Contraception and hormones Flashcards
1
Q
COCP pharmacology
A
MOA
- progestogens suppresses GnRH
- > decrease in FSH/LH
- estrogen/progestogens directly suppresses FSH
- lower FSH inhibits follicular development
- > prevents increase in estradiol
- low estradiol
- > less positive feedback on LH
- > more negative feedback on LH
- suppressed LH
- > no mid cycle LH surge
- > no ovulation
- additional progestogen effects
- > increases viscosity of cervical mucus
- > less favourable endometrium for implantation
- > impaired tubal mobility
- additional oestrogen effects
- > stabilises endometrium
- > decreases break through bleeding/cycle control
Efficacy
- failure rate
- > perfect = 0.3%
- > typical (missed doses) = 7%
- differences in efficacy
- > all oestradiol doses similar
- > all progestogen types similar
- > 24/4 regime may have higher efficacy
Drug interactions
- decreased efficacy with CYP450 inducers
- > carbomazopine/phenytoin/barbiturates
- > rifampin
- > HIV retrovirals
- > St Johns Wort
2
Q
COCP combinations
A
Monophasic
- microgynon
- > ethinyloestradiol + levonorgestrel
- > 30mcg/150mcg PBS limited
- > 20/100 or 50/125 also available
- Femme tab (first line)
- > 20mcg/100mcg only low dose PBS listed
Triphasic
- no evidence for greater control/SE profile
- triphasil
- > ethinyloestradiol + levonorgestrel
- > oestrogen mid peak/progestogen increases
- > PBS listed
Quadriphasic
- Qlaira
- > oestradiol valerate + dienogest
- > oestrogen only start/finish
- > increasing progestogen mid cycle
- > best evidence for heavy menstrual bleeding
Estelle/Diane
- 35mcg ethinyloestradiol + 2mg cyproterone acetate
- indicated for acne
Yaz
- 20mcg ethinyloestradiol + 3mg drospirenone
- benefits
- > lowest weight gain
- > good for acne
- > best evidence for mood
- increased VTE risk
Nuva ring
- dosage
- > 150mcg/day etonogestrel
- > 15mcg/day ethinyloestradiol
- systemic exposure
- > ethinyloestradiol approx 50% of OCP
- > etonogestrel approx same of desogestrel OCP
3
Q
COCP safety/adverse effects and management
A
Safety
- increased risk of VTE (3x 1/5,000)
- > lower than risk of pregnancy/post part (12x base)
- > increases with ethinyloestradiol dose
- > highest with drospirenone/lowest with levonorestrel
- increased risk of MI/CVA
- > OR = 1.7
- > absolute risk is low (2-20/million depending on age)
- increased risk of cancer
- > breast OR = 1.25
- > cervix OR = small
- increased risk of liver disease
- > cholestatic jaundice
- > gallstones
- > adenoma
Adverse Effects
- breakthrough bleeding
- > consider other causes of intermenstrual bleeding
- > increase from low dose oestrogen
- > change progestogen if at moderate dose oestrogen
- > consider vaginal ring
- > occurs more at start of extended regime
- nausea
- > reduce oestrogen dose
- > take pill at night
- > change to progestogen only
- mastalgia
- > reduce oestrogen/progestogen dose
- > change to drospirenone
- bloating
- weight gain
- > serial weights (water = oestrogen)
- > try drospirenone (diuretic effect)
- low mood
- > no evidence
- > consider drospirenone
- headache
- > reduce oestrogen/progestogen dose
- > extended regime if during pill break
- dysmenorrhoea
- > extended regime
- > reduce oestrogen/increase progestogen
- decreased libido
- > no evidence for any action
- dyslipidaemia
- > high LDL/low HDL
- > consider less androgenic progestogen
4
Q
Non contraceptive benefits COCP
A
Acne/hirsutism decreased
- mechanisms
- > increased levels of sex hormone binding globulin
- > decreased adrenal/ovarian androgens
- progestogens
- > cyproterone acetate/desogestrel/drospirenone
- > some evidence for superiority to levonorgestrel
- > little evidence for superiority compared to each other
Heavy menstrual bleeding
- all combinations decrease menstrual bleeding
- most effective = qlaira
Cycle control
- more regular/ability to skip
- > all combinations due to oestrogen suppression FSH
Premenstrual syndrome/premenstrual dysphoric disorder
- all combinations reduce mastalgia/primary dysmenorrhea
- Yaz only pill with evidence for effect on low mood
Lower cancer risk
- > ovarian
- > colorectal
- > endometrial
All cause mortality
- mixed evidence for lower rate compared to never used
- > including cancer and CVD
Perimenopausal women
