-
Follicular Phase
- primordial follicle develops into primary follicle: oocyte grows to develop into primary follicle
- primary follicle becomes secondary follicle: noe become granulosa cells
- layer of CT surronds follicle called theca folliculi
- follicular cells secrete estrogen and zona pellucida
- antrum begins to develop and distinguishes primary follicle to secondary follicle
- secondary follicle becomes mature preovulatory (graafian) follicle: antrum continues to fill w/fluid
- once mature the follicle bulges away from ovarian surface around day 14
- then form secondary oocyte and 1st polar body
-
Ovulation
- ovum or secondary oocyte still surronded by zona pellucida and granulosa cells (corona radiata) sweeps into abdominal cavity
- ovum then gets drawn into oviduct where fertilzation may or may not occur
- rupture of follicle ends the follicular phase
-
Luteal phase
- after ovulation granulosa cells and thecal cells will form corpus luteum
- corpus luteum degenerates within 14 days after formation if not fertilized
- if fertilized and implanted corpus luteum continues to grow and produce progesterone and estrogen until placenta takes over function (producing progesterone & estrogen)
-
Follicle-Stimulating Hormone (FSH)
- primarily acts on follicle cells
- stimulate growth of follicle
- stimulate estrogen secretions
-
Luteinizing hormone (LH)
- stimulates thecal cells
- produce androgens (from thecal cells) then get converted to estrogen w/in ovaries
- stimulate growth of follicle
- stimulate estrogen secretion
- LH surge brings about ovulation of mature follicle
-
Menses (days 1-5)
- characterized by a discharge of blood and endometrial debris from vagina
- occurs w/termination of ovarian luteal phase and onset of follicular phase
- estrogen and progesterone levels are reduced, then endometrium will slough off leaving only the basal layer
- day 5 estrogen production by ovarian growing follicles is beginning to rise
-
Proliferative phase (days 6-14)
- endometrium begins to repair itself and proliferate due to estrogen levels rise from new follicle
- at end of this phase estrogen levels peak, triggering surge in FSH & LH, which is responsible for stimulating ovulation and converts ruptured follicle to corpus luteum
-
Secretory Phase (days 15-28)
- after ovulation, secretory phase coincides w/ovarian luteal phase
- corpus luteum secretes progesterone and estrogen (inhibiting LH release from AP)
- progesterone converts endometrium into a richly vascularized tissue
- Fertilization: nutrients sustain the embryo until implanted in endometrial lining
- NO fertilization: at end of secretory phase corpus luteum degenerates as LH levels fall
- progesterone levels decrease reducing support for endometrium and functional layer sloughs off
- then new follicular phase & menstrual phase begins again
-
Estradiol
testosterone is substrate for aromatase then estradiol is product
-
Estrone
results from reaction between aromatase and androstenedione
-
Estriol
producted by placenta during pregnancy
-
amenorrhea
absence of menstruation
-
menorrhagia
excessive blood loss during menstruation
-
dysmenorrhea
pain prior to and during menstruation
-
Fertilization
- the process of a sperm penetrating an egg to for a new cell (zygote)
- occurs in the fallopian tube
- zygote divides and differentiates into a preembryo
-
Implantation
- implantation of preembryo into uterus lining begins 5 days after fertilization
- implantation usually complete 14 days after fertilization (range 8-18days)
- pregnancy is only established after implantation is complete
- Medical def & US fed polizy: defines pregnancy as implantation of fertilized egg in uterus wall
- conception: medical definition - conception = implantation
- Colorado definition = fed definition
-
contraceptives act to prevent pregnancy by
- suppressing ovulation
- preventing fertilization of egg
- inhibiting implantation of fertilized egg in uterine lining
-
Women NOT at risk for pregnancy
- sterile (physiologically, or via surgical procedure)
- trying to become pregnant
- actively pregnant
- postpartum
- not sexually active
-
Child of unintended pregnancy are at a greater risk for
- low birth weight
- dying in its first year
- being abused
- not receiving sufficient resources for healthy development
-
Ancillary (supporting) benefits for contraceptives
- prevention of STIs
