women's health Flashcards
ethinyl estradiol - MOA
- estrogen receptor agonist
- stabilise endometrial lining -> inhibit FSH from anterior pituitary -> suppress development of ovarian follicle -> make endometrium unsuitable for implantation of ovum -> reduce pregnancy
- cycle control
ethinyl estradiol - PK
1) absorption
- well absorbed orally (OD)
- onset 30-60 mins
- IV, IM, topical
2) distribution
- highly protein bound
3) metabolism
- by liver
** phase I: CYP3A4 hydroxylation
** phase IIL conjugation w glucuronide & sulfation -> hormonally inert ethinylestradiol glucuornide & ethinylestradiol sulfate (enterohepatic circulation)
4) elimination: faeces & urine
ethinyl estradiol - AE
1) breast tenderness
2) headache
3) fluid retention (bloating)
4) N, dizziness, weight gain
5) VTE
6) MI, stroke
7) liver damage
ethinyl estradiol - CI
1) history/susceptibility to arterial/venous thrombosis
2) advanced diabetes w vascular disease
3) HTN ≥ 160/100
4) avoid in breastfeeding (< 21 days postpartum) & breast cancer in women
norethindrone (progestin) - types
drosperinone (4th gen)
- diuretic, anti-androgenic, anti-mineralocorticoid
- can cause hyperkelaemia, thromboembolism, bone loss
norethindrone (progestin) - MOA
- progestin receptor agonist
- thicken cervical mucous -> prevent sperm penetration
- slow tubal motility -> delay sperm support
- induce endometrial atrophy
- inhibit LH release = prevent ovulation = make endometrium unsuitable for implantation of ovum
norethindrone (progestin) - PK
1) absorption
- well absorbed orally (OD)
2) distribution
- highly protein bound
3) metabolism
- liver
- reduction -> glucuronidation & sulfation
- some into ethinylestradiol
4) Excretion
- pee & shit
norethindrone (progestin) - AE
headache, dizziness, bloating, weight gain, unpredictable spotting & bleeding, amenorrhea, androgenic (Acne, oily skin, hirsutism)
norethindrone (progestin) - additional info
- ovulation suppression up to 1.5 yrs so X good if planning pregnancy
- potential ethinylestradiol AE
definition of HTN in pregnancy
- > 1 measurement at least 4 hrs apart of SBP > 140 DP > 90
- severe: 2 measurement of SBP > 160 +/- DBP > 110
categories of pregnancy HTN
1) < 20 wks gestation
2) ≥ 20 wks gestation
< 20 wks gestation for pregnancy HTN - chronic HTN
- pre-existing HTN or new onset of HTN before 20 wks gestation
- X proteinuria
< 20 wks gestation for pregnancy HTN - chronic HTN w superimposed preclampsia
new onset proteinuria
≥ 20 wks gestation for pregnancy HTN - gestational HTN
1) new onset HTN
2) X proteinuria
≥ 20 wks gestation for pregnancy HTN - preeclampsia - definition
- new onset HTN
- any new onset of
1) proteinuria
2) signs of end-organ dysfunction
3) uteroplacental dysfunction
** fetal growth restriction (IUGR)
** abnormal umbilical artery dopplers
** stillbirth/fetal demise
≥ 20 wks gestation for pregnancy HTN - preeclampsia - progression into eclampsia
- new onset of tonic-clonic, focal or multifocal seizure superimposed on preeclampsia
- complications
1) maternal: placental abruption, intracranial haemorrhage, DIVS, acute renal failure, neurologic sequlae, pulmonary odema, aspiration pneumonia, cardiopulmonary arrest
2) Fetal/neofetal: fetal bradycardia, preterm birth, fetal/neonatal death, perinatal depression/asphyxia
≥ 20 wks gestation for pregnancy HTN - preeclampsia - prevention of eclampsia
low dose aspirin
- recommend for high risk pt
** HTN on previous pregnancy, multifetal gestation (twins/>), autoimmune disease, DM, CKD - MOA: improve uroplacental blood flow by inhibiting thromboxane A2 -> reduce thromboxane-prostacyclin imbalance
- dose: 100mg or more daily
- regimen: after 12 wks, ideally before 16 wks, until delivery
monitoring parameters for pregnancy HTN
1) proteinuria
- UTP > 300mg
- dipstick > 2+
