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Disclosure Statement

I have nothing to disclose. Using the Best Evidence to Select the Best Contraceptive

Jody Steinauer, MD, MAS Dept. Ob/Gyn & Reproductive Sciences University of California, San Francisco

What proportion of your patients are Are you familiar with the US Medical women of reproductive age? Eligibility Criteria for Contraception?

A. 0% 33% 67% B. 20% 27% A. Yes

C. 40% 20% B. No D. 60% 33%

10% E. 80% 8%

F. 100% 2%

A. B. A. B. C. D. E. F.

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Would you offer a 20 year-old woman with Do you place IUDs in your practice?

migraine the combined oral contraceptive? 67%

64%

A. Yes A. Yes 33% B. It depends B. No C. No 28%

9%

A. B.

A. B. C.

Objectives

How comfortable would you be offering a Inspire you to prioritize contraceptive counseling and provision in your practice nulliparous woman an IUD if she had a

I mp lan t I nj e c tion C o ndi tion p atch , ring L N G -- IU D Cop per-IUD Sub -con dit ion Com bin ed p ill, Progesti n- only p ill

A nemia s a ) Thalass emia 1 1 1 1 1 2 b) Sickle cell disease‡ 2 1 1 1 1 2 c ) Iron-defic iency anemia 1 1 1 1 1 2 B enign ovaria n( including cysts) 1 1 1 1 1 1 tumors

B reast dise ase a ) Undia gnosed mas s 2 2 2 2 2 1 b) Be nign breast dise ase 1 1 1 1 1 1 Make you comfortable using CDC Medical Eligibility c ) Family history of cancer 1 1 1 1 1 1 history of Chlamydia and no current i) current 4 4 4 4 4 1 ii) past and no evidence3 of 3 3 3 3 1 c urr ent disease for 5 years

C ervical 1 1 1 1 1 1 e ctropion

C ervical 2 1 2 2 2 1 intraepithelial neoplasia (C IN)

C irrhosis a ) Mild (compensa ted) 1 1 1 1 1 1 b) Severe ‡ (decompensated)4 3 3 3 3 1 ( DVT) i) higher risk for re current 4 2 2 2 2 1 /Pulmonary D VT/PE

e mbolism (PE) ii) lower risk for re current3 2 2 2 2 1 D VT/PE b) Acute DVT/PE 4 2 2 2 2 2 i) higher risk for re current 4* 2 2 2 2 2 D VT/PE Criteria (MEC) to determine safety ii) lower risk for re current 3* 2 2 2 2 2 D VT/PE

d) Family history (first-degree2 1 1 1 1 1 r elatives)

( i) w ith prolonged 4 2 2 2 2 1 im mobiliz ation

( ii) without prolonged 2 1 1 1 1 1 im mobiliz ation

f) Minor surgery without 1 1 1 1 1 1 im mobiliz ation infection? 45% A. Very comfortable 36% Review basics, controversies, myths and new updates about contraceptive methods B. Somewhat comfortable 18% C. Uncomfortable

A. B. C.

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6.4 Million U.S. Pregnancies Annually

Jane is a 27 year-old woman taking combined 25 % Unintended oral contraceptive pills, who presents to your Despite method use clinic for an annual examination. She reports having missed two periods. Her urine 52 % pregnancy test is positive. Intended

23 % Unintended No method used

Jones PSRH 2008 Mosher Vital Health Stat 2010

Why did Jane get pregnant? Provider Barriers to Contraception

Jane ran out of pills last month. She tried to • Clinical Visit schedule an appointment, but because she – BP check to initiate estrogen-containing methods was overdue for a pap smear the clinic staff – No pap smear or other examination couldn’t call in refills. Today was the first day – Refill methods without seeing patient she could get an appointment. • Remember birth control – 48% using D or X rx counseled on contraception 1 • Knowledge about contraindications – US guidelines

Schwarz Ann Intern Med , 2007 .

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Case: US Guidelines Can my patient use this method?

After Jane has completed her pregnancy she US Medical Eligibility Criteria (MEC) returns to you for contraceptive counseling. 1 Can use the method No restrictions Jane has had migraine headaches since she 2 Can use the method Advantages generally was a teen. She has no aura and they have outweigh theoretical or not changed with the combined pill. proven risks. 3 Should not use method Theoretical or proven risks Can she use the pill again? unless no other method generally outweigh is appropriate advantages 4 Should not use method Unacceptable health risk

Birth Control Methods Where do you find the US MEC?

