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Birth Control: Contraceptive Choices & Management

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Alexandra Sible Herman, PharmD Date NMNPC 2019 Spring Conference April 1, 2019

OBJECTIVES

• Understand the mechanisms of action of contraceptive methods discussed, including long-acting reversible contraception (LARC), such as IUDs and implants, and short- acting .

• Describe differences in efficacy and safety among contraceptive options.

• Recognize and manage adverse effects of contraceptive methods.

• Given a patient scenario, discuss how to choose and initiate an appropriate contraceptive method, including evaluation of contraindications and indications and patient preferences.

CONTRACEPTION MANAGEMENT

• Undesired fertility: a “chronic condition”? • “Childbearing age” defined by CDC as 15-44 years old • Average age at in U.S. is ~12.5 years old • Average of in U.S. ~51 years old

• Patient’s reproductive life plan; contraceptive preferences; safety of methods – all may change

• Should be re-evaluated and managed appropriately throughout patient’s entire reproductive lifetime

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CONTRACEPTION MANAGEMENT

• Unintended • Nearly half of U.S. are described as “unintended” • Women who did not use a contraceptive method: 54% • Women who inconsistently used a contraceptive method: 41% • Women who consistently used a contraceptive method: 5%

• Pregnancy ambivalence • Do you want to become pregnant? Yes / No / Maybe • Often influences choice of method (especially re: effectiveness)

Source: Guttmacher.org

CONTRACEPTION MANAGEMENT

• The best contraceptive method is the one the patient will consistently use

• Shared, informed decision making helps a patient choose the most effective option that is safe for her and fits her lifestyle and preferences

EFFECTIVENESS

• • Long-acting reversible contraception (LARC) • IUD, implant • Short-acting reversible hormonal contraception • Shot • Pill, patch, ring • Barrier & behavioral methods •

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Source: Bedsider.org

SAFETY

• U.S. Medical Eligibility Criteria (MEC) for contraceptive use: https://www.cdc.gov/reproductivehealth/contracepti on/mmwr/mec/summary.html • App available for iOS and Android systems

SAFETY

Example of the MEC – many more disease states are included in full document

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LIFESTYLE & PREFERENCES

• A method that worked in the past • A method she heard about from a friend/family member/etc. • Methods in the news • Adherence • Convenience • Periods or no periods • Need to keep method hidden? • Return to fertility/desire for future pregnancies • Timing and spacing of pregnancies • …and more

Source: https://www.guttmacher.org/fact-sheet/contraceptive-use-united-states

LIFESTYLE & PREFERENCES

• The pill and female sterilization are the most popular forms of contraception in the U.S. • Contraceptive CHOICE Project: participants offered a method of their choice at no cost for 2-3 years • 75% of participants chose LARC (IUD or implant) • LARC methods were 20 times more effective than non-LARC methods

• LARC methods had higher continuation rates at 12 & 24 months • The Contraceptive CHOICE Project in Review: https://www.ncbi.nlm.nih.gov/pubmed/25825986

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• Robert Hatcher, et al. Managing Contraception, 14th ed. • $25 • https://managingcontraception.com/

METHODS

Sterilization (>99% effective) • Male sterilization: (no anesthesia) • Female sterilization • – withdrawn from market Dec 2018

• Tu b a l l i g a t i o n ( laproscopic surgery, requires anesthesia)

POP QUIZ!

True or False: A woman who has never given birth should not use an IUD.

