IE 3: Hormonal Contraception Slides

What does the menstrual cycle consist of? What is Day 1 of the cycle? What about day 14?

• 2 synchronized cycles (ovarian and uterine)

• Menarche → Menopause

• Day 1 of cycle = Day 1 of bleed

• Day 14 = ovulation (on an avg 28 day cycle)

  • 2 early weeks are the “follicular phase”

  • 2 late weeks are the “luteal phase”

When choosing a hormonal contraceptive, what should you take in consideration?

• Coexisting med conditions

• Age

• Risk factors

• Pt preferences (including intended purposes)

What are the different USMEC risk categories?

• 1 → No restriction (method can be used)

• 2 → Advantages generally outweigh theoretical or proven risks

• 3 → Theoretical or proven risks usually outweigh the advantages

• 4 → unacceptable health risk (method should not be used)

What are important CI for combined hormonal contraception (Category 4)?

• Breastfeeding and <21 days postpartum

• Smoker >35 years old

• Multiple risk factors for CVD

• Current or history of DVT or PE

• Major surgery with prolonged immobilization

• Migraine headache with aura

What are the combined hormonal contraception?

• Combined oral contraceptive pill (COC)

  • Monophasic, biphasic, triphasic, multiphasic

• Transdermal contraceptive patch

  • Xulane

• Contraceptive vaginal ring

  • NuvaRing, Annovera

The combined oral contraceptive pill contains what?

• Contains estrogen and progestin

  • Estrogen prevents ovulation by suppressing FSH

  • Progestin helps thicken cervical mucus, causes atrophy of endometrial lining

The COC pill that is monophasic means what?

• Monophasic: hormone content stays the same throughout the cycle

  • Most come in 28-day cycles with 21 days active pills, 7 days placebo

The COC pill that is biphasic means what?

• Biphasic: hormone content changes twice throughout cycle

  • Typically increase progestin on day 11 of a 28-day cycle

The COC pill that is triphasic means what? What about multiphase (extended cycle)?

• Hormone content changes 3 times during cycle

• Multiphasic (Extended Cycle): hormone content changes 4 or more times throughout cycle

What is estetrol in Estetrol/drosperinone (Nextellis)? When does it circulate in high levels and where can it be derived from? What activity does it do in tissues?

• Native estrogen with selective actions in tissues (NEST)

  • Circulates in high levels between mother and fetus during pregnancy and derived from plant sources

  • Maintains agonistic and antagonistic activity in different tissues

    
    

When can Estetrol/drosperinone (Nextellis) be less effective in?

• Females with BMI ≥30 kg/m²

When do you start combined oral contraceptives (COC)?

• Sunday-start method

• First day/same-day-start method

• Quick-start method

What is the Sunday start method?

• Start active tablets on first Sunday after menses begin

  • Use backup non-hormonal contraception for first 7 days after starting

What is the first day/same day start method?

• Take first active tablet the exact day that menses begin

  • No backup contraception is required

What is the quick start method?

• Start active tablets regardless of what day menses start (i.e. start now when pickup medication or at physician’s office)

  • Use backup contraception for first 7 days after starting

  • Can also instruct to use backup contraception until next menses occur

  • Note: Women will not have menses until all active tablets have been taken and hormone free week begins

If you miss one pill or late with one pill what should you do?

• Take missed pill as soon as remember

• Continue taking rest of pills as scheduled (even if it means taking 2 pills on same day). No backup contraception is needed.

If you miss 2 consecutive pills or more (during week 1 or 2 of cycle), what should you do?

• Take one missed pill as soon as remember

• Discard the rest of the missed pills and continue taking other pills as scheduled. Backup contraception should be used for 7 days.

If you miss 2 consecutive pills or more (during week 3, last week of active pills), what should you do?

• Take one missed pill as soon as remember

• Discard rest of the missed pills. Finish remaining active pills and omit hormone-free week (placebo). Start new pack instead. Backup contraception should be used for 7 days.

  
  

Xulane Transdermal contraceptive patch delivers what? What is the MOA?

