Contraceptive Update

1. Contraceptive Update Anita L. Nelson, MD Harbor-UCLA Medical Center

3. Learning Objectives At the conclusion of this presentation, the participant will be able to: Counsel patients on the full array of contraceptive choices, including mechanisms of action, failure rates, contraindications, potential side effects and complications, and non-contraceptive benefits Suggest ways of increasing successful patient utilization of contraceptive methods Describe new approaches to older contraceptive methods

4. Current Status ofFamily Planning Problems High unplanned/unwanted pregnancy rate Lack of societal consensus about family planning Limited choice of effective methods Lack of understanding of and compliance with birth control methods Risk taking behaviors at all ages Lack of system to provide preconceptional care

7. Prenatal Behaviors by Pregnancy Intention

8. Tiers of Contraceptive Efficacy Managing partial or complete detachment is relatively simple If the patch becomes partially or completely detached and remains detached, insufficient drug delivery occurs If the patch remains even partially detached: For less than one day (up to 24 hours), the patient should try to reapply it to the same place or replace it with a new patch immediately. “Patch Change Day” will remain the same For more than one day (24 hours or more) OR if patient is not sure how long patch has been detached, she may not be protected from pregnancy. She should stop current contraceptive cycle and start new cycle immediately by putting on a new patch. There is now a new “Day 1” and a new “Patch Change Day.” Back-up contraception must be used for the first week of the new cycle only Managing partial or complete detachment is relatively simple If the patch becomes partially or completely detached and remains detached, insufficient drug delivery occurs If the patch remains even partially detached: For less than one day (up to 24 hours), the patient should try to reapply it to the same place or replace it with a new patch immediately. “Patch Change Day” will remain the same For more than one day (24 hours or more) OR if patient is not sure how long patch has been detached, she may not be protected from pregnancy. She should stop current contraceptive cycle and start new cycle immediately by putting on a new patch. There is now a new “Day 1” and a new “Patch Change Day.” Back-up contraception must be used for the first week of the new cycle only

9. Importance of Contraceptive “Fit” Contraceptive “fit” – the safest, most effective birth control method that will work well for the user A good fit depends upon a woman’s Individual health profile Lifestyle Reproductive stage Preferences

10. Etonogestrel Contraceptive Implant Not currently a Family PACT benefit Single implant rod (4 cm x 2 mm) made of ethylene vinyl acetate Contains 68 mg of etonogestrel(3-keto-desogestrel) Effective for 3 years 6 pregnancies in 26,000 cycles Inhibits ovulation and thickens cervical mucus Rapid return of fertility Contraceptive Implant: Implanon Implanon is not currently a Family PACT benefit. Notice of its addition to the formulary will appear in the Medi-Cal Bulletin once approved. Implanon the newest contraceptive implant system that has completed worldwide phase III clinical trials, however is not yet available in the United States. It is a single rod, etonogestrel-releasing system that contains 68 mg of 3-keto-desogestrel, with a membrane of ethylene vinyl acetate. The initial release rate of etonogestrel is 60-70 mcg/day, and declines to about 40 mcg/day at 12 months, to 34 mcg/day by 24 months, and to 25-20 mcg/day by 36 months. Inhibition of ovulation is the primary mechanism of action and occurs within one day of insertion. Effective contraception lasts for three years. References: Croxatto HB. Clinical profile of Implanon: a single rod etonogestrel contraceptive implant. Eur J Contracept Reprod Health Care. 2000;(5supp2):21-28. Huber J, Wenzl R. Pharmacokinetics of Implanon. An integrated analysis. Contraception. 1998;58(6 Suppl):85S-90S. Le J, Tsourounis C. Implanon: a critical review. Ann Pharmacother. 2001;35(3):329-36. POSTED: September 25, 2002 REVIEWED: September 25, 2002Contraceptive Implant: Implanon Implanon is not currently a Family PACT benefit. Notice of its addition to the formulary will appear in the Medi-Cal Bulletin once approved. Implanon the newest contraceptive implant system that has completed worldwide phase III clinical trials, however is not yet available in the United States. It is a single rod, etonogestrel-releasing system that contains 68 mg of 3-keto-desogestrel, with a membrane of ethylene vinyl acetate. The initial release rate of etonogestrel is 60-70 mcg/day, and declines to about 40 mcg/day at 12 months, to 34 mcg/day by 24 months, and to 25-20 mcg/day by 36 months. Inhibition of ovulation is the primary mechanism of action and occurs within one day of insertion. Effective contraception lasts for three years. References: Croxatto HB. Clinical profile of Implanon: a single rod etonogestrel contraceptive implant. Eur J Contracept Reprod Health Care. 2000;(5supp2):21-28. Huber J, Wenzl R. Pharmacokinetics of Implanon. An integrated analysis. Contraception. 1998;58(6 Suppl):85S-90S. Le J, Tsourounis C. Implanon: a critical review. Ann Pharmacother. 2001;35(3):329-36. POSTED: September 25, 2002 REVIEWED: September 25, 2002

11. Implanon Summary Provided unsurpassed contraceptive efficacy By ovulation suppression and thickened cervical mucus Very low levels of progestin Follicular phase estrogen Rare medical contraindications Rapid return to fertility Bleeding patterns better than Norplant Weight changes less well tolerated Not currently a Family PACT benefit As previously stated, Implanon is not currently a Family PACT benefit. Notice of its addition to the formulary will appear in the Medi-Cal Bulletin once approved.As previously stated, Implanon is not currently a Family PACT benefit. Notice of its addition to the formulary will appear in the Medi-Cal Bulletin once approved.

14. Copper IUD

15. IUD Issues: Infection PID and IUD use: confined to early weeks Farley’s reports from multinational studies: 9/1000 cases of PID Infection confined to first 20 days Finnish study of 975 women in 1996: No cases of PID U.S. studies: “PID” rate 1/1000

16. Copper Intrauterine DevicesMechanisms of Action Interference with sperm transport from cervix to fallopian tube Inhibition of sperm capacitation or survival Viable sperm scarce in fallopian tubes of IUD users Inhibition of fertilization: no normally dividing fertilized ova in tubes or uterus Not an abortifacient

17. Condition of Ova Recovered From Fallopian Tubes at Ovulation

18. Comparison Between Current And Newly Approved Label 1 World Health Organization. Improving access to quality care in family planning. Medical eligibility criteria for contraceptive use. 2nd edition. Geneva, Switzerland: World Health Organization, 2000 2 Stanwood NL, Grimes DA, Schulz KF. Insertion of an intrauterine contraceptive device after induced or spontaneous abortion: a review of the evidence. BJOG 2001;108:1168-73 3 Grimes DA. Intrauterine device and upper-genital-tract infection. Lancet 2000;356:1013-9 4 Penney G, Brechin S, de Souza A, Bankowska U, Belfield T, Gormley M, et al. FFPRHC Guidance (January 2004). The copper intrauterine device as long-term contraception. J Fam Plann Reprod Health Care 2004;30:29-41; quiz 42 5Grimes DA. Intrauterine devices and pelvic inflammatory disease: recent developments. Contraception 1987;36:97-109 6Grimes DA. Intrauterine device and upper-genital-tract infection. Lancet 2000;356:1013-9 7 Penney G, Brechin S, de Souza A, Bankowska U, Belfield T, Gormley M, et al. FFPRHC Guidance (January 2004). The copper intrauterine device as long-term contraception. J Fam Plann Reprod Health Care 2004;30:29-41; quiz 42 1 World Health Organization. Improving access to quality care in family planning. Medical eligibility criteria for contraceptive use. 2nd edition. Geneva, Switzerland: World Health Organization, 2000 2 Stanwood NL, Grimes DA, Schulz KF. Insertion of an intrauterine contraceptive device after induced or spontaneous abortion: a review of the evidence. BJOG 2001;108:1168-73 3 Grimes DA. Intrauterine device and upper-genital-tract infection. Lancet 2000;356:1013-9 4 Penney G, Brechin S, de Souza A, Bankowska U, Belfield T, Gormley M, et al. FFPRHC Guidance (January 2004). The copper intrauterine device as long-term contraception. J Fam Plann Reprod Health Care 2004;30:29-41; quiz 42 5Grimes DA. Intrauterine devices and pelvic inflammatory disease: recent developments. Contraception 1987;36:97-109 6Grimes DA. Intrauterine device and upper-genital-tract infection. Lancet 2000;356:1013-9 7 Penney G, Brechin S, de Souza A, Bankowska U, Belfield T, Gormley M, et al. FFPRHC Guidance (January 2004). The copper intrauterine device as long-term contraception. J Fam Plann Reprod Health Care 2004;30:29-41; quiz 42

