The Trusted Source for Contraceptive and STI News and Research for More Than Three Decades

March 2014: Vol. 35, No. 3 Pages 25-36 Options might begin to emerge IN THIS ISSUE with new data out on LARC n LARC methods: Data Time to embrace evidence-based practice as choice options may expand emerges as choices might expand �������������������������������������cover rogress is being made on the long-acting reversible contraception n Interpregnancy intervals: (LARC) front to promote top-tier effective methods to women. What can be done to aid P According to the New York City-based Guttmacher Institute, spacing? ����������������������������������������28 in 2009, 8.5% of women using contraceptives relied on such LARC n Dysmenorrhea: Science methods as the implant (Nexplanon, Merck & Co., Whitehouse Station, eyes “little blue pill” for NJ) and the (IUD), reflecting a rise from 5.5% 1 treatment �������������������������������������29 in 2007 and 2.4% in 2002. Currently U.S.-approved IUDs include ParaGard, Teva Women’s Health, North Wales, PA, and Mirena, Bayer n contraception: HealthCare Pharmaceuticals, Wayne, NJ. Most of the women who use Will women see more long-acting reversible methods choose IUDs; nearly 8% of women using choices? ����������������������������������������31 contraception use the IUD, and less than 1% use the implant.1 n Adolescent patients: Not all With a 2012 American College of Obstetricians and Gynecologists providers discuss sex ����������������32 committee opinion stating that long-acting reversible contraceptives n Washington Watch: U.S. such as the IUD and the contraceptive implant are safe, effective, and 2 Supreme Court to review appropriate options for adolescents. (To read more about the opinion, contraceptive coverage ����������34 see the Contraceptive Technology Update article, “Long-acting methods Enclosed in this issue: EXECUTIVE SUMMARY n STI Quarterly: Research focus on pre-exposure prophylaxis; The American College of Obstetricians and Gynecologists says that long-acting revers- examine role of express STI ible contraception (LARC) methods are safe, effective, and appropriate options for teens, but some might perceive high discontinuation rates among younger women testing in clinics and therefore steer patients away from them.

Financial Disclosure: Consulting Editor Robert A. • Data from the St. Louis Contraceptive CHOICE Project indicates that discontinuation Hatcher, MD, MPH, Author Rebecca Bowers, and rates of LARC methods at six months is low (less than 10%) and is not increased in Executive Editor Joy Dickinson report no consultant,­ stockholder, speaker’s bureau, research, or other financial teens and young women. relationships with companies having ties to this field of • A new international study looking at the 13.5 mg IUD plus a 19.5 mg study. Melanie Deal, nurse reviewer, discloses that she is on the speakers bureau for Actavis and Merck & Co. and levonorgestrel device in advanced clinical trials suggest both are safe and effective. the advisory board for Actavis, Teva, and Hologic. Adam In the 13.5 mg and 19.5 mg groups, 21.9% and 19.1% discontinued the study over Sonfield, guest columnist, has no relevant relationships to disclose. three years, respectively, including 1.0% and 1.2% who stopped due to serious adverse events and 4.7% and 4.9% who left due to menstrual bleeding disturbances.

NOW AVAILABLE ONLINE! Go to www.ahcmedia.com. Call (800) 688-2421 for details. safe for teens: include options in your counsel- such a perception. The analysis indicates that ing,” December 2012, p. 133.) However, some rates of discontinuation of LARC methods at six providers might perceive high discontinuation months is low (less than 10%) and not increased rates among younger women and therefore steer in adolescents and young women.2 patients away from LARC methods.3 New analysis of data from the St. Louis Discontinuation rates measured Contraceptive CHOICE Project should eliminate Researchers at the Washington University School of Medicine in St. Louis designed the Contraceptive Technology Update® (ISSN 0274-726X), including STI Quarterly™, is published monthly by AHC Media, LLC, One Atlanta Plaza, 950 analysis to measure discontinuation within six East Paces Ferry Rd, Suite 2850, Atlanta, GA 30326. Telephone: (404) 262-7436. months among users of the levonorgestrel intra- Periodicals Postage Paid at Atlanta, GA 30304 and at additional mailing offices. uterine system, copper IUD, and the etonogestrel POSTMASTER: Send address changes to implant, and to identify baseline characteristics Contraceptive Technology Update®, P.O. Box 550669, associated with early discontinuation. They drew Atlanta, GA 30355. data from the project, a cohort study of 9,256 participants provided with no-cost contraception Subscriber Information and followed with telephone interviews at three Customer Service: (800) 688-2421 or fax (800) 284-3291. E-mail: and six months ([email protected]).­ Hours of operation: 8:30 a.m.- 6 p.m. Monday-Thursday; 8:30 a.m.-4:30 p.m. Friday, EST. The analysts used logistic regression to inves- Subscription rates: U.S.A., Print: 1 year (12 issues) with free AMA tigate characteristics associated with early dis- Category 1 CreditsTM or Nursing Contact Hours, $479. Add $19.99 for shipping & handling. Online only, single user: 1 year with free AMA continuation of the two IUDs and implant and Category 1 CreditsTM or Nursing Contact Hours, $429. Outside U.S., determined reasons for discontinuation. A total of add $30 per year, total prepaid in U.S. funds. Discounts are available for group subscriptions, multiple copies, site-licenses or electronic distribution. 6,167 participants were eligible for the analysis; For pricing information, call Tria Kreutzer at 404-262-5482. Back issues, follow-up data were available for 5,928 partici- when available, are $75 each.(GST registration number R128870672.) Photocopying: No part of this newsletter may be reproduced in any form pants. More than 90% (5,495) were using their or incorporated into any information retrieval system without the written method at six months and 433 (7%) had discon- permission of the copyright owner. For reprint permission, please contact AHC Media. Address: P.O. Box 550669, Atlanta, GA 30355. Telephone: tinued. Discontinuation rates were 7.3%, 8.0%, (800) 688-2421. World Wide Web: http://www.ahcmedia.com. and 6.9% for the levonorgestrel intrauterine sys-

Opinions expressed are not necessarily those of this publication. tem, copper IUD, and implant, respectively. Mention of products or services does not constitute endorsement. After adjusting for age, race, marital status, Clinical, legal, tax, and other comments are offered for general guid- ance only; professional­ counsel should be sought for specific situations. low socioeconomic status, and history of sexually AHC Media, LLC is accredited as a provider of continuing nursing transmitted infection, analysts found that unmar- education by the American Nurses Credentialing Center’s Commission on Accreditation. ried women were slightly more likely to discon- This activity has been approved for 15 nursing contact hours using a tinue compared with married women (adjusted 60-minute contact hour. odds ratio [OR] 1.26, 95% confidence interval Provider approved by the California Board of Registered Nursing, Provider #14749, for 15 Contact Hours. [CI] 1.01-1.59 and adjusted OR 1.62, 95% CI AHC Media, LLC is accredited by the Accreditation Council for 1.11-2.37, respectively). No other baseline char- Continuing Medical Education to provide continuing medical educa- tion for acteristics, including younger age (ages 14-19), physicians. were associated with early discontinuation. The AHC Media, LLC designates this enduring material for a maximum of 18 AMA PRA Category 1 Credits™. Physicians should claim only credit most common reason given for discontinuation commensurate with the extent of their participation in the activity. was cramping among IUD users and irregular or This activity is intended for OB/GYNs, nurses, nurse practitioners, and other family planners. It is in effect for 24 months from the date of frequent bleeding among implant users.3 publication. “Rates of discontinuation of long-acting Editor: Rebecca Bowers. reversible contraception at six months is low and Executive Editor: Joy Daughtery Dickinson (404) 262-5410 ([email protected]). not increased in adolescents and young women,” Production Editor: Kristen Ramsey. Director of Continuing Education and Editorial: Lee Landenberger. state the researchers. “Intrauterine devices and Copyright © 2014 by AHC Media, LLC. Contraceptive Technology the implant should be considered as first-line Update® and STI Quarterly™ are trademarks of AHC Media, LLC. The contraceptive options among all women to reduce trademarks Contraceptive Technology Update® and STI Quarterly™ are used herein under license. All rights reserved. unintended pregnancy.” (Interested in getting a LARC program going Editorial Questions at your facility? Visit the “LARC First” resource Questions or comments? web site, www.larcfirst.com, put together by the Call Joy Daughtery Dickinson (404) 262-5410. Contraceptive CHOICE Project. Get trouble- shooting tips on LARC insertions and removals,