- uPCR > 0.3 mg/dL
2) signs of end organ damage
- platelet count < 100
- LFT > 2x ULN
- double SCr but absence renal disease
- pulmonary oedema
- neuropsych probs
3) albumin-creatinine ratio (ACR)
- > 8 mg/mmol
- alternative to uPCR for women w chronic HTN
drug choice for pregnant HTN
1) methyldopa
- low potency, increased AE
- safety in pregnancy
2) labetalol
- monitor bronchoconstrictive effect, bradycardia
3) nifedipine ER
- monitor pedal odema, flushing, headache
4) hydrochlorothiazide
- 2nd/3rd line
- potential interference w normal blood volume expansion w pregnancy
5) hydralazine
- AE mimic severe preeclampsia & imminent preeclampsia
- N/V, palpitation, flushing, headache, tremor
aims of treatment for pregnancy HTN
BP < 140/90
types of barrier technique categories
1) condom
2) diaphragm w spermicide & cervical cap
types of condoms
1) External (male)
- CI: rubber/latex allergy
- advantage: STI protection
- disadvantage: high user failure rate, possible breakage
2) internal (Female)
- absolute CI: allergy to polyurethane, history of TSS
- advantage: inserted earlier, STI protection
- disadvantage: very high user failure rate, dislike ring hanging outside vagina
diaphragm w spermicide & cervical cap
- absolute CI: allergy to latex/rubber, recurrent UTI, history of TSS, abnormal gynecologic anatomy
- advantage: low cost, reusable
- disadvantage: high user failure rate, low protection against STI, increased risk for UTI, cervical irritation
combined oral contraceptives (COC) - components
1) progestin
2) estrogen
- ethinyl estradiol (EE)
- high dose ≥ 50 microgram
- moderate/standard dose 30-35 microgram
- low dose 15-20 microgram
- lower dose indication: young, underweight (< 50), age > 35, peri-menopausal, fewer side effect
- higher dose indication: obesity, early-mid cycle breakthrough bleeding/spotting, tendency to be non adherent
types of COC
1) monophasic
- same estrogen progestin every pill
- advantages: less confusing, less complicated instructions
2) multiphasic
- variable estrogen & progestin
- advantages: lower progestin = lower SE
3) conventional
- old: 21 days active + 7 days placebo = 28 days
- new: 24 days active + 4 days placebo = 28 days
** 3 additional active pill to shorten pill free interval -> reduce hormonal fluctuation -> lower SE
4) extended cycle/continuous COC
- 84 days -> 7 days placebo
- continuous X placebo
- advantages: convenient, lesser periods
initiation of COC
1) first day method
- start on first day of menstrual cycle
- no backup contraceptive required on first day
2) sunday start
- first sunday after menstrual cycle begin
- backup contraceptive for at least 7 days
- provide weekends free of menstrual period
3) quick start
- start now
- require backup contraceptive for at least 7 days & potentially till next menstrual cycle begin
factors affecting COC selection
1) hormonal content required
2) convenience
3) adherence level
4) tendency for oily skin, acne, hirsutism
5) medical condition: premenstrual syndrome, dysmenorrhoea
benefit of extra contraceptive
1) relief menstrual related problems
2) improve menstrual regularity
3) better for acne
4) premenstural dysphoric disorder
5) iron-deficient aneamia
6) PCOS
7) reduced risk from ovarian & endometrial cancer
8) reduced risk of ovarian cyst, ectopic pregnancy, pelvic inflam disease, endoemtriosis, uterine fibroids, benign breast disease
precautions for hormonal contraceptive - conditions
1) breast cancer
2) VTE
3) ischaemic stroke/MI
precautions for hormonal contraceptive- breast cancer
- healthy & young: benefit > risk
- age > 40: avoid
- fam history/risk factor: avoid
- current/recent Hx of breast cancer within past 5 yr: stop
precaution for hormonal contraceptive- VTE
- estrogen enter liver = increase hepatic production of clotting factors