21. Recent IUD Findings ParaGard is effective for 12 years (off label) 1 No increased risk of infertility in nulliparous IUD users 2 Chlamydia antibodies only predictor of infertility No increased risk of infection with IUD in HIV-infected women 3 IUD insertion immediately following first trimester abortion safe 4

22. Estimates of Cost Savings for Various Methods of Birth Control for a Fertile, Sexually Active Woman Over a Five-Year Period

23. Levonorgestrel-Releasing Intrauterine System (LNG IUS) Talking Points The product is as wide (32mm) as it is long with its arms fully extended. Small T shaped frame with a LNG containing cylinder. Potent progestin found in many combination oral contraceptive, progestin only pills, and implants. The LNG system releases LNG from the cylinder at 20 mcg per day into the uterine cavity for at least 5 years. Highly effective contraceptive protection. Published studies provide data on 12,000 women years of use . Two million women have used this method world-wide to date.Talking Points The product is as wide (32mm) as it is long with its arms fully extended. Small T shaped frame with a LNG containing cylinder. Potent progestin found in many combination oral contraceptive, progestin only pills, and implants. The LNG system releases LNG from the cylinder at 20 mcg per day into the uterine cavity for at least 5 years. Highly effective contraceptive protection. Published studies provide data on 12,000 women years of use . Two million women have used this method world-wide to date.

24. LNG IUS Typical Use Failure Rates (Pearl Index) First year 0.14% 5-year cumulative 0.71% Meta-analysis of comparative clinical trials showed no differences in efficacy compared to copper IUDs with = 250 mm2 copper

25. LNG IUS Plasma Concentrations of Levonorgestrel

26. LNG IUS: Menstrual Cycle Changes Months 1-4: increased days of spotting and bleeding (mean 1st month 16-17 days of spotting) After 6 months: average 1 day bleeding per month with some residual, unpredictable spotting By 12 months: mean bleeding days = 0; 80% had 1-3 days of spotting; 90% reduction in blood loss in women with menorrhagia; ? HbG 0.4 Amenorrhea: 20% by 12 months; 30% by 24 months; 60% by 12 years

27. LNG IUS: Treatment Heavy Bleeding Talking Points Overall reduction in menstrual blood loss is 90–97% Before-after study of 25 women Decrease menorrhagia in women with adenomyosis Significant increase in hemoglobin and decrease in uterine volume at 12 months Sources Andersson JK, Rybo G. Levonorgestrel-releasing intrauterine device in the treatment of menorrhagia. Br J Obstet Gynaecol 1990 Aug;97(8):690-4. Fedele L, Bianchi S, Raffaelli R, Portuese A, Dorta M. Treatment of adenomyosis-associated menorrhagia with a levonorgestrel-releasing intrauterine device. Fertil Steril 1997;68(3):426. Talking Points Overall reduction in menstrual blood loss is 90–97% Before-after study of 25 women Decrease menorrhagia in women with adenomyosis Significant increase in hemoglobin and decrease in uterine volume at 12 months Sources Andersson JK, Rybo G. Levonorgestrel-releasing intrauterine device in the treatment of menorrhagia. Br J Obstet Gynaecol 1990 Aug;97(8):690-4. Fedele L, Bianchi S, Raffaelli R, Portuese A, Dorta M. Treatment of adenomyosis-associated menorrhagia with a levonorgestrel-releasing intrauterine device. Fertil Steril 1997;68(3):426.

28. LNG-IUS: Treatment for Menorrhagia Due to Inherited Bleeding Disorders 16 women with inherited bleeding disorders 7 nulliparous; 9 parous (1 no NSVD) PBAC: 98-386 (median = 213) HBG: 12.1 (range 8.0-13.2) All women had at least 1 day/cycle when bleeding significantly affected life 38% had = 3 days/cycle

29. LNG-IUS: Treatment for Menorrhagia Due to Inherited Bleeding Disorders Hemostatic coverage provided during insertion Initial irregular bleeding similar to women with no bleeding problems At 3 months, all women reported improvement in menses At 9 months: 9/16 women had amenorrhea,7/16 women PBAC = 24-75 (median = 47) HBG range: 12.3-14.0 No woman had any days of significantly affected life

30. Menorrhagia Medical Therapy: LNG-IUS Advantages Long-term efficacy Effective: ~20% of patients amenorrheic at 1 year Highly effective contraception Delivery of progestin locally to endometrium 70 – 90% reduction in blood loss at 1 year Disadvantages Requires insertion Upfront initial cost The LNG-IUS delivers progestin locally in the endometrium, a potential advantage for avoiding systemic side effects. Like the injectable progestin, the contraceptive efficacy approaches that of surgical sterilization. The LNG-IUS may be the best option when the goal is amenorrhea, as approximately 20% do not have any bleeding by the end of one year after insertion. Reference: Milsom I, Andersson K, Anderesch B, Rybo G: A comparison of flurbiprofen, tranexamic acid, and levonorgestrel-release intrauterine contraceptive device in the treatment of idiopathic menorrhagia. Am J Obstet Gynecol 1991;164:879-83. The LNG-IUS delivers progestin locally in the endometrium, a potential advantage for avoiding systemic side effects. Like the injectable progestin, the contraceptive efficacy approaches that of surgical sterilization. The LNG-IUS may be the best option when the goal is amenorrhea, as approximately 20% do not have any bleeding by the end of one year after insertion. Reference: Milsom I, Andersson K, Anderesch B, Rybo G: A comparison of flurbiprofen, tranexamic acid, and levonorgestrel-release intrauterine contraceptive device in the treatment of idiopathic menorrhagia. Am J Obstet Gynecol 1991;164:879-83.

31. Menorrhagia Medical Therapy: Bleeding Reduction with LNG-IUS vs NSAID and Tranexamic Acid This slide displays the reduction in bleeding over a 12-month period for several therapies, although the patterns/timeframes of reduction differ among the methods. As this slide demonstrates, the LNG IUS reduces menstrual bleeding significantly more than several other methods. References: Milsom I, Andersson K, Anderesch B, Rybo G: A comparison of flurbiprofen, tranexamic acid, and levonorgestrel-release intrauterine contraceptive device in the treatment of idiopathic menorrhagia. Am J Obstet Gynecol 1991;164:879-83.This slide displays the reduction in bleeding over a 12-month period for several therapies, although the patterns/timeframes of reduction differ among the methods. As this slide demonstrates, the LNG IUS reduces menstrual bleeding significantly more than several other methods. References: Milsom I, Andersson K, Anderesch B, Rybo G: A comparison of flurbiprofen, tranexamic acid, and levonorgestrel-release intrauterine contraceptive device in the treatment of idiopathic menorrhagia. Am J Obstet Gynecol 1991;164:879-83.