26 CONTRACEPTIVE TECHNOLOGY UPDATE ® / March 2014 staff cross-training information, contraceptive Meier estimates for that period were 0.009 and counseling scripts, and more.) 0.010, respectively. Partial expulsions occurred in 4.56% and 3.58% of treatment groups, respec- New options in research tively. Ten of the 20 pregnancies were ectopic. Serious adverse events included six cases of pelvic More patients and providers might be inter- inflammatory disease and one partial uterine per- ested in intrauterine contraception with the 2013 foration.4 advent of Skyla, a new intrauterine system from Scientists note that in the 13.5 mg system and Bayer HealthCare Pharmaceuticals of Wayne, 19.5 mg system groups, 21.9% and 19.1% of NJ. The small, flexible plastic T-shaped device women discontinued for any adverse event over contains 13.5 mg levonorgestrel; its body mea- three years, including 1.0% and 1.2% who dis- sures 28 mm x 30 mm. The drug is released at an continued for serious adverse events and 4.7% average in vivo rate of approximately 6 mcg/day and 4.9% who discontinued for disturbances over three years. It is approved for up to three in menstrual bleeding, including , years of contraceptive use. (To read more above respectively. In total, 57% and 60% of women the device, see the CTU article, “FDA approves completed three years of treatment with the 13.5 smaller levonorgestrel intrauterine system — a mg system and 19.5 mg system, respectively.4 ‘mini-Mirena,’” March 2013, p. 25.) “By demonstrating the safety and efficacy of Andrew Kaunitz, MD, professor and asso- low-dose intrauterine contraceptive devices, this ciate chair in the Obstetrics and Gynecology study will help expand the contraceptive options Department at the University of Florida College available to women who have not had children of Medicine — Jacksonville, said, “I find the before,” says Anita Nelson, MD, professor in smaller LNG IUD a welcome option in my prac- the Obstetrics and Gynecology Department at tice, particularly for nulliparous women and the David Geffen School of Medicine at the others who may have a tighter or less flexible University of California in Los Angeles and cor- cervix.” responding author of the study. “Additionally, a A just-published international study looks at lower dose system may be preferable to women both the U.S.-approved 13.5 mg levonorgestrel who are seeking to reduce their exposure to syn- IUD, as well as a 19.5 mg levonorgestrel device thetic hormones.” that is now in advanced clinical trials in the United States. Both devices were found to be safe Don’t forget IUD for EC and effective in preventing pregnancies, data sug- gests.4 As more women become aware of the IUD as a To perform the study, researchers enrolled LARC option, don’t forget to educate on its use nulliparous and parous women ages 18-35 with as an extremely effective form of emergency con- regular menstrual cycles who were requesting traception (EC). contraception. Participants were randomized Planned Parenthood League of Massachusetts to three years of treatment with one of the two (PPLM) in Boston launched its EC4U cam- studied levonorgestrel intrauterine contraceptive paign in November 2013 to educate its patients systems. The primary outcome was the pregnancy about EC and raise awareness among women in rate, calculated as the Pearl Index. Massachusetts of the variety of EC options avail- Overall, 1,432 and 1,452 women in the 13.5 able to them. mg intrauterine contraceptive system and 19.5 All seven PPLM locations across Massachusetts mg intrauterine contraceptive system groups, carry the full range of EC options: the copper respectively, had a placement attempted and were IUD (ParaGard); levonorgestrel emergency con- included in the full analysis set to evaluate effi- traceptives pills Plan B One-Step (Teva) and Next cacy and safety. Mean (standard deviation) age Choice (Actavis, Parsippany, NJ); and the ulipris- was 27.1 (4.8) years; 39.2% were nulliparous. tal acetate pill, ella (Actavis). Over the three-year period, 0.33 pregnancies Staff members at the seven sites educate per 100 women-years (95% CI 0.16-0.60) were patients on the benefits of each of these methods. observed with the 13.5 mg intrauterine con- Information about the copper IUD denotes that it traceptive system compared with 0.31 per 100 is most effective method; it can be used up to five women-years (95% CI 0.15-0.57) with the 19.5 days after unprotected sex and also can be left in mg intrauterine contraceptive system. Kaplan- place as a highly effective method of contracep-

March 2014 / CONTRACEPTIVE TECHNOLOGY UPDATE ® 27 tion for up to 12 years after insertion. the study suggest that compared to women using In an announcement of the new program, barrier methods, the use of long-acting reversible Marty Walz, president and chief executive officer contraception (LARC) in the postpartum period of the Massachusetts organization, said, “As the increases the odds of achieving an optimal inter- state’s leading women’s healthcare provider and pregnancy interval nearly four times greater than advocate, PPLM is proud to launch EC4U as part those relying on barrier methods.4 of our work to increase access to emergency con- Members of the University of California, traception, reduce unintended pregnancies, and San Francisco (UCSF) Family PACT (Planning, keep women healthy.” Access, Care, and Treatment) evaluation team designed the study with an objective to determine REFERENCES the use of contraceptive methods, defined by effectiveness, length of coverage, and their associ- 1. Finer LB, Jerman J, Kavanaugh ML. Changes in use of long- ation with short interpregnancy intervals, control- acting contraceptive methods in the United States, 2007-2009. ling for provider type and client demographics. Fertil Steril 2012; 98(4):893-897. Family PACT is California’s Medicaid family 2. Kavanaugh ML, Frohwirth L, Jerman J, et al. Long-acting planning expansion program; the evaluation reversible contraception for adolescents and young adults: team has worked extensively on access to and patient and provider perspectives. J Pediatr Adolesc Gynecol quality of family planning care for low-income 2013; 26(2):86-95. women, men, and adolescents, explains Heike 3. Grunloh DS, Casner T, Secura GM, et al. Characteristics Thiel de Bocanegra, PhD, MPH, evaluation team associated with discontinuation of long-acting reversible contra- director in the UCSF Bixby Center for Global ception within the first 6 months of use. Obstet Gynecol 2013; Reproductive Health and assistant professor in 122(6):1,214-1,221. UCSF’s Department of Obstetrics, Gynecology, 4. Nelson A, Apter D, Hauck B, et al. Two low-dose levonorg- and Reproductive Sciences. estrel intrauterine contraceptive systems: a randomized con- It is difficult to have objective quality indica- trolled trial. Obstet Gynecol 2013; 122(6):1,205-1,213. n tors for contraceptive use because birth records and claims data do not capture pregnancy inten- tion or client contraceptive preference, says Thiel de Bocanegra. The Healthy People 2020 objective Interpregnancy interval to avoid pregnancies for 18 months after a birth is one of the few objective recommendations in — You can help women the field of family planning, she notes. Researchers identified a cohort of 117,644 There is work to do women from the 2008 California Birth Statistical Master file with second or higher order birth and educing the proportion of pregnancies con- at least one Medicaid (Family PACT or Medi- Rceived within 18 months of a previous birth Cal) claim within 18 months after index birth. is one of the objectives of the U.S. Department They looked at the effect of contraceptive method of Health and Human Services’ Healthy People provision on the odds of having an optimal inter- 2020, the national 10-year plan for health pro- pregnancy interval, controlling for covariates. motion and disease prevention.1 There is work to do. A 2013 published study indicates that more EXECUTIVE SUMMARY than one-third (35%) of all repeat pregnancies in New research indicates that provision of effective contra- the United States are conceived within 18 months ception at the time of postpartum follow-up is a key strat- of the previous birth.2 Such short interpregnancy egy for achieving optimal interpregnancy intervals. intervals are associated with adverse maternal • Results of the study suggest that, compared to women and child health outcomes, such as increased using barrier methods, the use of long-acting reversible risk of preterm birth and infants with low birth contraception in the postpartum period increases the odds 3 weight. of achieving an optimal interpregnancy interval nearly four New research released online indicates that times greater than those relying on barrier methods. provision of effective contraception at the time of • Short interpregnancy intervals are associated with adverse postpartum follow-up is a key strategy for achiev- maternal and child health outcomes, such as increased risk ing optimal interpregnancy intervals.4 Results of of preterm birth and infants with low birth weight.

