Advertisement
JOGC

No. 329-Canadian Contraception Consensus Part 4 of 4 Chapter 9: Combined Hormonal Contraception

      Abstract

      Objective

      To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality.

      Outcomes

      Overall efficacy of cited contraceptive methods, assessing reduction in pregnancy rate, safety, and side effects; the effect of cited contraceptive methods on sexual health and general well-being; and the availability of cited contraceptive methods in Canada.

      Evidence

      Medline and the Cochrane Database were searched for articles in English on subjects related to contraception, sexuality, and sexual health from January 1994 to December 2015 in order to update the Canadian Contraception Consensus published February-April 2004. Relevant Canadian government publications and position papers from appropriate health and family planning organizations were also reviewed.

      Values

      The quality of the evidence is rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice are ranked according to the method described in this report.

      Summary Statements

      • 1.
        Although highly effective with perfect use, typical use failure rates for combined hormonal contraceptives, including the combined oral contraceptive pill, are as high as 9% (II-2).
      • 2.
        The majority of qualified studies do not indicate decreased combined oral contraceptive pill efficacy in obese women; however, a small increase in contraceptive failure in women with a body mass index greater than 30 cannot be excluded (II-2).
      • 3.
        Combined oral contraceptive pills are associated with a number of non-contraceptive benefits, including but not limited to decreased menstrual bleeding, decreased acne, fewer endometriosis-related symptoms, and a decreased risk of ovarian and endometrial cancers (II-2).
      • 4.
        Combined oral contraceptive pills (COCs) are associated with an increased risk of venous thromboembolism (II-2). Potential differences in the risk of venous thromboembolism attributable to different progestin types and estrogen dosing in low-dose COCs do not currently justify preferential prescribing (III).
      • 5.
        Low-dose combined oral contraceptive pills (containing less than 50 μg of ethinyl estradiol) are not associated with an increased risk of myocardial infarction or cerebrovascular accident in women with no additional risk factors (II-2).
      • 6.
        Current epidemiological studies suggest that there is no increase in the risk of breast cancer or breast cancer mortality in women who have used combined oral contraceptive pills (COCs) compared with non-users (II-2). There may be a slight increase in breast cancer in current and/or recent COC users (II-2). The use of COCs in BRCA1/2 carriers is controversial but appears to be associated with a decreased risk of ovarian cancer and no increase in the risk of breast cancer (II-2).
      • 7.
        Combined oral contraceptive pills (COCs) are associated with a decreased risk of ovarian, endometrial, and colorectal cancers (II-2). A possible association has been shown between COC use and risk of cervical cancer (II-2), but causation has not been demonstrated.
      • 8.
        A blood pressure measurement is the only examination and/or investigation that is required prior to initiating combined hormonal contraception (CHC) in women who are otherwise healthy by history (II-2). Baseline weight and body mass index assessment might be helpful for monitoring changes in CHC users. Pelvic examination, Pap test, screening for sexually transmitted infections, and thrombophilia screening are not required prior to initiating CHC (III).
      • 9.
        Combined oral contraceptive pills and other combined hormonal contraception (CHC) can be started at any time during the menstrual cycle provided that pregnancy or the possibility of pregnancy can be reasonably ruled out. Where there is uncertainty, the benefits of starting CHC likely outweigh any risks (III).
      • 10.
        Starting combined hormonal contraception immediately (Quick Start) may improve short-term compliance and is not associated with an increase in unscheduled bleeding or other side effects (I).
      • 11.
        The highest risk of ovulation occurs when the hormone-free interval is prolonged for more than 7 days, either by delaying the start of combined hormonal contraception (CHC) or by missing active hormone doses during the first or third weeks of CHC (I). Ovulation rarely occurs after 7 consecutive days of CHC use (II-2).
      • 12.
        Emergency contraception (EC) and back-up contraception may be required in some instances of missed combined hormonal contraception (CHC), particularly when the hormone-free interval has exceeded 7 days. EC is rarely indicated for missed CHC in the second or third week of the cycle unless there are repeated omissions or failure to use back-up contraception after the missed doses (III).
      • 13.
        Combined oral contraceptive pill exposure just prior to or during pregnancy is not associated with an increased risk of major birth defects (II-2).
      • 14.
        The effectiveness of combined hormonal contraception (CHC), including combined oral contraceptive pills, may be affected by other medications, including but not limited to some anticonvulsants, some antiretrovirals, rifampicin, and griseofulvin. CHCs may affect the serum levels of other medications, including some anticonvulsants and antiretrovirals (II-2).
      • 15.
        The contraceptive patch may be less effective in women with a body weight ≥90 kg (II-2).
      • 16.
        Compared with the combined oral contraceptive pill, transdermal contraceptive patch use is associated with less breakthrough bleeding and spotting but more breast discomfort or pain, nausea and vomiting, and dysmenorrhea (I).
      • 17.
        Pharmacokinetic studies indicate that serum hormone concentrations of ethinyl estradiol and norelgestromin are maintained at ovulation inhibitory levels throughout at least 9 days of continuous transdermal contraceptive patch wear (II-2).
      • 18.
        The vaginal contraceptive ring is associated with less unscheduled bleeding than the combined oral contraceptive pill and the duration of menstrual bleeding is significantly shorter than that seen with the contraceptive patch (I).
      • 19.
        Serum levels of ethinyl estradiol and etonorgestrel are maintained at ovulation inhibitory levels for at least 28 days after the vaginal contraceptive ring has been inserted (II-2).
      • 20.
        Continuous and/or extended regimens of combined hormonal contraception (CHCs) have similar rates of adherence and effectiveness compared with 28-day cyclic CHC regimens (I).
      • 21.
        Continuous and/or extended (C/E) regimens of combined hormonal contraception (CHC) are associated with significantly less menstruation-associated symptoms than are cyclic CHC (I). Bleeding and/or spotting with C/E CHC regimens decreases with each successive cycle and is similar to or less than that with cyclic CHC (I).