- increase BMD
- decrease hot flushes and AUB
Gynaecological disorders
- pelvic pain disorders
- > dysmenorrhoea
- > endometriosis
- menstrual cycle disorders
- > oligomenorrhoea in PCOS
- > AUB
- > menstrual migraines
- decreased rate PID
- ovarian cyst prophylaxis
5
Q
COCP contraindications
A
THEM SCANDALS
- thrombophilia
- htn
- embolism
- mums breastfeeding <6 weeks post partum
- smoking >15 over 35yrs age
- cardiovascular
- > multiple CAD risk factors/known CAD or IHD
- > complicated valvular disease
- > peripheral vascular disease
- aura migraine
- neoplastic breast
- diabetes complicated by
- > nephropathy
- > retinopathy
- > vascular disease
- anti phospholipid syndrome in SLE
- liver
- > cirrhosis
- > hepatocellular adenoma
- SLE with anti-coagulant
6
Q
Oestrogen/progestogen formulations
A
Progestogens
- common
- > levonorgestrel (most androgenic)
- > norethisterone
- low androgen
- > desodestrel
- > etonogestrel (desogestrel metabolite)
- anti-androgen
- > cyproterone acetate
- fourth generation
- > drospirenone (anti androgen/spironolactone analogue)
- > dienogest (highly selective progestogen/anti-androgen)
Oestrogens
- ethinyloestradiol
- > synthetic derivative of 17 beta oestradiol
- oestradiol valerate
- > oestradiol combined with synthetic ester
- > more favourable haemostasis and CVD profile
7
Q
Using the OCP and nuva ring
A
Initiation
- can be started anytime during period
- > quick start = fulfil prescription immediately
- > sunday start = avoids weekend withdrawal bleeding
- need to reasonably rule out pregnancy
- starting 5 days after menses
- > breakthrough contraception more likely
- > use additional barrier method
- starting on 1st day of menses
- > greatest contraceptive effect
- pregnancy
- > avoid for first 3 weeks or longer if risk factors (VTE risk)
- > avoid while breast feeding
Regimes
- typical pill break
- > 21 active/7 inactive
- > 24/4 preferred (higher efficacy/less withdrawal)
- extended pill taking regime
- > run active pills back to back
- > safety demonstrated up to 12 months
- > most easily achieved with monophasic pills
- menstrually signalled regime
- > 4 day pill break after 4 days of spotting
Wrong doses
- missed 1 pill
- > take pill as soon as realised
- > continue taking as prescribed
- > may result in 2 pills in one day
- > no need for barrier contraception
- missed 2 pills
- > as above
- > use barrier method for one week
- missed 2 pills in first week/last week
- > consider emergency contraception if sex in past 5 days
- > skip placebo and continue on active if last week
- extra dose
- > do not skip a day
- > resume dosing as prescribed
Stopping
- continue until
- > menopause
- > development of contraindications
- return of menses
- > usually within 1 month
- return of fertility
- > immediately
Nuva ring
- starting
- > self inserted
- stopping
- > worn for 3 weeks/withdrawal bleed/7 day break
- replacement >5wks = pill for 7 days with new
- do not use barrier contraception/tampons are safe
8
Q
Systemic progestogen pharm
A
Indications
- intolerance of COCP
- contraindications for COCP
- > VTE
- > stroke/MI
- > HTN
- > thrombophilia
- > biliary disease
- breastfeeding
Contraindications
- pregnancy
- breast cancer
- liver disease
- AUB
MOA
- thicken cervical mucus/less favourable endometrium
- depot prevents ovulation
SE
- decrease HDL
- spotting/irregular menses
- weight gain (up to 2kg)
- low mood
- follicular cysts
- headache
Benefits
-protects against endometrial cancer
Drug interactions
- CYP450 inducers reduce efficacy
- > carbamazepine/phenytoin/barbituates
- > rifampin
- less interactions with depot
9
Q
Using IUDs
A
Starting
- Procedure
- > pre paracetamol/NSAIDs
- > less than 5 mins
- Copper
- > contraception within 5 days of ovulation
- Mirena
- > first week of menses/after 6 weeks post partum
- > barrier contraception for 7 days
- Contraindications
- > uterine abnormality
- > active PID
- > breast cancer for Mirena
Stopping
- fertility returns immediately
- copper
- > 10 years
- mirena
- > 5 years
Benefit
- reduced cancer by approx 1/3rd
- > cervical
- > ovarian
- Mirena reduces
- > menorrhagia
- > dysmenorrhea/endometriosis pain
- > endometrial hyperplasia
- > PID
- Copper has same periods as before
SE
