Hormonal Contraception

Question 1

What are the three natural oestrogens?

Answer 1

17β Oestradiol (E2)

• Most abundant and potent oestrogen
• Produced by ovarian granulosa cells

Oestrone (E1)

• Produced by ovaries and adrenals

Oestriol (E3)

• Only in pregnancy

Question 2

What transports oestrogen in the blood?

Answer 2

Sex hormone binding globulin (SHBG)

Question 3

What are the actions of oestrogen?

Answer 3

Development

• Pubertal breast and genital development

Menstrual cycle regulation

• Modulates FSH and LH release
• Cyclical changes in breast and uterus

Metabolic

• Increase bone mass
• Improve HDL:LDL ration
• Increases coagulability (increased stroke risk)

Question 4

Where are oestrogen receptors expressed?

Answer 4

Redundantly in breast and reproductive system

Non-redundantly in CVS, bone and CNS

Question 5

What secretes progesterone?

Answer 5

Corpus luteum

Placenta during pregnancy

Question 6

What transports progesterone in blood?

Answer 6

• Albumin
• Corticosteroids binding globulin

Question 7

Where can you find progesterone receptors?

Answer 7

Reproductive tract, breast and CNS.

Question 8

Describe the action of progesterone on the body.

Answer 8

Action is to prepare for pregnancy.

Uterine/Cervical effects:

• Decrease proliferation of endometrium
• Blocks further sperm by thickening cervix and decreasing secretion

Other effects:

• Glandular development in breast
• Block ovulation through decreasing LH and GnRH release
• Increase body temperature (CNS)

Question 9

Two types of oral contraceptives

Answer 9

1. Combined oral contraceptive (COC)
2. Progestogen only contraceptive

Question 10

What does the COC consist of ?

Answer 10

Contains synthetic oestrogen and synthetic progestogen

Synthetic oestrogen = ethinylestradiol

Question 11

How is ethinylestradiol different from estradiol?

Answer 11

Addition of ethinyl group reduces the otherwise high first pass metabolism of estradiol.

Question 12

Describe the mechanism of action of COCs

Answer 12

Inhibit ovulation by preventing release of FSH (oestrogen) and LH (progestogen) through negative feedback.

Also:

• Thicken cervical mucous (progestogen effect) forming barrier to sperm
• Thin endometrial lining (oestrogen + progestogen effect) to reduce sperm implantation.

Thus, COCs decrease likelihood of pregnancy by inhibiting ovulation, fertilisation and implantation.

Question 13

Describe the efficacy of the pill, in theory and in real life.

Answer 13

If used properly, >99%.

EFfectiveness is reduced by:

• Poor compliance
• Vomiting or severe diarrhoea
• Drugs that caused CYP3A4 induction

Question 14

Two types of regimens for COC

Answer 14

• 21 days OC + 7 days placebo
• 21 days OC + 7 days no pill

Question 15

What can occur durin the 7 hormone free days of the COC regimen?

Answer 15

Withdrawal bleeds

Question 16

What is meant by monophasic, biphasic and triphasic formulations of COCs?

Answer 16

Monophasic = same daily dose of EE + progestogen for day 1 to 21

Biphasic = constant EE and increased progestogen in 2nd half of cycle

Triphasic = increased EE in middle of cycle to decrease breakthrough bleeding, plus gradual increase in progestogen over day 1-21.

Question 17

What are the side effects of COC?

Answer 17

• Breakthrough bleeding (treated by increasing dose)
• Nausea
• Breast tenderness
• Chloasma (pigmentation of face)
• Depression, decreased libido
• Increased clotting

Question 18

In what cases is COC contraindicated?

Answer 18

• >35y.o.
• Smoker
• HTN
• OBese
• Genetic clotting abnormalities
• Pregnancy / breast feeding

Question 19

What are the cancer-related risks and benefits of COC?

Answer 19

Oestrogen exposure increases the risk of breast cancer.

However, COC protects against:

• Ovarian cancer
• Endometrial cancer
• Colorectal cancer

Question 20

Why might you use progestogen only OCs over COCs?

Answer 20

Contains no oestrogen, so useful when oestrogen is contraindicated

E.g. history of oestrogen-dependent cancer (breast)

Question 21

What is the mechanism of action of progestogen only OCs?

Answer 21

Inhibits ovulation due to inhibition of LH surge.

• Thickening of cervix and decrease in cervical mucous impedes sperm penetration
• Thinning endometrium decreases implantation

Question 22

What percentage of women still ovulation on OCs?

Why?

Answer 22

30-40%

• REquires meticulous compliance - same time everyday, 28/28 days. Hard to do!
• If you miss it by 3 hours, you need to use back-up contraception.

Question 23

What isthe most effective reversible contraceptive?

Answer 23

Long acting reversible contraceptive (LARC)

• IUD
• Progestogen implant

20x more effective than OCPs.