      Recommendations

      • 1.
        Health care providers should give clear instructions for hormonal contraceptive use, including how to manage missed hormonal contraception, as part of contraceptive counselling. Women should be provided with resources to refer to in the event of missed and/or delayed hormonal contraceptives or if they develop any signs of a serious adverse event while using hormonal contraception (III-A).
      • 2.
        Health care providers should consider advising women who are initiating contraception to start their combined hormonal contraception (CHC) immediately (Quick Start) provided that they are reasonably certain that the woman is not pregnant. Back-up contraception (barrier method) or abstinence should be used for the first 7 consecutive days of CHC use unless CHC was initiated on the first day of menses (I-A).
      • 3.
        Health care providers should consider the possibility of irregular pill taking, concomitant medication use, malabsorption, uterine or cervical pathology, pregnancy, or chlamydial infection in women presenting with persistent unscheduled bleeding on the combined oral contraceptive pill (III-A).
      • 4.
        If 1 combined oral contraceptive pill or other combined hormonal contraception (CHC) method is missed in the first week of use, back-up contraception or abstinence should be used until the CHC method has been used for 7 consecutive days. In the case of missed CHC in the second or third week of hormones, the hormone-free interval should be eliminated for that cycle (III-A).
      • 5.
        Back-up contraception should be used when 3 or more consecutive doses/days of combined hormonal contraception (CHC) have been missed in the second or third week of hormone use until the CHC has been used for 7 consecutive days. For practical reasons, the scheduled hormone-free interval should be eliminated in these cycles (I-A).
      • 6.
        Health care providers should be aware of other medications being used by combined hormonal contraception users and the possibility of drug interactions that could affect serum levels and effectiveness of either medication (II-2A).
      • 7.
        Health care professionals should be aware of the option of using continuous and/or extended combined hormonal contraception regimens and consider offering them to women for contraception, medical reasons, and personal preferences (III-A).
      • 8.
        Women using continuous and/or extended combined hormonal contraception regimens should be counselled about expected bleeding patterns and how to manage unscheduled bleeding or spotting (III-A).
      • 9.
        When a specific product has been prescribed to a woman, she should be informed if a generic substitution is being considered and her health care provider should be advised if a substitution is made. The woman should have the option to agree or disagree to the substitution and be informed about any difference in cost for a specific product (III-B).