• Delivers norelgestromin 0.15mg/day and ethinyl estradiol 35 mcg/day

• MOA: hormone passes into skin and metabolized by liver where norelgestromin is converted to norgestimate.

How should you use a transdermal contraceptive patch? What about other counseling points?

• How used: applied to skin once weekly to clean, dry hairless skin area on upper arm, shoulder, buttock or abdomen. Change patch on same day each week. During 4th week, patch is removed, menses occur.

• Other counseling: Rotate application site each week to prevent skin irritation.

  • Patch can be worn while taking shower, swimming, exercising, sauna

  • Remove patch by peeling off carefully, fold together, discard away from pets and children, do not flush down toilet

What are the pros/cons of the transdermal contraceptive path?

• Pros/Cons: easier to use for women who do not like taking pills, not good option for women who have history/risk of VTE (delivers 60% more estrogen), less effective in women >90kg

  
  

If no prior use of a hormonal contraceptive, how should you start using a patch?

• Apply on first day of menses or Sunday following start of menses

• Can also do Quick-Start method

• Wear patch for 7 days then change patch on day 8

• Use backup contraception for first 7 days after patch is applied

If switching from another CHC how should you start the patch?

• Apply patch on first day of withdrawal bleeding. No backup contraception needed.

• If applied later than first day of withdrawal bleeding, then use backup method for 7 days

If the patch falls off for <24 hours, what should you do?

• Reapply the patch ASAP. No backup contraception needed

If the patch falls off for ≥24 hours, what should you do?

• Apply new patch as soon as remember.

• Start new 4-week cycle

• Use backup contraception for first 7 days after applying patch

• Delay of menses may occur d/t new cycle of patches

If detached patch or delayed application occurs during 3rd week, what should you do?

• Omit hormone free week, start new patch and new cycle.

• If cannot start new patch, use backup contraception or abstain from intercourse until new patch can be applied.

What happens if you forgot to change the patch?

• If forgot to apply new patch after hormone free week:

  • Apply new patch as soon as remember. Use backup contraception until new hormone patch has been on for 7 days.

• If forgot to apply new patch during weeks 2 or 3 and delay in wearing new patch is <48 hours:

  • Apply new patch immediately and change Patch Change Day. No backup contraception is needed.

• If forgot to apply new patch during weeks 2 or 3 and delay in wearing patch is ≥48 hours:

  • Apply new patch immediately. Start new 4-week cycle. Use backup contraception for 7 days.

• If forgot to remove patch during hormone free period:

  • Remove patch as soon as remember. Start new cycle on regular patch change day. No backup contraception needed.

  • There should be not more than 7 days where there is no patch worn.

  • If >7 days without a patch (extended hormone free period), then use backup method for 7 days after applying new patch.

For the contraceptive vaginal ring (NuvaRing) what does it release? What is the MOA?

• Releases 0.12mg/day etonogestrel and 0.015mg/day ethinyl estradiol

• MOA: delivers hormones through vaginal mucosa using a nonbiodegradable, flexible, transparent, colorless ring

How is the contraceptive vaginal ring (NuvaRing) used?

• How used: insert ring vaginally by squeezing ends of ring so that they meet and insert. Leave ring in place continuously for 3 weeks at a time.During 4th week, ring is removed, withdrawal bleeding occurs.
  

What are other counseling points on the contraceptive vaginal ring?

• douching is not recommended but ring can be left in place during intercourse and when using tampon or topical creams. DO NOT USE DIAPHRAGM CONCURRENTLY

What are SE of the vaginal ring?

• Foreign body sensation, vaginal sx, discomfort

What are pros/cons of the vaginal ring?

• improved adherence since do not have to change as often,
  cannot be used in women who are prone to vaginal irritation or are not comfortable with insertion

When should you start the vaginal ring? How do you insert/remove it?

• Insert ring vaginally on or before 5th day of menstrual cycle.

  • Same day of the week each time.

  • Can make insertion easier with standing and raising one leg, squatting or lying down. A tampon application can also assist

  • Exact position of ring is not important if there is sufficient contact with the vaginal walls

• To remove the ring, hook index finger under rim or grasp ring with index and middle
  finger to pull the ring out.