Medical Condition

MEC Category

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Migraine and Combined Hormonal Migraine, COC*, and Stroke Contraception (CHC)

Synergistic effect of Migraine and COC

OR 8.7 (95% CI 5.0-15.0) 1 OR 13.9 (95% CI 5.5-35.1) 2

*COC= combined oral contraceptive pills Etminan BMJ , 2005. Tzourio BMJ, 1995.

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WHO/US: Headaches and CHC* WHO/US: Headaches and CHC*

Initiate Continue 1 Non-migrainous 1 Non-migrainous 2 Migraine Migraine (i) w/o focal neurologic symptoms (i) w/o focal neurologic symptoms Age < 35 2 Age < 35 2 3 Age > 35 3 Age > 35 3 4 (ii) w/ focal neurologic symptoms 4 (ii) w/ focal neurologic symptoms 4 4 (at any age) (at any age)

Focal symptoms = AURA = vision changes, numbness, parasthesias Focal symptoms = AURA = vision changes, numbness, parasthesias Non-focal = Prodrome, photo/phonophobia, N/V Non-focal = Prodrome, photo/phonophobia, N/V

Absolute Risk of Stroke Case: Counseling Issues

After reviewing the US and WHO MEC you No COC COC decide Jane can use the pill again. Healthy 6 per 100,000 ♀ /yr 12 per 100,000 ♀ /yr Migraine 12 per 100,000 ♀ /yr 19 per 100,000 ♀ /yr But is it the best method for her? Migraine + aura 18 per 100,000 ♀ /yr 30 per 100,000 ♀ /yr

Stroke in pregnancy: 34 per 100,000 ♀ / year

Speroff & Darney Clinical Guide for Contraception 2005

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Helping patients choose the best method How effective is the combined oral Future Pregnancy Plans contraceptive for prevention of pregnancy? 8% failure rate in 1 year Patient Preference How many pills, on average, Side effects do women forget to take each Safety month (not including placebo)? Efficacy Convenience Friend experiences Initial plan Typical use ≠ Perfect use

Oral Contraceptives 2010: Missed Pills Contraceptive Method Use, U.S.*

10 million = 800,000 40 pregnancies each year Most effective 6 Diary 35 Effective EMD 30 28% Least effective 5 5 ← 25 pills 4 20 15 3 10 6.6% 2 5

Mean Pills Missed Mean Pills 0 1 ← admit 1 0 1 2 3 Method Mosher Vital Health Statistics, 2010 Cycle *Among the 38 million women currently Hou, Ob Gynecol, 2010 using birth control Alan Guttmacher Institute, Facts In Brief, 2010.

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Contraception Methods Natural Family Planning Least effective Most effective Failure Rate 94% >99% Contraceptive Method <83% 92% Perfect Use Typical Use

Episodic Daily Weekly Monthly 3 Mo’s 3 yrs 5 yrs 10 yrs Permanent No Method 85% 85% Periodic Abstinence ® Ring Progestin Standard Days Method * 5% 12% OCPs Copper BTL Implant IUD Hysteroscopic Ovulation Method 3% 22% Barrier Vasectomy Patch DMPA LNG-IUS (IM or SQ) Symptothermal 2% 13-20% Two-Day Method ® 3% 14% EC

Combined Hormonal Progestin Only IUC Sterilization * Including Cycle Beads National Center Health Statistics; Contraceptive Technology

Barrier Methods Hormonal Methods

Failure Rate Failure Rate Contraceptive Method Contraceptive Method Perfect Use Typical Use Perfect Use Typical Use Withdrawal 4 % 18 % Combined Hormonal Pills <1 % 8 % Condoms 2 % 17 % Progestin Only Pills <1 % 8 % Cervical Cap (parous/nullip) 26%/9% 32%/16% Transdermal Patch <1 % 8 % Sponge (parous/nulliparous) 20%/9% 32%/16% Vaginal Ring <1 % 8 % Female Condoms 5 % 27 % 3-Month Injection <1 % 3 % Diaphragm 6 % 16 % Implants <1 % <1 % Copper IUD/LNG IUS <1 % <1 %

National Center Health Statistics; Contraceptive Technology National Center Health Statistics; Contraceptive Technology

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Frequency of Intervention

• Permanent: sterilization • Every 10 years: IUD • Every 5 years: IUD • Every 3 years: implant • Every 3 Months: injection • Monthly: vaginal ring • Weekly: patch • Daily: pill, NFP • Episodic: barrier methods, NFP Increasing efficacy http://www.fhi.org/nr/shared/enFHI/Resources/EffectivenessChart.pdf

Daily: Natural Family Planning Natural Family Planning: Two-day Method ®

• Help women identify fertile days • Study of 450 women – 3,928 cycles – Fertility window 6-8 days • Failure rates: – Failure rate 12-22% – 14% typical use • Two-day method ® – 3% perfect use (no intercourse) – Simple, accurate method – quicker to learn – 6% semi-perfect (barriers or withdrawal) – Two questions • Mean fertile window 12 days • Did I note secretions today? • High acceptability • Did I note secretions yesterday? • If yes to either, consider fertile

Arevalo, Fertil Steril , 2004.