      Key Words

      Abbreviations:

      AED (antiepileptic drug), ART (antiretroviral therapy), BMI (body mass index), CDC (Centers for Disease Control and Prevention), C/E (continuous and/or extended), CHC (combined hormonal contraception), COC (combined oral contraceptive pill), Cu-IUD (copper intrauterine device), CYP3A4 (cytochrome P450-3A4), DVT (deep vein thrombosis), E2 (17 beta-estradiol), E2V (estradiol valerate), EC (emergency contraception), EE (ethinyl estradiol), ENG (etonogestrel), FPV (fosamprenavir), HDL (high-density lipoprotein), HFI (hormone-free interval), HIV (human immunodeficiency virus), HPV (human papillomavirus), IUC (intrauterine contraceptive), IUD (intrauterine device), IUS (intrauterine system), LNG (levonorgestrel), MI (myocardial infarction), PE (pulmonary embolism), PI (Pearl Index (the number of contraceptive failures per 100 women-years of use)), PK (pharmacokinetic), POP (progestin-only pill), RCT (randomized controlled trial), SHBG (sex hormone binding globulin), SOGC (Society of Obstetricians and Gynaecologists of Canada), STI (sexually transmitted infection), UPA (ulipristal acetate), UPI (unprotected intercourse), VTE (venous thromboembolism), WHO (World Health Organization), WY (women-years)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Obstetrics and Gynaecology Canada
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. United Nations Department of Economics and Social Affairs Popluation Division. World Contraception Use 2015. Available at: http://www.un.org/en/development/desa/population/publications/dataset/contraception/wcu2015.shtml. Accessed on June 29, 2015.

        • Rotermann M.
        • Dunn S.
        • Black A.
        Oral contraceptive use among women aged 15 to 49: results from the Canadian Health Measures Survey.
        Health Rep. 2015; 26: 21-28
        • Black A.
        • Yang Q.
        • Wen S.W.
        • et al.
        Contraceptive use by Canadian women of reproductive age: results of a national survey.
        J Obstet Gynaecol Can. 2009; 31: 627-640
      2. Health Canada. Drug Product Database. Available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php. Accessed on January 11, 2016.