• Discard by placing it in the foil packaging it came with and placing in trash.

• Do not flush down toilet and keep out of reach of children and pets.

• Ring CAN be left in place during sexual intercourse and with tampon use

In NuvaRing, it the ring is accidentally removed and it has been <3 hours, what should you do?

• Rinse ring with cool to lukewarm water. Reinsert ASAP and within the 3 hours

If the ring is accidentally removed and it has been >3 hours, what should you do?

• Reinsert ASAP. Use backup contraception until ring has been in place for 7 days.

• If delay in insertion occurs during 3rd week, insert new ring and start new cycle

If you forgot to remove the ring after 3rd week and it has left in for up to 1 extra week, what should you do?

• Remove ring when remember during the 4th week. Start new cycle as scheduled.

• No backup contraception is needed.

If the Nuvaring has been >4 weeks in place, what should you do?

• Remove ring as soon as possible. Rule out possible pregnancy.

• Start new cycle by inserting new ring and use 7 days of backup contraception

For the New FDA approved contraceptive vaginal ring (Annovera), what does it deliver?

• Delivers segesterone acetate 0.15mg/day and 0.013mg/day ethinyl estradiol

For Annovera, how should it be used?

• Ring is left in place for 3 weeks continuously then removed during 4th week. Hormone free period occurs for 7 days.

In Annovera, if the ring has been accidentally removed for <2 hours, what do you do? If the ring has been removed for >2 hours, what do you do?

• If ring has been accidentally removed for <2 hours, wash the ring and place It back in.

• If ring has been removed for >2 hours, wash the ring and place back in. Use backup contraception for 7 days.

Too much estrogen can cause what S/E?

• Bloating, Breast tenderness

• Mood Changes

• HA, nausea

• Heavy menses

• Fibroid growth

• Melasma

• Vision Changes

• Cyclic weight gain

Not enough estrogen can cause what?

• Breakthrough bleeding early in cycle

• Light menses

• Vaginal dryness

• Spotting

• No withdrawal bleeding

Too much progestin can cause what?

• Acne (androgen excess)

• Hirsutism (androgen excess)

• Decrease in sex drive

• Depression

• Increased appetite

• Increase in sex drive (androgen excess)

• Less energy

• Noncyclical weight gain

• Cholestatic jaundice (androgen excess)

• Yeast infx

• Hair loss (androgen excess)

• Swelling in arms/legs (androgen excess)

Not enough progestin can cause what S/E?

• Breakthrough bleeding late in cycle

• No withdrawal bleeding

• Heavy menses

With the side effect of breakthrough bleeding (early or late), what should you consider?

• Usually improves within 3 months of use. If still occurs after 3 months (up to 6 months for extended regimens), consider increase estrogen or progestin

With the side effect of weight gain, what should you consider?

• Too much progestin can increase appetite (noncyclic weight gain); too much estrogen can cause water retention (cyclic weight gain). Consider low dose estrogen and low dose progestin or recommend product with drospirenone

With the side effect of HA/migraines, what should you consider?

• Sharp decrease in estrogen during placebo week can cause HA
  during or before menses occur. Consider lower estrogen or replace placebo with estrogen (i.e. Seasonique). Shorter placebo or extended cycle regimens can help

With the S/E of Acne, what should you consider?

• Can be caused by progestin with high androgenic properties. Consider lower progestin or substitute for 3rd or 4th generation progestin

What are some serious AE of CHCs?

• Abdominal pain (tenderness)

  • Sign of liver problem, gallbladder disease, blood clot

• Chest pain (SOB, coughing)

  • Sign of PE or MI

• Headache

  • Sign of hypertension, stroke, migraine

• Eye problems (double, blurry vision)

  • Sign of retinal artery thrombosis

• Severe leg pain (calf or thigh)

  • Sign of DVT or if numbness/weakness then sign of hemorrhagic or thrombotic stroke

COC undergo hepatic metabolism via CYP enzymes so what can affect efficacy?

