Contraceptives

1. Explain the menstrual cycle, including hormones involved and key steps in the cycle.

1. Menstrual Cycle series of hormonal regulated events to prepare the female body for pregnancy starting at 12 years old and lasts for 28- 30 days

2. Follicular Phase - Days 1-13 where the endometrium is sloughed off and FSH steadily increases until dominant follicle emerges and secretes estrogen to develop the follicle and thicken endometrial lining.

3. Ovulation phase - Day 13-15 where LH surges from the prolonged estrogen level increase and a high volume, thin, clear mucus, with high elasticity is produced to aid in fertilization if 2 days prior.

4. Luteal Phase - Day 16-28 when the corpus luteum begins to form and androgens and progesterone levels increase for fertilization. If no fertilization corpus luteum degenerates, progesterone and estrogen levels decrease.

2. Describe the biosynthesis, pharmacokinetics, and physiologic effects of estrogen and progestins.

3. Define key terms associated with contraception, such as breakthrough bleeding (BTB), spotting, amenorrhea, withdrawal bleeding, back-up method, perfect use.

• Breakthrough bleeding (BTB): Bleeding during active pills requiring a pad/tampon.

• Spotting: Less bleeding than menses, not requiring a pad/tampon.

• Amenorrhea: Absence of menses.

• Withdrawal bleeding: Bleeding due to hormone withdrawal in a medication

• Back-up method: Additional contraception (condom, spermicide, diaphragm).

• Perfect use: Correct and consistent use of contraception.

• Typical use: actual inconsistent and incorrect use of contraceptive

4. Describe the indication, physical assessment, and treatment goals to consider with the use of contraception.

• Indications: Assessing interest, reproductive knowledge, and potential need for a pregnancy test.

  • Reasonably certain a woman is not pregnant based on:

    • lack of sexual intercourse since start of last menses,

    • 7 days or less than start of normal menes,

    • within 4 weeks postpartum

    • perfect use of contraception,

    • nearly (85%) or fully breastfeeding, amenorrheic and less than 6 months postpartum

• Physical assessment: Blood pressure (less than 160/110 mmHg), absence of vascular disease safe for hormonal contraceptives.

  • If BP greater than 140/90 refer to PCP for further info.

• Treatment goals: Preventing pregnancy by inhibiting sperm-ovum contact or preventing implantation. Additional goals include managing premenstrual dysphoric disorder (PMDD), improved dysmenorrhea, menstrual cycle regularity, decreased acne, manage endometriosis and polycystic ovarian syndrome.

5. Explain the nonpharmacologic and pharmacologic therapies.

• Non-pharmacologic: Abstinence, periodic abstinence (natural family planning or ovulation method), spermicides, barrier methods (condoms, diaphragm, cervical cap).

• Pharmacologic: Combined hormonal contraception (oral, transdermal, vaginal), progestin-only contraception (pills, injectables, implants, intrauterine devices).

6. For each class of medication, explain the mechanism of action, relevant pharmacokinetic/pharmacodynamic parameters, relevant pharmacology, formulation, contraindications/precautions, common and serious ADRs, common DDIs, and monitoring parameters.

Combined Hormonal Contraceptives

• MOA: Estrogens suppress FSH and prevent development of dominant follicle as well as stabilize endometrial lining for bleeding control.

  

  MOA: Progestins decrease GnRH to decrease LH and FSH, thicken cervical mucus to stop sperm , slow tubal motility, delay sperm transport, alter endometrial lining to inhibit implantation.

  

  Pharmacokinetics: both metabolised by CYP3A4 and by first pass hepatic and excreted as urine

• Formulations: Oral, patch, vaginal ring.

• Contraindications

  • Known or suspected pregnancy

  • breastfeeding women < 6 weeks postpartum

  • current breast cancer

  • 35+ age and heavy smoker 15+ cigs a day

  • uncontrolled HTN > 160/100 mmHg

  • acute or history of DVT/PE with high risk of recurrence, thrombogenic mutations

  • major surgery with prolonged immobilization

  • migraines with aura

  • migraines without aura for 35+ age

  • multiple risk factors for CV disease like old age, smoking, diabetes, HTN

  • diabetes with vascular or microvascular complications

  • diabetes for 20+ years

    

• Serious ADRs: Described using the acronym ACHES

  • Abdominal pain, Chest pain, Headaches, Eye problems, Severe leg pain

  • if any stop contraceptive and seek medical help.

