Barriers Behavior Methods and Emergency Contraceptives Anita L

Barriers, Behavior Methods and Emergency Contraceptives Anita L. Nelson, MD Harbor-UCLA Medical Center Contemporary Forums

Conflict of Interest Disclosure Anita L. Nelson, MD Grants/ Research Bayer, Merck, Pfizer, Teva Bayer, Merck, Honoraria/ Speakers Bureau Pfizer, Teva, Watson Consultant/ Advisory Board Agile, Bayer, Merck, Teva, Watson Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 2

Learning Objectives At the end of this presentation, the participant will be able to: • Estimate underutilization of male condoms and suggest possible challenges to better use. • Counsel couples on fertility awareness methods. • Estimate the effectiveness of different methods of EC and their mechanisms of action. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 3

“Ten months ago, I would have called this (the condom) an invention of the devil, but now I find that its inventor must have been a man of good will. . . ” Jacques Casanova, 1758 Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 4

Condom Use and Remaining Need l Worldwide, 6 -9 billion condoms used each year l 24 billion condoms needed l Under-utilization not only from non-using couples but also from intermittent, inconsistent use by “condom users” Cecil M, et al. Contraception. 2010; 82(6) 489 -90. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 5

Male Condom Typical first year failure rate: 17. 4%; range 220% l Advantages: l u u u l Male participation Inexpensive Readily available u u Protects well against STDs Cervical dysplasia reduced Special applications: u u u Premature ejaculation Antisperm antibody Female allergy to sperm Kost K, et al. Contraception. 2008; 77(1): 10 -21. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 6

Male Condom Update Inconsistent use common 1 l Many new sizes needed 2 l New materials: polyisoprene l New incentives: ribbing, scents, vibrating rings l New market strategies: to women l New barriers: removed to locked cases l New biomarkers for failure 3 l Addition of condoms to COCs could reduce STDs, unintended pregnancies and abortions 4 l 1. Nelson AL, Am J Obstet Gynecol. 2006; 164(6): 1710 -5. 2. Cecil M, et al. Contraception. 2010; 82(6) 489 -90. 3. Walsh T, et al. Contraception. 2012; 86(1): 55 -61. 4. Pazol K, et al. Public Health Rep. 2010; 125(2): 208 -17. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 7

STI Risk Reduction l Use of condoms reduces risks of infection l HIV 80% reduction in transmission (male infected to female non-infected) u 28. 6% fewer births of HIV-positive babies than use of nevirapine in first 72 hours (potential) u l Gonorrhea u and Chlamydia Systematic review showed 80% reduction Nelson A. Chapter 12, Contraception, 1 st ed. Blackwell Publishing, 2011. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 8

STI Risk Reduction l Herpes u u Simplex Virus: Failed Vaccine Trial: frequent use reduced HSV-2 risk by 25% 18 month study: use of condoms >25% of time reduced HSV-2 acquisition risk 92% l HPV: Consistent use – incidence of infection reduced 70% Nelson A. Chapter 12, Contraception, 1 st ed. Blackwell Publishing, 2011. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 9

The Male Condom Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 10

Consistent Condom Use Reported by Women Who Had Sexual Intercourse in the Prior 14 Days by Coital Activity Acts of coitus 1 2 3 4 5* More than 5 * All # women who had coitus 48 34 35 28 29 43 217 % used condoms consistently 67% 65% 66% 61% 38% 40% 56% * Cochran-Armitage test for trend over number of acts of coitus: p=0. 001 Nelson AL. Am J Obstet Gynecol. 2008; 194(6): 1710 -6. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 11

Reasons Given for Not Using a Condom Percent of Reason responses Not perceived to be at risk 44% He withdrew / pulled out / “took care” 33% Used “rhythm” / Not at risk 12% Ran out/did not have any condoms 39% Dislike/Did not want to use condoms 33% Dislike condoms 15% Did not want to use condoms 19% Nelson AL. Am J Obstet Gynecol. 2008; 194(6): 1710 -6. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 12

Reasons Given for Not Using a Condom (cont’d) Reason Forgot condom Percent of responses 9% Not necessary / Lazy 7% Alternative method 7% Other 3% Nelson AL. Am J Obstet Gynecol. 2008; 194(6): 1710 -6. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 13

Other Worrisome Reasons Offered for Non-Use of Condoms l “Too drunk” l “He wanted me to use EC” l “I do not know how to use it” l “I did not think about it” l “I see the same person” l “In a rush” l “I never check” l “He told me to get on the pill” Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 14

