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%)
Types of emergency contraception, MOA + how to use them
- Copper IUD (>99% effectiveness)
- insert within 5 days
- MOA: inhibits sperm migration, damages ovum, damage/disrupts transport of fertilised ovum - Ella tablet (ulipristal 30mg) (60-80% effectiveness)
*DO NOT GIVE IF PT ON PROGESTIN-containing within 5days, + DO NOT TAKE PROGESTIN 5d AFTER
- take 1 tablet ASAP, within 120 hours (5 days)
- MOA: progestin receptor modulator: slows release of GnRH inhibiting ovultion, thins uterine lining, directly inhibits follicular rupture - Postinor 2 tablet (levonorgestrel 0.75mg) (effectiveness less than ulipristal)
*less effective in morbidly obese patients
- take 2 tablets ASAP, preferably within 12h BUT NO LATER THAN 72H
- MOA: progestin: slows release of GnRH inhibiting ovulation, thins uterine lining (?)
*ALL require prescription in SG
**NAUSEA COMMON S/E with oral options: if pt vomits within 3h of taking tablets, REDOSE
impact of menstrual cycle disorders
-ve impact on individual’s QoL, reproductive health & long-term detrimental health effects
- AMENORRHEA: INCREASED risk of osteoporosis
- PCOS: increased risk of diabetes
Overview of amenorrhea + management
Definition: absence of menstrual bleeding in a 90day period
Types:
Primary: absence of menses by age 15 in females who NEVER menstruated *rare, <0.1% of population
Secondary: absence for 3 cycles in a PREVIOUSLY menstruating female *3-4% of population;
- occurs more frequently in:
<25 yo with history of menstrual irregularities
Competitive athletes
Massive weight loss
Etiology (broad categories)
1. Anatomical causes eg. pregnancy, uterine structural abnormalities
2. Endocrine disturbances -> chronic anovulation
3. Ovarian insufficiency/ failure
Treatment:
- Identify underlying cause
- Nonpharmacological: weight gain, reduce exercise intensity, stress management
- Pharmacological: COC/ Estrogen only/ Progestin only/ Copper IUD etc.
Overview of Menorrhagia + treatment
Definition: HEAVY menses bleeding
- Menstrual blood loss >80ml per cycle OR bleeding >7d per cycle
Possible pathophysiology:
Uterine-related factors:
- fibroids
- adenomyosis
- endometrial polyps
- gynecologic cancers
- alterations in hypothalamic-pituitary-ovarian (HPO) axis (EXCESSIVE GnRH/FSH/LH)
Coagulopathy factors: *PLATELETS AFFECTED
- Cirrhosis
- von Willebrand disease
- idiopathic thrombocytopenic purpura
Treatment (pharmacological):
*contraception desired: COC/ Progestin IUD/ Progestin only oral contraceptive/ Projestin injection
*Contraception NOT desired: NSAIDs/ Tranexamic acid (slows down breakdown of blood clots) during menses/ Cyclic progesterone
Non-pharmacological: endometrial ablation to hysterectomy (whole uterus removed)
Dysmenorrhea overview + treatment
Definition: crampy pelvic pain WITH or JUST BEFORE menses
Types:
Primary [MOA]: release of prostaglandins & leukotrienes -> vasoconstriction -> cramps
Secondary: most likely cause ENDOMETRIOSIS
Non-pharmacological management:
- Topical heat therapy
- Exercise
- Acupuncture
- Low-fat vegetarian diet etc
Pharmacological:
- NSAIDs *prostaglandins
- COC (2nd line)
- Progestin injections/ IUD (3rd line; secondary to ability to render pts amenorrheic)
Premenstrual syndrome (PMS) overview & treatment
Definition: CYCLIC pattern of symptoms occurring 5 days BEFORE menses that RESOLVE at ONSET of menses
- most do not report impairment of daily activities
Symptoms:
[Somatic]
- Bloating
- Headache
- Weight gain
- Fatigue
- Dizziness/ Nausea
- Appetite changes etc
[Affective]
- Anxiety/ Depression
- Angry outburst
- Social withdrawal
- Forgetfulness
- Tearful
- Restlessness etc
**if SEVERE mood symptoms: Premenstrual Dysphoric Disorder (PDD) -> PSYCHIATRIC CONDITION
Pharmacological treament:
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- COC for PHYSICAL symptoms (not so much for mood symptoms)
PCOS overview + treament
Definition: ovaries produce ABNORMAL amount of ANDROGENS
- small cysts (fluid-filled sacs) form in the ovaries
Presentation:
- Menstrual irregularities
- Androgen excess:
-> Acne/hirutism/obesity
-> metabolic disorders/ insulin resistance -> risk for DM, CVS disease
Treatment:
- COC (can consider antiandrogenic progestin if acne/ hirutism)
- Metformin
Definition/ Etiology/ Clinical presentation of menopause
Definition: PERMANENT CESSATION of menses following loss of ovarian follicular activity
Etiology:
Natural -> occurs in stages: perimenopause, menopause, post-menopause
INDUCED -> experienced ANY TIME before natural menopause with removal of BOTH OVARIES/ iatrogenic ablation of ovarian function (Eg. chemotherapy, pelvic radiation)
*ovaries produce LESS and UNEVEN levels of hormones
Clinical presentation:
1. VASOMOTOR SYMPTOMS (VMS): hot flushes, night sweats *MOST COMMON
- Intense feeling of heat on face
- Rapid/ irregular HR
- Flushing/ reddened face
- Perspiration
- Cold sweats
- Sleep disturbances
- Feeling of anxiety
*occurs several times a day; thought to be due to THERMOREGULATORY DYSFUNCTION; initiated at level of HYPOTHALAMUS by ESTROGEN WITHDRAWAL
- Genitourinary syndrome of menopause (GSM): collection of symptoms due to changes in labia, clitoris, vestibule, vagina, urethra & bladder because of DECREASED ESTROGEN
- Genital dryness
- Burning/ irritation/ pain
- Sexual symptom of lubrication difficulty
- Impaired sexual function/ libido/ painful intercourse
- Urinary urgency
- Dysuria
- Recurrent UTI - Psychological/ cognitive
*likely multi-factorial (Stress/ hormonal fluctuations)
- Depression/ anxiety
- Poor concentration/ memory
- Mood swings - Bone fragility
*DECREASED ESTROGEN -> MORE BONE LOSS
** increased risk of OSTEOPOROSIS & FRACTURES
**increased JOINT PAIN
Non-pharmacological management of menopause
*reasonable to try if MILD vasomotor and/or vulvovaginal symptoms
MILD vasomotor:
- layered clothing that can be removed/ added as necessary
- Lower room temp
- Less spicy food/ caffeine/ hot drinks
- More exercise
- Dietary supplements *conflicting: ISOFLAVONES (phytoestrogen; from soybean/ legumes), BLACK COHOSH (herb from north america, no significant DDI; possible serotonergic activity at hypothalamus)
MILD vulvovaginal:
nonhomornal vaginal lubricants/ moisturisers
When is menopausal hormone therapy (MHT) indicated?