28 CONTRACEPTIVE TECHNOLOGY UPDATE ® / March 2014 Analysis indicates the average length of con- at http://1.usa.gov/1b0tm4e. traceptive coverage was 3.81 months, with most 2. Gemmill A, Lindberg LD. Short interpregnancy intervals in women receiving user-dependent hormonal con- the United States. Obstet Gynecol 2013; 122(1):64-71. traceptives as their most effective method (55%, 3. Institute of Medicine (US) Committee on Understanding n=65,103) and one-third (33%; n=39,090) with Premature Birth and Assuring Healthy Outcomes; Behrman RE, no contraceptive claim. A much smaller percent- Butler AS, editors. Preterm Birth: Causes, Consequences, and age used barrier methods (7%, n=8,320), fol- Prevention. Washington, DC: National Academies Press (US); lowed by LARC (LARC, n=5,131, 4%). 2007. According to the research, women who used 4. Thiel De Bocanegra H, Chang R, Howell M, et al. LARC methods had 3.89 times the odds and Interpregnancy intervals: impact of postpartum contracep- women who used user-dependent hormonal tive effectiveness and coverage. Am J Obstet Gynecol 2013; methods had 1.89 times the odds of achieving doi:10.1016/j.ajog.2013.12.020. n an optimal birth interval compared to women who used barrier methods only. Women with no method had 0.66 times the odds. When consider- ing user-dependent methods, for each additional Check treatment options month of contraceptive coverage, the odds of having an optimal birth interval increased by 8% for dysmenorrhea (odds ratio 1.08, confidence interval: 1.08-1.09). Women who were seen by Family PACT or by rimary dysmenorrhea, or painful menstrua- both Family PACT and Medi-Cal providers had Ption, is the most common cause of pelvic pain significantly higher odds of optimal birth inter- in women; as many as 90% of adolescent girls vals compared to women served by Medi-Cal and more than 50% of menstruating women only, researchers report.4 worldwide report symptoms, with 10-20% of them describing their pain as severe and distress- Time for a change ing.1-5 Early research indicates that women with mod- “Access to and utilization of family planning erate to severe menstrual cramps might find relief services are critical to achieving a longer birth in vaginal administration of sildenafil citrate interval,” state the UCSF researchers. “The posi- (Viagra, Pfizer., New York City), a drug com- tive association of optimal birth intervals cor- monly used for erectile dysfunction.6 responding to the method tier demonstrates the Why look at what is commonly called “the advantage of using methods with longer duration little blue pill” for possible pain relief of severe and lower rates of contraceptive failure.” menstrual cramps? Sildenafil citrate, which is a It is time to make structural changes to allow nitric oxide donor drug, might help with pelvic more women to get access to effective, revers- pain because it might augment relaxant effects of ible methods as easily as they receive irreversible the drug on myometrial cells, reverse the vasocon- sterilization during their delivery and hospi- talization, says Anita Nelson, MD, professor in the Obstetrics and Gynecology Department EXECUTIVE SUMMARY at the David Geffen School of Medicine at the University of California in Los Angeles. Early research indicates that women with moderate to se- “We also need to change the timing of the vere menstrual cramps might find relief in vaginal adminis- tration of sildenafil citrate (Viagra, Pfizer), a drug commonly routine postpartum visit from six to three weeks used for erectile dysfunction. after delivery, before it’s too late,” says Nelson. • Primary dysmenorrhea, or painful menstruation, is the “Unless we show women how important we most common cause of pelvic pain in women; as many as think contraception is to their children, we will 90% of adolescent girls and more than 50% of menstruat- continue to have unintended and short-interval ing women worldwide report symptoms, with 10-20% of pregnancy.” them describing their pain as severe and distressing. • Nonsteroidal anti-inflammatory drugs (NSAIDs), which REFERENCES likely act by reducing uterine hypercontractility, offer effec- tive treatment of primary dysmenorrhea. Combined oral 1. U.S. Department of Health and Human Services. Healthy contraceptives also are effective at easing menstrual cramp- People 2020. Topics and objectives. Family planning. Accessed ing.

March 2014 / CONTRACEPTIVE TECHNOLOGY UPDATE ® 29 striction caused by prostaglandins, and improve project grant (R01) funding from the National uterine blood flow.7,8 Although nitric oxide donor Institutes of Health to pursue further testing of drugs cause vasodilatation and successfully alle- the drug for primary dysmenorrhea treatment, viate pain, the incidence of side effects, such as says Legro. , might be too high for routine clinical “If future studies confirm these findings, silde- use with oral route, researchers note. nafil may become a treatment option for patients Rapid absorption and quick pain relief are of with primary dysmenorrhea,” said Legro. “Since utmost importance in treating dysmenorrhea, says primary dysmenorrhea is a condition that most Richard Legro, MD, professor of obstetrics and women suffer from and seek treatment for at gynecology and public health sciences at Penn some points in their lives, the quest for new medi- State University’s College of Medicine in Hershey, cation is justified.” PA. Vaginal administration accomplishes both and avoids the first pass effect of drug adminis- What’s available now? tration, he notes. Vaginal administration has been effective in What causes menstrual cramping? other treatments, observes Legro. One example is Prostaglandin is produced in the at the bromocriptine given for the treatment of hyperp- time of menstruation and can cause uterine rolactinemia; has been associ- contractions that are associated with menstrual ated with and orthostatic hypertension. cramping. Women who produce high levels of Data indicates that when the drug has been given prostaglandin have more intense contractions and vaginally, it has ameliorated those side effects,9 he more severe cramping. notes. A systematic review of evidence indicates that nonsteroidal anti-inflammatory drugs (NSAIDs), Check the details which likely act by reducing uterine hypercon- tractility, offer effective treatment of primary To conduct the study, researchers developed a dysmenorrhea. Unfortunately, not all women double-blind, randomized, controlled trial com- can use NSAIDs; gastrointestinal effects are not paring vaginal preparation of sildenafil citrate uncommon.10 Even in those women who are able (100 mg single dose) to a placebo in 62 patients to use NSAIDs, such drugs are not completely with primary dysmenorrhea. effective.11 The primary outcome was total pain relief For women who want an alternative to over four consecutive hours comparing sildenafil NSAIDs, birth control pills represent an effective citrate to placebo. Secondary outcomes were pain option for treatment of painful menstrual cramps. relief as measured by the visual analog scale and Oral contraceptives prevent ovulation, which in uterine artery pulsatility index. Subjects included turn reduces the amount of prostaglandin pro- women ages 18 to 35 with moderate to severe duced in the uterus. By doing so, birth control symptoms. Of the 29 women screened for the pills relieve menstrual cramping. According to study, 25 were randomized to receive sildenafil or Contraceptive Technology, the levonorgestrel the placebo drug. intrauterine device (Mirena, Bayer HealthCare Data indicates the sildenafil citrate group had Pharmaceuticals, Wayne, NJ) also is an excellent better pain relief compared with the placebo choice for women with dysmenorrhea because group [mean standard deviation (SD): 11.9 (3.2) menstrual blood loss and duration of bleeding are versus 6.4 reduced.12 (2.1), respectively; difference in means = 5.3; 95% confidence interval (CI): (2.9,7.6); P < REFERENCES 0.001)]. On the visual analog scale, sildenafil citrate provided better pain relief than placebo 1. Davis AR, Westhoff CL. Primary dysmenorrhea in adolescent at each time point. At the two-hour point, the girls and treatment with oral contraceptives. J Pediatr Adolesc pulsatility index was significantly lower in the Gynecol 2001; 14:3-8. sildenafil citrate group compared with the pla- 2. Durain D. Primary dysmenorrhea: assessment and manage- cebo group [mean SD: 1.6 (0.6) versus 2.3 (0.5), ment update. J Midwifery Womens Health 2004; 49:520-528. respectively; difference in means = -0.7; 95% CI: 3. Ortiz MI, Rangel-Flores E, Carrillo-Alarcón LC, et al. (-1.2, -0.1);P = 0.01)].6 Prevalence and impact of primary dysmenorrhea among The research group has applied for research Mexican high school students. Int J Gynaecol Obstet 2009;

