Using the Best Evidence to Select the Best Contraceptive Jody Steinauer, MD, MAS Dept. Ob/Gyn & Reproductive Sciences University of California, San Francisco

Disclosure Statement I have nothing to disclose.

Do you place intrauterine contraception in your clinical practice? a.Yes b.No

How comfortable would you be offering a woman an IUD if she had a history of Chlamydia and no current infection? a.Very comfortable b.Somewhat comfortable c.Uncomfortable

Would you offer a 20 year-old woman with migraine the combined oral contraceptive? a.Yes b.It depends c.No

Objectives Remember contraception in your clinical practice. Find evidence about contraception for women with possible contraindications. Encourage women to use longer acting methods. Address recent controversies and myths. Review extremely recent & important information.

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

6.4 Million US Pregnancies Annually 52 % Intended 48 % Unintended Jones PSRH 2008

6.4 Million U.S. Pregnancies Annually 52 % Intended 25 % Unintended Despite method use 23 % Unintended No method used Henshaw Family Planning Perspectives, 1998

Why did Jane get pregnant? Jane ran out of pills last month. She tried to schedule an appointment, but because she was overdue for a pap smear the clinic staff couldnt call in refills. Today was the first day she could get an appointment.

Provider Barriers to Contraception Clinical Visit BP check to initiate estrogen-containing methods No pap smear or other examination Refill methods without seeing patient Remember birth control 48% using D or X rx counseled on contraception 1 Knowledge about contraindications US guidelines Schwarz Ann Intern Med, 2007.

Case: Counseling Issues After Jane has completed her pregnancy she returns to you for contraceptive counseling. Jane has had migraine headaches since she was a teen. She has no aura and they have not changed with the combined pill. Can she use the pill again?

Can my patient use this method? 1Can use the methodNo restrictions 2Can use the methodAdvantages generally outweigh theoretical or proven risks. 3Should not use method unless no other method is appropriate Theoretical or proven risks generally outweigh advantages 4Should not use methodUnacceptable health risk WHO Medical Eligibility Criteria (MEC) www.reproductiveaccess.org www.who.int

Medical conditions Birth control methods MEC Category

US MEC: 2010 Current WHO MEC contains > 1800 recommendations No need to adapt most recommendations Science is the same Recommendations are used around the world CDC accepted majority of WHO recommendations Adapted a few for the US context

U.S. Medical Eligibility Criteria for Contraceptive Use (USMEC) United States Medical Eligibility Criteria for Contraceptive Use http://www.cdc.gov/reproductivehealth/unintendedpregnancy/USMEC.htm http://www.cdc.gov/reproductivehealth/unintendedpregnancy/USMEC.htm

US MEC: 2010 Existing WHO guidance Breastfeeding and CHC Breastfeeding and progestin only methods Postpartum IUDs Ovarian cancer and IUDs Fibroids and IUDs DVT/PE and hormonal contraception Valvular heart disease and IUDs New medical conditions Rheumatoid arthritis Endometrial hyperplasia Inflammatory bowel disease Bariatric surgery Solid organ transplantation Peripartum cardiomyopathy

Migraine and Combined Hormonal Contraception (CHC)

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

WHO/US: Headaches and CHC* Non-migrainous 1 Migraine (i) w/o focal neurologic symptoms Age < 352 Age > 353 (ii) w/ focal neurologic symptoms4 (at any age) Focal symptoms = AURA = vision changes, numbness, parasthesias Non-focal = Prodrome, photo/phonophobia, N/V

WHO/US: Headaches and CHC* InitiateContinue Non-migrainous1 2 Migraine (i) w/o focal neurologic symptoms Age < 352 3 Age > 353 4 (ii) w/ focal neurologic symptoms4 4 (at any age) Focal symptoms = AURA = vision changes, numbness, parasthesias Non-focal = Prodrome, photo/phonophobia, N/V

Absolute Risk of Stroke No COCCOC Healthy 6 per 100,000 /yr12 per 100,000 /yr Migraine 12 per 100,000 /yr19 per 100,000 /yr Migraine + aura 18 per 100,000 /yr30 per 100,000 /yr Stroke in pregnancy: 34 per 100,000 / year Speroff & Darney Clinical Guide for Contraception 2005

Case: Counseling Issues After reviewing the US and WHO MEC you decide Jane could use the pill again. But is it the best method for her?