*estrogen as main contributor to relief of symptoms
Reserved for MODERATE/ SEVERE symptoms/ INSUFFICIENT response to non-pharmacological
**SHOULD NOT BE USED SOLELY FOR:
- treatment of low libido
- CVD prevention
- Depression/ Anxiety/ Cognitive/ Memory issues
- Itchy skin/ Hair loss
- Treatment of osteoporosis *but can prevent loss
Types of MHT available
- Estrogen only
- appropriate if no intact uterus/ only local vaginal estrogen given
Dosage forms:
a. Oral tablets
- relatively inexpensive
*HIGHEST dose required -> HIGHER risk of S/E
*potential for MISSED DOSES -> irregular bleeding
*take at SAME TIME EVERYDAY; continuous cycle
b. Systemic topical (pessary/ gels *let dry)
- Lower systemic dose then oral
- Convenient
- Continuous estrogen release
*EXPENSIVE
*Skin irritation (rotating sites help mitigate)
*Gel: more variability in absorption
c. Local vaginal (pessary/ creams)
- Lowest estrogen dose -> no need concomitant progestin
- Continuous estrogen release
*inconvenient/ uncomfortable
*vaginal discharge
*ONLY FOR LOCALISED UROGENITAL ATROPHY
- Estrogen + Progestin
*progestin: IF STILL HAVE INTACT UTERUS: protect endometrium from OVERGROWTH (+ risk of endometrial cancer)
types:
i. Continuous-cyclic
*Progestin added on either 1st or 15th of month, for 10-14days -> withdrawal bleeding when progestin stopped
- REGULATES MENSES -> predictable bleeding
ii. Continuous-combined: estrogen + progestin DAILY -> NO withdrawal bleeding ALTHOUGH chance of breakthrough bleeding INITIALLY
*AFTER SEVERAL MONTHS: amenorrhea likely to occur
MHT vs COC
Physiologic goal
MHT: to replace/ supplement endogenous estrogen to ALLEVIATE SYMPTOMS & RISKS of lower estrogen production
COC: SUPPRESS hypothalamus-pituitary-ovarian axis to AVOID OVULATION
Amount of ethinyl estradiol equivalents
MHT: 10-15mcg
COC: 20-50mcg
Common formulations of estrogen used
MHT: 17-beta estradiol, Conjugated equine estrogens (CEE)
COC: ethinyl estradiol, estradiol
Onset of MHT, monitoring
Onset of action: may take 2-3 months of use before seeing vast improvement of menopausal symptoms
*continue MHT (systemic/ local) PROVIDED there is a need, patient aware of benefit vs risk, FOLLOW UP IS DONE
Monitoring:
- Annual mammography
- Endometrial surveillance
-> estrogen only: ANY VAGINAL BLEEDING
-> Continuous-cyclic (progestin for 10-14d): if bleeding occurs WHEN PROGESTIN IS STILL ON
-> Continuous-combined (estrogen+progestin daily): if bleeding if PROLONGED, HEAVIER than normal, FREQUENT, PERSISTS after >10months after treatment started
*upon DISCONTINUATION: 50% chance of symptoms RETURNING
Pharmacological options for vasomotor symptoms in menopause (other than MHT)
*MHT: ‘gold standard’
- Antidepressants (not 1st line)
- Serotonin & Norepinephrine Reuptake Inhibitors (SNRIs): venlafaxine
- Selective Serotonine Reuptake Inhibitors: Paroxetine - Gabapentin
- for NIGHT SWEATS/ SLEEP DISTURBANCES - Tibolone ($$$): synthetic steroid with estrogenic, progestogenic & androgenic effects
- Improves mood, libido, menopause symptoms, vaginal atrophy (less than estrogen)
- Protects against bone loss
* risk of stroke, breast cancer recurrence, endometrial cancer
**ONLY INDICATED IN POSTMENOPAUSAL WOMEN >/=12months since last natural period