32. RCT: LNG-IUS vs Transcervical Resection of the Endometrium: PBAC Score In a trial comparing the LNG-IUS and transcervical resection of the endometrium for menorrhagia, both approaches proved to be highly effective. In the study, 60 patients were randomized to one of the two treatments. In the surgical group, one patient did not complete the trial when she learned of her assigned therapy because she decided that she did not want an irreversible procedure. In the levonorgestrel IUS group, six patients discontinued therapy before follow-up was completed. In three, spotting that continued after 9 months led to termination of the therapy. In two, pain after insertion led to removal of the device. One at 17 days and the other at 5 months. In the last patient, the device was expelled. In those who completed 20 months of follow-up, the reduction in bleeding from baseline as evaluated with the pictorial blood loss assessment chart (PBAC) score was very similar, falling from a value of 418 to 12 in the levonorgestrel IUS group and from 378 to 6.6 in the surgery group. The authors described the reductions in both groups as dramatic, noting that the LNG-IUS was just as effective in long-term users but reversible. Reference: Kittelsen N, Istre O: A randomized study comparing levnorgestrel intrauterine system (LNB-IUS) and transcervical resection of the endometrium (TCRE) in the treatment of menorrhagia: preliminary results Gynecol Endos 1998;7:61-65.In a trial comparing the LNG-IUS and transcervical resection of the endometrium for menorrhagia, both approaches proved to be highly effective. In the study, 60 patients were randomized to one of the two treatments. In the surgical group, one patient did not complete the trial when she learned of her assigned therapy because she decided that she did not want an irreversible procedure. In the levonorgestrel IUS group, six patients discontinued therapy before follow-up was completed. In three, spotting that continued after 9 months led to termination of the therapy. In two, pain after insertion led to removal of the device. One at 17 days and the other at 5 months. In the last patient, the device was expelled. In those who completed 20 months of follow-up, the reduction in bleeding from baseline as evaluated with the pictorial blood loss assessment chart (PBAC) score was very similar, falling from a value of 418 to 12 in the levonorgestrel IUS group and from 378 to 6.6 in the surgery group. The authors described the reductions in both groups as dramatic, noting that the LNG-IUS was just as effective in long-term users but reversible. Reference: Kittelsen N, Istre O: A randomized study comparing levnorgestrel intrauterine system (LNB-IUS) and transcervical resection of the endometrium (TCRE) in the treatment of menorrhagia: preliminary results Gynecol Endos 1998;7:61-65.

33. RCT: LNG-IUS vs Endometrial Resection for DUB: Results at 12 Months In a parallel-group controlled trial designed to evaluate the relative efficacy of the levonorgestrel-releasing intrauterine system (IUS) and hysteroscopic endometrial resection for control of dysfunctional uterine bleeding, 70 women ranging in age from 38 to 53 were randomized to one of the two treatments. At the end of 12 months, the reduction in the pictorial blood loss assessment chart score (PBAC) was 79% for those treated with the levonorgestrel IUS and 89% for those treated with surgery. Sixty-five percent of women treated with levonorgestrel IUS versus 71% of women who underwent endometrial resection achieved amenorrhea or hypomenorrhea. The proportion of women who were satisfied or very satisfied was 85% and 94% for the IUS and surgery groups, respectively. Recurrent menorrhagia was observed at 12 months in 4 of the 35 women who received an IUS (including two with partial explusion of the device) and 3 of the 35 women who underwent hysteroscopic endometrial resection. None of these differences were statistically significant, indicating that the efficacy of the progestin-releasing IUS for control of bleeding is similar to endometrial resection. Reference: Crosignani PG, Verecellini P, Mosconi P, et al: Levonorgestrel-release intrauterine device versus hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding. Obstet Gynecol 1997;90:257-63 In a parallel-group controlled trial designed to evaluate the relative efficacy of the levonorgestrel-releasing intrauterine system (IUS) and hysteroscopic endometrial resection for control of dysfunctional uterine bleeding, 70 women ranging in age from 38 to 53 were randomized to one of the two treatments. At the end of 12 months, the reduction in the pictorial blood loss assessment chart score (PBAC) was 79% for those treated with the levonorgestrel IUS and 89% for those treated with surgery. Sixty-five percent of women treated with levonorgestrel IUS versus 71% of women who underwent endometrial resection achieved amenorrhea or hypomenorrhea. The proportion of women who were satisfied or very satisfied was 85% and 94% for the IUS and surgery groups, respectively. Recurrent menorrhagia was observed at 12 months in 4 of the 35 women who received an IUS (including two with partial explusion of the device) and 3 of the 35 women who underwent hysteroscopic endometrial resection. None of these differences were statistically significant, indicating that the efficacy of the progestin-releasing IUS for control of bleeding is similar to endometrial resection. Reference: Crosignani PG, Verecellini P, Mosconi P, et al: Levonorgestrel-release intrauterine device versus hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding. Obstet Gynecol 1997;90:257-63

34. 6 month follow up 25 LNG-IUS 21 women continued with LNG-IUS 3 amenorrheic 16 reduced bleeding 3 unchanged – 1 requested hysterectomy 25 thermal balloon ablation 2 amenorrheic 16 reduced bleeding 4 unchanged requested hysterectomy 1 worsened RCT: Thermal Balloon Ablation vs LNG-IUS in Treatment of Menorrhagia In a randomized study of 50 women with menorrhagia, the levonorgestrel intrauterine system (LNG-IUS) was found to be as effective as endometrial thermal balloon ablation when measured on a pictorial menorrhagia scoring method. Median scores fell dramatically, signaling improvement in perception of menorrhagia, in both groups. At 6 months, the scores were slightly lower in the LNG-IUS group than in the thermal balloon ablation, although the advantage was not statistically significant (P=.689). Of the 25 women treated with LNG-IUS, 19 had reduced bleeding or became amenorrheic. Of the 25 women treated with ablation, 18 reduced bleeding of became amenorrheic. The authors of the study concluded that the similarity of efficacy between the two methods suggests that the choice between these treatments should be based on the women’s own needs and preferences. Reference: Barrington JW, Arunkalaivanan AS, Abdel-Fattah M: Comparison between the levonorgestrel intrauterine system (LNG-IUS) and thermal balloon ablation in the treatment of menorrhagia. Eur J Obstet Gynecol Reprod Biol 2003;108:72-4.In a randomized study of 50 women with menorrhagia, the levonorgestrel intrauterine system (LNG-IUS) was found to be as effective as endometrial thermal balloon ablation when measured on a pictorial menorrhagia scoring method. Median scores fell dramatically, signaling improvement in perception of menorrhagia, in both groups. At 6 months, the scores were slightly lower in the LNG-IUS group than in the thermal balloon ablation, although the advantage was not statistically significant (P=.689). Of the 25 women treated with LNG-IUS, 19 had reduced bleeding or became amenorrheic. Of the 25 women treated with ablation, 18 reduced bleeding of became amenorrheic. The authors of the study concluded that the similarity of efficacy between the two methods suggests that the choice between these treatments should be based on the women’s own needs and preferences. Reference: Barrington JW, Arunkalaivanan AS, Abdel-Fattah M: Comparison between the levonorgestrel intrauterine system (LNG-IUS) and thermal balloon ablation in the treatment of menorrhagia. Eur J Obstet Gynecol Reprod Biol 2003;108:72-4.

35. Menorrhagia: Conclusion from Trial Data Comparing LNG-IUS to Surgery “Surgery reduces menstrual bleeding at one year more than medical treatments, but levonorgestrel IUS appears equally beneficial in improving quality of life and may control bleeding as effectively as conservative surgery over the long term” The conclusion from the Cochrane Review is the levonorgestrel IUS appears to be a reasonable alternative to surgery for long-term control of heavy menstrual bleeding. Reference: Marjoribanks J, Lethaby A, Fahrquhar C: Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database Syst Rev 2003;2:CD003855The conclusion from the Cochrane Review is the levonorgestrel IUS appears to be a reasonable alternative to surgery for long-term control of heavy menstrual bleeding. Reference: Marjoribanks J, Lethaby A, Fahrquhar C: Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database Syst Rev 2003;2:CD003855