        • Upton G.C.
        The phasic approach to oral contraception: the triphasic concept and its application.
        Int J Fertil. 1983; 28: 121-140
        • Van Vliet H.A.
        • Grimes D.A.
        • Helmerhorst F.M.
        • et al.
        Biphasic versus triphasic oral contraceptives for contraception.
        Cochrane Database Syst Rev. 2006; : CD003283
        • Van Vliet H.A.
        • Grimes D.A.
        • Lopez L.M.
        • et al.
        Triphasic versus monophasic oral contraceptives for contraception.
        Cochrane Database Syst Rev. 2011; : CD003553
        • Dickey R.P.
        • In Durant O.K.
        Managing contraceptive pill patients.
        ed 8. Essential Medical Information Systems, Dallas, TX1994
        • Weems Chihal H.L.
        • Peppler R.D.
        • Dickey R.P.
        Estrogen potency of oral contraceptive pills.
        Am J Obstet Gynecol. 2003; 121: 75-83
        • Fotherby K.
        Bioavailablity of orally administered sex steroids used in oral contraceptives and hormone replacement therapy.
        Contraception. 1996; 544: 59-69
        • Fotherby K.
        Variability of pharmacokinetic parameters for contraceptive steroids.
        J Steroid Biochem. 1983; 19: 817-820
        • Kuhl H.
        Comparative pharmacology of newer progestogens.
        Drugs. 1996; 51: 188-215
        • Fotherby K.
        • Caldwell A.D.
        New progestins in oral contraception.
        Contraception. 1994; 49: 1-32
        • Krattenmacher R.
        Drospirenone: pharmacology and pharmacokinetics of a unique progestogen.
        Contraception. 2000; 62: 29-38
        • Jensen J.T.
        Evaluation of a new estradiol oral contraceptive: estradiol valerate and dienogest.
        Expert Opin Pharmacother. 2010; 11: 1147-1157
        • Trussell J.
        Contraceptive failure in the United States.
        Contraception. 2011; 83: 397-404
        • Dinger J.
        • Minh T.D.
        • Buttmann N.
        • et al.
        Effectiveness of oral contraceptive pills in a large U.S. cohort comparing progestogen and regimen.
        Obstet Gynecol. 2011; 117: 33-40
        • Dinger J.C.
        • Cronin M.
        • Mohner S.
        • et al.
        Oral contraceptive effectiveness according to body mass index, weight, age, and other factors.
        Am J Obstet Gynecol. 2009; 201: 263.e1-263.e9
        • Rosenberg M.J.
        • Waugh M.S.
        • Meehan T.E.
        Use and misuse of oral contraceptives: risk indicators for poor pill taking and discontinuation.
        Contraception. 1995; 51: 283-288
        • Potter L.
        • Oakley D.
        • de Leon-Wong E.
        • et al.
        Measuring compliance among oral contraceptive users.
        Fam Plann Perspect. 1996; 28: 154-158
        • Rosenberg M.J.
        • Waugh M.S.
        • Burnhill M.S.
        Compliance, counseling and satisfaction with oral contraceptives: a prospective evaluation.
        Fam Plann Perspect. 1998; 30: 89-92
        • Vessey M.
        Oral contraceptive failures and body weight: findings in a large cohort study.
        J Fam Plann Reprod Health Care. 2001; 27: 90-91
        • Burkman R.T.
        • Fisher A.C.
        • Wan G.J.
        • et al.
        Association between efficacy and body weight or body mass index for two low-dose oral contraceptives.
        Contraception. 2009; 79: 424-427
        • Westhoff C.L.
        • Hait H.I.
        • Reape K.Z.
        Body weight does not impact pregnancy rates during use of a low-dose extended-regimen 91-day oral contraceptive.
        Contraception. 2012; 85: 235-239
        • Merki-Feld G.S.
        • Skouby S.
        • Serfaty D.
        • et al.
        European society of contraception statement on contraception in obese women.
        Eur J Contracept Reprod Health Care. 2015; 20: 19-28
        • McNicholas C.
        • Zhao Q.
        • Secura G.
        • et al.
        Contraceptive failures in overweight and obese combined hormonal contraceptive users.
        Obstet Gynecol. 2013; 121: 585-592
        • Holt V.L.
        • Scholes D.
        • Wicklund K.G.
        • et al.
        Body mass index, weight, and oral contraceptive failure risk.
        Obstet Gynecol. 2005; 105: 46-52
        • Yamazaki M.
        • Dwyer K.
        • Sobhan M.
        • et al.
        Effect of obesity on the effectiveness of hormonal contraceptives: an individual participant data meta-analysis.
        Contraception. 2015; 92: 445-452
        • Westhoff C.L.
        • Torgal A.H.
        • Mayeda E.R.
        • et al.
        Ovarian suppression in normal-weight and obese women during oral contraceptive use: a randomized controlled trial.
        Obstet Gynecol. 2010; 116: 275-283
        • Edelman A.B.
        • Carlson N.E.
        • Cherala G.
        • et al.
        Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity.
        Contraception. 2009; 80: 119-127
        • Westhoff C.L.
        • Torgal A.H.
        • Mayeda E.R.
        • et al.
        Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women.
        Contraception. 2010; 81: 474-480
        • Howard B.
        • Trussell J.
        • Grubb E.
        • et al.
        Comparison of pregnancy rates in users of extended and cyclic combined oral contraceptive (COC) regimens in the United States: a brief report.
        Contraception. 2014; 89: 25-27
        • Speroff L.
        • Darney P.
        Oral contraception. A clinical guide for contraception.
        ed 5. Lippincott, Williams & Wilkins, Philadelphia, PA2010
        • Rossmanith W.G.
        • Steffens D.
        • Schramm G.A.
        Comparative randomized trial on the impact of two low-dose oral contraceptives on ovarian activity, cervical permeability, and endometrial receptivity.
        Contraception. 1997; 56: 23-30
        • Mitra P.K.
        • Roychadhuri J.
        Effect of oral contraceptives on the ultrastructure of the endometrium.
        J Gynaecol Endocrinol. 1987; 3: 13-15
        • Dinh A.
        • Sriprasert I.
        • Williams A.R.
        • et al.
        A review of the endometrial histologic effects of progestins and progesterone receptor modulators in reproductive age women.
        Contraception. 2015; 91: 360-367
        • Curtis K.M.
        • Tepper N.K.
        • Jatlaoui T.C.
        • et al.
        U.S. medical eligibility criteria for contraceptive use, 2016.
        MMWR Recomm Rep. 2016; 65: 1-103
        • World Health Organization
        Medical eligibility criteria for contraceptive use.
        ed 5. WHO, Geneva, Switzerland2015
        • Tepper N.K.
        • Phillips S.J.
        • Kapp N.
        • et al.
        Combined hormonal contraceptive use among breastfeeding women: an updated systematic review.
        Contraception. 2016; 94: 262-274
        • Petersen J.F.
        • Bergholt T.
        • Nielsen A.K.
        • et al.
        Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy. Danish nationwide historical cohort 1995-2009.
        Thromb Haemost. 2014; 112: 73-78
        • Kamel H.
        • Navi B.B.
        • Sriram N.
        • et al.
        Risk of a thrombotic event after the 6-week postpartum period.
        N Engl J Med. 2014; 370: 1307-1315
      3. International Headache Society. IHS Classification ICHD-3 Beta. Available at: http://ihs-classification.org/en/. Accessed on February 26, 2016.