- new generation progestin increase protein C resistance & higher risk of clots
- risk factors: > 35 yo, obesity, smoker, immobilisation, cancer, hereditary thrombophilia
- consider low dose estrogen w older progestin, progestin only contraceptive, barrier method
contraindication for hormonal contraceptive
1) current/history breast cancer past 5 yrs
2) DVT/PE (and anticoagulant)
3) major surgery w prolonged immobilisation
4) < 21 days postpartum w other risk factor
5) < 6 wk postpartum if breastfeeding
6) thrombogenic mutation
7) SLE + unknown APLA
8) migrane w aura
9) SBP > 160, DP > 100
10) HTN w vascular disease
11) current/history of ischaemia heart disease
12) cardiomyopathy
13) smoking ≥ 15 sticks/day + age ≥ 35 yo
14) history of cerebrovascular disease
15) DM > 20 yrs or w complications
adverse effects of hormonal contraceptive- general
- occur with early use, improve 3-4th cycle after adjusting to hormone levels
- need counselling
adverse effect of hormonal contraceptive- conditions
1) breakthrough bleeding
- early/mid cycle: increase estrogen
- late cycle: increase progestin
2) acne
- change to less androgenic progestin
- consider increase estrogen
- if on Progesterone only pills (POP) then change to COC
3) bloating
- reduce estrogen
- change to progestin w mild diuretic effect (drosperinone)
4) N/V
- reduce estrogen
- take pills at night/change to POP
5) headache
- if occur in pill-free wk then switch to extended cycle/continuous/shorter pill interval
6) menstrual cramp
- increase progestin/switch to extended cycle/continuous
7) breast tenderness/weight gain
- keep both estrogen/progestin as low as possible
DDI for hormonal contraceptive
1) rifampicin
- Abx alter gut flora -> alter metabolism -> less active drug
- additional contraception until rifampicin stop for at least 7 days
2) anticonvulsant
- reduce free serum concentration
- phenytoin, carbamazepine, barbiturate, topiramate, oxcarbazepine, lamotrigine
3) HIV ART
- reduce effectiveness
counselling for missed doses of hormonal therapy
1) miss 1 dose < 48 hrs
- take missed dose immediately, continue the rest as per usual
- maybe 2 pills per day
- X need additional contraceptive
2) miss 2/> dose > 48 hrs
- take last missed dose immediately, discard missed doses
- continue rest as per normal (maybe 2 pills/day)
- backup contraceptive 1 wk
3) missed during last wk of hormonal tablet (day 15-21)
- finish remaining active pills in current stack
- skip hormone free interval, start new pack next day
- backup contraceptive at least 7 days
progesterone only pill (POP) - indication
breast feeding, intolerant to estrogen, condition that preclude estrogen
progesterone only pill (POP) - types
1) norethindrone
2) levonorgestrel: 28 active pills (continuous)
3) drospirenone: 24 active, 4 inactive
progesterone only pill (POP) - regimen
1) within 5 days of menstrual cycle/bleeding: X back up
2) any other day: back up for 2 days(drosperinone 7 days)
progesterone only pill (POP) - missed doses
- N/L: late by > 3 dose then take exra & continue, backup 2 days
- D: < 24 h take extra & continue, ≥ 2 active pills missed: backup for 7 days
transdermal contraceptive
- estrogen + progestin
- X effective if > 90kg
- once weekly for 3 wks + 1 patch free wk
- tissue irritation
vaginal ring
- estrogen + progestin
- use 3 wks then discard
- tissue irritation, risk of expulsion
progestin injection
- IM injection every 12 wks
- good for adherence
- delayed return to fertility
- variable breakthrough bleeding esp within first 9 months (amenorrheic)
- weight gain, short term bone loss = reduced bone mineral desnity
long acting reversible contraception (LARC)
- hormonal + non hormonal that includes IUD
- very effective
- reversible upon removal
intrauterine device (IUD) - MOA