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Extended Cycle: Daily: Combined Oral Contraceptives Shortened hormone-free week • Estrogen + progestin • 23, 24 or 26 days hormones + 2-5 d placebo • Traditional prescription flawed – Decreased ovarian activity at end of placebo – Daily x 3 weeks / 1 week off – Shorter withdrawal bleeds • Extended cycle may ↑efficacy – Similar breakthrough bleeding

– 3 FDA-approved products in US

Spona Contraception , 1996 Bachman Contraception , 2004 Baerwald, Contraception, 2004. Endrikat Contraception , 2001.

Extended Cycle: Tricycle Breakthrough Fewer hormone-free weeks Bleeding/Spotting • 12 weeks hormone/1 week off 20

• 15 Ethinyl estradiol and levonorgestrel 12 • 84 days LNG 150 µg/EE 30 µg; 7 days placebo 10 6 6 Days/Cycle • Decreased breakthrough bleeding over time 5 4

Median Number of BTB/Spotting 0 1 (1-84) 2 (93-175) 3 (183-266) 4 (274-357) Cycle (days)

Anderson FD, et al., Contraception , 2003. Anderson Contraception , 2003

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Extended Cycle: Choosing a COC Continuous Use • Continuous for one year • Estrogen dose – Increased spotting in first six months –Low dose = < 50 mcg – Median 1.5 days spotting in last trimester • Progestin type • FDA-approved: ethinyl estradiol and levonorgestrel –1st -generation: norethindrone – 90 mcg levonorgestrel + 20 mcg EE –Second-generation: levonorgestrel –Third-generation: desogestrel –Drospirenone: spironolactone derivative

Miller Obstetrics and Gynecology , 2003. Kwiecen, Contraception , 2003. Foidart, Contraception , 2006. Kemmeren BMJ 2001; Lidegaard BMJ 2009

VTE & oral progestin type Choosing a COC • • Desogestrel and drosperinone OCPs may Careful with very low-dose estrogen – ↑ bleeding • Monophasic fine increase risk of VTE • No clear benefit of drospirenone • BUT. . . Absolute risk remains low – PMDD: fewer sxs 6 months – equivalent at 2 yr – Acne: Equivalent to other pills Non-pregnant, no COCs: 4.4 per 10,000 ♀- yrs Levonorgestrel COCs: 5.0 per 10,000 ♀- yrs 30 or 35 mcg EE + 2nd generation progestin Desogestrel COCs: 6.5 per 10,000 ♀- yrs Shortened or erased placebo week if possible Drosperinone COCs: 7.8 per 10,000 ♀- yrs Monophasic

PREGNANCY: 29 per 10,000 ♀- yrs VanViet Cochrane 2006 LaGuardia Contraception , 2003 Lidegaard 2009 BMJ Freeman Womens Health 2001 Heinemann 2007 Contraception van Vloten Cutis 2002

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Jane no longer wants to take a pill every day. Daily: She asks you about other birth control Progestin-only Pills (POPs) methods which she doesn’t have to think • about as often. 35 mcg norethindrone DAILY – No hormone free interval!! What can you offer her? • Primary mechanism = cervical mucus thickening • Requires punctual dosing Weekly 5-10 years – If > 3 hours late, need back up x 48 hours 3 months

Monthly 3 years

Weekly: Patch Monthly: Ring

• Norelgestromin and EE • Ethinyl estradiol and etonogestrel – 20mcg EE & 150mcg norelgestromin – 15 mcg EE & 120 mcg desogestrel • One patch q week for 3 weeks, then no x 1 wk • One ring each month: • Few side effects – comparable to pills except: – Ring in x 3 wks – – 20% skin irritation – 2% stopped method Ring out x 1 week • Few side effects – comparable to pills except – More breast sx / spotting in first 2 cycles than pills – Spotting: less spotting – 3% detached –RCT 46% >= 1 detachment – Discharge: 1% stop method • Prescribe replacement patch – Discomfort: 2.5% stop method – Expulsion: RCT: 20% expelled at least once Dieben Obstet Gynecol, 2002 Creinin Obstet Gynecol 2008 Creinin Obstet Gynecol, 2008