30 CONTRACEPTIVE TECHNOLOGY UPDATE ® / March 2014 107:240-243. similar to those associated with use of high-dose 4. Fedorowicz Z, Nasser M, Jagannath VA, et al. Beta-2- 50 mcg ethinyl oral contraceptives, says adrenoceptor agonists for dysmenorrhoea. Cochrane Database Kaunitz. Syst Rev 2012; doi: 10.1002/14651858.CD008585.pub2. An investigational combination hormonal con- 5. Ju H, Jones M, Mishra G. The prevalence and risk factors of traceptive patch has been designed to deliver a low dysmenorrhea. Epidemiol Rev 2014; 36(1):104-113. dose of ethinyl estradiol and levonorgestrel compa- 6. Dmitrovic R, Kunselman AR, Legro RS. Sildenafil citrate in rable to low-dose combination oral contraceptives. the treatment of pain in primary dysmenorrhea: a randomized Developed by Agile Therapeutics of Princeton, NJ, controlled trial. Hum Reprod 2013; 28(11):2,958-2,965. as AG200-15, the drug is under review by the FDA. 7. Facchinetti F, Sgarbi L, Piccinini F, et al. A comparison of The company has registered the trademarked name glyceryl trinitrate with diclofenac for the treatment of primary Twirla for the investigational drug. It is designed to dysmenorrhea: an open, randomized, cross-over trial. Gynecol deliver 120 mg/day levonorgestrel with 25 mg/day Endocrinol 2002; 16:39-43. ethinyl estradiol. (To read more about the drug, see 8. Moya RA, Moisa CF, Morales F, et al. Transdermal glyceryl the CTU articles “Check methods with combined trinitrate in the management of primary dysmenorrhea. Int J hormones,” April 2013, p. 40, and “Data out on Gynaecol Obstet 2000; 69:113-118. potential ,” August 2012, p. 9. Kletzky OA, Vermesh M. Effectiveness of vaginal bromocrip- 88.) tine in treating women with hyperprolactinemia. Fertil Steril In a phase III pivotal trial of AG200-15, results 1989; 51(2):269-272. suggest the study drug had significantly greater 10. Dawood MY. Primary dysmenorrhea: advances in pathogen- compliance (defined as no missed days of contra- esis and management. Obstet Gynecol 2006; 108:428-441. ception in the cycle) than an oral contraceptive.1 11. Berkley K. Primary dysmenorrhea: an urgent mandate. Pain Of 1,328 women (mean age, 26.4 years; 60% Clinical Updates 2013; available at http://bit.ly/1eSPFfg. new hormonal contraceptives users; 46% non- 12. Nelson AL, Baldwin SB. Menstrual disorders. In: Hatcher Caucasian; 33% obese), 998 received the patch and RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 330 received an oral contraceptive for the first six 20th revised edition. New York: Ardent Media; 2011. n study cycles. Women in the study were treated for one year (13 cycles) with the patch or for six cycles with the Pill, followed by seven cycles of patch use. Options being eyed for Subjects recorded patch application and pill-taking on diary cards. Cycles with perfect compliance transdermal contraception were defined as cycles with 21 days of patch wear without missed days or any patch worn for more ransdermal contraception provides a family than seven days or cycles with 21 days of pill-taking Tplanning option that is not dependent on daily without days of missed pills. dosing. While potential options are in development, Over the first six cycles, the percentage of cycles the only transdermal contraceptive approved in the with perfect compliance was significantly higher in United States is the Ortho Evra patch, marketed by the patch versus the pill group (90.5% vs. 78.8%, Ortho Women’s Health & Urology, Raritan, NJ. Evra received Food and Drug Administration EXECUTIVE SUMMARY (FDA) approval in 2001. Since that time, its label- ing has been edited to address issues relating to the Transdermal contraception provides a family planning risk of venous thromboembolism and exposure to option that is not dependent on daily dosing. The only contraceptive hormones seen with Ortho Evra as transdermal contraceptive approved in the United States is compared to certain combined oral contraceptives. the Ortho Evra patch. • An investigational combination hormonal contraceptive (See the Contraceptive Technology Update article, patch has been designed to deliver a low dose of ethinyl “Set to change: Patch, drospirenone OC labels,” estradiol and levonorgestrel comparable to low-dose com- February 2012, p. 13.) bination oral contraceptives. Developed by Agile Therapeu- Many women prefer using a weekly patch to tics as AG200-15, the drug is under U.S. regulatory review. having to remember daily oral contraceptive tablets, • Bayer HealthCare has submitted an application for market- says Andrew Kaunitz, MD, professor and associate ing authorization in the European Union for a transparent chair in the Obstetrics and Gynecology Department low-dose contraceptive patch containing ethinyl estradiol/ at the University of Florida College of Medicine — gestodene. Gestodene, while used in as a contraceptive Jacksonville. The currently marketed ethinyl estra- agent in Europe for many years, is not available in any U.S.- diol/ norelgestromin patch results in blood levels approved contraceptive.