The Top 5 Reasons For Not Using A Condom 1. “I didn’t know him well enough to ask him to use one. ” 2. “After two months, I knew we were in love, so we stopped using them. ” 3. “He would get mad at me if I asked him to. ” 4. “He’s from Kansas, so I know he’s diseasefree. ” 5. “We don’t like them. ” Real excuses collected by the PPLA clinic in Santa Monica, 1993. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 15

The Top 12 Reasons For Not Using A Condom 6. 7. 8. 9. 10. 11. 12. “I know I should, but. . . ” “I’m on the pill. ” “Well, I did once!” “He’s too big for the condom to fit. ” “I’m in a monogamous relationship. ” “We didn’t have any. ” “S/He looked clean. ” Real excuses collected by the PPLA clinic in Santa Monica, 1993. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 16

The Top 18 Reasons For Not Using A Condom 13. “She’s a virgin. ” 14. “You can’t get AIDS from a woman. ” 15. “He worked for TRW. He must be clean. ” 16. “Well, I already have herpes and warts. ” 17. “I’m not in a high-risk group. ” 18. “I can’t feel anything when we use them. ” Real excuses collected by the PPLA clinic in Santa Monica, 1993. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 17

Male Condoms: Sizes l Snug fitting u l Larger size—more headroom u l Beyond 7, Studded Beyond 7, Exotica Snugger Fit, Life. Styles Snugger Fit, Trojan Ultra Fit Trojan Ultra Pleasure, Trojan Very Sensitive, Bareback, Trojan Her Pleasure, Midnight Desire, Pleasure Plus, Life. Styles Xtra Pleasure, Inspiral, Durex Enhanced Pleasure, Life. Styles Natural Feeling Larger size—roomy from top to bottom u Anita L. Nelson, MD Maxx, Trojan Large, Magnum XL, Magnum, Durex Maximum, Life. Styles Large, Avanti, Crown, Trojan Supra Barrier Methods 2013 Contemporary Forums 18

Need for New Condom Sizes l French u clinical condom trial, 2003: 39% said latex condom too small or too large l US Survey 2009: 1661 men 17% condoms too long u 12% condom too short u 32% too tight u 10% too loose u l Australia: 3/5 reasons: Too tight, too short, too loose Cecil M, et al. Contraception. 2010; 82(6) 489 -90. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 19

Male Condoms: Other Characteristics l Sensitivity, texture, extra strength, desensitizing, pleasure producing, flavor/scent, color, lubrication l Desensitizing condoms with “climax control lubricant featuring benzocaine that helps prolong sexual pleasure and aids in prevention of premature ejaculation” (Durex Performax, Trojan Extended Pleasure) l Spermicidally lubricated condoms Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 20

Recently Introduced Condoms Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 21

Female Barrier Update l Contraceptive sponge variably available l Female condom FC 2 (nitrile) l Use of female vs. male condom u Less ejaculation, less active coitus, shorter coital duration 1 l New female condoms under development l SILCs diaphragm l 2 day method l Standard days method with beads 1. Haddad L, et al. Contraception. 2012; 86(4) 391 -6. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 22

Fem. Cap Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 23

Contraceptive Sponge l Approved by FDA in 1983, withdrawn in 1994, and reapproved in 2005 l Disposable polyurethane foam disk containing 1 gram N-9 l Single use device moistened and placed high in vault to cover cervix l Mechanisms of action: spermicide (24 hours) plus device absorbs semen and blocks cervix Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 24

Female Condom – Take 2: FC 2 l Made of nitrile (synthetic latex) FDA approved Reduced cost compared to FC 1 u Still more expensive than male condom u Comparable to FC 1 in breakage, invagination, slippage and misdirection, efficacy, ease of insertion, comfort and overall experience u Internationally, other female condoms: u l The Reddy Condom l National Sensation Panty Condom Schwartz J. The Female Patient. 2009; 34: 26 -9. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 25

Fertility Awareness Methods l Ovulation detection methods often combined to increase effectiveness: u u u l Calendar Basal body temperature Cervical mucus Sympto-thermal Cervical palpation Post ovulation Typical failure rate: 25. 3% Kost K, et al. Contraception. 2008; 77(1): 10 -21. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 26

Calendar or Rhythm Method l Collect information about menses from at least 6 months of experience l Assumptions: u u u l Formulas used to calculate at risk days: u l Sperm vulnerable for 3 days Ovum vulnerable for 24 hours Luteal phase lasts 14 +/- 2 days Cycle day [length of shortest cycle – 18] to Cycle day [length or longest cycle – 11] On average 13 days of abstinence/month u Anita L. Nelson, MD Provides 67. 8% of coverage of peak risk days Barrier Methods 2013 Contemporary Forums 27

