Hormonal health (contraception, menstrual cycle, menopause) Flashcards
Types of contraception
- Inhibiting viable sperm from coming into contact with a mature ovum *BARRIER / PREVENT OVULATION
- Preventing fertilised ovum from successfully implanting in the endometrium * creating UNFAVOURABLE uterine environment
Types of barrier techniques in contraception
- Condoms
- CI: allergy to latex/ rubber
- additional STI protection
*HIGH user FAILURE rate, poor acceptance, possibility of breakage - Condems, internal (female)
- CI: allergy to polyurethane, history of Toxic Shock Syndrome (TSS)
- can be inserted ahead of time + STI protection if used correctly
*VERY HIGH user failure rate, ring hanging outside vagina - Diaphragm with spermicide // Cervical cap
- CI: allergy to latex, rubber or spermicide; RECURRENT UTIs; abnormal gynaecologic anatomy
- low cost, reusable
*HIGH user failure rate, LOW protection against STIs, INCREASED risk of UTI, cervical IRRITATION
Composition of combined oral contraceptives (& its effects)
- Progestins
- thickens cervical mucus -> prevent sperm penetration, slow tubal motility (Delay sperm transport), induce endometrial atrophy
- blocks LH surge; (+ estrogen) prevent ovulation
- provides MOST contraceptive effect
eg. different gens, VARY in progestional activity & inherent androgenic effects (*androgen-to-progesterone activity ratio)
**androgenic SE: acne, oily skin, hirutism - Estrogen
- suppresses FSH release; (+ progestin) PREVENT ovulation
- STABILISES endometrial lining, provide cycle control
eg. ethinyl estradiol (EE) *most common // estradiol valerate // esterol // mestranol
- Doses: HIGH dose >/=50ug, Moderate dose/standard dose 30-35ug, LOW dose 15-20ug
Considerations in selecting dose of estrogen
High doses of EE associated with VASCULAR, EMBOLIC events, CANCERS, significant A/E
Factors favouring LOWER doses of EE (20-25ug)
- Adolescence
- Underweight (<50kg)
- Age >35y/o
- Peri-menopausal
- Fewer S/E
Factors favouring HIGHER doses of EE (30-35mcg)
- Obesity/ >70.5kg
- Early to mid cycle breakthrough bleeding/ spotting
- Tendency for non-adherence
Considerations for progestogenic component (in COC)
4 gens, less androgenic effects in newer gens
eg.
Drospirenone (4th gen):
- Analogue of spironolactone
- Anti-mineralocorticoid, some anti-androgenic action (~30% of cyproterone)
- LESS water retention, LESS acne
*CAN CAUSE hyperkalemia, thromboembolism & bone loss
Cyproterone (4th gen):
*estelle-35/ diane-35 (cypro 2mg, EE 35mcg)
- anti-androgenic, antigonadotrophic
- Primary indication: treat EXCESSIVE-ANDROGEN related conditions (Severe acne, hirutism); SHOULD NOT BE USED SOLELY FOR CONTRACEPTION
**HIGH RISK OF THROMBOEMBOLISM
Types of COC (pill-based & cycle-based)
Pill aspect:
1. Monophasic COC: same amounts of estrogen & progestin in every pill
- less confusing, less complicated missed-dose instructions
- Multiphasic COC: variable amounts of estrogen & progestin
- mimics normal body hormonal levels throughout cycle; tend to have LOWER progestin overall -> LESSER S/E
Cycle:
1) Conventional cycle COC
* traditional: 21d active + 7d placebo = 28d
- NEWER formulations: 24d active + 4d placebo = 28d -> shortened pill-free interval -> potentially reduce hormone fluctuations between cycles -> LESSER SE
2) Extended-cycle/ continuous COC
- 84d followed by 7d placebo *CONTINUOUS: NO PLACEBO
-> convenient, LESS periods
Ways of initiating COC
- 1st-day method: start on 1st day of menstrual cycle
-> No backup contraceptive required - Sunday start: start on 1st Sunday AFTER menstrual cycle begins
-> REQUIRES BACKUP CONTRACEPTIVE for at least 7d
-> May provide WEEKENDS FREE of menstrual periods - Quick start: START NOW
-> require backup contraceptives for at least 7d and potentially UNTIL NEXT menstrual cycle begins
Factors in selecting a COC
- Hormonal content required