- improvements in menstrual cycle regularity
- prevention of malignancies
- management of perimenopause
-
monophasic
- all pills within monthly pack contain the same hormones at same dose
- usually contain 21 days of combined hormone pills (active phase) followed by 7 days of placebo pills (inactive phase)
- to reduce duration of withdrawal bleeding newer products extend duration of estrogen/progestin to 24 days (active) & 4 days (inactive) - known as 24/4
-
multiphasic
- contain hormone doses that fluctuate throughout course and mimic natural changes in estrogen and progestin that occur during menstrual cycle
- most biphasic & triphasic provide 21 day (active) regimens varying concentration of estrogen/progestin followed by 7 day (inactive)
- allows for lower total hormone dose w/out clincal difference in efficacy from monophasic
-
Extended cycle COC
- increase number of hormone-containing pills from 21 to 84 followed by 7 day placebo
- result is reduction in menstrual cycle to 4/yr maintaining contraceptive efficacy
- Lybrel provides hormone-pills for a year and having only one menstruation per yr
-
Continuous combination COC
- provide estrogen/progestin for 21 days, then give a low dose of hormones for an additional 4-7 (days during placebo phase)
- developed to provide contraception while reducing menstrual bleeding and other hormone withdrawal symptoms
-
Iron added to COC
provided to promote hematologic stability (prevent hemoglobin reductions) in response to blood loss during menstruation
-
Folate added to COC
to reduce the risk of having a prenancy affected w/spina bifida or another neural tube defect
-
MOA of contraceptives
- suppressing FSH release, preventing formation of dominant follicle
- Estrogen:estrogen component is supplied to privde better cyclic control
- mestronal provides endometrial support
- Progestin: provide majority of contraceptive effect exerted by COCs
-
Progestin MOA
- suppression of ovulation and thickening of cervical mucus
- inhibit ovulation: by suppressing release of GnRH from hypthalamus and by preventing mid-menstrual cycle FSH and LH peaks necessary for development and release of ova
- thickening cervical mucosa: this inhibits sperm penetration to upper genital tract
- may transform endometrium into unsuitable environment for embryo implantation (unclear)
-
2nd generation progestins
- Norgestrel/Levonorgestrel
- more potent than 1st gen
- provide androgenic activity
- androgenic side effects: acne, unwanted hair growth (hirsutism)
-
3rd generation progestins
- Desogesrel
- Norgestimate
- minimize androgenic, estrogenic and glucocorticoid effects
- same potency as 2nd gen
-
4th generation progestins
drospirenone: provides anti-mineralcorticoid activity
-
1st generation progestins
- Ethynodiol diacetate
- Norethindrone
- lowest progestational potency
- short half-lives
-
Norethindrone
- no glucocorticoid activity
- minimal androgenic actiity
- acetate is considered prodrug
-
Norgestal/Levonorgestal
- levonorgestal is only active isomer
- norgestal products contain twice amount of progestin than levonorestal
- levonorgestal is long-acting
- levonorgestal potent androgenic activity but no glucocorticoid activity
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Norgestimate
- prodrug progestin: yields norelgestromine and levonorgestrel
- deacetylation occurs in intestine and liver
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Desogestrol
- prodrug: produces etonogestrel
- high selectivity for progesterone receptors and very low androgenic activity
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Drospirenone
- synthetic analog of spironolactone
- antimineralocorticoid activity
- antiandrogenic activity
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Dienogest
- synthetic progestin in Natazia
- highly protein bound w/ volume of distribution of 40L
- NO glucocorticoid activity
- NO mineralcorticoid activity
- effective antiandrogen
-
Quick Start
- patient takes first pill on day of office visit (after pregnancy test)
- instructed to use a 2nd method of contracaeption for 7 days
- successful in getting women to start COCs and to continue COCs through 2nd cycle
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First-Day Start
- take first pill on the first day of next menstrual cycle
- backup method is not required
- Natazia is recommended for first day start w/9 days of back up contraceptive