• DDIs:

  • CYP3A4 inducers (PS PORCS) decrease efficacy by increasing liver clearance causing BTB or spotting.

  • CYP3A4 inhibitors (G ❤ PACMAN) increase efficacy by decrease liver metabolism

  • antibiotics decrease CHC efficacy by reducing bacteria and gut metabolism causing BTB or spotting may need back up

  • lamotrigine can increase or decrease levels with CHC changing seizure control

  • warfarin can increase or decrease levels with CHC should monitor INR for risk of thrombosis and bleeding

  • theophylline can decrease levels with CHC changing respiratory control

  • cyclosporine can increase levels with CHC should monitor the concentration of cyclosporine and signs and symptoms of renal and hepatic cyclosporine

Combined Oral Contraceptives

• Monophasic - same amount of estrogen and progestin in 21 or 28 day of active pills with 7 days of placebo

• Multiphasic - contains variable amounts of estrogen and progestin for 21 days then 7 days of placebo for a lower total monthly dose of progestin

  • Biphasic - Azurette white 21d combo, light-green 2d placebo, light blue 5d estrogen only

  • Triphasic - Tri-Lo-Marzia - white 7d combo, light blue 7d combo, blue 7 day combo, doses of estrogen and progestin varies between days

  • Quadphasic - Natazia dark yellow 2d estrogen, medium red 5d combo, light yellow 17d combo, dark red 2d estrogen, white 2 day placebo,

• Extended Cycle - Seasonale and Jolessa contains 84d of active tablets then 7 days of placebo to produce 4 cycles a year

  • may cause more BTB or spotting

  • better for anemic, dysmenorrhea, menorrhagia, endometriosis conditions

• Continuous cycle - Lybrel or Amethyst that has no placebo tables at all

  • higher BTB and spotting from higher estrogen/progestin exposure

  • long term effects unknown

  • may be hard to determine pregnancy since irregular periods

• Shortened Hormone Free Interval - Lo Loestrin-24 Fe,Beyaz,Yaz

  • contains 21-24 days of active tablets

  • shorten menses and decrease hormone withdrawal side effects

  • better for patients with dysmenorrhea or heavy menstrual cycles

Drospirenone and Ethinyl Estradiol

• less antimineralocorticoid and antialdosterone activity

• increased risk of blood clots 74% compared to other low-dose oral contraceptives

• examples of Yasmin,Yaz,Beyaz

• Minastrin 24 Fe and Lo Minastrin Fe

  • chewable tablet formulation with same hormonal levels as Loestrin

  • need doctor approval to substitute

COC- starting contraception

• day 1 of menstrual flow no backup but more rapid contraceptive effects

• first sunday start need backup contraceptive for 7 days, but maybe no bleeding on weekends

• Immediate starting regardless of menstruation need backup for 7 days

COC - missed doses

• 1 active pill - take ASAP even if 2 same day no backup

• 2 consecutive - take last missed pill and discard other missed even if means starting new pack along with backup for 7 days

• 3+ consecutive - consult package insert

Combined Transdermal Patch

• Norelgestromin and EE aka Xulane

  • provides slow sustained hormone release causing constant blood levels

  • increased risk for VTE from higher estrogen then CHC

  • best for women with menstrual migraines

  • avoid in women weighing 90+ kg

  • ADR: same as COC (weight gain, menstrual irregularities, breast tenderness) along with skin irritation resolved by site rotation or anti-inflammatory products

  • Patient Counseling:

    • start after 5 days of menses onset for no backup

    • start other days use backup for 7 days

    • apply 1 patch a week for 3 weeks then remove for 1 along with 5 days backup each first week

    • do not cut it and no need to remove for bathing, swimming, exercise

  • Missed Dose:

    • less than 24 hrs apply new patch and no backup

    • 24+ or unsure apply new patch and restart cycle with 7 days backup

Combined Vaginal Ring

• Etonogestrel and EE aka Nuvaring

  • for 28 days releases 15 mcg of EE and 120 mcg of Etonogestrel a day for 3 weeks

  • ADR: same as COC along with higher thromboembolic risk, decreased nausea headache breast tenderness, increased risk for less libido. ring specific being foreign body sensation, device expulsion, vaginal symptoms

  • Patient counseling

    • start on or before 5th day of menstrual cycle for no backup

    • start other days 7 days backup

    • may be placed anywhere in vagina for 3 weeks then removed for 1 week

    • bleeding in first 2-3 days of ring removal.