• CYP inhibitors and inducers can impact efficacy of COCs, lower doses of hormonal content are likely to see greater impact

• Other drugs may also have altered metabolism and clearance with concurrent COC use

In general, if using interacting meds for more than 2 months, what should you do?

• Switch COC to DMPA or intrauterine device to avoid interaction and eliminate need for long term backup method.

Which antibiotics are inducers and what should you do with your COC?

• Antibiotics

  • Rifampin/Rifabutin (Major Inducers)

  • Broad spectrum antibiotics

  • Recommend backup contraception for 7-28 days after rifampin d/c

How do BZD interact with estrogens and what should you consider long term?

• Benzodiazepines

  • Compete with estrogens which can reduce the effect of estrogen or increase benzos effect

  • If long-term use, consider switching products or increase to product with higher estrogen.

What does St John’s Wort do to OC? What do you do?

• St. John’s Wort: decrease OC effectiveness, d/c SJW or switch products

For corticosteroids, theophylline, aspirin, APAP, what can they do? What should you do to doses?

• Corticosteroids, theophylline, aspirin, APAP:

  • Clearance and metabolism of these drugs can be affected so increases risk of side effects

  • May need to reduce doses to prevent risks if use long-term

For anticonvulsants, what should you do to you COC?

• Anticonvulsants

  • Long term seizure disorder- switch product

  • Phenytoin, phenobarbital, carbamazepine (inducers)- can cause breakthrough bleeding, reduce efficacy of COC

For Drospirenone containing products, what do you monitor?

• K+

What are the Progestin only formulations?

• Progestin-only pill (POP, mini-pill)

  • contains norethindrone or drospirenone

• Injectable (IM or SQ)

  • depo-medroxyprogesterone acetate (DMPA)

• Intrauterine device (IUD)

  • Mirena, Kyleena, Liletta, Skyla

• Subdermal implant (under skin)

  • Nexplanon

When should you avoid use in with Progestin only formulations?

• Avoid use of progestin-only contraceptives in individuals who may be pregnant or have known or suspected breast cancer

• Avoid use in undiagnosed abnormal vaginal bleeding and acute liver disease

  
  

What are the different generation Progestin only pills? The higher the generation, the lower what?

• 1st generation: norethindrone; 2nd generation: levonorgestrel; 3rd generation: norgestimate, norelgestromin; 4th generation: drospirenone

• The higher the generation, the lower the androgenic side effects

Drospirenone has what properties?

• Drospirenone has anti-androgenic and anti-mineralcorticoid properties

POPs can reduce what estrogen related sx?

• Migraines, cramping, breast tenderness

How can POP be used in postpartum, after abortion/miscarriage? What can it slightly increase risk of in women >70kg?

• In postpartum, can be initiated as early as 1-4 weeks following delivery in patients who are not breastfeeding but general recommendation is to initiate 6 weeks after delivery for patients who are exclusively breastfeeding and at least 3 weeks after delivery for partial breastfeeding.

• POP can be started the following day after abortion or miscarriage

• Slight increase in unintended pregnancy in women > 70kg

When should someone start POP? When do you use backup contraception? What is the caution of use?

• Start the first day of menstrual period

• Take at the SAME time each day

• If first dose starts on day other than first day of menstrual period, then use backup contraception for first 48 hours.

• There are no placebo pills or breaks between packs.

• Use with caution depending on weight. Risk of unintended pregnancy is slightly increased if >70kg

If POP dose is missed by <3 hours, what should you do?

• Take as soon as remember, even if it means taking 2 pills in one day. No backup contraception is needed

If POP dosed is missed by >3 hours, what should you do?

• Take missed dose as soon as remember.

• Backup contraception must be used for next 48 hours.

• Recommend emergency contraception if unprotected intercourse took place

If 2 or more doses are missed, what should you do?

• Take first missed dose as soon as remember. Take normal scheduled POP for that day. (2 pills total)

• Then take 2nd missed dose tomorrow and normal scheduled POP (2 pills total)

• Use backup contraception for next 48 hours

For injectable progestin-only contraceptive, what does Depo-Provera (DPMA) contain?