How effective is the combined oral contraceptive for prevention of pregnancy? Typical use Perfect use

Natural Family Planning Contraceptive Method Failure Rate Perfect UseTypical Use No Method85% Periodic Abstinence Standard Days Method *5%12% Ovulation Method3%22% Symptothermal2%13-20% Two-Day Method 3%14% * Including Cycle Beads National Center Health Statistics; Contraceptive Technology

Barrier Methods Contraceptive Method Failure Rate Perfect UseTypical Use Withdrawal4 %18 % Condoms2 %17 % Cervical Cap (parous/nullip)26%/9%32%/16% Sponge (parous/nulliparous)20%/9%32%/16% Female Condoms5 %27 % Diaphragm6 %16 % National Center Health Statistics; Contraceptive Technology

Hormonal Methods Contraceptive Method Failure Rate Perfect UseTypical Use Combined Hormonal Pills 10 mm at day 7 of placebo week! If delay in new pack may ovulate! Baerwald, Contraception, 2004.

Extended Cycle: Shortened hormone-free week 23, 24 or 26 days hormones + 2-5 d placebo Decreased ovarian activity at end of placebo Shorter withdrawal bleeds Similar breakthrough bleeding 3 FDA-approved products in US New quadriphasic pill 2 d E, 22 d E+P, 2d E Start on cycle d 1; backup x 9 d Spona Contraception, 1996 Bachman Contraception, 2004 Endrikat Contraception, 2001.

Extended Cycle: Fewer hormone-free weeks 12 wks hormone/1 wk off Ethinyl estradiol and levonorgestrel 84 days LNG 150 g/EE 30 g; 7 days placebo Decreased breakthrough bleeding over time Anderson Contraception, 2003

Tricycle Breakthrough Bleeding/Spotting Anderson FD, et al., Contraception, 2003.

Extended Cycle: Continuous Use Continuous for one year Increased spotting in first six months Median 1.5 days spotting in last trimester FDA-approved: ethinyl estradiol and levonorgestrel 90 mcg levonorgestrel + 20 mcg EE Miller Obstetrics and Gynecology, 2003. Kwiecen, Contraception, 2003. Foidart, Contraception, 2006.

Choosing a COC Estrogen dose Low dose = < 50 mcg Progestin type 1 st -generation: norethindrone Second-generation: levonorgestrel Third-generation: desogestrel Drospirenone: spironolactone derivative VTE risk Increased risk with 3 rd generation progestin OR= 1.7 (1.4-2.0) Increased risk with drospirenone OR = 1.64 (1.27 to 2.10) Kemmeren BMJ 2001; Lidegaard BMJ 2009

Choosing a COC Careful with very low-dose estrogen bleeding Monophasic fine No drospirenone Increased risk VTE PMDD: fewer sxs 6 months equivalent at 2 yr Acne: Equivalent to other pills 30 or 35 mcg EE + 2nd generation progestin Shortened or erased placebo week if possible Monophasic VanViet Cochrane 2006 LaGuardia Contraception, 2003 Freeman Womens Health 2001 van Vloten Cutis 2002

Jane no longer wants to take a pill every day. She asks you about other birth control methods which she doesnt have to think about as often. What can you offer her? Weekly Monthly 3 months 3 years 5-10 years

Daily: Progestin-only Pills (POPs) 35 mcg norethindrone DAILY No hormone free interval!! Primary mechanism = cervical mucus thickening Requires very punctual dosing If > 3 hours late, need back up x 48 hours

Weekly: Transdermal Contraception Patch Norelgestromin and EE 20mcg EE & 150mcg norelgestromin One patch each week for 3 weeks, then week off Better compliance than with pill (88% v. 78%) Audet JAMA, 2001

Weekly: Patch Few side effects comparable to pills except: 20% skin irritation 2% stopped method More breast discomfort in first 2 cycles (19%) than pills (6%) More spotting (20%) than pills in first 2 cycles 3% detached recent RCT 46% experience at least one detachment in one cycle Prescribe replacement patch Creinin Obstet Gynecol 2008

Patch and VTE* 2 studies, 2 results No association: 1,2 59K patch & 147K OC users Risk of non-fatal VTE: OR=0.9 (CI 0.51.6) 1 OR=1.1 (CI 0.62.1) 2 All were new users No chart review Association: 3 99K patch & 257K OC users Risk of non-fatal VTE: OR=2.4 (CI 1.1-5.5) 3 New users: OR=2.2 (0.8-6.1) Charts reviewed 1.Jick SS Contraception 2006; 2. Jick SS Contraception 2007 3. Cole JA Obstet Gynecol 2007 Case control studies from insurance claims. Patch vs. 35mcgEE/norgestimate Better study supports increased risk.