March 2014 / CONTRACEPTIVE TECHNOLOGY UPDATE ® 31 P less than .001). Compliance with the patch 4. Heger-Mahn D, Warlimont C, Faustmann T, et al. Combined improved over the six treatment cycles, while com- ethinyl estradiol/gestodene contraceptive patch: two-center, open- pliance with the Pill worsened over the six cycles.1 label study of ovulation inhibition, acceptability and safety over Additional research indicates the investigational two cycles in female volunteers. Eur J Contracept Reprod Health low- patch is as effective as conventional Care 2004; 9(3):173-181. oral contraceptives; an additional finding of the trial 5. Benagiano G, Primiero FM, Farris M. Clinical profile of contra- is that the efficacy of the investigational patch did ceptive progestins. Eur J Contracept Reprod Health Care 2004; not decline in obese women.2 9(3):182-193. n “Should this lower-estrogen patch receive FDA- approval, our patients would have access to a lower dose transdermal contraceptive system,” says Clinicians missing mark Kaunitz, who served as lead clinical investigator in the AG200-15 trials. on sex talk with teens Potential option eyed s a family planning clinician, you should be Aprepared to discuss sexuality with your ado- Berlin, Germany-based Bayer HealthCare sub- lescent patients. Know, however, that you might mitted an application for marketing authorization be the first provider to do so. In a study looking at in the European Union for a new transparent low discussions held between pediatricians and family dose contraceptive patch containing ethinyl estra- medicine physicians and teen-age patients, results diol/ gestodene in September 2012, confirms com- show less than two-thirds of such interactions pany spokesperson Marcy Funk. Named FC-Patch included talk about sex, sexuality, or dating during Low, the patch is transparent and contains 0.55 annual visits.1 mg ethinyl estradiol and 2.1 mg gestodene. While Previous studies on discussions of sex during doc- gestodene has been in use as a contraceptive agent tors’ visits have been based on information teens or in European countries for more than 20 years, no physicians have reported after visits.2,3 To capture U.S.-approved birth control method contains it. naturally occurring conversations, scientists in the In a 2013 study, a combined oral contraceptive current study used audio recordings of annual visits, containing 0.03 mg of ethinyl estradiol and 0.15 mg including camp and sports physicals, for 253 ado- levonorgestrel and the Bayer patch showed com- lescents. The patients, ages 12 to 17, visited pedia- parable influence on hemostatic endpoints.3 Both tricians and family medicine physicians at 11 North treatments were well-tolerated by subjects.3 Carolina clinics. Earlier research indicates that the good skin The researchers listened to the recordings for absorption properties of gestodene, and the low any mention of sexual activity, sexuality, or dating. absolute dose required for contraceptive efficacy, Their analysis shows physicians brought up sex in suggest it can be offered in a small patch size.4,5 65% of visits, with conversations lasting an average of 36 seconds. The other 35% of visits included no REFERENCES mention of sex. “As researchers, we knew no study has existed 1. Kaunitz A, Archer DF, Foegh M. Increased compliance with a low-dose combination contraceptive patch (AG200-15) compared with a low-dose combination oral contraceptive (COC) in a phase EXECUTIVE SUMMARY 3 clinical trial. Contraception 2012; 86(2):178. 2. Kaunitz AM, Mishell DR, Foegh ML. Comparative Phase 3 In a study looking at discussions held between pediatri- cians and family medicine physicians and teen-age patients, Study of AG200-15, a Low-Dose Estrogen, and Levonorgestrel results show less than two-thirds of such interactions Contraceptive Patch. Presented at the 60th Annual Clinical included talk about sex, sexuality, or dating during annual Meeting of the American College of Obstetricians and visits. Gynecologists. San Diego; May 2012. • Physicians brought up sex in 65% of visits, with conversa- 3. Junge W, Heger-Mahn D, Trummer D, et al. Investigation of the tions lasting an average of 36 seconds. The other 35% of hemostatic effect of a containing 0.55 mg ethinyl visits included no mention of sex. estradiol and 2.1 mg gestodene compared with a monophasic oral • Engage adolescents in discussions about sex. In the cur- contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg rent study, none of the adolescents initiated discussions levonorgestrel: an open-label, randomized, crossover study. Drugs on sex, which reinforces the need for clinicians to start the R D 2013; 13(3):223-233. conversation.

32 CONTRACEPTIVE TECHNOLOGY UPDATE ® / March 2014 that has examined how these conversations University research program focused on adolescents sounded, and we wanted a better idea of where cur- during the past 17 years. “I often ask specifically rent practice stands regarding these discussions,” about kissing because it is a very common experi- explains Stewart Alexander, PhD, associate profes- ence, is associated with far less social disapproval sor of medicine in the Department of Medicine at than other forms of sexual interaction, and is easy Duke to acknowledge.” University Medical Center, Durham, NC. For young people who don’t identify a current “Initially, we were planning to examine the qual- relationship, clinicians can follow up with a ques- ity of counseling teens about sex but found that the tion about past relationships and behaviors, or conversations were quite different — even when with a question about sexual contact with someone they occurred.” who wasn’t considered a relationship partner, says As researchers listened to the provider-patient Fortenberry. interactions, they realized that specific training When responding to reports of specific sexual might be able to help providers improve these dis- behaviors, including abstinence, Fortenberry sug- cussions, says Alexander, who served as lead author gests a question such as “what was good (or bad) of the current paper. The research team is devel- about your decision to have sex?” or “what was oping training to address these issues, Alexander good (or bad) about your decision to abstain?” states. What is “sex talk?” Check your approach Some clinicians use questions about pubertal It is important for providers to engage adoles- development as an entrée to asking about sex, says cents in discussions about sex. In the current study, Fortenberry. However, asking young men about none of the adolescents initiated discussions on sex, pubic hair development or young women about which reinforces the need for clinicians to start the their menstrual periods does not constitute “sex conversation. As research progresses in identifying talk.” [Looking for more information on conduct- successful strategies providers can use to engage ing initial reproductive health visits in teens? Check teens in discussions to help promote healthy sexual the HEEADSSS (Home environment, Education development and decision making, what can you do and employment, Eating, peer-related Activities, to facilitate such interactions with your adolescent Drugs, Sexuality, Suicide/depression, and Safety patients? from injury and violence) method of interviewing For starters, clinicians wishing to address issues covered in the Contraceptive Technology Update of sexuality with adolescents should remember article, “How to get into heads of teens in initial that confidentiality discussions are best when they visit,” January 2014, p. 8.] occur before the topics of sex are introduced, says Clinicians also should remember that many Dennis Fortenberry, MD, MS, professor of pediat- young people are still developing a sexual identity rics and medicine at the Indiana University School so that unwarranted assumptions about hetero- of Medicine in Indianapolis. Younger adolescents sexuality often are revealed through the use of spe- might have limited understanding of the legal and cific words that presume the gender of a partner, ethical nuances of confidentiality, but almost all observes Fortenberry. Gender-neutral questions can have definite understandings of privacy, explains allow discussions with sexual minority youth who Fortenberry, a co-author of the current study. often feel invisible in sexuality discussions, he states. One way to introduce sexuality with young patients is to ask first about relationships, says REFERENCES Fortenberry. For young people in a relationship, follow-up questions can address specific behaviors 1. Alexander SC, Fortenberry JD, Pollak KI, et al. Sexuality talk with their relationship partner, their feelings about during adolescent health maintenance visits. JAMA Pediatr 2013; those behaviors (including whether the behavior doi: 10.1001/jamapediatrics.2013.4338. was consensual), and expectations for future behav- 2. Henry-Reid LM, O’Connor KG, Klein JD, et al. Current pedia- iors, he states. trician practices in identifying high-risk behaviors of adolescents. “These types of questions allow exploration as Pediatrics 2010; 125(4):e741-e747. well of the adolescent’s boundaries about sexual 3. Kitts RL. Barriers to optimal care between physicians and activity, which are quite clearly formed for many,” lesbian, gay, bisexual, transgender, and questioning adolescent says Fortenberry, who has guided an Indiana patients. J Homosex 2010; 57(6):730-747. n

March 2014 / CONTRACEPTIVE TECHNOLOGY UPDATE ® 33 for any contraceptive coverage to which they object on religious grounds.1