36. Hysterectomy vs LNG-IUSTreatment for Menorrhagia 107 hysterectomies Complications in 35 women: bladder and bowel perforation, fistula, bowel obstruction, wound rupture, infection, etc. 119 LNG-IUS 31 had IUS removed due to bleeding/spotting or hormonal symptoms 24 had hysterectomy by 1 year more likely to develop asymptomatic ovarian cysts Mean cost per women for LNG-IUS was 36% cost of hysterectomy In a multicenter randomized comparison of the levonorgestrel intrauterine system (LNG-IUS) and hysterectomy, 226 women with menorrhagia were assigned to LNG-IUS or hysterectomy. At the end of 12 months, both treatments were associated with substantial and comparable improvements in quality of life, the primary endpoint of the trial. Of the 119 women assigned to LNG-IUS, 68% continued to use the system at the conclusion of the trial. Most of the remaining patients had removal of the IUS due to bleeding/spotting or hormonal symptoms, and approximately 85% of these patients proceeded to hysterectomy. Of the 117 women assigned to hysterectomy, 107 actually underwent the procedure. Of these, 35 had complications ranging from minor infection to bowel perforation and bowel obstruction. Overall costs were calculated to be approximately 3 times greater in the surgical group. The authors concluded that LNG-IUS is a cost effective alternative to hysterectomy in women with menorrhagia. Reference: Hurskainen R, Teperi J, Rissanen P, et al: Quality of life and cost effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial. Lancet 2001;357:273-7In a multicenter randomized comparison of the levonorgestrel intrauterine system (LNG-IUS) and hysterectomy, 226 women with menorrhagia were assigned to LNG-IUS or hysterectomy. At the end of 12 months, both treatments were associated with substantial and comparable improvements in quality of life, the primary endpoint of the trial. Of the 119 women assigned to LNG-IUS, 68% continued to use the system at the conclusion of the trial. Most of the remaining patients had removal of the IUS due to bleeding/spotting or hormonal symptoms, and approximately 85% of these patients proceeded to hysterectomy. Of the 117 women assigned to hysterectomy, 107 actually underwent the procedure. Of these, 35 had complications ranging from minor infection to bowel perforation and bowel obstruction. Overall costs were calculated to be approximately 3 times greater in the surgical group. The authors concluded that LNG-IUS is a cost effective alternative to hysterectomy in women with menorrhagia. Reference: Hurskainen R, Teperi J, Rissanen P, et al: Quality of life and cost effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial. Lancet 2001;357:273-7

37. LNG IUS as Alternative to Hysterectomy Talking Points 56 women aged 33-49, scheduled to have hysterectomy for heavy uterine bleeding, three hospitals in Finland Randomized to LNG IUS or current medical treatment At an average follow-up of three years (range 23-49 months), 13 of 27 women (48%) were still using the LNG IUS The system may provide a long-term alternative to hysterectomy A case-series report of 50 women in Britain shows similar results. Of 50 women scheduled for hysterectomy due to heavy bleeding, 41 who received LNG IUS were taken off the list after nine months, with four developing complete amenorrhea. Source Lahteenmaki P, Haukkamaa M, Puolakka J, Riikonen U, Sainio S, Suvisaari J, Nilsson CG. Open randomized study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy. BMJ 1998 Apr 11;316(7138):1122. Talking Points 56 women aged 33-49, scheduled to have hysterectomy for heavy uterine bleeding, three hospitals in Finland Randomized to LNG IUS or current medical treatment At an average follow-up of three years (range 23-49 months), 13 of 27 women (48%) were still using the LNG IUS The system may provide a long-term alternative to hysterectomy A case-series report of 50 women in Britain shows similar results. Of 50 women scheduled for hysterectomy due to heavy bleeding, 41 who received LNG IUS were taken off the list after nine months, with four developing complete amenorrhea. Source Lahteenmaki P, Haukkamaa M, Puolakka J, Riikonen U, Sainio S, Suvisaari J, Nilsson CG. Open randomized study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy. BMJ 1998 Apr 11;316(7138):1122.

38. LNG IUS Versus Hysterectomy:Outcomes and Costs 236 women age 35-49 with menorrhagia Randomized to hysterectomy versus LNG-IUS 5-year follow-up No difference in Health-related Quality Of Life 42% of LNG-IUS users underwent hysterectomy

39. Menstrual Blood Loss: Median Pictorial Blood Assessment Chart

40. LNG IUS: Other Applications Suggested By Literature Treatment of primary menorrhagia Treatment of menorrhagia due to leiomyoma, adenomyosis, diabetes Treatment for dysmenorrhea due to endometriosis Treatment for PMS symptoms Endometrial protection from tamoxifen-induced changes Treatment for endometrial hyperplasia Source of progestin in hormone replacement therapy IUS in oocyte donor during ovarian stimulation

42. Depo Medroxyprogesterone Acetate (DMPA) Dose: 150 mg every 11-13 weeks Highly effective with consistent and correct use First year : 0.25-0.3% Five-year cumulative : 0.9% Typical use first-year failure rate: 3.0% Very convenient and private Special clinical applications

43. DMPA: Clinical Applications Sickle cell anemia Mental retardation Breast feeding Seizure disorders

44. DMPA Issues Side effects: Menstrual irregularities tend toward amenorrhea with time Slow return to fertility (10 months average delay to conception) Concerns: Weight gain (1-3 kg with long-term use) Low estrogen levels (bone density effects) Removes incentive for condom use

45. DMPA and Weight Change: Recent Observational Studies

46. DMPA And Weight Gain Mechanisms Pelkman, et al: the only placebo-controlled, prospective study N=20; 20-35 years old Run-in period First 4 sessions (~2 months) assessed effects of endogenous hormones on weight change Administration of DMPA or saline control Intensively evaluated every 2 weeks (total 8 weeks) for changes in weight, energy expenditure, and food consumption

47. DMPA: No Change in BMR, Appetite, or Weight Results: In this short-term, prospective, randomized trial of normal weight women, Depo-Provera did not result in weight gain, appetite increase, or a change in the basal metabolic rate (BMR). While this was a small study, the design was such that it clearly showed a lack of effect on weight gain mechanisms, specifically, appetite increase or change in BMR. More randomized, controlled-trials are needed to definitively address this issue. All patients, including DMPA users, should be counseled to maintain good nutrition and exercise habits.   Reference Pelkman CL, Chow M, Heinbach RA, Rolls BJ. Short-term effects of a progestational contraceptive drug on food intake, resting energy expenditure, and body weight in young women. Am J Clin Nutr 2001;73:19-26.Results: In this short-term, prospective, randomized trial of normal weight women, Depo-Provera did not result in weight gain, appetite increase, or a change in the basal metabolic rate (BMR). While this was a small study, the design was such that it clearly showed a lack of effect on weight gain mechanisms, specifically, appetite increase or change in BMR. More randomized, controlled-trials are needed to definitively address this issue. All patients, including DMPA users, should be counseled to maintain good nutrition and exercise habits.   Reference Pelkman CL, Chow M, Heinbach RA, Rolls BJ. Short-term effects of a progestational contraceptive drug on food intake, resting energy expenditure, and body weight in young women. Am J Clin Nutr 2001;73:19-26.

48. DMPA: Black Box Warning Women who use Depo-Provera Contraceptive Injection may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible. It is unknown if use of Depo-Provera Contraceptive Injection during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporotic fracture in later life.

49. DMPA: Black Box Warning Depo-Provera Contraceptive Injection should be used as a long-term birth control method (e.g. longer than 2 years) only if other birth control methods are inadequate.

50. Clinical Suggestions at Initiation to Cope with New Labeling Encourage all DMPA users to use calcium supplements Teens need 1300 mg of calcium daily High calcium intake by teens protects against trabecular bone loss, even in pregnancy1 Advise patients of possible DMPA impacts on BMD and probable 2-year limitation for continuous use

51. Recommendations Since Publication of Black Box Warning Evaluate underlying risks for low BMD in adolescent women desiring prolonged DMPA Cigarette smoking Corticosteroid use Eating disorders Excessive exercise patterns For women without additional risk factors for low BMD, 2 year restriction appears unwarrantedDialogues in Contraception Editorial Board, 2005

52. Recommendations Since Publication of Black Box Warning Bone mineral density screening should not be recommended to a client for the sole purpose of evaluating appropriateness of DMPA usage Calif. Office of Family Planning, 2005

53. Recommendations Since Publication of Black Box Warning The current evidence on DMPA use and skeletal health indicates that concerns regarding BMD should not restrict initiation or continuation of DMPA use in adults or teens. Because the clinical implications of dual energy X-ray absorptiometry testing in premenopausal women are not well established, DXA assessment is not recommended for DMPA users.

54. Recommendations Since Publication of Black Box Warning Because the safety of bisphosphonates in reproductive-age women is not established, such medications should not be prescribed to current or former DMPA users. Adequate calcium intake should be encouraged, but this recommendation applies for all women regardless of contraceptive use.