EE Exposure with combined hormonal contraception van den Heuvel, Contraception 2005 (*30 mcg EE COC) AUC (pg/ml): Patch = 37.7 + 5.6 COC = 22.7 + 2.8 Ring = 11.2 + 2.7

Patch & Body Weight 3,319 patch users, 22,160 cycles 15 failures overall 0.8% failure 7 of them wt>80Kg 5 of them wt >90kg (90kg (198 lbs) Zieman M, Fertil & Steril, 2002

Monthly: Contraceptive Vaginal Ring Ethinyl estradiol and etonogestrel 15 mcg EE & 120 mcg desogestrel One ring each month: Ring in vagina x 3 wks Ring removed x 1 week Constant, low hormone levels Miller Obstet and Gynecol, 2005.

Monthly: Ring Few side effects comparable to pills except Spotting: only 5% (significantly less in first month) Discharge: 1% stop method Discomfort: 2.5% stop method Expulsion: recent RCT: 20% expelled at least once during 3-week period Dieben Obstet Gynecol, 2002 Creinin Obstet Gynecol, 2008

Monthly: Extended Cycle Ring RCT of 561 : 4wk, 8 wk, 12 wk, continuous: All regimens well-tolerated Extended: bleeding days, spotting days Potential for use on a monthly basis Serum levels for 35 days I instruct patients to remove ring the last 3-4 days of the month if they want withdrawal bleed. Miller Obstet Gynecol, 2005

Every 3 months: Progestin Injection Medroxyprogesterone acetate 150 mg IM One injection every 12-13 weeks Very effective Typical use failure = 3% 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) SQ low-dose (104 mg) version now available

Progestin Injection & BMD BMD decreases by 1-2% per year FDA: limit to 2 yrs. in young women WHO & ACOG do not agree Bone loss reverses by 1 year after discontinuation. No indication for DEXA Weigh risks against risk of pregnancy New evidence of increased fractures (OR 1.4, CI1.2-1.6) Overall risk is VERY low and returns to baseline 2yrs after d/c. Meier, J Clin Endocrin Metab, 2010. Scholes Arch Pediatr Adolesc Med, 2005.; Scholes, Epidemiology, 2002; ACOG 2008 Com Opin 415.

Progestin Injection: Delay Traditionally recommend caution after > 14 weeks from last DMPA injection WHO recommends 4-week grace period Repeat up to 16 weeks

Missed Hormonal Contraceptives: New Recommendations Guidelines for CHC and DMPA For CHC: The hormone free interval (HFI) not > 7 days In the 1 st week Back-up should be used after >1 missed dose until 7 days of use occur. Consider EC. In the 2 nd and 3 rd week If < 3 days are missed, eliminate the next HFI If > 3 days are missed, back-up contraception and consideration of EC should be added Soc Ob GYN of Canada, JOGC 2008; 219:1050-62

Every 3 years: Single-Rod Implant Etonogestrel 60mcg/day Efficacy > 99% Very easy & well tolerated to insert 1 year continuation: 75%-90% Reasons for discontinuation: Bleeding (11-40%) Mood swings (10%) Weight gain (10%) Blumenthal Eur J Contracept Reprod Health Care, 2008

Progestin Implant: Side Effects Bleeding: Irregularly irregular (40%) Amenorrhea: 22% 7% frequent: > 5 B-S episodes in 90-day period 18% prolonged: at least 1 B-S episode > 14 days 20% have B-S for >50 days in first 90-day period Generally NOT heavy Weight: minor changes (2.3%) Mean weight gain = 3.7 lbs at year 2 Blumenthal Eur J Contracept Reprod Health Care, 2008. Mansour Eur J Contracept Reprod Health Care 2008.