inhibit sperm migration, damage ovum, damage/disrupt transport of fertilised ovum
intrauterine device (IUD) - precautions
X use if
- pregnant
- current STI
- undiagnosed vaginal bleeding
- malignancy of genital tract
- uterine anomalies
- uterine fibroids
intrauterine device (IUD) - types
1) levonorgestrel IUD
- reduce menstrual flow
- ideal if concomitant menorrhagia
- 5 yrs
2) copper IUD
- heavier bleeding
- ideal if concomitant amenorrhea
- 10 yrs
amenorrhoea definition
X menstrual bleeding in 90 day period
amenorrhoea - categories
1) primary/functional
- X menses by age 15 in females who never menstruated
- rare
2) secondary
- absence for 3 cycles in previously menstruating
- more freq in < 25 yo w past history, competitive athlete, massive weight loss
amenorrhoea - aetiology
1) anatomical
- pregnancy, uterine structural abnormalities, X shedding of endometrial lining
2) X ovulation = X proper sequence of estrogen production -> progesterone production -> estrogen/progesterone withdrawal
- endocrine disturbances = chronic anovulation
- ovarian insufficiency/failure
- affect GnRH, FSH, LH (low body fat, weight loss)
amenorrhoea - treatment
non pharmaco
- weight gain, reduce exercise intensity, stress management
pharmaco
- COC
menorrhagia - definition
- menstrual blood loss > 80ml per cycle
- bleed > 7 days per cycle
- basically heavy flow
menorrhagia - pathophysiology
1) uterine related factors
- fibroids
- adenomyosis
- endometrial polpys
- gynaecologic cancer
- alteration in HPO axis
2) coagulopathy factor
- cirrhosis
- Von willebrand disease
- idiopathy thrombocytopenic purpura
menorrhagia - treatment
non pharmaco: endometrial ablation to hysterectomy
pharmaco
- want contraceptive: COC
- X contraceptive: NSAID, tranexamic acid (help clot), cyclic progesterone
dysmenorrhea - definition
crampy pelvic pain w/just before menses
dysmenorrhea - categories
1) primary
- X find cause
- release prostaglandin & leukotriene -> vasoconstriction -> cramp
2) secondary
- underlying anatomic/physiologic cause
- endometriosis
dysmenorrhea - treatment
1) nonpharmaco
- topical heat therapy
- exercise
- acupuncture
- low fat vegetarian diet
2) pharmaco
- 1st line: NSAID
- 2nd line: COC
- 3rd line: progestin injection/progestin IUD
premenstrual syndrome (PMS) - symptoms
1) somatic/physical
- bloating, headache, weight gain, fatigue, dizziness, nausea, appetite change
2) affective/mood
- anxiety, depression, angry outburst, social withdrawal, forgetfulness, tearful, restlessness
premenstrual syndrome (PMS) - premenstrual dysphoric disorder (PMDD)
severe mood symptoms, psychiatric disorder
premenstrual syndrome (PMS) - pharmacological therapy
SSRIs, COC for physical
premenstrual syndrome (PMS) - non pharmaco
increase exercise, vitamins, reduce caffeine & refined sugar & sodium
polycystic ovary syndrome (PCOS) - presentation
1) menstrual irregularities
2) androgen excess
- acne, hirsutism, obesity
- metabolic disorder/insulin resistance
PCOS treatment
1) COC
2) metformin
menopause definition
permanent cessation of menses following loss of ovarian follicular activity
menopause aetiology
1) natural
- occur in stages: perimenopause, menopause, postmenopause
2) induced
- any time before natural menopause w removal of both ovaries/iatrogenic ablation of ovarian function
categories of menopause symptoms
1) vasomotor symptoms (VMS): hot flush/night sweat
2) genitourinary syndrome of menopause (GSM)
3) psychological/cognitive
4) bone fragility
5) others
menopause symptoms - vasomotor sypmtoms
- hypothalamus level estrogen withdrawal -> thermoregulation dysfunction
1) intense feeling of heat on face
2) rapid/irregular HR
3) flushing/redden face
4) perspiration
5) cold sweat
6) Sleep disturbances
7) feeling of anxiety
menopause symptoms - genitourinary syndrome