- Convenience
- Adherence
- Tendency for oily skin, acne, hirutism
- Medical conditions eg. premenstrual syndrome, dysmenorrhea (crampy menstrual pain)
Benefits of contraception
- relief from menstrual related problems
- improvement in menstrual regularity
- better for acne
- premenstrual dysphoric disorder
- iron-deficient anemia
- PCOS
- reduced risk of ovarian & endometrial cancers
- Reduced risk of ovarian cysts, ectopic pregnancy, pelvic inflammatory diseases, endometriosis, uterine fibroids, benign breast disease
Risks/ CI in COC use
- BREAST CANCER
- Absolute CI for history (within 5yrs)/ existing pts -> STOP
- risk increases with duration & age >40 (but returns to same levels as those who never used COC after discontinuation) -> AVOID if >40
- if healthy & young, benefits of pregnancy prevention > risk
- Family history/ risk factors of breast cancer -> AVOID - Venous Thromboembolism (VTE)
*ESTROGEN increases hepatic production of factor VII, X, & fibrinogen of coagulation cascade (increased clotting factors)
**NEW GEN PROGESTINS (drosperinone, cyproterone, desogestrel) -> unknown MOA, possibly increase protein C resistance
*Rate of VTE
- non-pregnant women: 4-5 per 10,000
- COC pill users: 9-10 in 10,000
- Normal pregnancy: ~30 in 10,000
Risk factors: >35 yo, Obesity, Smoker, Immobilisation, Cancer, Hereditary thrombophilia
**REDUCE RISK: LOW DOSE estrogen with OLDER progestins // PROGESTIN-only contraceptive // BARRIER methods - Ischemic stroke/ Myocardial infarction
*more associated with ESTROGEN than progestins; SYNERGISTIC with other risk factors: age, HTN, MIGRANE HEADACHE W AURA, obesity, dyslipidemia, smoking, prothrombotic mutations
** absolute CI in ALL COC: MIGRANE W AURA
Rest: risk factors to consider LOW DOSE estrogen/ progestin-only /barrier
ABSOLUTE CONTRAINDICATIONS
- Current/ recent history (<5y) BREAST CANCER
- History/ acute/ current (+ on anticoagulant therapy) DVT/PE pts
- major surgery with PROLONGED immobilisastion
- <21d postpartum WITH OTHER RISK FACTORS - <6 weeks postpartum IF BREASTFEEDING (thrombophilic factors remain elevated)
- Thrombogenic mutations
- SLE with +ve OR unknown APLA
- Migrane with aura
- SBP > 160mmHg OR DBP >100 mmHg
- HTN with VASCULAR disease
- current/history of ischemia heart disease
- Cardiomyopathy
- Smoking >/=15 sticks/ day AND age >/=35 y/o
- History of cerebrovascular disease
- Diabetes > 20years OR with complications
common adverse effects of COC + management
Breakthrough bleeding
- if early/mid cycle -> increase estrogen
- if late cycle -> increase progestin
Acne: change to less androgenic progestin; can consider to increase estrogen
- if on POP -> change to COC
Bloating *Estrogen: reduce estrogen
- take pills at night/ change to POP
Headache *EXCLUDE MIGRANE W AURA
- Usually occurs in pill-free week -> switch to extended cycle/continuous/ shorter pill-free interval
Menstrual cramps: increase progestin/ switch to extended cycle/ continuous
Breast tenderness/ weight gain: keep BOTH estrogen & progestin AS LOW AS POSSIBLE
**S/E tends to occur during EARLY COC use; may improve by 3rd-4th cycle AFTER adjusting to hormone levels
-> Counsel to persevere COC for 2-3 months BEFORE changing product UNLESS serious A/E
DDI of COCs
- Rifampin
*theoretical interaction with abx (altered gut flora -> metabolism altered -> less active drug); rifampin w SIGNIFICANT interaction
-> use ADDITIONAL contraception until rifampin DISCONTINUED for AT LEAST 7d - Anticonvulsants
*reduces free serum conc of BOTH estrogen & progestins
eg. phenytoin, carbamazepine, barbiturates, topiramate, oxacarbazepine, lamotrigine - HIV antiretrovirals
*reduces effectiveness of BOTH COC & antiretrovirals
- protease inhibitor: ritonavir, darunavir
IN GENERAL: lower dose of hormone in COC -> GREATER risk of interaction compromising efficacy
Missed dose procedure for COC