    • discard foil in pouch not down toilet

  • Missed Dose:

    • less than 3 hours rinse ring with warm water reinsert with no backup.

    • more than 3 hours rinse with warm water and reinsert with 7 days backup.

Progestin Only

• Micronor aka Errin

  • norethindrone containing best for those intolerant or contraindicated to estrogen products

  • Patient Counseling

    • no adverse effect on lactation

    • less effective than COC

    • higher incidence of ectopic pregnancy

  • ADR

    • irregular menses

    • decreased duration and amount of menstrual flow

    • spotting amenorrhea

• Norgestrel

  • Opill OTC

  • Patient Counseling

    • no adverse effect on lactation

    • less effective than COC

    • higher incidence of ectopic pregnancy

• Progestin Only Pill Patient Counsel

  • must be taken at same time daily or lower efficacy

  • must start on Day 1 otherwise backup for 2 days after start

  • less than 3 hr missed dose take pill ASAP no backup

  • more than 3hr missed dose take pill ASAP with 2 days backup (EC)

• DPMA

  • best for breastfeeding, estrogen intolerant, medical condition preventing estrogen

  • Contraindicated for current diagnosis of breast cancer

  • ADR

    • BBW for decreased bone mineral density

    • menstrual irregularities (spotting, prolonged bleeding, amenorrhea)

    • significant weight gain of 5 lbs in first year

    • breast tenderness

    • depression

    • acne

    • hirsutism

  • Start every 3 months within 7 days of onset of menstrual bleeding

  • if administered after 7 days backup contraception

• Nexplanon

  • long acting reversible contraceptive (LARC) rod that lasts up to 3 years

  • not for overweight or obese women

  • ADR

    • irregular menstrual bleeding first 6-12 months

    • longer heavier periods with spotting

    • headache

    • mood changes

    • acne

    • weight gain

  • DDI with CYP450 inducers (PS PORCS)

  • surgically start within first 5 days of menstrual cycle in women with no previous contraceptives

    • backup for 7 days if any other day

    • removed and replaced every 3 years

Intrauterine Device (IUD) LARC

• MOA:

  • inhibit sperm migration

  • damage ovum or stop transport

  • endometrial suppression and thickening of cervical mucus (levonorgestrel)

• Types

  • Copper Paragard - replaced every 10 years and no DDI

  • Mirena/Kyleena/Liletta - replaced every 5 years and small amounts of levonorgestrel

  • Skyla - replaced every 3 years and smallest amounts of levonorgestrel

• Insert by a trained clinician

  • start first 7 days of menses

  • 7 days backup if after first week

• Contraindications

  • current pelvic inflammatory disease (PID) or STD

  • undiagnosed abnormal vaginal bleeding

  • malignancy of genital tract

  • allergy to IUD or Wilson’s disease for Copper

• Early danger Signs (PAINS)

  • Period Late (pregnancy abnormal spotting or bleeding)

  • Abdominal pain or pain with intercourse

  • Infection exposure or abnormal vaginal discharge

  • Not feeling well with fever or chills

  • String missing, shorter, or longer

• ADRs

  • risk of PID first 20 days after insertion

  • vaginal inflammation

  • ovarian cysts

  • acne

  • headache

Return to Fertility

Emergency Contraceptive

7. For each specified medication, recall brand/generic names, dosage forms, and when backup

8. Given a patient case, develop appropriate, evidenced-based non-pharmacologic and pharmacologic treatment recommendations.

above tables

9. Provide thorough patient counseling for hormonal contraceptives, including initiation, administration, missed doses, adverse effects of hormonal contraceptives.

above tables