Update In Contraception 2014: New Options, New Controversies

1. Update In Contraception 2014: New Options, New Controversies Women’s Health Initiative August 19, 2014 Cleve Ziegler, M.D

2. Disclosure CME Speaker: Bayer, Schering-Plough (Merck), Bayer, Wyeth (Pfizer) Advisory Board: Bayer, GSK, Schering-Plough (Merck)

3. Outline of This Presentation • Physiology of Menstruation • Anthropology of Menstruation • Cultural Attitudes Toward Menstruation • Update In New Contraceptive Methods • Concept of Extended Cycle Contraception and Menstrual Suppression

4. Menstruation:Anatomy

5. Menstruation:Normal Physiology

6. Menstruation:Good or Bad? Normal Physiological Process Pathological Entity Ridding the body of toxins Sign of fertility and femininity Physiological anemia and reduction in cardiovascular disease Dysmenorrhea Menorrhagia Endometriosis Ovarian cancer Breast cancer Premenstrual syndrome Migraine headache Epilepsy

8. Address Risks Caused by Unplanned Changes in Methods UnintendedPregnanciesEach Year Unintended PregnanciesUsing Contraception 50 % 20 % Finer LG. Perspect Sex Reprod Health. 2006; Moreau C. Contraception. 2007. Frost JJ. In Brief. 2008.

9. “Love, Sex, Freedom and the Paradox of the Pill” “Arriving at a moment of social and political upheaval, the Pill became a handy proxy for wider trends: the rejection of tradition, the challenge to institutions, the redefinition of women’s roles” Nancy Gibbs, Time Executive Editor Time Magazine, May 3, 2010.

12. *not head-to-head comparison of contraceptive methods Unintended Pregnancy in First Year of Contraceptive Use* Women with Unintended Pregnancy within First Year of Use (%) COC=combined oral contraceptive; POP= progestin only pill; DMPA=depot medroxyprogesterone; LNG-IUS=levonorgestrel releasing intrauterine system Trussell J. Contraception 2004; 70: 89-96.

13. Opinions About Contraceptive Methods. Percentage of Respondents with “Very Favourable” Opinion, 2002 Canadian Contraception Study. Values in % *Based on Respondents Familiar with Method Fisher WA et al. JOGC 2004;June :580-590.

14. Most Commonly Used Contraceptive Methods by Canadian Women % of women Column totals may exceed 100% as women were allowed to choose more than one method. Base: Women aged 15-50 who have had vaginal intercourse in the previous 6 months, n=2,341 DMPA=depot medroxyprogesterone Back et al. J Obstet Gynaecol Can 2009;31(7):627–640.

15. Menstruation:Ethnic Preferences Cultural Preferences Geographic Trends

17. The Oral Contraceptive 21/7 Phasic 21/7 Phasic

18. Change in Estrogen and Dose 160 140 120 80 60 40 20 0 Ethinyl Estradiol Mestranol Estrogen (µg) 1960 1970 1980 1990 2000 Year of Introduction Thorneycroft IH. Infert Clin North Am. 2000;11:515-529.

21. Understanding Risk: Cardiovascular Adverse Events Most serious cardiovascular adverse events associated with all COCs Venous thrombo- embolism Stroke Myocardial infarction Farley et al., Contraception 1996; 57(3)211-30.

22. Putting the VTE Risk into Context Ten Thousand Women Years:                                           Non Pregnant Non Users OC Users Pregnant Women Dinger Contraception 2007

23. Increased Impact of Age and BMI on VTE Incidence in COC Users* BMI: body mass index *Risk estimates based on 115 VTEs in 116,708 WY of exposure Dinger, EURAS Study, Presentation EC Prague 2008.

24. Impact of Multiple Risk Factors on VTE Risk During OC Use 1 Risk Factor 2 Risk Factors 3 Risk Factors ** Family or personal history of VTE Based on EURAS study results: not yet published

26. The Spin Doctors at Work… • 1. Preferential prescribing of new preparations to new users • 2. Most VTE in first 6 months, newer users at higher risk • 3.Preferential prescribing of new drugs to higher risk patients because of perceived “safety”. • 4. Preferential prescribing of drospirenone to hyperandrogenic women who have underlying vascular disease

27. The EVRA Transdermal System

28. NuvaRing • 1 ring per cycle • Regimen: • 3 weeks of ring-use • 1 ring-free week • Daily release: • 15 µg ethinylestradiol • 120 µg etonogestrel

29. Pharmacokinetic profileNuvaRing and 30 EE/150 DSG COC Css OC Css OC Timmer & Mulders, Clin Pharmacokinet, 2000;39:233–42

32. World Wide Usage of IUD Prevalence of IUD use in women aged 15-49, married or in union (2005) D’Arcangues et a., Contraception. 2007; 75: S2-S7

33. Mirena • Intrauterine system (IUS) • Releases up to 20 μg/day of levonorgestrel (progestin) • No estrogen • 5 years of treatment Indications • Contraception

34. 2- Inhibition of sperm function Contraception with LNG-IUS Mirena provides contraception througha combination of 3 main actions: Minor effect on ovarian function 3- Prevention of endometrial growth 1- Thickening of cervical mucus

35. Menstrual cycle in awoman with Mirena Endometrium in resting state Resulting in scanty bleeding Effect of LNG-IUS on the Endometrium Normal menstrual cycle Days of cycle

37. Back to The Future:Depo-provera

38. Implanon

39. Implanon

40. Recommendations: • 1. Use 2nd generation pill with lowest estrogen dose as first choice • 2.If adverse effects occur, switch to 3rd or 4th generation pill. • 3.Patients at high risk for VTE should use progestin only pill, DMPA, or IUS. • 4.Use 2nd generation pill in older women