contraception pharmacology
Pharmacology of contraception (female, hormonal)
Contraception = reversible control of fertility to prevent pregnancy, STIs
The ideal contraception (doesn’t exist):
Fully reversible
100% effective
Convenient and easy to use – maintenance-free
Free of adverse side effects
Cheap
Prevents STI transmission
Types of female hormonal contraception
The pill (combined estrogen and progesterone oral contraceptive pill)
Mini pill (low dose progesterone pill)
Depo-Provera (progesterone injection)
Progesterone implant (implanon)
Intra-uterine device
Nuva ring
Emergency contraception
Estrogens (umbrella term)
Naturally occurring
Estradiol ß most biological activity + main ovary hormone secretion
Estriol – placental estrogen (high during pregnancy)
Estrone – main estrogen in menopausal women ß from androgens
Synthetic (in COCP)
Ethynyl estradiol (EE) – most common
Mestranol (converts to EE)
Effect: growth, ovulation, +endometrium, vaginal cornification (keratin)
Progestogen (umbrella term)
Progesterone (natural)
If taken orally à progesterone metabolised à ineffective à for contraception, progestin ingested and converted to progesterone
Progestin (synthetic)
Wide range of activity (eg. able to bind to oestrogen, progesterone, testosterone and cortisteroid receptors) à complex array of effects
Heaps of types, mainly: derivatives of 19 nor-testosterone and derivatives of levonorgestrel
1: The combined oral contraceptive pill (COCP)
7 green sugar pills simulate period à withdrawal bleeding occurs + gives body break from steroid hormones
Don’t have to take – but there so that user can get used to taking pills ever day
21 pink hormonal pills
A: How it works
Different pills differ in amount of estrogen and type of progestin
Originally 100 μg estrogen dose
Now 20-50 μg estrogen dose with progestin
Start taking on 1st day of natural cycle
Estrogen
Prevents ovulation ß negative feedback suppress estrogen peak
Progesterone
Hostile cervical mucus (more difficult for sperm to penetrate)
Hostile endometrium (more difficult for conceptus to implant)
Normally progesterone aids implantation, but here, progesterone is continuous leading to atrophic endometrium
B: Preparations
Early pills had monophasic preparation: amount of estrogen = progesterone
Biphasic prep and triphasic prep: various amounts of active ingredients
Approximately mimics hormonal cycles
Reduce overall amounts of steroids
C: Effectiveness
However, fairly forgiving; if you miss pill:
Take within 12 hours
Or double next dose
If missed for 2 days – continue, but this cycle and next assume lack of protection0.2-3% failure (mostly due to poor compliance)
Theoretical effectiveness 99.9%
User effectiveness 97-98%
D: Reasons for failure
Poor compliance
Most dangerous to miss pills either side of the sugar pills – increase window for recovery of anterior pituitary (FSH, LH had been previously suppressed by negative feedback)
Poor absorption (metabolised; vomiting or diarrhoea within 2 hours)
Interference from other drugs
Broad-spectrum antibiotics affect normal bowel flora à affects enterohepatic circulation of estrogen à so estrogen is secreted but not reabsorbed à blood levels fall à negative feedback inhibited
E: Reversibility
Median of 3 months before conception
Possible post-pill amenorrhea (absence of menstrual period in a woman of reproductive age), but does not cause infertility
F: Side-effects – most are dose-dependent (hence lower dose if experienced)
Some pills induce liver metabolism of estrogens à have to switch to pills with a higher estrogen concentration or a non-estrogen pill
DVT and pulmonary embolism
Due to E&P screwing around with factors that affect blood clotting
Hypertension (more likely in old, heavier women + with family history)
Myocardial infarction + coronary artery disease
Women over 35 who smoke à 8-fold risk; dose related
Stroke
Due to E&P screwing around with factors that affect blood clotting
Increased risk only for smokers + those with other risks for stroke
Hepatic effects in predisposed women; rare
Increased risk of breast cancer
Decreased risk of ovarian and endometrial cancer
Progestin counters estrogen proliferation
Mild nausea, flushing, dizziness, sore breasts
Mood changes
Diabetic effect – abnormal glucose
Acne, hirsutism ß androgenic effects
G: Relative contraindications
Migraines (especially with aura), hypertension, diabetes mellitus, gallbladder disease, obstructive jaundice of pregnancy
H: Absolute contraindications
History of thromboembolic disease
Cerebral vascular disease, myocardial infarction, coronary artery disease
Congenital hyperlipidaemia
Suspected cancer of reproductive tract (eg. abnormal vaginal bleeding), breast, or of other hormone-dependent or hormone-responsive neoplasia
Poor liver; history of liver tumour
Pregnancy, breast-feeding
Women over 35 who smoke >15 ciggies a day
2: Mini-pill
A: How it works
Progestin only and in a lower dose
Hostile cervical mucus
Hostile endometrium
Suppresses ovulation in about 2/3 of women
No hormone-free week (progesterone levels easily slip below)
B: Market
Breast-feeding (estrogen inhibits lactation)
Also, prolactin (not very effectively) inhibits pregnancy – but combined with mini-pill quite effective, though not as effective as COCP
Estrogen intolerance
Progesterone intolerance when in high doses
C: Effectiveness
Theoretical: 99%; user effectiveness: 96-97.5%
D: Reasons for failure
Late, missed pills ß mini-pill not forgiving like COCP; same time, every day
Poor absorption of pill
However, unlike COCP, not influenced / interfered by other
E: Side effects
Irregular, unpredictable spotting (bleeding) and breakthrough bleeding
F: Contraindications
Undiagnosed vaginal bleeding
Benign or malignant liver disease
Breast cancer
3: Depo-Provera (DMPA - depot medroxyprogesterone acetate)
A: How it works
· Intramuscular medroxyprogesterone acetate injection every 3 months
o Converts to progesterone
· Ovulation suppression, hostile cervical mucus, hostile endometrium
B: Market
· Estrogen intolerance / breast-feeding
· Poor compliance
C: Effectiveness - 99%
D: Reasons for failure - late injections
E: Side effects – breakthrough bleeding; infertility may persist for many months
4: Progesterone implant (implanon)
A: How it works
· Rod, about half a matchstick in size, inserted into inner arm
· Slow, continuous release of progestin for 5 years
· Ovulation suppression, hostile cervical mucus, hostile endometrium
B: Effectiveness – 0-0.1% failure à most effective hormonal contraception
C: Reasons for failure – insertion error
5: Intra-uterine device (IUD) (mirena) – most widely used (worldwide)
A: How it works
· Progestins: local release à hostile cervical mucus, hostile endometrium
· Physical presence + spermicide à inhibits sperm movement and function
· Slow release over 5-10 years (new versions longer)
B: Market
· Women with complete families
· Intolerance to systemic progesterone or progesterone
C: Effectiveness - 0.1% failure rate
D: Reasons for failure – IUD expelled from uterus; rare
6: Nuva Ring
Small flexible vaginal ring à new ring inserted at beginning of each cycle
Removed for 7 days after 21 days for withdrawal bleeding
Progesterone + estrogen à absorbed through vaginal mucosa
Fewer side effects than COCP
More practical effectiveness than COCP due to reduced need for compliance
7: Emergency contraception
A: How it works
· Currently: 2 huge doses of levonorgestrel (type of progestin) either 12 hours apart or as a single double dose
o Effective even if 5 days after
· Hostile endometrium & cervical mucus, delays/prevents ovulation
· Interferes with function of corpus luteum
· Alterations in tubular transport of sperm, ovum and embryo
B: Effectiveness – 60-70% effective in preventing a pregnancy that would have otherwise occurred