- If one dose missed (<48h)
- take missed dose IMMEDIATELY, continue rest as usual (2 pills on same day)
- no additional contraceptive methods required - if 2 or more consecutive doses missed (>48h)
- take missed dose IMMEDIATELY , discard the rest of missed doses
- Continue the rest as usual (may have 2 pills on the same day)
- BACKUP CONTRACEPTIVE required for AT LEAST 1 week
**IF PILLS MISSED during LAST WEEK of hormonal tablets (Eg. day 15-21):
- Finish remaining active pills in current pack
- SKIP hormone-free interval; start new pack NEXT DAY
- BACKUP contraceptive for at least 7d
Use of Progesterone Only Pill (POP), initiation & missed doses
*typical-use failure: 7% (~ COC)
GOOD FOR: breast feeding, intolerant to estrogen (eg. N/V), conditions that preclude estrogen
ONLY TRUE CI is current/recent history of BREAST CANCER
eg. Norethindrone, levonorgestrel - 28 active pills (continuous) // Drospirenone - 24 active, 4 inactive pills
Initiation:
- Within 5d of menstrual cycle/bleeding (no backup required)
- Any other day (BACKUP CONTRACEPTIVE for 2d; 7d for drospirenone)
Missed doses:
- N/L: if late >3h -> take extra & continue the rest as usual; BACKUP contraceptive for 2d
- Drospirenone: if LATE <24h, take extra and continue; if >/=2 active pills missed, BACKUP needed for 7d
Other options for contraception (apart from barrier & oral contraceptives)
- Transdermal contraceptives
- Both estrogen & progestin component
- Typical use failure rate 7% ~COC
- Not as effective in pts weighing >90kg
**applied 1x weekly for 3 weeks, followed by 1 patch-free week
- MOA: similar to COCs
- SE: similar to COC + application side reactions - Vaginal rings
- Both estrogen & progestin component
- Typical use failure rate 7% ~COC
- used for 3 weeks then discarded
*precise placement NOT NEEDED; hormones are ABSORBED (unlike diaphragms/ cervical caps)
- SE: similar to COC + tissue irritation + risk of expulsion
**transdermal patch/ ring: CONTINUOUS, HIGHER exposure to estrogen -> INCREASED RISK of VTE
- Progestin injections [Depo-Provera: depot medroxyprogesterone acetate, DMPA]
- IM injection q12 weeks
- good for adherence issues BUT need regular doctor visit
- typical use failure rate 4% <COC
- WILL HAVE variable breakthrough bleeding esp 1st 9months (more frequent SE) -> 50% become amenorrheic after 12months, 70% after 2 years
- SE: weight gain (more than other types of contraceptives), short term term bone loss -> DECREASED BONE MINERAL DENSITY (BMD) *black box warning (but no clear data to show actual fracture risk)
**AVOID in OLDER WOMEN, OSTEOPOROSIS RISK FACTORS (eg. long term steroids); if >2years usage, evaluate other options - Long acting reversible Contraception (LARC): intrauterine devices (IUD), implants (can be hormonal/ non-hormonal)
- HIGHLY effective; typical-use rates ~ perfect-use rates ~ <1%
- effects QUICKLY REVERSIBLE upon removal
*not commonly used -> invasiveness
-> IUD: inhibits sperms migration, damages ovum, damages/disrupts transport of fertilised ovum *if + progestin: endometrial suppression, thickens mucus
*SHOULD NOT BE INSERTED IF: pregnant, current STI, undiagnosed vaginal bleeding, malignancy of genital tract, uterine anomalies, uterine fibroids
**GENITAL RISK: uterine perforation, expulsion, pelvin infection
1) Levonorgestrel IUD (progestin)
- decreases menstrual flow, typically causes spotting, amenorrhea -> IDEAL if concomitant menorrhagia
- effective UP TO 5 years
2) Copper IUD
- causes HEAVIER menses/ bleeding (as compared to levonorgestrel) -> IDEAL if concomitant amenorrhea
- effective UP TO 10 years
- can be used as emergency contraception
-> Subdermal progestin implants: single 4cm long implant, contains 68mg of etonogestrel
- lasts for 3 years
- causes irregular bleeding patterns WITH CONTINUED USE: amenorrhea (22%), prolonged bleeding (18%), spotting (34%), frequent bleeding (7%)