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Sunday Start
- start active pills on first sunday after starting menstrual cycle
- result in "period free" weekends
- may affect compliance if obtaining refills on weekend may be difficult
- backup for 7 days after intiating sunday start
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Estrogen Excess adverse effects
- nausea
- breast tenderness
- cyclic weight gain (fluid retention)
- manage: decrease CHC, consider progestin-only or IUD
- dysmenorrhea
- menorrhagia
- uterine fibroid growth
- manage: consider exteneded-cycle, NSAIDs for dysmenorrhea
-
Estrogen Deficiency adverse effects
- vasomotor symptoms: nervouseness, decreased libido
- breakthrough bleeding and spotting
- manage: increase estrogen CHC
- amenorrhea
- manage: test for pregnancy, continue if amenorrhea is accecptable
-
Progestin Excess adverse effects
- increased appetite
- noncyclic weight gain
- bloating, constipation
- depression
- fatigue
- irritability
- manage: decrease progestin in CHC
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Progestin Excess (Androgen excess) adverse efffects
- acne
- oily skin
- hirsutism
- hari loss
- arm/leg edema
- libido increase
- manage: decrease progestin CHC, choose less androgenic progestin
-
Progestin Deficency adverse effects
- breakthrough bleeding and spotting
- manage: increae progestin CHC
- dysmenorrhea
- menorrhagia
- manage: consider extended-cycle or continuous OC, consider IUD or progestin only, NSAIDs for dysmenorrhea
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Warning signs for CHC Serious side effects (ACHES)
- Abdominal pain, hepatic mass/tenderness, jaundice: liver/gallbaldder, pancreatitis, thrombosis of abdominal artery/vein
- Chest pain ( SOB, coughing hemoptysis): PE, MI
- Headache (or dizziness): HTN, stroke, vascular spasm
- Eye problems (diplopia, blurred vision, flashing lights vision loss: HTN, stroke, vascular disorder, retinal artery thrombosis
- Severe leg pain, swellin, warmth (calf/thigh): DVT
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Transdermal Patch (Ortha Evra)
- contains EE, and norelgestromin (metabolite of norgestimate)
- effectiveness may be decreased by pts weighing more than 90kg (198lbs)
- potential for excess estrogen
- applied to abdomen, buttocks, upper torso, upper arm
- worn for 3 weeks then off for 1 week
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Transdermal patch adverse effects
- application-site reactions
- breast discomfort
- headache
- menstrual cramps
- nausea
- upper respiratory tract infection
- ACHES (especially VTE)
- potential for excess estrogen
-
Vaginal Ring (nuvaring)
- contains EE and etonogestrel (desogestrol)
- worn for 3 weeks then of for 4th week (1 week off)
- low incidence of breakthrough bleeding or spotting
- reasons for discontinuation - foreign-body sensation, device expulsion, vaginal symptoms
- AVOID: if pt is prone to vaginal irritation, or uncomfortable inserting ring
-
Vaginal ring adverse effects
- vaginitis
- headache
- upper respiratory tract infection
- leukorrhea
- sinusitis
- weight gain
- sensations of ring
- nausea
- ACHES
-
Vaginal ring administration
- ring inserted on/before 5th day of menstrual cycle
- ring removal is allowed as long as ring is reinserted w/in 3hrs
- if longer than 3hrs then 2nd method of contraceptive used until ring has been in place for 7 days
-
Progestin Only Pills (POPs)
- contain either norethindrone/norgestrel
- supplied as 28 day
- monophasic regimens
- contain only progestin
- Breast-feeding: POPs most commonly selected for breast feeding mothers
-
Missed POPs
- missed dose is considered missing a pill by 3hrs
- If POP is taken more than 3hrs late, pt should use backup method of contraception for 48hrs
- EC considered if intercourse occurred recently
-
Depo Provera
- contains only progesterone analog medroxyprogesterone acetate
- administered by deep IM injection
- inhibits ovulation for more than 3 months
- SQ formulation inhibts ovulation for 14 weeks, but dosed still at once/3months
- SQ formulation: approved for treatment of endometriosis-associated pain
-
MOA of Depo Provera
inhibition of FSH and LH surge preventing ovulation
-
Depo Provera adverse effects
- menstrual irregularities
- irregular spotting
- heavy bleeding
- possible risk of decrease in BMD
-