Calculation of Fertile Period Shortest Cycle (Days) 21 23 25 27 29 32 35 First Fertile (Unsafe) Day 3 5 7 9 11 14 17 Longest Cycle (Days) 21 23 25 27 29 32 35 Last Fertile (Unsafe) Day 10 12 14 16 18 21 24 Day 1 = First day of menstrual bleeding. Hatcher RA, et al. Contraceptive Tech. 18 th Ed. New York: Ardent Media, 2004 Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 28

Newer Methods to Identify At-Risk Days l Standard Days Methods with Cycle. Beads l 2 -day method l Persona (not available in US) l Computer program l OV-Watch® l Urinary u Anita L. Nelson, MD ovulation kits Not recommended–too late! Barrier Methods 2013 Contemporary Forums 29

Cycle Beads l Color coded string of beads helps women identify days of cycle pregnancy is likely and unlikely Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 30

2 -Day Method l Simplified Billings technique l Woman checks introital secretions daily and asks herself 2 questions: Was I dry yesterday? u Am I dry today? u l Only if the answers to both questions are yes is intercourse allowed l Failure rates comparable to other FAMs Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 31

Persona l Hand-held ovulation detection monitor l Not available in US l Enter menses each month l Check each day: indicator light provides direction Red/Green – obvious interpretation u Yellow – dip test strip in urine to detect LH and E 3 G levels u l Light turns green or red l Over time, computer able to reduce number of uncertain (yellow light) days Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 32

Other Monitors l Lady u Free Biotester Hand held microscope to check saliva for ferning l OV-Watch® Fertility Predictor Wrist computer u Analyzes chloride ions in perspiration on wrist during sleep u Surge in chloride ions occurs 6 days prior to ovulation u Message on watch: “Fertile Day 01 – 06” u Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 33

Lactational Amenorrhea l Support women inclined to nurse their newborns u l Benefit to mother u u u l Sexual activity, contraception will not affect nursing Bonding with newborn Protection against ovarian, premenopausal breast cancer Lower cost than formula Benefit to newborn u u u Anita L. Nelson, MD Perfectly balanced nutrition Bonding with mother Reduction in newborn allergies and infections Barrier Methods 2013 Contemporary Forums 34

Contraceptive Sexual Practices l Withdrawal. l Rectal intercourse. l Oral intercourse. l Other. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 35

LNG-only EC Single-dose Versus 2 -dose Regimens 2 doses 1 dose 0. 75 mg 1. 5 mg Pregnancies 7/560 4/600 Effectiveness 86. 8% 92. 9% Headaches 14. 5% 21. 3% Breast tenderness 8. 8% 12. 9% ● No differences seen in nausea, vomiting, dizziness, lower abdominal pain, or heavy menses. Arowojolu AO, et al. Contraception. 2002; 66: 269 -73. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 36

LNG EC Mechanisms of Action l Cebus monkey: LNG EC inhibited or delayed ovulation. Once fertilization had taken place, EC did not prevent establishment of pregnancy 1 l Human: LNG administered during luteul phase did not cause significant endometrial changes 2 l Human: LNG EC blocks or delays ovulation, due either to prevention or delay of LH surge, rather than inhibiting implantation 3 1. Ortiz ME, et al. Hum Reprod. 2004; 19: 1352 -6. 2. von Hertzen H, et al. Fam Plann Perspect. 1996; 28: 52 -7, 88. 3. Gemzell-Danielsson K, et al. Hum Reprod Update. 2004; 10: 341 -8. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 37

LNG EC Mechanisms of Action l 99 women l Ovulation (day 0) calculated from LH, E 2 and P 4 levels obtained just prior to EC ingestion l Cycle day of IC derived from patient history l No pregnancies occurred when IC occurred day -5 to day -2 and EC taken before or on day 0 u 4 -5 pregnancies expected, 0 occurred l All pregnancies occurred when IC was day -1 to day 0 and EC was day +2 u 3 -4 pregnancies expected, 3 occurred Novikova N, et al. Contraception 2007; 75: 112 -8. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 38

Cycle Phase: Endocrinological vs Patient Estimate Women in Cycle Phase Follicular Periovulatory Luteal Number 41 30 20 Percent believing they are in phase Follicular 39% 13% 7% Periovulatory 17% 23% 18% Luteal 39% 53% 68% Unknown 5% 11% 17% Novikova N, et al. Contraception. 2007; 75: 112 -8. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 39

Meloxicam 15 mg Boosts LNG-EC Efficacy l Cox-2 inhibitor added to LNG-EC l Cyclo-oxygenase (Cox-2) catalyses final step of PG synthesis needed for follicle rupture % Failed Follicle Rupture Follicle Size 15 -17 mm ≥ 18 mm Overall LNG-EC + Placebo LNG-EC + Meloxicam 50% 16% 70% 39% 66% 88% Massai MR, et al. Hum Reprod. 2007; 22(2): 434 -9. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 40

