Contraceptives and Abortificants

Question 1

Examples pituitary gonadotropins

Answer 1

1. FSH: follicular stimulating hormone. Stimulates development/capture of Graafian ovarian follicles, until
   ovulation.
2. LH: luteinising hormone. Promotes maturation of the follicle, formation of the corpus luteum and secretion of oestrogen.

Question 2

Oestrogen

Answer 2

Primarily secreted by ovarian follicles: some production via adrenal cortex, corpus luteum, placenta, liver and testes » Oestrogens

During puberty
» Maturation of female reproductive organs
» Development of secondary sexual characteristics
» Accelerated growth
» Closure of the long bone epiphyses

Oestrogens post puberty
» Regulation of menstrual cycle
» pregnancy


Question 3

Progesterone

Answer 3

Pro-gestational or pro-pregnancy hormone
» Prepare uterus for pregnancy
» Maintain the endometrium to facilitate implantation
» Suppress further ovulation

Question 4

Oestrogen regulation of the menstrual cycle

Answer 4

» Follicle development
» Stimulates mid-cycle LH surge
» Stimulates growth of myometrium and endometrium » Stimulates mucus production in cervix
» Metabolic actions: salt retention, anabolic actions, regulation of lipid levels. Inhibition of FSH and LH release from pituitary

Question 5

Pharmacokinetics exogenous synthetic oestrogen

Answer 5

Esterified or semi-synthetic derivatives
» Oestradiol valerate, ethinyloestradiol (EE, 99% of OCs),
mestranol (used in a few OCs)
» Active orally, less rapidly metabolised
» All very lipid soluble, readily absorbed.
» Circulate bound to albumin and globulin.
» enterohepatic recylcing
» Conjugates excreted in urine and bile
» Subject to many drug interactions
» Dose varies depending on use
» 20-50μg in OC; 1-3mg in breast cancer

Question 6

Progesterone in the menstrual cycle

Answer 6

LH surge stimulates synthesis and secretion of progesterone from corpus luteum
» Stimulates secretory phase of menstrual cycle
» Maintain endometrium for implantation and nourishment of the embryo
» Relaxation of uterine smooth muscles
» Decrease levels of LH and oestrogen receptors
» Thermogenic


Question 7

Progesterone pharmacokinetics

Answer 7

Naturally occurring progesterone » Inactivated in liver
» Very weak action
» Has to be administered parenterally

Synthetic progestogens
» More potent
» Norethisterone, levonorgestrel, etonogestrel,
cyproterone, gestodene/desogestrel
» Can be administered orally or parenterally

Question 8

OCP mechanisms of action

Answer 8

Exogenous oestrogen
» Suppressed FSH release
» Impaired selection of dominant follicle and follicle development
» Decreased chance of ovulation

Exogenous Progestogen
»  Modifed secretory activity of uterine cervix
»  Decreased LH release
»  Impaired ovulation and tubal motility
»  Decrease chance of fertilization

After several cycles, effective inhibition of GnRH, FSH, LH, and endogenous ovarian steroids
» Thickened cervical mucus
» Decreased endometrial proliferation,
secretions and menstrual flow
» Reduced chance of ovulation and implantation

Question 9

Oestrogen only formulations

Answer 9

Suppress ovulation
» BUT Frequent bleeding in latter stages of cycle
» Increasing the dose to prevent the bleeding causes severe nausea, breast tenderness and increases the risk of
thrombembolic adverse reactions

Combine with progestogen

Question 10

Phased oestrogen formulations

Answer 10

Phased oestrogens » 1,2,3 phases

» Believed to be closer to normal cycle and would have less side effects.

Question 11

Phasic formulations OCP

Answer 11

Monophasic OCs
» Fixed ratio of oestrogen to progestogen for 21 days
» Good protection against mood swings » Can be used to extend the cycle

Biphasic Ocs
» 2 different amounts of progestogen during the 1st and 2nd phases of the cycle
» Days 7-10 (follicular phase), low levels
» Days 11-14 (luteal phase), increased levels

Triphasic Ocs mimic the natural cycle

Question 12

Triphasic OCPs

Answer 12

The theory of the triphasic oral contraceptives is that the lowest possible doses are used, hence fewer adverse reactions. Clinical trials show little difference in cycle control cf monophasic. There are two types:

1. Progesterone triphasic
2. Oestrogen triphasic

Question 13

Progesterone triphasic OCPs

Answer 13

Oestrogen
» Low during 21 days, with maybe a slight increase mid-cycle

Progesterone
» Increased 3 times during the cycle to mimic normal hormone release

Question 14

Oestrogen triphasic OCPs

Answer 14

Oestrophasic dosage
» Progestogen level remains constant - 1mg norethisterone acetate days 1-21.
» EE 20μg day 1-5, 30 μg days 6-12, 35 μg days 13-21

Question 15

Mini pill

Answer 15

» Women unable to take oestrogens
» Less effective and breakthrough bleeds more common
» Can be taken while breastfeeding
» Very low dose
» Has to be taken at the same time each day

Question 16

Medroxyprogesterone IM depot

Answer 16

» Deep IM injection lasts 12 weeks
» No interactions with enzyme inducing drugs » Cannot be removed after injection
» Side effects: amenorrhoea, irregular bleeding, breast tenderness, acne, weight gain, decreased bone density

Question 17

Etonogestrel implant

Answer 17

» Long term contraception - up to 3 years
» Provides highly effective, long-acting contraception
» Popular with breast feeding mothers
» Changes in bleeding pattern is common, can include irregular bleeding, a change in frequency of bleeding, prolonged bleeding or cessation of periods.
» As dose decreases over time, bleeding frequency may increase.

Question 18

The ‘morning after pill’

Answer 18

» 2 x 750μg levonorgestrel, repeated @ 12 hrs
» OR 1 x 1.5mg levonorgestrel is as effective
» 2x high dose OC, repeated @ 12 hrs is also used

Should be used within 72 hrs of unprotected intercourse (effective up to 5 days)
Antiemetic administered 1 hr before

Question 19

Copper-impregnated IUD

Answer 19

Efffective if inserted up to 5 days after unprotected intercourse

Question 20

Mifepristone

Answer 20

(RU-486)
Mifepristone is an abortifacient, not a contraceptive
» Synthetic steroid that blocks progesterone (required to continue pregnancy)
» Effective up to 7 weeks
» Initial treatment is mifepristone (200-600mg oral),
followed by a subsequent treatment with misoprostol (400-800μg) 48 hours later.

A typical regimen currently used in Australia is 200mg mifeprestone, followed by 800μg misoprostol intravaginally, 48 hours later. Most women will abort within the next 6 hours. Success rate is 97.5%

Question 21

Mifepristone contraindications

Answer 21

» IUD
» Bleeding history
» 49 days into pregnancy » Ectopic pregnancy

Question 22

IUD

Answer 22

» Decrease sperm motility, viability
» Inhibit implantation, follicular developmetn
» Most effective emergency contraception and provides
contraception for the rest of the cycle
» Can provide contraception for years.
» Good for women who need to take enzyme inducing drugs for other conditions, eg phenytoin

Problems associated with IUDs: dysmenrrhoea, PID, uterine perforation. No STD protection, can be expelled by the uterus

Question 23

The ‘male pill’

Answer 23

Testosterone works well, can reduce libido.

IM testosterone + low daily oral dose of proestogen works
» Not popular with men or women