55. DMPA Onset of action immediate if DMPA given in first 5 days of menstrual cycle If given after that period, must use back-up method for at least 7 days Continuation rates may be lower than reported clinical trials due to system barriers Teens have high discontinuation rates and stop-start pattern of use

58. Oral Contraceptive Pills Safe and well-tested -- the gold standard: 45 years of clinical experience in US Best studied medication in history Failure rate with consistent and correct use < 1% Typical first year failure rate is 8% Rapidly reversible: Only 2 week average delay in fertility Extensive non-contraceptive benefits Clinical experience in US since 1960Clinical experience in US since 1960

59. “Birth control pills are not dangerous, but there are dangerous women out there. Find them and keep them away from the pill, and the pill will do its work well.”

60. OC Failure by Body Weight >70.5 kg and OC Estrogen Dose A sub-analysis was conducted stratified by OC estrogen dose Results indicated that weight-associated risk of OC failure was higher among the women who reported using very low dose OCs This, and other previously published reports, allude to an explanation that hormonal contraceptive users of heavier weight have an overall enhanced metabolic rate that leads to a more rapid drug metabolism thus providing insufficient serum steroid levels for proper contraceptive efficacy A sub-analysis was conducted stratified by OC estrogen dose Results indicated that weight-associated risk of OC failure was higher among the women who reported using very low dose OCs This, and other previously published reports, allude to an explanation that hormonal contraceptive users of heavier weight have an overall enhanced metabolic rate that leads to a more rapid drug metabolism thus providing insufficient serum steroid levels for proper contraceptive efficacy

61. Oral Contraceptives and the Risk of Breast Cancer for Women of Age 35-64 Population based, case control study 4,575 women with breast cancer 4,685 control women Current users: RR = 1.0 (0.8-1.3) Former users: RR = 0.9 (0.8-1.0) No consistent increases with increasing estrogen dose or duration of use No association with family history of breast cancer or young initiation

62. Non-Contraceptive Health Benefitsof Oral Contraceptives Proven Reduction in Risk: Ovarian Cancer Endometrial Cancer Pelvic Inflammatory Disease Ectopic Pregnancy Benign Breast Disease Menorrhagia Dysmenorrhea Iron Deficiency Anemia Low Bone Density

63. Reduction in Total Acne Lesions

64. Incidence of Events Commonly Attributable to OC Use

65. Treatment of PMDD with 24/4 drospirenone with 20 mcg EE

66. New Developments in OCs Concern for use in obese women > 35 Change in placebo pills Placebo pills replaced by low-dose E2 New start/utilization patterns Extended/continuous use 84/7 product Monophasic progestin-dominant pills Quick start First day start each cycle

67. Extended OC Applications: Control of Menstrual Cycle Timing or Convenience Honeymoons Business meetings Travel Sporting events Military campaigns Examinations Life

68. Extended Cycle OC Trial: Scheduled Withdrawal Bleeding/Spotting Days It is not possible to directly compare the bleeding patterns associated with a 91-day cycle OC (SEASONALE) with that of a 28-day cycle regimen, like Nordette®, because of the inherent differences in the number of annual hormone free days and scheduled bleeding days. [Anderson, p 93] The number of annual hormone free days with SEASONALE is 28 days compared with 91 days for women receiving Nordette. [Anderson, p 93] On a per cycle basis, the number of withdrawal bleeding days was similar in both treatment groups. [Anderson, p 94-95] After one year, women receiving SEASONALE experienced a median of 10 scheduled withdrawal bleeding/spotting days compared with 36 days for the women receiving Nordette. This is mainly due to the design of SEASONALE, which has only 4 scheduled hormone-free cycles compared with 13 for Nordette. [Anderson, p 93] Anderson FD, Hait H, and the Seasonale-301 Study Group. A multicenter, randomized study of an extended-cycle oral contraceptive. Contraception. 2003;68:89-96. It is not possible to directly compare the bleeding patterns associated with a 91-day cycle OC (SEASONALE) with that of a 28-day cycle regimen, like Nordette®, because of the inherent differences in the number of annual hormone free days and scheduled bleeding days. [Anderson, p 93] The number of annual hormone free days with SEASONALE is 28 days compared with 91 days for women receiving Nordette. [Anderson, p 93] On a per cycle basis, the number of withdrawal bleeding days was similar in both treatment groups. [Anderson, p 94-95] After one year, women receiving SEASONALE experienced a median of 10 scheduled withdrawal bleeding/spotting days compared with 36 days for the women receiving Nordette. This is mainly due to the design of SEASONALE, which has only 4 scheduled hormone-free cycles compared with 13 for Nordette. [Anderson, p 93] Anderson FD, Hait H, and the Seasonale-301 Study Group. A multicenter, randomized study of an extended-cycle oral contraceptive. Contraception. 2003;68:89-96.

69. Extended Cycle OC Trial: Unscheduled Bleeding/Spotting Days These are some examples of OCs covered by Family PACT (the brand names being mentioned here is not a particular endorsement by Family PACT) Extended-cycle regimen patients reported slightly more unscheduled breakthrough bleeding and/or spotting compared with those in the 28-day regimen group. [Anderson, p 93] Of the total number of possible days of unscheduled bleeding/spotting (336 for the extended-cycle regimen and 273 for the 28-day cycle regimen) a median of 26 days were reported by the 91-day regimen patients compared with 13 days reported by the 28-day regimen patients. [Anderson, p 93] The incidence of breakthrough bleeding/spotting decreased throughout the study in both treatment groups, and by the last extended-cycle of the study, the incidence of breakthrough bleeding was comparable in the two treatment groups. [Anderson, p 96] Anderson FD, Hait H, and the Seasonale-301 Study Group. A multicenter, randomized study of an extended-cycle oral contraceptive. Contraception. 2003;68:89-96. These are some examples of OCs covered by Family PACT (the brand names being mentioned here is not a particular endorsement by Family PACT) Extended-cycle regimen patients reported slightly more unscheduled breakthrough bleeding and/or spotting compared with those in the 28-day regimen group. [Anderson, p 93] Of the total number of possible days of unscheduled bleeding/spotting (336 for the extended-cycle regimen and 273 for the 28-day cycle regimen) a median of 26 days were reported by the 91-day regimen patients compared with 13 days reported by the 28-day regimen patients. [Anderson, p 93] The incidence of breakthrough bleeding/spotting decreased throughout the study in both treatment groups, and by the last extended-cycle of the study, the incidence of breakthrough bleeding was comparable in the two treatment groups. [Anderson, p 96] Anderson FD, Hait H, and the Seasonale-301 Study Group. A multicenter, randomized study of an extended-cycle oral contraceptive. Contraception. 2003;68:89-96.

70. Extended Cycle OC Trial: Median Days of Breakthrough Bleeding/Spotting Women taking SEASONALE (as with any OC product) report varying degrees of breakthrough bleeding, especially during the first few months of use. [Anderson, p 94] With SEASONALE, there were fewer days of unscheduled, or breakthrough, bleeding with each successive cycle. [Anderson, p 94] In addition, the onset of breakthrough bleeding was more likely to occur later during the cycle than early in the cycle. [Anderson, p 94] By the end of the study, the incidence of breakthrough bleeding was comparable among women in both treatment groups. [Anderson, p 95] Most of the women who reported that they experienced breakthrough bleeding during the SEASONALE cycle had 5 days or less of unscheduled bleeding per cycle. [Anderson, p 95] Anderson FD, Hait H, and the Seasonale-301 Study Group. A multicenter, randomized study of an extended-cycle oral contraceptive. Contraception. 2003;68:89-96. Women taking SEASONALE (as with any OC product) report varying degrees of breakthrough bleeding, especially during the first few months of use. [Anderson, p 94] With SEASONALE, there were fewer days of unscheduled, or breakthrough, bleeding with each successive cycle. [Anderson, p 94] In addition, the onset of breakthrough bleeding was more likely to occur later during the cycle than early in the cycle. [Anderson, p 94] By the end of the study, the incidence of breakthrough bleeding was comparable among women in both treatment groups. [Anderson, p 95] Most of the women who reported that they experienced breakthrough bleeding during the SEASONALE cycle had 5 days or less of unscheduled bleeding per cycle. [Anderson, p 95] Anderson FD, Hait H, and the Seasonale-301 Study Group. A multicenter, randomized study of an extended-cycle oral contraceptive. Contraception. 2003;68:89-96.