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METHODS IUD (>99% effective) • Non-hormonal: Copper IUD (Paragard®) • Mechanism of action: Copper ions inhibit sperm; inflammatory reaction in endometrium • FDA approved for 10 years; effective 12+ years

• Hormonal: all contain (a progestin; LNG) • Mechanism of action: Thickening of cervical mucus; alteration of endometrium; some anovulatory effects • Serum levels of LNG are lower than with implant or pill • Good option for women who cannot take • IUDs are an appropriate option for adolescents; women who have not had children; women not in a monogamous relationship

Source: Mirena; Skyla; Kyleena; and Liletta prescribing information; Managing Contraception; Paragard prescribing information

METHODS LNG IUDS

Name Levonorgestrel Replace after _ years FDA / off-label

Mirena ® 52 mg (20 mcg/day) 5 years / 7 years

Liletta ® 52 mg (18.6 mcg/day) 5 years / 7 years

Kyleena ® 19.5 mg (17.5 mcg/day) 5 years

Skyla ® 13.5 mg (14 mcg/day) 3 years

Source: Mirena; Skyla; Kyleena; and Liletta prescribing information; Micromedex: Levonorgestrel

METHODS Implant (>99% effective) • Nexplanon ® • Contains 68mg (a progestin)

• Releases ~40-70 mcg daily

Source: Nexplanon prescribing information.

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METHODS Implant

Mechanism of Action How to Use Notes

Thickening of cervical mucus; Implanted under the skin in the FDA approved for 3 years of use; evidence alteration of endometrium; upper arm that it remains effective for 4-5 years suppression of Steady delivery of hormones

Good option for women who cannot take estrogen

Source: Nexplanon prescribing information; Ali, et al. Extended effectiveness of the etonogestrel-releasing … for 2 years beyond U.S. FDA Product Labeling. 2017.

METHODS Ring • Nuvaring ® etonogestrel/ethinyl estradiol 120/15 mcg/day

• AnnoveraTM segesterone acetate/ethinyl estradiol 150/13 mcg/day • Approved August 2018 • >99% effective (perfect use) • 91% effective (typical use)

Source: Nuvaring and Annovera package insert

METHODS Ring

Mechanism of Action How to Use Notes

Progesterone and estrogen combination Nuvaring Adherence may be higher vs. pill 1 ring inserted into the vagina Prevention of ovulation; thickening of for 3 weeks, then removed for 1 Easier to hide than patch or pill cervical mucus, inhibiting sperm week (off-label: use continuously for 4 weeks, then replace with Estrogen component also helps to new ring) Continuous, steady release of hormones & lowest serum levels of stabilize endometrium, decreasing Annovera hormones vs. other combined breakthrough bleeding 1 ring inserted into vagina for 3 weeks, then removed for 1 week; hormonal methods clean, dry, and store ring during off week; repeat

Source: Nuvaring and Annovera package insert

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METHODS Patch

• Xulane ® norelgestromin and ethinyl estradiol 150/35 mcg/day • >99% effective with perfect use • 91% effective typical use

METHODS Patch

Mechanism of Action How to Use Notes

Progesterone and estrogen combination 1 patch applied each week for Adherence may be higher vs. pill 3 weeks, then 1 week off (off- Prevention of ovulation; thickening of label: wear for 3 weeks, Higher estrogen exposure than pills or cervical mucus, inhibiting sperm remove and replace with new ring à may increase VTE risk patch immediately) Estrogen component also helps to stabilize endometrium, decreasing Less effective in women >90kg (198 lbs) breakthrough bleeding

Source: Xulane prescribing information; Managing Contraception

METHODS Shot • Depomedroxyprogesterone (DMPA) 150 mg (IM), 104 mg (SQ) • 99.8% effective perfect use • 94% effective typical use

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METHODS Shot Mechanism of Action How to Use Notes

Prevention of ovulation; thinning of IM or SQ injection every 3 May require appointment or pharmacy endometrium months (11-15 weeks) visit for injection Easier to keep hidden vs. other methods High discontinuation rate compared to other methods (~44-77% in various studies) Good option for women who can’t take estrogen Slow baseline return to fertility (~10 months avg; up to 18+ months)

Source: Depo Provera prescribing information; Managing Contraception

METHODS

Barrier Methods

Method Effectiveness – perfect use Effectiveness – typical use Male 98% 82% 95% 79% Sponge 80-91% 76-88% Diaphragm N/A 71-85% 82% 72% *best used with another method