Implant: Bleeding Treatment Estrogen reduces number of bleeding days with 6-rod implant (and DMPA) 50 mcg Ethinyl Estradiol x 14-21 d Mifepristone reduces number of days Plus 20 mcg EE NSAIDS mixed results Ibuprofen 800mg po TID x 5 d Mefenemic acid 500 mg po BID x 5 d Aspirin 80 mg po qd x 10 d I recommend 1) Ibuprofen 2) 30 mcg COC or higher dose ERT

Every 5-10 Years: Intrauterine Devices (IUD, IUC, IUD, IUS) Levonorgestrel Intrauterine System (LNG-IUS) Levonorgestrel 20 mcg/day 0.1% failure (1 yr) 1.1% (7 yr ) Copper T 380A IUD 0.8% failure (1 yr) 1.2% failure (7 yr) Lockhat Fertil Steril, 2005 Comparable to BTL failure rate of 1.8% /10 yrs 10 years 5 years

Worldwide Use of IUD Population Reference Bureau, 2002. Asia % Using IUD Europe Latin America & Caribbean AfricaOceania North America

IUD Review Current IUDs do NOT cause PID!!! Transient increased risk at time of insertion STI at time of insertion increases risk GC/CT screening can follow CDC guidelines Okay to screen on insertion day treat if + Beyond time of insertion Overall decreased risk with LNG IUS No increased risk with Copper IUD Okay to treat for PID with IUD in place Svensson L, et al. JAMA. 1984; Sivin I, et al. Contraception. 1991. Farley T, et al. Lancet. 1992; Hubacher, NEJM, 2003.

Rate of PID by Duration of Use Rate per 1000 Woman- Years 20 days 21 days - 8 years n= 20,000 women. Adapted from Farley T, et al. Lancet. 1992;339:785-788. Baseline PID risk: 1-2 cases /TWY Duration

IUDs in Nulliparous Women Use by nulliparous women is safe and effective 1-4 LNG-IUS is appropriate for nulliparous women with menorrhagia and/or dysmenorrhea IUD expulsion, bleeding, and pain are slightly more likely among nulliparous women 2-5 Suhonen S. Contraception 2004;69:507-512 Nelson AL. Obstet Gynecol Clin North Am. 2000;27:723-740 Dardano KL, Burkman RT. Am J Obstet Gynecol. 1999;181:1-5 Li C. Contraception 2004;69:247-250 Treiman K, et al. Population Reports. 1995

IUD & Vaginal Bleeding Study Group Mean Blood Loss (mL) Control35 Paragard 50-80 Mirena5 After 12 mos: average 90% decrease blood Increased spotting common in first 3-6 months 50% have amenorrhea by 1 year Speroff & Darney Clinical Guide for Contraception 2005

Is Jane a candidate for an IUD? Women of any reproductive age seeking long-term, highly effective contraception

Postpartum Intrauterine Contraception

2010 US MEC: Postpartum IUD Insertion Postpartum (BF or non-BF women) including post- caesarean section LNG-IUDCu-IUD = 17 years Can be effective up to 5 days after unprotected sex No exam or pregnancy test required

Emergency Contraception Levonorgestrel 1.5 mg Single-dose tablet Labeled for 72 hours from last intercourse Two tablet dose new name Same as old Plan B Labeling: 1 tab Q12 hours; off label: 2 tablets at once Ulipristal Acetate (UPA): 30 mg Selective progesterone receptor modulator Taken orally in single 30 mg dose Approved in Europe(2009) for up to 5 days

Jane You counsel Jane about the other options available, emphasizing those with high efficacy that require less intervention. She ends up choosing a highly effective IUD which you place that same day.

Summary Unintended pregnancy remains a common problem in the US Many effective methods available Minimize barriers to contraception Provider, systemic, and patient Encourage more effective methods Use USMEC guidelines

Resources WHO and US Medical Eligibility Criteria for Contraceptive Use www.who.int www.cdc.gov www.cdc.gov www.reproductiveaccess.org A Pocket Guide to Managing Contraception UCSF Family Planning Consult Service (415) 443-6318

Acknowledgments Thanks to all who have shared slides Carolyn Sufrin Mike Policar Phil Darney Sarah Prager

Documents

Using the Best Evidence to Select the Best Contraceptive Jody Steinauer, MD, MAS Dept. Ob/Gyn & Reproductive Sciences University of California, San Francisco