Wave of lawsuits emerges

This compromise has satisfied some but not all of the administration’s critics, and one result Contraceptive coverage has been a wave of lawsuits; nearly 80 of them are pending as of January 2014.2 More than 30 heads to Supreme Court of those lawsuits have been brought by nonprofit organizations that object to the scope and struc- By Adam Sonfield ture of the accommodation, with some plaintiffs Senior Public Policy Associate arguing that the requirement to sign a form assert- Guttmacher Institute ing their objection to contraceptive coverage in Washington, DC order to take advantage of the accommodation is itself a violation of their religious rights. ith Congress in a seemingly perpetual state of However, most of the pending lawsuits, includ- Wdeadlock, one of the most anticipated actions ing the two before the Supreme Court, have been on federal reproductive health policy will instead brought by for-profit companies, which are eligible be taken by the U.S. Supreme Court this spring. for neither the exemption nor the accommoda- On March 25, 2014, the Supreme Court is slated tion. These cases involve challenges under the First to hear oral arguments on two challenges to the Amendment’s protection for religious exercise Affordable Care Act’s (ACA) contraceptive cover- and under a 1993 federal law called the Religious age guarantee: Sebelius v. Hobby Lobby Stores, in Freedom Restoration Act. One central question which the 10th Circuit Court of Appeals sided with is whether a company can cite these protections: an Oklahoma-based craft supply chain store, and Does it qualify as a “person” that can have reli- Conestoga Wood Specialties v. Sebelius, in which gious beliefs and put them into practice? the Third Circuit ruled against a Pennsylvania-based In the two Supreme Court cases, the businesses furniture manufacturer. A final ruling on the cases are for-profit corporations owned privately by is likely to be announced in June. members of a single family, and both the own- The federal contraceptive coverage guarantee — ers and the corporations themselves are plaintiffs. part of a broader requirement for private health In both cases, the plaintiffs object to coverage of plans to cover dozens of key preventive care services specific contraceptive methods and services: emer- without out-of-pocket costs for patients — has been gency contraceptive pills (including Plan B and met with controversy since the outset. Social con- ella); copper and hormonal intrauterine devices; servatives inside and outside of Congress repeatedly and counseling and education about these meth- have demanded that the requirement be repealed or ods, which they assert can cause an abortion. that it exempt any employer asserting a religious or In part because of these specifics, it is unclear moral objection to coverage of some or all forms of whether any of the other lawsuits might remain contraception, regardless of the beliefs and needs of relevant even after the Supreme Court issues a rul- employees and dependents. ing. It does not appear that the contraceptive cov- The Obama administration has tried to defuse erage guarantee itself is in danger of being struck these objections, by crafting an exemption for down, but a ruling could have a significant effect health plans offered by houses of worship and on how many women will be able to obtain cover- other religious employers, narrowly defined, and age and how expansive that coverage might be. by providing an “accommodation” for religiously affiliated nonprofit organizations, such as some What is to come? universities, hospitals, and social relief agencies. Employees of those latter organizations still must That question is a meaningful one to the mil- receive coverage of the full range of contraceptive lions of Americans who have already benefited methods and services without out-of-pocket costs, from the coverage protections and from the mil- but that coverage must be provided by the organiza- lions more who will gain these protections going tion’s insurance company. The employer, however, forward. According to a Guttmacher Institute does not have to “contract, arrange, pay, or refer” study released in December, the proportion of

34 CONTRACEPTIVE TECHNOLOGY UPDATE ® / March 2014 privately insured U.S. women who paid $0 out of pocket for oral contraceptive pills increased CNE/CME OBJECTIVES & INSTRUCTIONS sharply, from 15% in fall 2012 (before the con- traceptive coverage guarantee took effect for most o earn credit for this activity, please follow these Tinstructions. women) to 40% in spring 2013 (after the require- 1. Read and study the activity, using the provided references ment came into force for millions).3 for further research. A similar increase, from 23% to 52%, was 2. Scan the QR code below or log on to www.cmecity.com seen among users with private insur- to take a post-test; tests can be taken after each issue or ance, although media reports and evidence from collectively at the end of the semester. First-time users will have to register on the site using the 8-digit subscriber insurance companies’ own publicly available doc- number printed on their mailing label, invoice or renewal uments indicate that the federal rules are being notice. interpreted inconsistently for some methods and 3. Pass the online tests with a score of 100%; you will be services.4 allowed to answer the questions as many times as needed The impact of the guarantee can be expected to achieve a score of 100%. to grow further as it is phased in to additional 4. After successfully completing the last test of the semester, your browser will be automatically directed to the activity plans: the number of covered workers enrolled in evaluation form, which you will submit online. “grandfathered” plans — existing plans given a 5. Once the completed evaluation is received, a credit letter temporary reprieve from many of the ACA’s new will be emailed to you instantly. rules — has been declining rapidly, as Congress intended, from 48% in 2012 to 36% in 2013.5 fter reading Contraceptive Technology Update, the Aparticipant will be able to: • identify clinical, legal, or scientific issues related to REFERENCES development and provisions of contraceptive technology or other reproductive services; 1. Department of the Treasury, Department of Labor, • describe how those issues affect services and patient care; Department of Health and Human Services. Coverage of certain • integrate practical to problems and information into daily practices, according to advice from nationally preventive services under the Affordable Care Act: final rules. recognized family planning experts; 78 Fed Reg 39870-39899 (July 2, 2013). Accessed at http://1. • provide practical information that is evidence-based usa.gov/1fhgqKR. to help clinicians deliver contraceptives sensitively and 2. American Civil Liberties Union. Challenges to the federal effectively. n contraceptive coverage rule. Accessed at http://bit.ly/1dyk97Q. 3. Finer LB, Sonfield A, Jones RK. Changes in out-of-pocket payments for contraception by privately insured women during implementation of the federal contraceptive coverage require- ment. Contraception 2014; 89(2):97-102. 4. Sonfield A. Implementing the federal contraceptive coverage To reproduce any part of this newsletter for promotional­ pur- guarantee: progress and prospects. Guttmacher Policy Review poses, please contact: 2013;16(4):8-12. Stephen Vance 5. Kaiser Family Foundation and Health Research and Phone: (800) 688-2421, ext. 5511 Educational Trust. Employer Health Benefits: 2013 Annual Fax: (800) 284-3291 Email: [email protected] Survey. Menlo Park, CA: Kaiser Family Foundation and To obtain information and pricing on group ­discounts, multiple Chicago: Health Research and Educational Trust; 2013. copies, site-licenses, or electronic distribution please contact: Accessed at http://bit.ly/1dj0J5H. n Tria Kreutzer Phone: (800) 688-2421, ext. 5482 Fax: (800) 284-3291 Email: [email protected] COMING IN FUTURE MONTHS Address: AHC Media 3525 Piedmont Road, Bldg. 6, Ste. 400 Atlanta, GA 30305 USA n Science investigates n Using social media To reproduce any part of AHC newsletters for educational pur- intrauterine ball to promote adolescent poses, please contact: contraceptive health The Copyright Clearance Center for permission Email: [email protected] n n Website: www.copyright.com Potential herpes Nitrous oxide checked Phone: (978) 750-8400 simplex virus therapy in for pain management Fax: (978) 646-8600 focus with IUD insertion Address: Copyright Clearance Center 222 Rosewood Drive Danvers, MA 01923 USA

March 2014 / CONTRACEPTIVE TECHNOLOGY UPDATE ® 35 Editorial Advisory Board Chairman: Robert A. Hatcher, MD, MPH Senior Author, Contraceptive Technology 1. What is the approved indication for use Professor of Gynecology and Obstetrics of Skyla, the levonorgestrel intrauterine Emory University School of Medicine, Atlanta system? David F. Archer, MD Amy E. Pollack, MD, MPH A. Three years Professor of OB/GYN Senior Lecturer The Jones Institute for School of Public Health B. Five years Reproductive Medicine Columbia University C. 10 years The Eastern Virginia New York City Medical School D. 12 years Norfolk Michael Rosenberg, MD, MPH Kay Ball, RN, PhD, CNOR, Clinical Professor of OB/GYN FAAN and Epidemiology Perioperative Consultant/ University of North Carolina 2. The U.S. Department of Health and Hu- Educator President, Health Decisions man Services’ Healthy People 2020 seeks K&D Medical Chapel Hill Lewis Center, OH to reduce the proportion of pregnancies Wayne Shields conceived within what timespan from a Melanie Deal, MS, WHNP-BC, FNP President & CEO, Association previous birth? Nurse Practitioner of Reproductive Health Professionals A. 12 months San Francisco State University Student Health Washington, DC B. 18 months Services San Francisco James Trussell, PhD C. 24 months Professor of Economics Linda Dominguez, RNC, and Public Affairs D. 30 months WHNP Director Clinicial Consultant Office of Population Southwest Women’s Health Research Albuquerque, NM 3. A systematic review of evidence indicates Princeton (NJ) University Andrew M. Kaunitz, MD which is the most effective treatment of Professor and Associate Susan Wysocki, WHNP-BC, primary dysmenorrhea? Chairman FAANP Department of OB/GYN President & CEO A. Topical heat therapy University of Florida iWomansHealth B. Fennel College of Medicine Washington, DC C. Nonsteroidal anti-inflammatory drugs Jacksonville Anita L. Nelson, MD D. Vitamin B6 Professor, OB-GYN David Geffen School of Medicine University of California, 4. What are the hormones contained in the Los Angeles AG200-15 contraceptive patch under development by Agile Therapeutics? Contraceptive Technology Update is endorsed by the National Association of Nurse Practitioners in A. Ethinyl estradiol and gestodene Women’s Health and the Association of Reproduc­tive B. Ethinyl estradiol and norethindrone Health Profes­sionals as a vital information source for acetate healthcare professionals. C. Ethinyl estradiol and desogestrel D. Ethinyl estradiol and levonorgestrel