Source: Bedsider.org; Managing Contraception

METHODS Behavioral Methods Method How to do it Notes

Abstinence Complete avoidance of vaginal intercourse Poor real-world adherence

Rhythm method Avoidance of vaginal intercourse during woman’s TM fertile period (~3-6 days before & 24 hours after ~88% effective (typical use of cyclebeads ) ovulation). Examples: Calendar tracking; cyclebeads TM Withdrawal Male withdraws his penis from the vagina prior to 96% effective with perfect use; 78% effective ejaculation typical use Cervical mucus checks; Basal body temperature; 95-99% effective with perfect use; 76-88% etc. Natural Cycles app is FDA approved effective typical use Lactational up to 6 months after birth IF exclusively Effectiveness up to ~98% in some studies breastfeeding, at least q4h during the day and q6h at night, and amenorrheic

Source: Bedsider.org; Managing Contraception; Natural Cycles FDA approval: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm616511.htm

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METHODS

Emergency Contraception Method Mechanism of Action How to Use Notes

Levonorgestrel Prevention of ovulation 1 tablet taken within 72 hours - Should be offered to all women (Plan B One Step; Next of unprotected intercourse using short-acting hormonal Choice; My Way, etc. ) (more effective the earlier it is contraception to have on hand in taken; may use up to 120 hrs the event of missed doses but less effective) ~98-99% effective; less effective in obese women 30 mg Progesterone receptor 1 tablet taken within 120 hours ~98-99% effective; less effective (Ella) modulator; inhibits or (5 days) of unprotected in obese women delays ovulation; may intercourse prevent implantation Copper IUD May interfere with Place within 5 days of Most effective emergency implantation unprotected intercourse contraceptive method (1/1000 failure rate)

Source: Bedsider.org; Managing Contraception

POP QUIZ!

True or False: Progestin-only oral contraceptives are less effective than combined oral contraceptives.

METHODS

Pill (progestin-only) • Norethindrone 0.35mg – “mini pill”; POP • 99.7% effective (perfect use)

• 91% effective (typical use)

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METHODS Pill (Progestin-Only)

Mechanism of Action How to Use Notes

Primarily works by thickening cervical 1 tablet by mouth every day As effective as combined oral mucus; ovulation suppressed in only at the SAME TIME (>3 hours contraceptives with correct use ~60% of users late = “missed dose”) Take m id-day? Thickening of cervical mucus occurs ~2- No placebo tablets; take 4 hours after taking the pill & lasts continuously Good option for women who can’t take about 22 hours estrogen

Source: Managing Contraception

METHODS Pill (combined: estrogen and progestin) • Contain ethinyl estradiol (EE) and a progestin • A few contain mestranol, which is metabolized to EE • 99.7% effective perfect use • 91% effective typical use

• Picking a pill to start • How much estrogen? • Which progestin? • Monophasic vs. multiphasic? • Which bleeding pattern?

METHODS Pill (Combined)

Mechanism of Action How to Use Notes

Progesterone and estrogen combination 1 tablet by mouth every day (at There is no clear evidence to indicate a about the same time) significant difference in efficacy, side effects, Prevention of ovulation; thickening of or tolerability between formulations cervical mucus, inhibiting sperm May skip placebos to avoid withdrawal bleeding Estrogen component also helps to stabilize endometrium, decreasing breakthrough bleeding

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Estrogen Progestin Monophasic vs. Multiphasic Bleeding Pattern

EE content varies from “Generation” may refer to Monophasic: same amount of Placebos induce a 10mcg-50mcg year marketed; structure; or estrogen & progestin in each withdrawal bleeding that activity (estrogenic, active tablet mimics the Higher EE = increased risk of androgenic, progestational) – VTE not standardized Multiphasic: varying amounts of No clear medical reason to and/or progestins have a regular “period” 1st: norethindrone – may have higher Lower EE = increased risk of irregular bleeding throughout the pack incidence of breakthrough Continuous/extended use 2nd: le vo n o r g e s tre l – more androgenic bleeding activity (increased risk of acne, Designed to more closely mimic may provide medical hirsutism, dyslipidemia) “natural” menstrual cycle & benefits Possible decrease in efficacy 3rd: norgestimate; desogestrel – lower reduce side effects with very low EE content? androgenic activity; increased risk of Improved efficacy? VTE (???) No clear evidence of reduced In general, start with a 4th: drosperinone – has anti- side effects Possible increase in pill that contains 30- mineralocorticoid & anti-androgenic breakthrough bleeding effects; increased risk of VTE (???) 35mcg EE Can become confusing when pills are missed No long-term data on No significant evidence to choose a particular safety of continuous use progestin In general, start with a monophasic regimen Patient preference; use monophasic pill Source: Pharmacist’s Letter. Document: 23(12):231207; Comparison of oral contraceptives and non-oral alternatives.

