to prevent pregnancy up to 5 days without a deterioration of efficacy or contraindication of weight
• it is a progesterone receptor modulator

Question 31

*she says to study MOA more than anything*