• 150 mg medroxyprogesterone in aqueous microcrystalline suspension

What is the MAO of Depo-provera injectable?

• blocks ovulation reliability within 24 hours of dose

What are some additional S/E in injectable progestin only?

• can cause modest weight gain, irregular bleeding (during first 3 months) then amenorrhea by end of year 1

When can injectable progestin only contraceptive been initiated in lactating pts?

• 6 weeks postpartum

What are some pros/cons of injectable progestin only contraceptives?

• Return to fertility is delayed, prolonged use can cause bone loss and negative effects on BMD, efficacy is independent of weight, avoids first pass metabolism

  
  

How is DMPA started? When should backup be used? When is the next dose?

• Give first injection within 5 days of start of menstruation to ensure no existing pregnancy.

• If >7 days since start of cycle, use backup method for first 7 days (week)

• Can start at any time as long as woman is not pregnant but use of backup contraception will differ.

• Next dose in 3 months (12 weeks)

• There is a 2-week grace period should a dose be delayed

  
  

Pts should administer dose of DMPA how often? What is the grace period?

• q12 weeks

• There is a grace period of up to 2 weeks but if patients are more than 1 week overdue for their dose, they should receive pregnancy test before next dose. EC is considered

What is a concerning side effect in DMPA?

• Amenorrhea can be concerning side effect.

  • Counsel that individuals may experience irregular bleeding for short period of time followed by cessation of menstrual bleeding

What is the counseling points with bone loss in DMPA? What can you consider to help?

• Short term bone loss can occur but some studies say that it can be irreversible with greater duration of use.

• In 2004, FDA issued warning that DMPA should be continued >2 years only if other contraceptive methods are inadequate.

• Consider supplementation with Calcium 1000mg/day and Vitamin D 800 IUs (20mcg)/day

What is the MOA of the Progestin Intrauterine Device (IUD)?

• Contains levonorgestrel, actual presence of foreign body within uterus prevents implantation and disrupts endometrial lining. Local effects of thickening cervical mucus and inhibit sperm motility.

What are the pros/cons ofProgestin IUD?

• Has high efficacy and good option for individuals who dislike pills

• Device may not be tolerated due to excessive bleeding/spotting, infections or pain.

• Must be inserted by trained healthcare provider

With initial insertion of IUD, what can happen? What can happen in using an IUD that can help pts who experience anemia?

• Spotting may be common with initial insertion of IUD

• Menstrual bleeding is significantly reduced overall which is beneficial for patients who are experiencing iron-deficiency anemia

What is the greatest risk in using a progestin IUD? What are major warning signs of pelvic infection?

• Greatest risk of pelvic infection is within first 20 days following insertion of device

• Major warning signs for pelvic infection (PAINS):

  • P: period is late

  • A: abdominal pain or pain with intercourse

  • I: infection, abnormal or odorous vaginal discharge

  • N: not feeling well, fever, chills

  • S: string (missing, shorter, longer)

How long can Progestin IUDs be used for?

• 3-5 years

Subnormal progestin implant (Nexplanon) contains what? How long can a single rod implant be used up to?

• Contains 68 mg etonogestrel (active metabolite of desogestrel)

• Single-rod implant indicated for contraceptive use up to 3 years

What is the MOA of Nexplanon, the pros/cons, and how can it be used in postpartum+lactating women?

• MOA: maintains sustained release of progestin

• Pros/cons: lower doses of hormones, rapid return to fertility (within 6 weeks of removal), can cause local bruising upon insertion/removal

• Special populations: Can be used as early as 4 weeks postpartum and lactating women

When should nexplanon be placed?

• Should be placed between days 1-5 of onset of menses, no backup
  contraception needed

• If placed after 5th day from onset of menses, backup method used for first 7 days.

• If patient is currently using oral contraceptives, DMPA or IUD, placement of Nexplanon can occur any time without regard to menses

What are counseling points on Nexplanon?

• Swelling, irritation at site for few days after insertion and irregular bleeding can occur

• Can cause amenorrhea, continued prolonged bleeding, spotting or frequent bleeding. Varies per patient.