ADVERSE EFFECTS

• Evaluate • Discuss alternatives • Offer reassurance, education & counseling • Respect patient choice to discontinue any method at any time

ADVERSE EFFECTS Method Common Side Effects/Complications Serious Side Effects/Complications

Copper IUD Heavier, crampier periods Infection; expulsion; perforation; pregnancy complications LNG IUD Spotting; Infection; e x p u lsio n ; p e rfo ratio n ; p re gn an c y complications Implant Irregular periods; unpredictable Difficult removal; infection (very rare) breakthrough bleeding; headache; acne Shot Irregular periods; spotting; amenorrhea; Boxed warning: decreased bone mineral density acne; weight gain (reversible) Progestin-only pill Irregular periods; spotting; amenorrhea Not to be used in women with history of breast cancer in last 5 years Combined methods Spotting/breakthrough bleeding; decreased VTE/MI/Stroke (~100/100,000) (pill/patch/ring) libido; nausea/vomiting Increased risk of MI/stroke in smokers >35; hypertension, diabetes, hyperlipidemia, or obesity; migraine with aura (stroke risk only)

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MANAGING ADVERSE EFFECTS OF COMBINED PILLS

• No significant differences in formulations shown in RCTs • Switching to a different formulation may resolve issues, but no clear algorithm

Side Effect What to do

Nausea, vomiting Take w ith food; take in the evening

Breakthrough bleeding Usually resolves in 3-6 cycles; take at same time each day; adherence; smoking cessation; more common with very low dose EE; may be less common with norethindrone Acne Consider anti-androgenic progestin (e.g. drosperinone); avoid levonorgestrel Weight gain No evidence that CHCs promote weight gain vs. placebo; consider lifestyle factors

CASES

Discuss what contraceptive method(s) you would recommend for each of the following patients…

CASES

• A 38-year-old female who smokes ~20 cigarettes per day. • She has a past medical history significant for hypertension, well-controlled with lisinopril 40mg once daily (118/78 mmHg in office today). • She is married and in a healthy relationship. Her husband is supportive of any contraceptive choice she wants to make, but they both prefer not to use . • She does not have any children, and does not think she wants any children now or in the future. But she would like to wait until after her 40th birthday to make any permanent decisions.

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CASES

• A 15-year-old female with a history of heavy menstrual periods; no other significant PMH. • She is newly sexually active with her boyfriend, who is 16 and attends high school with her. He is willing to wear condoms, but she is very afraid of pregnancy and wants something more. • She does not want her parents to know that she is sexually active or using contraception. • She plans to attend college after high school, and does not want to have a baby until after graduating college.

CASES

• A 21-year-old female with a past medical history of complex partial seizures. • She takes topiramate 200mg by mouth twice daily, which has been effective in controlling her seizures. • She is not in a monogamous relationship; is sexually active with men she meets on Tinder. • She does not want children now, and says she would like to wait until she is at least 30 before having her first child.

CASES

• A 24-year-old female who gave birth to her first child four months ago. She has no significant PMH. She delivered vaginally with no complications. • She is married and in a healthy relationship. She and her husband are sexually active, about 2-3 times per month since the baby was born. • She would like to have another child within the next year. She wouldn’t mind if she got pregnant again now, but thinks it might be better to wait at least a few more months.

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THANK YOU!

QUESTIONS?

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