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2012-04-02 23:58:00
Regis University

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  1. 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
  2. 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
  3. 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)
  4. Follicle-Stimulating Hormone (FSH)
    • primarily acts on follicle cells
    • stimulate growth of follicle
    • stimulate estrogen secretions
  5. 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
  6. 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
  7. 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
  8. 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
  9. Estradiol
    testosterone is substrate for aromatase then estradiol is product
  10. Estrone
    results from reaction between aromatase and androstenedione
  11. Estriol
    producted by placenta during pregnancy
  12. amenorrhea
    absence of menstruation
  13. menorrhagia
    excessive blood loss during menstruation
  14. dysmenorrhea
    pain prior to and during menstruation
  15. 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
  16. 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
  17. contraceptives act to prevent pregnancy by
    • suppressing ovulation
    • preventing fertilization of egg
    • inhibiting implantation of fertilized egg in uterine lining
  18. Women NOT at risk for pregnancy
    • sterile (physiologically, or via surgical procedure)
    • trying to become pregnant
    • actively pregnant
    • postpartum
    • not sexually active
  19. 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
  20. Ancillary (supporting) benefits for contraceptives
    • prevention of STIs
    • improvements in menstrual cycle regularity
    • prevention of malignancies
    • management of perimenopause
  21. 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
  22. 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
  23. 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
  24. 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
  25. Iron added to COC
    provided to promote hematologic stability (prevent hemoglobin reductions) in response to blood loss during menstruation
  26. Folate added to COC
    to reduce the risk of having a prenancy affected w/spina bifida or another neural tube defect
  27. 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
  28. 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)
  29. 2nd generation progestins
    • Norgestrel/Levonorgestrel
    • more potent than 1st gen
    • provide androgenic activity
    • androgenic side effects: acne, unwanted hair growth (hirsutism)
  30. 3rd generation progestins
    • Desogesrel
    • Norgestimate
    • minimize androgenic, estrogenic and glucocorticoid effects
    • same potency as 2nd gen
  31. 4th generation progestins
    drospirenone: provides anti-mineralcorticoid activity
  32. 1st generation progestins
    • Ethynodiol diacetate
    • Norethindrone
    • lowest progestational potency
    • short half-lives
  33. Norethindrone
    • no glucocorticoid activity
    • minimal androgenic actiity
    • acetate is considered prodrug
  34. 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
  35. Norgestimate
    • prodrug progestin: yields norelgestromine and levonorgestrel
    • deacetylation occurs in intestine and liver
  36. Desogestrol
    • prodrug: produces etonogestrel
    • high selectivity for progesterone receptors and very low androgenic activity
  37. Drospirenone
    • synthetic analog of spironolactone
    • antimineralocorticoid activity
    • antiandrogenic activity
  38. Dienogest
    • synthetic progestin in Natazia
    • highly protein bound w/ volume of distribution of 40L
    • NO glucocorticoid activity
    • NO mineralcorticoid activity
    • effective antiandrogen
  39. 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
  40. 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
  41. 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
  42. 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
  43. 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
  44. Progestin Excess adverse effects
    • increased appetite
    • noncyclic weight gain
    • bloating, constipation
    • depression
    • fatigue
    • irritability
    • manage: decrease progestin in CHC
  45. 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
  46. 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
  47. 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
  48. 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
  49. Transdermal patch adverse effects
    • application-site reactions
    • breast discomfort
    • headache
    • menstrual cramps
    • nausea
    • upper respiratory tract infection
    • ACHES (especially VTE)
    • potential for excess estrogen
  50. 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
  51. Vaginal ring adverse effects
    • vaginitis
    • headache
    • upper respiratory tract infection
    • leukorrhea
    • sinusitis
    • weight gain
    • sensations of ring
    • nausea
    • ACHES
  52. 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
  53. 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
  54. 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
  55. 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
  56. MOA of Depo Provera
    inhibition of FSH and LH surge preventing ovulation
  57. Depo Provera adverse effects
    • menstrual irregularities
    • irregular spotting
    • heavy bleeding
    • possible risk of decrease in BMD
  58. 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
  59. 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
  60. 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
  61. 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
  62. 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
  63. 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)
  64. 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
  65. 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)
  66. 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
  67. Behavioral Methods
    • abstinence: 100% effective for preventing pregnancy
    • protects against STI
    • NO financial costs
    • disadvantage - having self control and partners' commitment to abstinence
  68. Barrier Methods
    • Condoms (male or female)
    • diaphragm
    • cervical cap
    • spermicides
    • vaginal sponge
  69. 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)
  70. 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
  71. 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
  72. 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
  73. 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
  74. Perfect-use contraceptive efficacy
    • following the exact directions for contraceptive
    • perfect-use is a result of the product failure alone
  75. 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
  76. Contraceptions that almost guarantees correct and consistent use among users
    • sterilization
    • implants (implanon)
    • copper IUD
    • levonorgestrel IUS
  77. 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
  78. CHC reduce the risk of:
    • ovarian cysts
    • ectopic pregnancy
    • PID (pelvic inflammatroy disease)
    • benign breast disease
  79. 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
  80. 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
  81. 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
  82. Hypertension while on COC
    • CHCs can cause small increases (6-8 mm Hg) in blood pressure
    • choices for hypertensive women: POPs, and DMPA
  83. 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
  84. 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
  85. 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
  86. 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)
  87. 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
  88. postpartum contraceptive use
    • If contraceptives are needed use: POPs and IUDs (progesterone or copper)
    • AVOID: CHC
  89. 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)
  90. 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
  91. Progesterone antagonist EC
    • ulipristal acetate: prevents prenancy by inhibiting or delaying ovulation
    • RX only
    • can be taken w/in 5 days (120hrs)