71. Oral Contraceptives: Quick Start With conventional start of OCs, up to 25% of women do not start their pills due to: Pregnancy Change in method Confusion about pill instructions Fear of possible side effects Quick start with OCs protocol Start with first pill in pack Provide backup method for 7 days Provide EC if indicated

72. Quick Start Versus First Day Start

73. Percentage of Pill Users, By Behavior Related to Effective Contraceptive Use

74. Oral Contraceptive Compliance:Number of Active Pills Missed

75. Application of Contraceptive Patch on Abdomen The patch can be applied to the buttocks, upper outer arm, lower abdomen (shown), or upper torso (not the breasts) The patch is beige in color, very thin, and pliableThe patch can be applied to the buttocks, upper outer arm, lower abdomen (shown), or upper torso (not the breasts) The patch is beige in color, very thin, and pliable

76. Contraceptive Patch Administration Simple administration schedule Apply weekly for 3 weeks Apply same day-of-the-week 1 week patch-free The patch uses a 28-day, four week cycle. A new patch is applied each week for three weeks - 21 total days. Every new patch will be applied on the same day of the week. This day is known as the “Patch Change Day” Week four is patch-free. Withdrawal bleeding is expected during this time The patch uses a 28-day, four week cycle. A new patch is applied each week for three weeks - 21 total days. Every new patch will be applied on the same day of the week. This day is known as the “Patch Change Day” Week four is patch-free. Withdrawal bleeding is expected during this time

77. Contraceptive Patch: Distribution of Pregnancies by Baseline Body Weight Deciles (n=3319 subjects) While patch is highly efficacious for the vast majority of women, the patch may be less efficacious in women >198 lbs This phenomenon was also seen with Norplant but no data is available for other hormonal methods. The NIH is currently funding a study to look at the impact of weight on contraceptive efficacy 5 pregnancies among the 83 subjects with body weight ? 90 kg (198 lbs) (3% of study population) 10 pregnancies among the 3236 subjects with body weight ? 198 lbs. were uniformly distributed Healthcare professionals who consider the patch for women at or above 198 lbs should discuss the individual needs of the women in choosing the most appropriate method of contraception While patch is highly efficacious for the vast majority of women, the patch may be less efficacious in women >198 lbs This phenomenon was also seen with Norplant but no data is available for other hormonal methods. The NIH is currently funding a study to look at the impact of weight on contraceptive efficacy 5 pregnancies among the 83 subjects with body weight ? 90 kg (198 lbs) (3% of study population) 10 pregnancies among the 3236 subjects with body weight ? 198 lbs. were uniformly distributed Healthcare professionals who consider the patch for women at or above 198 lbs should discuss the individual needs of the women in choosing the most appropriate method of contraception

78. Contraceptive Patch Comparative Data: Efficacy (pregnancies per 100 women per year) The efficacy data are reported as the Pearl Index’s Comparing the total Pearl to the method Pearl, one can infer that there were few patch failures associated with poor user compliance A contraceptive with high compliance would be associated with an overall failure rate (method plus user failure) that is very similar to the method failure alone, as seen with the transdermal patch In the patch group, 4 method-failure pregnancies and 1 user-failure pregnancy occurred among 811 women treated for 5240 cycles In the OC group, 4 method-failure and 3 user-failure pregnancies occurred among 605 women treated for 4167 cycles While the numerical differences in Pearl Index’s are not statistically significant, this demonstrates that the transdermal contraceptive system is a highly effective method of contraception Additional evidence that better compliance contributed to the low probability of pregnancy with the patch is seen from analysis of 6-cycle data, a treatment duration all participants were to complete. After 6 cycles, the overall probability of pregnancy with the patch was half that of the OC (0.6% vs 1.2%) while the method failure probability of pregnancy was nearly the same (0.4% vs 0.6%) The efficacy data are reported as the Pearl Index’s Comparing the total Pearl to the method Pearl, one can infer that there were few patch failures associated with poor user compliance A contraceptive with high compliance would be associated with an overall failure rate (method plus user failure) that is very similar to the method failure alone, as seen with the transdermal patch In the patch group, 4 method-failure pregnancies and 1 user-failure pregnancy occurred among 811 women treated for 5240 cycles In the OC group, 4 method-failure and 3 user-failure pregnancies occurred among 605 women treated for 4167 cycles While the numerical differences in Pearl Index’s are not statistically significant, this demonstrates that the transdermal contraceptive system is a highly effective method of contraception Additional evidence that better compliance contributed to the low probability of pregnancy with the patch is seen from analysis of 6-cycle data, a treatment duration all participants were to complete. After 6 cycles, the overall probability of pregnancy with the patch was half that of the OC (0.6% vs 1.2%) while the method failure probability of pregnancy was nearly the same (0.4% vs 0.6%)

79. Contraceptive Patch:Mean Proportion of Participants’ Cycles with Perfect Compliance An important advantage of the transdermal contraceptive system is its simple weekly dosing schedule This is important because while OCs have failure rates in clinical trials around 1%, Trussell, et al., estimate that actual use failure rates can be as high as 7% In this trial, compliance with the dosing schedule of the patch was statistically better than that of the OC Since incorrect and inconsistent use of contraception can lead to higher pregnancy rates – it is hoped that the improved compliance profile of the patch will result in improved “actual use” efficacy in broad usage An important advantage of the transdermal contraceptive system is its simple weekly dosing schedule This is important because while OCs have failure rates in clinical trials around 1%, Trussell, et al., estimate that actual use failure rates can be as high as 7% In this trial, compliance with the dosing schedule of the patch was statistically better than that of the OC Since incorrect and inconsistent use of contraception can lead to higher pregnancy rates – it is hoped that the improved compliance profile of the patch will result in improved “actual use” efficacy in broad usage

80. Contraceptive Patch:Compliance by Age Group Usage of the patch resulted in increased compliance across all age groups Compliance rates were similar for all age groups using the patch, whereas the rates varied among the age groups for OCs Therefore, the increased compliance seen with the patch is a potential benefit to a wide range of womenUsage of the patch resulted in increased compliance across all age groups Compliance rates were similar for all age groups using the patch, whereas the rates varied among the age groups for OCs Therefore, the increased compliance seen with the patch is a potential benefit to a wide range of women

81. Contraceptive Patch Peel Force:Health Club Study Results Mean peel force (kg) measurements were similar for all activities studied: Normal conditions 0.31 Cool water 0.33 Sauna 0.28 Treadmill 0.23 Whirlpool 0.30 Combination of activities 0.47 No significant difference between activities 1.1% of patches (1/87) completely detached The exercise study evaluated the patch under various conditions of heat and humidity and found that it adhered well This slides illustrates the results of measurements taken to determine patch adhesion after certain health club activities There were no significant differences in adhesion measurements between the activities Only 1 out of 87 patches was replaced due to complete detachment in this study The exercise study evaluated the patch under various conditions of heat and humidity and found that it adhered well This slides illustrates the results of measurements taken to determine patch adhesion after certain health club activities There were no significant differences in adhesion measurements between the activities Only 1 out of 87 patches was replaced due to complete detachment in this study

82. Managing partial or complete detachment is relatively simple If the patch becomes partially or completely detached and remains detached, insufficient drug delivery occurs If the patch remains even partially detached: For less than one day (up to 24 hours), the patient should try to reapply it to the same place or replace it with a new patch immediately. “Patch Change Day” will remain the same For more than one day (24 hours or more) OR if patient is not sure how long patch has been detached, she may not be protected from pregnancy. She should stop current contraceptive cycle and start new cycle immediately by putting on a new patch. There is now a new “Day 1” and a new “Patch Change Day.” Back-up contraception must be used for the first week of the new cycle only Managing partial or complete detachment is relatively simple If the patch becomes partially or completely detached and remains detached, insufficient drug delivery occurs If the patch remains even partially detached: For less than one day (up to 24 hours), the patient should try to reapply it to the same place or replace it with a new patch immediately. “Patch Change Day” will remain the same For more than one day (24 hours or more) OR if patient is not sure how long patch has been detached, she may not be protected from pregnancy. She should stop current contraceptive cycle and start new cycle immediately by putting on a new patch. There is now a new “Day 1” and a new “Patch Change Day.” Back-up contraception must be used for the first week of the new cycle only