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Monthly: Non-oral HC and VTE Extended Cycle Ring

3 • RCT of 561 ♀: 4wk, 8 wk, 12 wk, continuous: 2 case-control studies Retro cohort, 9.4 m ♀-yrs – • No association - new users • Attributable risk: All regimens well-tolerated – 1 OR=1.1 (CI 0.6–2.1) – +5.7/10K (vs. non) – Extended: ↓ bleeding days, spotting days • Association - all users – 2 – +1.5/10K (vs. COC) • Potential for use on a monthly basis OR=2.4 (CI 1.1-5.5) • NNT (switch to COC): – Serum levels for 35 days 3 Retro cohort, 9.4 m ♀-yrs – 2000 ring users • Attributable risk: – 1250 patch users I instruct patients to remove ring the last 3-4 days – +7.6/10K (vs. non) • No info on BMI, smoking, fam hx of the month if they want withdrawal bleed. – +3.5/10K (vs. COC)

1. Jick SS 2007 Contraception Miller Obstet Gynecol , 2005 2. Cole JA 2007 Obstet Gynecol 3. Lidegaard 2012 BMJ

EE Exposure with Every 3 months: combined hormonal contraception Progestin Injection • Medroxyprogesterone acetate 150 mg IM – AUC (pg/ml): One injection every 12-13 weeks Patch = 37.7 + 5.6 • Very effective COC = 22.7 + 2.8 – Typical use failure = 3% Ring = 11.2 + 2.7 • Side effects: – Delayed return to fertility (9-10 months) – Irregular bleeding, amenorrhea (50% at 1 yr) – Weight gain (5 lbs at 1 year, 16 lbs at 5 yrs) van den Heuvel, Contraception 2005 • (*30 mcg EE COC) SQ low-dose (104 mg) version – same SE

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Progestin Injection & BMD Progestin Injection: Delay

• BMD decreases by 1-2% per year • Traditionally recommend caution after > 14 • FDA: limit to 2 yrs. in young women weeks from last DMPA injection – WHO & ACOG do not agree • WHO recommends 4-week grace period – Bone loss reverses by 1 year after discontinuation. – Repeat up to 16 weeks – No evidence of increased fractures. • No indication for DEXA • Weigh risks against risk of pregnancy

Meier, J Clin Endocrin Metab, 2010 . Scholes Arch Pediatr Adolesc Med , 2005.; Scholes, Epidemiology , 2002; ACOG 2008 Com Opin 415.

Missed Hormonal Contraceptives: Every 3 years: New Recommendations Single-Rod Implant

• Guidelines for CHC and DMPA • Etonogestrel 60mcg/day • For CHC: • New version replaced old in 2011 – The hormone free interval (HFI) not > 7 days – Identical but with radiopaque rod st – – In the 1 week Easier-to-use inserter – • Back-up should be used after >1 missed dose until 7 days of Must complete FDA-approved training use occur. Consider EC. – In the 2 nd and 3 rd week • Efficacy > 99% • If < 3 days are missed, eliminate the next HFI • 1 year continuation: 75%-90% • If > 3 days are missed, also 1 week back-up contraception – Reasons for discontinuation: and consideration of EC should be added Bleeding ( up to 40%)

Soc Ob GYN of Canada, JOGC 2008; 219:1050-62 Blumenthal Eur J Contracept Reprod Health Care, 2008

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Progestin Implant: Side Effects Implant: Bleeding Treatment

• Bleeding: “Irregularly irregular” (40%) Therapy Evidence? – Amenorrhea: 22% 1. COC x 21d/7d (3 mo) or Estrogen alone Minimal – 7% frequent: > 5 B-S episodes in 90-day period (0.5 mg estradiol x 21 d) (3 mo) – 18% prolonged: at least 1 B-S episode > 14 days 2. Cyclic progestin (MPA 10bid) x 21d/7d Anecdotal (3mo) – 20% have B-S for >50 days in first 90-day period – Generally NOT heavy 3. POP daily up to 3 mo Anecdotal • 4. NSAIDs, COX-2 inhibitors x 5-10d Minimal Treatment of bleeding Tranexamic acid 500 bid x 5d Anecdotal

Blumenthal Eur J Contracept Reprod Health Care, 2008 Adapted from Mansour et al 2010, and 2011 Contraception Mansour Eur J Contracept Reprod Health Care 2008 .