36 CONTRACEPTIVE TECHNOLOGY UPDATE ® / March 2014 QUARTERLY

New data emerges on use of pre-exposure prophylaxis (PrEP)

No link seen between regimen use and increased sexual risk behavior

re-exposure prophylaxis (PrEP) with teno- Biological markers eyed fovir disoproxil fumarate and emtricitabine P(Truvada, Gilead Sciences, Foster City, CA) Questions have been raised whether taking the has proven effective in HIV prevention in high-risk drug regimen could lead to a behavioral effect called groups, with the Food and Drug Administration risk compensation, whereby individuals adjust their approving such indication for emtricitabine’s use in behavior in response to a change in their perceived 2012. level of risk. While participants in the iPrEX trial While the Centers for Disease Control and self-reported decreases in sexual risk behavior over Prevention (CDC) has provided interim guidance the course of the study, scientists involved in the for PrEP use, a national survey of infectious disease current analysis decided to examine those findings physicians shows only 9% have prescribed it.1 Those more closely by studying biological markers of risk numbers might change; just-published data indicates behavior. that there is no link between use of the PrEP regimen and increased sexual risk behavior.2 The findings build upon data from the 2010 EXECUTIVE SUMMARY Global Pre-exposure Prophylaxis Initiative (iPrEx) Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil clinical study, which reported that emtricitabine, fumarate and emtricitabine (Truvada, Gilead Sciences) has originally approved to treat HIV-positive patients, proven effective in HIV prevention in high-risk groups, with also was effective in preventing new infections in the Food and Drug Administration approving such indica- 3 people likely to come in contact with the virus. A tion for emtricitabine’s use in 2012. 2012 follow-up study bolstered such findings, with • While the Centers for Disease Control and Prevention has data suggesting that taking emtricitabine regularly provided interim guidance for PrEP use, a national survey of reduced risk of HIV infection by more than 90%.4 infectious disease physicians shows only 9% have prescribed (To read Contraceptive Technology Update’s latest it. coverage of PrEP research and protocols, see “Check • More providers might consider PrEP use now that just-pub- interim guidance for PrEP in men, women,” October lished data indicates that there is no link between use of the 2012, p. 113.) PrEP regimen and increased sexual risk behavior.

Statement of Financial Disclosure: Consulting Editor Robert A. Hatcher, MD, MPH, Author Rebecca Bowers, and Executive Editor Joy Dickinson report no consultant, stock- holder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. Melanie Deal, nurse reviewer, discloses that she is on the speakers bureau for Actavis and Merck & Co. and the advisory board for Actavis, Teva, and Hologic. To perform the study, investigators assessed medicine in the Division of Infectious Diseases, sexual practices at baseline and quarterly thereafter; Department of Medicine, at University of California perceived treatment assignment and PrEP efficacy San Diego, and lead author of the current paper, beliefs were assessed at 12 weeks. Among partici- says, “I personally have been a proponent of PrEP, pants with one or more follow-up behavioral assess- but upon talking to colleagues, I found a great deal ment, sexual behavior, syphilis, and HIV infection of differences in opinions and practices just within were compared by perceived treatment assignment, our San Diego HIV community. This led me to actual treatment assignment, and perceived PrEP wonder how PrEP opinions and practices truly dif- efficacy. fered among infectious diseases physicians across Overall, acute HIV infection and syphilis the country and what clinical practice factors con- decreased during follow-up. Compared with partici- tributed to those views.” pants believing they were receiving placebo, partici- Karris and the research team surveyed adult pants believing they were receiving emtricitabine/ infectious disease physicians from a national net- tenofovir disoproxil fumarate reported more recep- work about their opinions and current practices of tive anal intercourse partners prior to initiating drug PrEP. While most clinicians supported PrEP, only (12.8 vs. 7.7, P = 0.04). Belief in receiving the study 9% had provided it. Despite CDC guidance, PrEP drug protocol was not associated with an increase practices were variable and clinicians reported many in receptive anal intercourse with no condom from barriers to its real-world provision, survey findings baseline through follow-up (risk ratio [RR] 0.9, indicate. 95% confidence interval [CI]: 0.6-1.4; P = 0.75), nor An analysis of the actual use of tenofovir/emtric- with a decrease after stopping study drug (RR 0.8, itabine was presented at the 2013 Interscience 95% CI: 0.5-1.3; P = 0.46). In the placebo arm, there Conference on Antimicrobial Agents and were trends toward lower HIV incidence among Chemotherapy. It drew data from a nationally rep- participants believing they were receiving the study resentative patient database, as well as information drug protocol (incidence rate ratio [IRR] 0.8, 95% from more than 50% of the dispensing pharmacies CI: 0.4-1.8; P = 0.26) and also believing it was highly in the United States, and applied an algorithm to effective (IRR 0.5, 95% CI: 0.1-1.7; P = 0.12).2 exclude the use of tenofovir/emtricitabine for any “Our results suggest that HIV prevention strate- other reason but as PrEP.5 gies such as Truvada don’t result in risk compen- A total of 1,774 individuals were prescribed sation because they provide an opportunity for PrEP between January 2011 and March 2013, the participants to actively engage in and reduce their data shows. Half of the users of tenofovir/emtric- risk of HIV infection,” says Robert Grant, MD, itabine for PrEP were women; 32% of users were MPH, professor at the University of California, in the South, with 24% in the Northeast and West, San Francisco and an investigator in the university- and 18% in the Midwest. PrEP prescribers were affiliated Gladstone Institutes. “Engagement, which mainly primary care providers, including emergency also includes counseling, provision of condoms, and department clinicians; infectious diseases specialists management of other sexually transmitted infec- accounted for just 12% of prescriptions.5 tions leads to motivation, which comes at a time A coalition of more than 50 women from lead- when motivation for preventing new HIV infections ing AIDS and women’s health organizations is is vital to curbing the spread of this worldwide epi- looking to U.S. government agencies to coordinate demic.” a national agenda for more information on how PrEP can best be made available as to more women Who’s using protocol? at risk of HIV infection. The U.S. Women and PrEP Working Group issued the call to govern- The CDC offers support on PrEP use at its site, ment officials following release of data at the 2013 http://1.usa.gov/1fzbtkI. (See other resource infor- Conference on Retroviruses and Opportunistic mation at end of this story.) The interim guidance Infections showing that none of three interventions includes information for injecting drug users, het- tested in a large scale trial among African women, erosexually active adults, and men who have sex known as VOICE (Vaginal and Oral Interventions with men. However, clinicians are slow to embrace to Control the Epidemic) – daily oral tenofovir, PrEP, results of a national survey show.1 daily oral tenofovir/emtricitabine, and daily 1% Maile Karris, MD, assistant professor of vaginal tenofovir gel – provided additional protec-