- cause: decreased estrogen -> changes to anatomy
- symptoms
1) genital dryness
2) burning, irritation, pain
3) Sexual symptoms of lubrication difficulty
4) impaired sexual function/libido/painful intercourse
5) urinary urgency
6) dysuria
7) recurrent UTI
menopause symptoms - psychological/cognitive
- cause: stress + hormonal fluctuation
- symptoms
1) depression/anxiety
2) poor concentration/memory
3) mood swing
menopause symptoms - bone fragility
- decreased oestrogen = more bone loss
- increase risk of osteoporosis & fracture
- increase joint pain
menopause symptoms - others
hair loss, breast pain, digestive problem, frequent urination, urinary pain, brittle nails, fatigue, dizziness, weight gain, memory lapses
menopause nonpharmaco - vasomotor
- layered clothing that can be removed/added when necessary
- lower room temp
- less spicy/caffeine/hot drinks
- more exercise
- dietary supplements (isoflavones, black cohosh)
menopause nonpharmaco - vulvovaginal
nonhormonal vaginal lubricant/moisturiser
indications for monopausal hormonal therapy (MHT)
- moderate/severe symptoms
- insufficient response to non pharmaco
- treat symptoms affecting QoL
Types of MHT - categories
1) estrogen only
2) estrogen + progestin
MHT - estrogen - dosage forms (list)
1) oral
2) systemic topical
3) local vaginal
MHT - estrogen - oral dosage form
- start new pack once old finish
- advantages: cheap
- disadvantages
1) dose dependent SE
2) potential for missed dose = irregular bleeding
MHT - estrogen - systemic topical - formulations
1) patches
- replaced twice a wk
- site rotation to prevent irritation (lower back -> abdomen -> butt)
2) Gel
- packaging has ruler to measure dose
- site rotate: arm/thigh daily
MHT - estrogen - systemic topical - advantages & disadvantages
1) Advantages
- lower systemic dose
- convenient
- continuous release
2) disadvantage
- more expensive
- skin irritation
- gel more variability in absorption
MHT - estrogen - local vaginal - general
- pessary, cream
- inserted twice/wk
- insert tablet before bedtime to reduce movement
MHT - estrogen - local vaginal - advantage & disadvantage
1) Advantage
- lowest estrogen dose
- continuous release
2) disadvantage
- inconvenient/uncomfortable
- vaginal discharge
- only for localised urogenital atrophy (X systemic absorption)
MHT - estrogen + progestin - requirement
intact uterus
MHT - estrogen + progestin - types of regimen
1) continuous cyclic
- progestin added on either 1st or 15th of month for 10-14 days
- withdrawal bleeding when progestin stopped
- regulate menses = more regular bleeding
2) continuous combined
- both daily
- X withdrawal bleeding
- chance of amenorrhoea
MHT - estrogen + progestin - role of progestin
1) Reduce risk of endometrial cancer
2) maybe improve VMS
MHT vs COC
1) physiologic goal
- MHT: replace/supplement endogenous estrogen to relieve S&s of lower estrogen production
- COC: suppress HPO axis to avoid ovulation
2) amt of ethinylestradiol equivalent
- MHT: 10-15 mcg
- COC: 20-50 mcg
MHT precaution/CI
1) breast cancer
2) VTE
- surgery, cardiovascular disease, uncontrolled BP, stroke, heavy smoking, endometrial cancer
MHT monitoring
1) Annual mammogram (breast cancer)
2) endometrial surveillance
- unopposed estrogen: vaginal bleeding
- continuous cyclic: bleeding occur when progestin on
- continuous combine: bleeding prolonged, heavier than normal, frequent, persist > 10 month after treatment start
other pharmaco therapy for VMS
1) antidepressant
- SNIR: venlafaxine
- SSRIs: paroxetine
2) gabapentin
- night sweat, sleep disturbances
other pharmaco therapy for PMS
tubolone
- improve mood, libido, menopause symptom, vaginal atrophy
- protect against bone loss
- indication: postmenopausal ≥ 12 months since last natural period
- EXPENSIVE