Every 3 -10 Years: Intrauterine Devices IUD Review (IUD, IUC, IUD, IUS) • Current IUDs do NOT cause PID!!! Copper T 380A IUD – Transient increased risk at time of insertion 0.8% failure (1 yr) – STI at time of insertion increases risk Levonorgestrel Intrauterine – GC/CT screening can follow CDC guidelines System (LNG-IUS) – Okay to screen on insertion day – treat if + 10 years • Levonorgestrel 20 mcg/day • Beyond time of insertion • 0.1% failure (1 yr) • Overall decreased risk with LNG IUS New LNG IUS – 13.5 mcg/day 3-5 years • No increased risk with Copper IUD • 3 years • Okay to treat for PID with IUD in place Svensson L, et al. JAMA . 1984; Sivin I, et al. Contraception . 1991. Lockhat Fertil Steril, 2005 Farley T, et al. Lancet . 1992; Hubacher, NEJM, 2003.

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Routine GC/CT screening IUC, Nulliparity NOT necessary ! & Infertility • • Retrospective cohort, n=57,728 IUDs Nulliparity is not a contraindication – May have increased pain with insertion • Evidence-based STI screening, treat if + test – Overall PID risk = 0.54% May have increased risk of expulsion • IUDs do NOT cause infertility All women: Risk of PID Screened Women: Risk of PID Non-screening = Screening Same day = Pre-insertion – Tubal factor 1 ° infertility is not associated with OR= 1.05 (0.78, 1.43) OR=.997 (.64, 1.54) prior IUD use (OR=1)

Women appropriately selected Same-day screening fine, for non-screening Same (may be better) results < 26 yo Hubacher 2003 N Engl J Med Sufrin et al In press , Obstet Gynecol

Permanent: Is Jane a candidate for an IUD? Tubal Sterilization • Postpartum Women of any reproductive age seeking salpingectomy long-term, highly effective contraception • Silicone Band (Yoon, Fallope) • Filshie Clip • Electrosurgical dessication – unipolar lowest failure Failure risk 0.5-1.8% Increases over time

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Permanent: Post-exposure: Hysteroscopic Tubal Sterilization Oral Emergency Contraception • Coils inserted into proximal tubes via Levonorgestrel 120 mg x 1, up to 5 days hysteroscopy – Induces scarring reaction in tubes Ulipristal Acetate • Back-up method x 3 mo, confirm w/ HSG • Selective progesterone receptor modulator • Proposed mechanism: 1 – Delay follicular rupture • Low failure rate (0.26% at 5 yrs) • Will not harm existing pregnancy • Non-invasive • Dosing : 30mg, FDA-approved up to 5 days

1. Brache 2010 Hum Reprod

Emergency Contraception: Alternatives to LNG EC & Ulipristal Ulipristal Acetate acetate? Effectiveness: 1,2 • Copper IUD “Non-inferior” to LNG: 1.4% vs. 2.2% – VERY effective as EC up to 7 days! – More effective than LNG EC Meta-analysis of 3445 ♀ 120 hrs: OR = .55 (.32-.93) • Mifepristone (10, 25 or 50 mg) 24 hrs: OR = .35 (.11-.93) – More effective than LNG **May be more effective for obese women 3 • Yuzpe regimen Side effects: Headache (20%), nausea (12%) – More side effects and less effective

1. Glasier 2010 Lancet 2. Creinin 2006 Obstet Gynecol Cheng 2008 Cochrane Database 3. Moreau, 2012 Contraception

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Jane Summary

• You counsel Jane about the other options • Unintended pregnancy remains a common available, emphasizing those with high problem in the US. efficacy that require less intervention. She • We can minimize barriers to successful ends up choosing a highly effective IUD which contraception. you place that same day. • Consider including efficacy in your contraception counseling in addition to other priorities of the patient.

References

• Many easily accessible resources exist to help solve contraception quandaries. . . .

www.cdc.gov

www.acog.org www.arhp.org

http://www.managingcontraception.com/ http://www.who.int/reproductivehealth/publications/family_planning UCSF Family Planning Consult Service (415) 443-6318 Thanks to Carolyn Sufrin for sharing some slides. . . http://www.cochrane.org/

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Resources Acknowledgments

• • WHO and US Medical Eligibility Criteria for Thanks to all who have shared slides Contraceptive Use – Carolyn Sufrin – – www.who.int Mike Policar – – www.cdc.gov Phil Darney – – www.reproductiveaccess.org Sarah Prager • A Pocket Guide to Managing Contraception • UCSF Family Planning Consult Service – (415) 443-6318

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