- Short term
- > bleeding very common
- > pelvic pain common
- > PID in first month (rare)
- First 3 months
- > copper = menorrhagia/dysmenorrhoea/longer menses for 3 months (same as Mirena by 6 months)
- Mirena = over 50% menorrhagia/spotting (primarily in first 3 months/often resolves by 6/20% amenorrhea at 1 year)
- Long term
- > expulsion <5%
- > perforation 0.01%
- > malposition 10% (pain/irregular bleeding)
- > weight gain/acne/mastalgia
10
Q
emergency contraception
A
(Prostrinor) Levonorgestrel 1.5mg
- MOA
- > prevents ovulation
- > ineffective during/after LH surge
- Drug interactions
- > reduced by CYP450 inducers
- SE
- > safe in breast feeding
- > headaches
- > dysmenorrhoea/abnormal bleeding
- > nausea/vomitting (repeat dose if within 2hrs)
(Ella) Ulipristal acetate 30mg
- MOA
- > progesterone receptor modulator
- > prevents ovulation
- > effective before/during LH surge
- Drug interactions
- > reduced by CYP450 inducers
- > failure with progestogens within 5 days
- SE
- > safety unknown in breast feeding
- > headaches
- > dysmenorrhoea/abnormal bleeding
- > nausea/vomitting (repeat dose if within 3hrs)
Copper IUD
- MOA
- > cytotoxic/sperm motility/unfavourable endometrium
- > effective 5 days after ovulation
Comparison
- Failure at 5 days
- > levonorgestrel = 2% (high in obese)
- > ulipristal acetate = 1.5% (not as affected by weight)
- > copper IUD = 0.1% (not affected by weight)
- Access
- > levonorgestrel = no prescription/cheapest
- > ulipristal = need prescription ($50)
- > IUD = prescription plus insertion ($100)
- Timing
- > levonorgestrel = licensed for within 3 days
- > IUD/ulipristal = licensed for within 5 days
11
Q
Contraceptive efficacy
A
> 99%
- IUDs
- implant
- vastectomy/tubal ligation
> 91%
- depot
- nuva ring
- COCP
- mini pill
> 80%
- diaphragm
- condom
- female condom
> 75%
- withdrawal
- fertility based awareness
12
Q
Mini pill overview
A
Mini Pill -1/3rd to 1/5th OCP level progestogen ->levonorgestrel 30mcg (Microlut PBS) ->norethisterone 350mcg (Micronor not PBS) dosing ->maximal effect in 3 hrs/relatively ineffective by 21hrs ->take at same time (3hrs) every day/3 hrs before sex -starting pill ->must start on first day of menses/later = 48hrs condoms ->taken continuously/no pill free break -missed or delayed pill ->48hrs of condoms -stopping ->fertility returns immediately -amenorrhoea ->10%
13
Q
Implanon
A
Implant
- etonogestrel
- > 68mg subdermally (40x2mm plastic rod)
- > releases 60mcg/day down to 30mcg/day
- dosing
- > 3 years
- starting
- > immediate contraceptive effect
- > local anaesthesia and applicator
- stoping
- > local anaesthesia, scalpel, forceps
- > fertility returns immediately
- amenorrhoea
- > 20%
- disadvantage
- > irregular bleeding
14
Q
Depot
A
Depot
- 150mg medroxyprogesterone IM
- > cervical mucus
- > suppresses ovulation
- dosing
- > 3 months
- starting
- > first 7 days = no barrier contraception
- > any other time = barrier for 24 hrs
- > can be started while breastfeeding <6wks PP
- stopping
- > fertility returns by 10 months in 50%
- > can take up to 18 months for fertility to return
- amenorrhoea
- > 50%
- disadvantages
- > irregular bleeding
- > weight gain
- > irreversible
15
Q
Combined HRT
A
Cyclical
- Regime (progestogen for 21 days on, 7 days off)
- > combined preparation
- > oestrogen + progestogen (seperate pills PBS listed)
- Indication
- > spontaneous menses
- > amenorrhoea <18mnths
- Oral
- > NATURAL PROGESTERONE prometrium (reduced breast cancer maybe, probably doesn’t reduce benefit of estrogen alone therapy on CVD risk)
- > oestradiol 1-2mg + norethisterone 1mg (Trisequens not PBS)
- > oestradiol valerate 1-2mg (Progynova PBS) + medroxyprogesterone 2.5-10mg (Provera PBS)
- Patch
- > oestradiol 50mcg + norethisterone 140mcg (Estalis PBS)
Continuous
- Regimes
- > combined oral preparation
- > oestrogen + progestogen oral (seperate pills PBS listed)
- > combined patch
- > oestrogen (oral/transdermal) + Mirena
- Indication
- > after 18mths amenorrhoea
- Oral
- > conjugated oestrogen 0.625mg + medroxyprogesterone 2.5-mg (Premia not PBS)
- > oestradiol valerate 1-2mg (Progynova PBS) + medroxyprogesterone acetate 2.5-10mg (Provera PBS)
- Patch
- > oestradiol 50mcg + norethisterone 140mcg (Estalis PBS)