83. Contraceptive Patch: Forgot to Apply/Change Patch (in any Patch Cycle) If a patient forgets to change her patch, management is relatively simple At the start of any patch cycle: (Week 1/Day 1): May not be protected from pregnancy; should apply the first patch of her new cycle as soon as remembered; new “Patch Change Day” and a new “Day 1”. Patient must use back-up contraception for the first week of new cycle In the middle of the patch cycle (Week Two/Day 8 or Week Three/Day 15) one or two days (up to 48 hours): Should apply a new patch immediately; next patch applied on usual “Patch Change Day”; no back-up contraception is needed More than two days (48 hours or more): May not be protected from pregnancy; should stop the current contraceptive cycle and start new four-week cycle immediately by putting on a new patch; new “Patch Change Day” and new “Day 1”; patient must use back-up contraception for one week 4. At the end of the patch cycle (Week 4/Day22): Remove patch when remembered; next patch applied on usual “Patch Change Day”, which is day after Day 28. Under no circumstances should there be more than a 7-day patch-free interval between dosing cycles. If so, patient may not be protected from pregnancy; backup contraception must be used for 7 days; risk of ovulation increases each day beyond recommended contraceptive-free period; if coital exposure has occurred during extended patch-free interval, possibility of fertilization should be consideredIf a patient forgets to change her patch, management is relatively simple At the start of any patch cycle: (Week 1/Day 1): May not be protected from pregnancy; should apply the first patch of her new cycle as soon as remembered; new “Patch Change Day” and a new “Day 1”. Patient must use back-up contraception for the first week of new cycle In the middle of the patch cycle (Week Two/Day 8 or Week Three/Day 15) one or two days (up to 48 hours): Should apply a new patch immediately; next patch applied on usual “Patch Change Day”; no back-up contraception is needed More than two days (48 hours or more): May not be protected from pregnancy; should stop the current contraceptive cycle and start new four-week cycle immediately by putting on a new patch; new “Patch Change Day” and new “Day 1”; patient must use back-up contraception for one week 4. At the end of the patch cycle (Week 4/Day22): Remove patch when remembered; next patch applied on usual “Patch Change Day”, which is day after Day 28. Under no circumstances should there be more than a 7-day patch-free interval between dosing cycles. If so, patient may not be protected from pregnancy; backup contraception must be used for 7 days; risk of ovulation increases each day beyond recommended contraceptive-free period; if coital exposure has occurred during extended patch-free interval, possibility of fertilization should be considered

84. If the patient wants a change day adjustment, she does so by applying a new patch during the fourth week therefore shortening the patch-free interval by applying a new patch on the first occurrence of the desired dayIf the patient wants a change day adjustment, she does so by applying a new patch during the fourth week therefore shortening the patch-free interval by applying a new patch on the first occurrence of the desired day

85. Contraceptive Patch: Switching From OC Apply patch on 1st day of withdrawal bleeding If no withdrawal bleeding within 5 days of the last active (hormone-containing) pill, pregnancy must be ruled out prior to start of patch If starting patch after the first day of withdrawal bleeding, a non-hormonal contraceptive should be used concurrently for 7 days If more than 7 days elapse after taking the last active pill, patient may have ovulated Patient should consult clinician before initiating treatment with patch A woman who wishes to switch from an OC to the contraceptive patch should begin treatment by applying her first patch on her first day of withdrawal bleeding If there is no withdrawal bleed within 5 days of the last active, hormone-containing pill, pregnancy must be ruled out If patch therapy starts later than the first day of withdrawal bleeding, a non-hormonal method of contraception should be used simultaneously for 7 days A woman who wishes to switch from an OC to the contraceptive patch should begin treatment by applying her first patch on her first day of withdrawal bleeding If there is no withdrawal bleed within 5 days of the last active, hormone-containing pill, pregnancy must be ruled out If patch therapy starts later than the first day of withdrawal bleeding, a non-hormonal method of contraception should be used simultaneously for 7 days

86. Extended Use of Contraceptive Patch

87. Contraceptive Patch: Bold Warning The pharmacokinetic (PK) profile for the ORTHO EVRA® patch is different from the PK profile for oral contraceptives in that it has higher steady state concentrations and lower peak concentrations. AUC and average concentration at steady state for ethinyl estradiol (EE) are approximately 60% higher in women using ORTHO EVRA® compared with women using an oral contraceptive containing EE 35 µg. In contrast, peak concentrations for EE are approximately 25% lower in women using ORTHO EVRA®.

88. Inter-subject variability results in increased exposure to EE in some women using either ORTHO EVRA® or oral contraceptives. However, inter-subject variability in women using ORTHO EVRA® is higher. It is not known whether there are changes in the risk of serious adverse events based on the differences in pharmacokinetic profiles of EE in women using ORTHO EVRA® compared with women using oral contraceptives containing 35 µg of EE. Increased estrogen exposure may increase the risk of adverse events, including venous thromboembolism. Contraceptive Patch: Bold Warning2006 Addition

89. VTE Risk of Patch vs OCs 68 newly diagnosed, idiopathic cases of VTE OR comparing the contraceptive patch to norgestimate-35 EE OC was 0.9 (95% CI 0.5–1.6) The overall incidence rate for VTE was 52.8 per 100,000 women-years (95% CI 35.8–74.9) among users of the contraceptive patch 41.8 per 100,000 women-years (95% CI 29.4–57.6) among users of norgestimate-35 The age-adjusted VTE incidence rate ratio (IRR) for current use of the contraceptive patch vs. norgestimate-35 was 1.1 (95% CI 0.7–1.8) Conclusion: Risk of nonfatal VTE for contraceptive patch is similar to the risk for OCs containing 35 mcg ethinylestradiol and norgestimate.

90. VTE Risk of Patch vs OCs Second study included chart review OR for current users of contraceptive patch compared to current users of norgestimate-35 EE OC was 2.4 (95% CI 1.1-5.5) Conclusion: Increased risk of VTEs for current users of contraceptive patch compared to current users of OCs containing 35 mcg ethinylestradiol and norgestimate Longer follow-up for VTE, heart attack and stroke has been requested by FDA

91. Very low dose 120 mcg/day etonogestrel 15 mcg/day ethinyl estradiol Flexible Transparent Outer diameter: 54 mm Thickness: 4 mm One ring per cycle: 3 weeks ring-in 1 week ring-free Contraceptive Vaginal Ring NuvaRing® is a soft, flexible, transparent ring that is about the size of a silver dollar. It releases a continuous dose of estrogen and progestogen. NuvaRing® should be placed in the vagina for three weeks and then removed for one week during which the patient should experience minimal bleeding. A blue placebo ring is available so that women can feel it and see that it is flexible and thus conform to the vaginal shape. NuvaRing® is a soft, flexible, transparent ring that is about the size of a silver dollar. It releases a continuous dose of estrogen and progestogen. NuvaRing® should be placed in the vagina for three weeks and then removed for one week during which the patient should experience minimal bleeding. A blue placebo ring is available so that women can feel it and see that it is flexible and thus conform to the vaginal shape.

92. Contraceptive Vaginal Ring Advantages A monthly method Easily inserted by the woman Discreet Lowest EE dose (15 µg/day) Constant serum concentrations Avoids GI interference with absorption Avoids hepatic first-pass metabolism

93. Contraceptive Vaginal Ring Placement Although some women may be aware of NuvaRing® in the vagina, most women do not feel it once it is in place. If the woman feels discomfort, NuvaRing® is probably not inserted back far enough in the vagina. She may use her finger to gently push NuvaRing® further into her vagina. There is no danger of NuvaRing® being pushed too far up in the vagina or getting lost. NuvaRing® should be removed 3 weeks after it is inserted. It can be removed by hooking the index finger under the forward rim or by holding the rim between the index and middle finger and pulling it out. The ring should be placed in the foil pouch and disposed of in a wasted receptacle out of the reach of children or pets.Although some women may be aware of NuvaRing® in the vagina, most women do not feel it once it is in place. If the woman feels discomfort, NuvaRing® is probably not inserted back far enough in the vagina. She may use her finger to gently push NuvaRing® further into her vagina. There is no danger of NuvaRing® being pushed too far up in the vagina or getting lost. NuvaRing® should be removed 3 weeks after it is inserted. It can be removed by hooking the index finger under the forward rim or by holding the rim between the index and middle finger and pulling it out. The ring should be placed in the foil pouch and disposed of in a wasted receptacle out of the reach of children or pets.