Subdermal Progestin Implant
- known as Implanon
- contains etonogestrel (an active metabolite of desogestrel)
- administered under skin of upper arm using preloaded inserter
- implant is effective for 3yrs
- effectiveness reduced in women weighing more than 130% of ideal body weight
-
Implanon adverse effect
- irregular menstrual bleeding
- amenorrheic w/continued use
- headache
- vaginitis
- weight gain
- acne
- breast & abdominal pain
- contraindicated: women who are pregnant, have active liver disease, history of thromboembolic event, history of breast cancer
-
Paragard (IUD)
- contains no hormones
- device wrapped with copper wire
- continuously used for 10yrs
- increases: copper ions, prostaglandins, WBC impairing sperm and tubual function, secondary MOA is interference w/implantation
- can be used for postcoital contraceptive w/in 5 days
- Does NOT affect ovulation
- women will continue to have menstrual cycles
-
Mirena (IUS)
- contains levonorgestrel
- can be used for 5 yrs
- irritates the endometrial lining and tissue such that sperm and ova are not viable
- release of levonorgestrel suppresses the endometrium
- see decrease in menstrual flow
- reduction in menstrual bleeding
- Good choince for women w/menorrhagia or dysmenorrhea
-
Both Paragard & Mirena
- inserted and removed by healthcare provider
- creates low-grade intrauterine inflammation, endometrial suppression, environment toxic to ova & sperm
- non-conducive to embryo implantation
-
Paragard & Mirena adverse effects
- pelvic inflammatroy disease (PID)
- infectious morbidity high during first 20 days
- perforation, expulsion or embedding in endometrium
- PAINS
- paragard specific: dysmenorrhea, increased menstrual bleeding
- mirena specific: amenorrhea, spotting (usually declines over time)
-
Warning signs for IUD/IUS (PAINS)
- Period is late (paragard), abnormal spotting or severe bleeding
- Abdominal pain, severe cramping, abdominal pain w/sex
- Infection exposure (STI), symptoms of vaginal infection (abnormal vaginal discharge)
- Not feeling well, fever, chills
- Strings from IUD are missing, are longer or shorter than norm
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Contraindications w/ Paragard & Mierna
- pregnancy
- distorted uterine canal
- unknown source of genital bleeding
- active PID or high risk PID (pelvic inflammatory disease)
- postpartum endometritis/post-abortion infection w/3months
- known/suspected uterine or cervical malignancy
- mucopurulent cervicitis
- copper IUD: contraindicated for pts w/ Wilson's disease (copper allergy)
-
Emergency Contraception (EC)
- ulipristal acetate: available as a progesterone antagonist
- copper IUD also an option w/in 72 hrs
- high dose COCs or progestin-only can be used as an EC
-
Behavioral Methods
- abstinence: 100% effective for preventing pregnancy
- protects against STI
- NO financial costs
- disadvantage - having self control and partners' commitment to abstinence
-
Barrier Methods
- Condoms (male or female)
- diaphragm
- cervical cap
- spermicides
- vaginal sponge
-
Condoms
- prevents semen from reaching ovum
- protect against many STIs and HIV (except for lamb condoms)
- efficacy decreased by oil-based lubricants (except in female condom)
- not damaged by heat (female condom only)
-
Diaphragm
- is reusable rubber cap inserted into vagina and covers cervix to decrease access of sperm to ovum
- must be fitted properly by healthcare provider
- use w/spermicide to increase effectiveness
- Toxic Shock Syndrome (TSS): diaphragm must be removed w/in 24hrs to avoid TSS
- reduces risk of gonorrhea, trichomonas, HPV
-
Cervical Cap
- fits snuggly over cervix
- Femcap, Lea's Shield: Femcap in 3 sizes, Lea's Shield in 1 size only (and held in place by vaginal wall)
- must be filled w/spermicide prior to insertion
- TSS: must removed w/in 48hrs to prevent TSS
- increased risk for cervical dysplasia (have pap smear 3months after use)
- DOES NOT protect: against STIs or HIV
- less effective following vaginal childbirth due to changes in woman's cervix
-
Spermicides
- are chemical surgactant that destroy sperm cell walls to inhibit mobility and ability to reach ovum
- comes in creams, films, foams, gels, suppositories, sponges, tablets
- Has high failure rate if used alone
- enhances effectiveness in: cervical caps, diaphragms
- if used alone must reapply before each act of sex