2 Supplement to Contraceptive Technology Update ® / March 2014 tion against HIV.6 on PrEP for HIV prevention. PrEP Watch includes information on Male and female condoms are “wonderful” HIV data, additional research, cost, access, and advocacy efforts in prevention options that work for many women the United States and across the globe. n and their partners, observed Erika Aaron, RN, CRNP, MSN, assistant professor in the Division What is the role of Infectious Diseases and HIV Medicine at Drexel University School of Medicine in Philadelphia, in of express STI testing? a statement released by the U.S. Women and PrEP Working Group. However, some women feel that eclining resources in the face of increasing they can’t insist their partners use condoms, and Ddemand are causing sexually transmitted infec- many young women and their HIV-positive part- tion (STI) clinics to review new strategies to maxi- ners want to have children, Aaron said. mize efficiency without compromising quality of “Those women need other options to protect care. Just-published research suggests express STI themselves from HIV; PrEP can help them stay testing, which bypasses lengthy interviews and phys- HIV-negative,” she stated. “We have a moral ical examinations, might be a viable option.1 imperative to find ways to make it available to Just-published research centers on a cohort of women who need it and who can use it.” men attending two Baltimore STI clinics. The paper was published by Susan Tuddenham, MD, MPH, a REFERENCES fellow in the Division of Infectious Diseases at the Johns Hopkins University (JHU) School of Medicine 1. Karris MY, Beekmann SE, Mehta SR, et al. Are we prepped for in Baltimore, and Khalil Ghanem, MD, PhD, preexposure prophylaxis (PrEP)? Provider opinions on the real- assistant professor of medicine in the Division of world use of PrEP in the United States and Canada. Clin Infect Dis Infectious Diseases at the JHU School of Medicine 2013; doi: 10.1093/cid/cit796. and assistant professor in JHU’s Bloomberg School 2. Marcus JL, Glidden DV, Mayer KH, et al. (2013) No evidence of Public Health. Researchers designed the retro- of sexual risk compensation in the iPrEx trial of daily oral HIV pre- spective study to define the contribution of the phys- exposure prophylaxis. PLoS ONE 2013; 8(12): e81997. ical examination in detecting clinically meaningful 3. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemo- diagnoses that might not be identified by current prophylaxis for HIV prevention in men who have sex with men. laboratory methods and to identify characteristics NEJM 2010; 363(27):2,587-2,599. that can stratify men into the appropriate risk cat- 4. Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir egory. concentrations and pre-exposure prophylaxis efficacy in men who For determining men’s risk of missed diagnosis have sex with men. Sci Transl Med 2012; 4:151ra125. based on initial screening, patients were retro- 5. Mera RM, Rawlings MK, Pechonkina A, et al. Status of spectively stratified into three groups based on the Truvada (TVD) for HIV pre-exposure prophylaxis (PrEP) in self-reported reason for their visit. The first group the United States: an early drug utilization analysis. Presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy. Denver; September 2013. EXECUTIVE SUMMARY 6. Marrazzo J, Ramjee G, Nair G, et al. Pre-exposure prophylaxis Declining resources in the face of increasing demand are for HIV in women: daily oral tenofovir, oral tenofovir/emtric- causing sexually transmitted infection (STI) clinics to review itabine, or vaginal tenofovir gel in the VOICE Study (MTN 003). new strategies to maximize efficiency without compromis- 20th Conference on Retroviruses and Opportunistic Infections. ing quality of care. Atlanta; March 2013. •Just-published research suggests express STI testing, which bypasses lengthy interviews and physical examinations, RESOURCE might be a viable option in this direction. • Express STI testing at the Pima County Health Department • AVAC, a New York City-based non-profit organization uses in Tucson, AZ, allows patients to complete the screening education, policy analysis, advocacy, and a network of global process in 30 minutes or less. Symptomatic STIs such as collaborations to accelerate the ethical development and global delivery of AIDS vaccines, male circumcision, microbicides, PrEP, chlamydia are more rapidly detected and treated, which and other emerging HIV prevention options as part of a compre- helps to decrease the amount of untreated infections within hensive response to the pandemic. It maintains a web site, www. the community, as well as serving as a disease control mea- prepwatch.org, which serves as a clearinghouse for information sure to preventing new infections.

March 2014 / Supplement to Contraceptive Technology Update ® 3 included men who were asymptomatic present- ing for clients who wanted only testing services and ing for general checkups, while the second group were asymptomatic and/or short on time. included all men who came in complaining of How is it determined which patients are best symptoms such as discharge, dysuria, genital lesion, served by express testing? genital itching, rash, and irritation/odor. The third Patients who present for testing as a part of rou- group included asymptomatic men who presented tine screening, those who are between relationships, as known contacts of STI-infected partners. or those who are simply concerned they might Only men coming in for their first clinic visit have had an exposure are ideal for express testing were included in this analysis. services, says Garcia. Some patients will want only After stratifying men on the basis of reason for express testing and would rather wait until they visit, the researchers compared proportions for receive test results before taking any unnecessary diagnoses that would have been missed without antibiotics, he notes. physical examination. Logistic regression was used Express testing allows patients the ability to com- to assess which factors were most predictive of plete the screening process in 30 minutes or less, missed diagnoses. depending on the number of clients present at any Of 140,052 patient visit records, 58,073 met given time, says Garcia. Another benefit of express the entry criterion; the other 81,979 records were testing is that asymptomatic STIs such as chlamydia excluded because they represented multiple visits. are more rapidly detected and treated, thus help- A total of 29,172 men were asymptomatic, 23,971 ing to decrease the amount of untreated infections were symptomatic, and 4,929 were asymptomatic within the community as well as serving as a disease contacts of an infected partner. Analysis suggests control measure to preventing new infections, he 2.7% of asymptomatic patients, 10.4% of symp- notes. Gonorrhea, syphilis, and HIV likewise have tomatic patients, and 4.5% of contact patients been successfully detected and appropriate treat- would have had missed diagnoses if no physical ment has been offered within a shorter timeframe, examination had been performed. For symptomatic he states. patients, if those reporting rash, lesion, or genital “Increase in routine STI testing, treatment and itch were examined, the percent with missed diag- medical interventions aid in supporting improved noses would drop to 3.7%. health of the community at large,” advocates In a podcast on www.stdpreventiononline.org, Garcia. (For more information on express testing, a website run by the Centers for Disease Control see the Contraceptive Technology Update article, and Prevention-sponsored Internet & STD Center “Express STI testing — Can it work in your clinic?” of Excellence, Ghanem states there are ways to August 2009, p. 90.) It looks at the experience of enhance clinic efficiency without compromis- Denver Metro Health Clinic, the largest STI clinic ing patient care, as long as the right subgroup of and HIV testing facility in the Rocky Mountain patients is targeted and as long as clinic leaders region, which uses a triage system to identify know their limitations of their facilities. (Download low-risk individuals who qualify for an express, the podcast at http://bit.ly/1idRiGB.) testing-only visit to screen for major communicable “I think an expedited approach to a subset of diseases without a physical examination. A 2008 patients can enhance efficiency, as long as clinics evaluation of the service indicates the triage system have the resources to track those patients who were safely and effectively identifies those appropriate not treated at the time of their expedited visit and for express visits, reduces waiting times for patients, bring them back in a timely manner for treatment,” and increases clinic throughput.2 Ghanem says in the podcast. REFERENCES How does testing work? 1. Tuddenham S, Ghanem KG. Toward enhancing sexually trans- Pima County, AZ, is home to more than one mil- mitted infection clinic efficiency in an era of molecular diagnostics: lion people. Its county health department, based in the role of physical examination and risk stratification in men. Sex Tucson, has used express STI testing since 2008, Transm Dis 2013; 40(11):886-893. says Francisco García, MD, MPH, health depart- 2. Shamos SJ, Mettenbrink CJ, Subiadur JA, et al. Evaluation of a ment director. The “Express Testing” process began testing-only “express” visit option to enhance efficiency in a busy as an alternative effort to offer expedited STI test- STI clinic. Sex Transm Dis 2008; 35(4):336-340. n

4 Supplement to Contraceptive Technology Update ® / March 2014