94. Contraceptive Vaginal Ring Pharmacokinetics 

95. Contraceptive Vaginal RingEfficacy Significant differences between US and European studies: US: 1.8 pregnancies/100 woman-years Europe: 0.6 pregnancies/100 woman-years Temporary removal rates may account for difference in efficacy: United States Europe Worst 10% of users 24-174 hours 0-6 hours Worst 5% of users 72-174 hours 1-6 hours Temporary removal not recommended now

96. Contraceptive Vaginal Ring versus 30 mcg OC: Cycle Control

97. Quick Start Ring vs Pill: Bleeding Patterns

98. Contraceptive Vaginal Ring:Extended Use (Off Label)

99. Contraceptive Vaginal Ring Local Effects Leukorrhea/Vaginal Flora Leukorrhea - 6 % of patients per year No significant normal to abnormal or abnormal to normal change in flora Cervical cytology Vaginal cytology Low incidence of shift of normal to abnormal Colposcopy/ Vaginoscopy The frequency of normal to abnormal changes was low A similar number of subjects showed abnormal to normal changes in microbiology and colposcopy No abnormal findings Ulcerations, Acetowhite epithelium Erythema Laceration

100. Contraceptive Vaginal RingLocal Effects Interaction with vaginal medications Spermicides/water-based formulation: No Anti-mycotics/oil-based formulation: Yes, but: Interaction most likely caused by formulation No effects on efficacy and safety Impact on infection Decrease in recurrence of BV

101. Contraceptive Vaginal Ring: Acceptability (ITT group, Last assessment)

102. Contraceptive Vaginal Ring:  Events Leading to Discontinuation

103. Contraceptive Vaginal Ring: Pharmacokinetics and Drug Interactions No daily fluctuations in serum hormone concentrations EE exposure is half that with a 30 mcg OC Etonogestrel exposure is comparable with a 30 EE/150 DSG OC Tampon or anti-mycotic co-administration has not been shown to impair hormone release and/or absorption

104. “Ten months ago, I would have called this (the condom) aninvention of the devil, but now I find that its inventor must have been a man of good will ...”Jacques Casanova, 1758

105. Male Condom Typical first year failure rate: 15%; range 2-20% Advantages: u Male participation u Protects well against STDs u Inexpensive u Cervical dysplasia reduced u Readily available Special applications: u Premature ejaculation u Antisperm antibody u Female allergy to sperm

106. The Male Condom

107. Make room for the condom that’s captureda whopping 60% market share in Japan.

108. Polyurethane Condom

110. Male Condoms: Sizes Snug fitting Beyond7, Studded Beyond 7, Exotica Snugger Fit, LifeStyles Snugger Fit, Trojan Ultra Fit Larger size—more headroom Trojan Ultra Pleasure, Trojan Very Sensitive, Bareback, Trojan Her Pleasure, Midnight Desire, Pleasure Plus, LifeStyles Xtra Pleasure, Inspiral, Durex Enhanced Pleasure, LifeStyles Natural Feeling Larger size—roomy from top to bottom Maxx, Trojan Large, Magnum XL, Magnum, Durex Maximum, LifeStyles Large, Avanti, Crown, Trojan Supra

111. Male Condoms: Other Characteristics Sensitivity, texture, extra strength, desensitizing, pleasure producing, flavor/scent, color, lubrication 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) Spermicidally lubricated condoms

112. Recently Introduced Condoms

114. 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 disease-free.” 5. “We don’t like them.”

115. The Top 12 Reasons For Not Using A Condom 6. “I know I should, but...” 7. “I’m on the pill.” 8. “Well, I did once!” 9. “He’s too big for the condom to fit.” 10. “I’m in a monogamous relationship.” 11. “We didn’t have any.” 12. “S/He looked clean.”

116. 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.”

117. Barrier Methods Male latex condoms are effective in preventing the sexual transmission of HIV infection and can reduce the risk for other STDs (i.e. gonorrhea, chlamydia and trichomonas) They are likely to be more effective in preventing infection transmitted by fluids from mucosal surfaces … than protecting those transmitted by skin-to-skin contact (HSV, HPV, syphilis and chancroid)

118. Barrier Methods Vaginal spermicides are not effective in preventing cervical gonorrhea, chlamydia or HIV infection Condoms lubricated with spermicide are no more effective than other lubricated condoms in protective agents transmission of HIV and other STDs

119. Female Barrier MethodsFailure Rates

120. Spermicides: STD issues FDA warning label proposed January 16, 2003: “Sexually transmitted diseases (STDs) alert: This product does not protect against the AIDS virus (HIV) or other sexually transmitted diseases (STDs).” “Frequent use (more than once a day) of this product can increase vaginal irritation, which may increase the risk of becoming infected with the AIDS virus (HIV) or other STDs from infected partners.”

121. Lea’s Shield Single size, cup shaped silicone device covering cervix No fitting needed Vaginal walls stabilize One-way valve allows exit for cervical secretions and air No vacuum needed Posterior end thicker to fill fornix Loop on anterior end to facilitate removal

122. Lea’s Shield Use Use with spermicide to fill bowl Placement correct if cervix covered and strap behind symphysis and patient comfortable Use for multiple acts of intercourse for up to 48 hours Must be left in place for 8 hours after last exposure Reusable for 6-12 months Wash with mild soap and water and air dry after use Monthly vinegar and water soak for one hour

123. FemCap

124. Contraceptive Sponge Today® Sponge approved by FDA in 1983, withdrawn in 1994, and reapproved in 2005 Single use device moistened and placed high in vault to cover cervix. Disposable polyurethane foam disk containing 1 gram N-9 Mechanisms of action: spermicide (24 hours)plus device absorbs semen and blocks cervix

125. Cycle Beads Color coded string of beads helps women identify days of cycle pregnancy is likely and unlikely (Not a Family PACT benefit) This is helpful as a teaching aid, however, cycle beads are not a benefit of Family PACT.This is helpful as a teaching aid, however, cycle beads are not a benefit of Family PACT.

127. LNG-only ECSingle-dose Versus 2-dose Regimens

128. WHO EC Study: Single Dose Vs Two Doses Used Within 120 Hours

129. How Long After the Morning After?WHO Pooled Data (Yuzpe and LNg), 1998

130. Advance Prescription versus Prescription on Demand

131. EC Advance Prescription versus Prescription on Demand Does not decrease use of primary method 1 Does not increase STI rates 2

132. LNG EC Mechanisms of Action Cebus monkey: LNG EC inhibited or delayed ovulation. Once fertilization had taken place, EC did not prevent establishment of pregnancy 1 Human: LNG administered during luteul phase did not cause significant endometrial changes 2 Human: LNG EC blocks or delays ovulation, due either to prevention or delay of LH surge, rather than inhibiting implantation 3

133. Emergency Contraception (EC): Under-utilization in U.S. Public lack of awareness. Telephone survey of 1000 women and 300 men found: Only 36% aware that “anything could be done” after unprotected intercourse to prevent pregnancy Only 1% of women had ever used EC

135. I’m sorry, lady, I’m morally opposed to birth control pills.Viagra, Cialis, Levitra

136. DON’T EVER GIVE UP!

137. Processing Forms Download Now: Evaluation Form Continuing Education Form No Web Access Now: Call 1-877-FAMPACT for forms All participants that return an evaluation form will receive a Certificate of Participation Those requesting CE credit must return evaluation and CE form-indicate CE requesting Complete forms and fax to 213 368-4410 Thank you for your participation! Once you see the File Transfer Box, click on the file and then click download. Do this for each file.Once you see the File Transfer Box, click on the file and then click download. Do this for each file.