- DOES NOT protect against: STIs, may increase HIV transmission
- AVOID: if high risk for HIV or infected w/HIV
-
Vaginal Sponge
- sponge called Today
- contains 1g of spermicide
- provides 24hr protection w/out need for spermicide reapplication
- TSS: must be removed after 24 to 30hrs to prevent TSS
- sponge effectiveness is reduced after vaginal childbirth
- DOES NOT protect against: STIs, HIV
- cannot be reused
-
Perfect-use contraceptive efficacy
- following the exact directions for contraceptive
- perfect-use is a result of the product failure alone
-
Typical-use contraceptive efficacy
- an average user who does not always use method correctly or consistently
- typical-use failures are a result of user failure in addition to product failure
-
Contraceptions that almost guarantees correct and consistent use among users
- sterilization
- implants (implanon)
- copper IUD
- levonorgestrel IUS
-
Contraceptive use in the US
- 90% of women are using contraceptives
- 10% are not (4.5 million women)
- women <30 use "pills"
- women ages 30-44 use sterilization
-
CHC reduce the risk of:
- ovarian cysts
- ectopic pregnancy
- PID (pelvic inflammatroy disease)
- benign breast disease
-
WHO categories of CHC
- Category 1: Do not restrict use of COC for following conditions
- Category 2: Some conditions may trigger potential concerns w/CHCs, bue benefits outweigh risks
- Category 3: Conditions may be adversely impacted by CHCs, risks outweigh benefits. Providers use cautions and monitor if CHC is dispensed
- Category 4: Refrain from providing CHC for women w/ following diagnoses
-
Smoking while on COC
- increased risk of MI if smoking andCOC > 50mcg EE
- COC user who smoked increase risk of VTE
- contraindication: smoking 15 or more cigarettes/day and > 35yrs (category 4)
- category 3: less than 15 cigs/day and > 35yrs
- consider progestin only in these populations
-
Migraines while on COC
- women of any age who have migraine w/aura SHOULD NOT use CHC
- in general women who develop migraines (with or w/out aura) while on CHC should discontinue CHC use
- consider progestin only, intrauterine, barrier contraceptives
-
Hypertension while on COC
- CHCs can cause small increases (6-8 mm Hg) in blood pressure
- choices for hypertensive women: POPs, and DMPA
-
Dyslipidemia while on COC
- estrogen enhances LDL removal and increases HDL
- progestin decreases HDL and increases LDL
- low dose CHC has NO affect on dyslipidemia
-
Breast Cancer
- women w/ recent personal history of breast should NOT use CHC
- CHC can be considered in women w/out evidence of disease for 5yrs
-
VTE while on COC
- estrogesns increase hepatic production of factor VII, factor X, and fibrinogen, increasing coagulation cascade
- however the risk is less than risk of thrmoboembolic event incurred during prgnancy
- higher risk with patch: compared to COC or ring
- CHC contraindication: women w/history of thromboembolic event
- alternatives: hormone free methods (IUD), POP, DMPA, levonorgestrel IUS
- EC does not increase risk of VTE
-
CHC side effects
- Make sure pt stays on CHC for first 3 months, normally side effects will subside after 3 months
- Contact PCP if warning signs for severe symptoms occurs (ACHES)
-
Drug interaction with COC
- Rifampin: may decrease the efficacy of COC
- PHB, PHT, CBZ: may induce the metabolism of estogen and progestin causing breakthrough bleeding and potentially reducing efficacy of contraceptive
- same interactions w/POP, implanon (as well as NNRTIs)
- NO drug interactions w/ IUD or IUS
-
postpartum contraceptive use
- If contraceptives are needed use: POPs and IUDs (progesterone or copper)
- AVOID: CHC
-
Breast-Feeding w/contraceptives
- Avoid: CHCs in first 6 weeks postpartum
- DMPA: should be avoid until 6 weeks after postpartum (woman not breast feeding can use DMPA right away)
- POPs: avoid until 6 weeks after delivery (if not breast feeding can start 1-4weeks)
-
Progestin-only EC
- Plan B: consists of two tablets containing .75mg levonorgestrel
- Generic for Plan B is Next Choice
- taken w/in 72hrs
- 1 dose taken right away, 2nd dose 12hrs later
- Plan B one-step: contains 1tablet of 1.5mg levonorgestrel
- Yuzpe method: is use of COC for EC
-
Progesterone antagonist EC
- ulipristal acetate: prevents prenancy by inhibiting or delaying ovulation
- RX only
- can be taken w/in 5 days (120hrs)
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