Challenges of OTC EC l Patient has to pay out of pocket for LNG EC l Many pharmacies do not carry u 2008 telephone survey of all 1460 pharmacies in LA County as sham adult patient l 69% had EC available l 19% referred “elsewhere” l 12% said nothing could be done or hung up Nelson AL, et al. Contraception. 2009; 79(3): 206 -10. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 41

Challenges of OTC EC l Misinformation u u u u provided callers: “Abortion Pill” “Used to be available, isn’t anymore” “Have to be 21 to buy” “Only women can buy” “You could be pregnant if you had sex last night” “Have to take within 12 hours” “Have to take within 24 hours” “Have to wait 48 hours to take” Nelson AL, et al. Contraception. 2009; 79(3): 206 -10. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 42

Challenges of OTC EC l Unprofessional comments made: “You could use it, or you could have a beautiful little baby” u “Why aren’t you on the pill? ” u u “Are you married or single? ” “Have you had sex before? ” u “How long have you known him? u “Did he ejaculate inside you? ” u “Did he come inside you? ” u Nelson AL, Jaime CM Contraception. 2009; 79(3): 206 -10. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 43

Ulipristal Acetate l Selective progesterone receptor modulator 30 mg micronized version u Works as well as LNG in first 72 hours u u May be given up to 120 hours l Prevents u ovulation and fertilization Works even after the luteinizing hormone surge has begun Fine P, et al. Obstet Gynecol. 2010; 115(2 Pt 1): 257 -63. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 44

Ulipristal Acetate for Emergency Contraception 1553 treatments of women 48 -120 hours after unprotected intercourse l 30 mg Ulipristal acetate orally l Pregnancy rate l u u Overall 2. 1% 48 -72 2. 3% 72 -96 2. 1% 96 -120 1. 3% Cycle length increased a mean of 2. 8 days l Duration of bleeding did not change l Fine P, et al. Obstet Gynecol. 2010; 115(2 Pt 1): 257 -63. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 45

Ulipristal Acetate Ovulation Suppression up to 120 Hours l 34 women on ulipristal vs. 34 placebo with follicle ≥ 18 mm l All women ovulated l Ulipristal given Before LH surge start u After LH rise before peak u After LH peak u # Suppressed 8/8 11/14 1/16 Brache V. et al Human Reprod. 2010 25: 2256 -63. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 46

Ulipristal Acetate Adverse Events % of ITT n= 1, 553 Headache 9. 3 Nausea 9. 2 Abdominal pain 6. 8 Dysmenorrhea 4. 1 Dizziness 3. 5 Fatigue 3. 4 Fine P, et al. Obstet Gynecol. 2010; 115(2 Pt 1): 257 -63. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 47

Overweight and Obese Women Have Higher EC Failure Rates with LNG-EC Pregnancy Rates BMI LNG-EC UPA-EC < 25 kg/m 2 1. 3% 1. 1% 25 - 29. 9 kg/m 2 2. 5% 1. 1% ≥ 30 kg/m 2 5. 8% 2. 6% Further coitus 7. 3% 5. 6% Glaiser A, et al. Contraception. 2011; 84(4): 363 -7. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 48

Remaining Issues for UPA: Role in Quick Start Protocols u Concern: Ulipristal acetate is a selective progesterone receptor modulator (SPRM). l u Binds to progesterone receptor to block progesterone action If provide pharmacologic doses of progestin in contraceptive near time of administration of SPRM, will that diminish effect of SPRM? Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 49

Copper IUD for EC 8400 postcoital copper IUD placements 1 u Pregnancy rate 0. 1% to 0. 7% l Prospective trial: 1963 Cu. T 380 A placements within 120 hours 2 u No pregnancies; No PID u 94. 3% parous women continued at 12 months u 88. 2% nulliparous women continued for 1 year l Chinese trial: 1933 women within 120 hours 3 u Pregnancy rate: 0. 13% l 1. Trussell J, et al. Fertil Control Rev. 1995; 4: 8 -11. 2. Wu S, et al. BJOG. 2010; 117: 1205 -10. 3. Bilian X. Contraception. 2007; 75: S 31 -4. Anita L. Nelson, MD Barrier Methods 2013 Contemporary Forums 50

If you’ve been swept off your feet You’ve got 3 days to get them back on the ground Anita L. Nelson, MD Emergency contraception Use within 3 days of opening Barrier Methods 2013 Contemporary Forums 51