        • Roach R.E.
        • Lijfering W.M.
        • van Hylckama Vlieg A.
        • et al.
        The risk of venous thrombosis in individuals with a history of superficial vein thrombosis and acquired venous thrombotic risk factors.
        Blood. 2013; 122: 4264-4269
        • Martinelli I.
        • Lensing A.W.
        • Middeldorp S.
        • et al.
        Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.
        Blood. 2016; 127: 1417-1425
        • Baglin T.
        • Bauer K.
        • Douketis J.
        • et al.
        Duration of anticoagulant therapy after a first episode of an unprovoked pulmonary embolus or deep vein thrombosis: guidance from the SSC of the ISTH.
        J Thromb Haemost. 2012; 10: 698-702
      4. Glaxo Smith Kline. Lexiva (fosamprenavir calcium) [Package Insert]. Research Triangle Park, NC: Glaxo Smith Kline; 2013. Available at: https://www.viivhealthcare.com/media/32193/us_lexiva.pdf. Accessed on December 6, 2016.

      5. Insert. GSKLfcP. Glaxo Smith Kline, Research Triangle Park, NC2015
        • Bahamondes L.
        • Valeria Bahamondes M.
        • Shulman L.P.
        Non-contraceptive benefits of hormonal and intrauterine reversible contraceptive methods.
        Hum Reprod Update. 2015; 21: 640-651
        • Fraser I.S.
        • Romer T.
        • Parke S.
        • et al.
        Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing estradiol valerate and dienogest: a randomized, double-blind phase III trial.
        Hum Reprod. 2011; 26: 2698-2708
        • Farquhar C.
        • Brown J.
        Oral contraceptive pill for heavy menstrual bleeding.
        Cochrane Database Syst Rev. 2009; : CD000154
        • Hoaglin D.C.
        • Filonenko A.
        • Glickman M.E.
        • et al.
        Use of mixed-treatment-comparison methods in estimating efficacy of treatments for heavy menstrual bleeding.
        Eur J Med Res. 2013; 18: 17
        • Larsson G.
        • Milsom I.
        • Lindstedt G.
        • et al.
        The influence of a low-dose combined oral contraceptive on menstrual blood loss and iron status.
        Contraception. 1992; 46: 327-334
        • Matteson K.A.
        • Rahn D.D.
        • Wheeler 2nd, T.L.
        • et al.
        Nonsurgical management of heavy menstrual bleeding: a systematic review.
        Obstet Gynecol. 2013; 121: 632-643
        • Haile Z.T.
        • Teweldeberhan A.K.
        • Chertok I.R.
        Association between oral contraceptive use and markers of iron deficiency in a cross-sectional study of Tanzanian women.
        Int J Gynaecol Obstet. 2016; 132: 50-54
        • Gambacciani M.
        • Cappagli B.
        • Lazzarini V.
        • et al.
        Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density.
        Maturitas. 2006; 54: 176-180
        • Kuohung W.
        • Borgatta L.
        • Stubblefield P.
        Low-dose oral contraceptives and bone mineral density: an evidence-based analysis.
        Contraception. 2000; 61: 77-82
        • Nappi C.
        • Bifulco G.
        • Tommaselli G.A.
        • et al.
        Hormonal contraception and bone metabolism: a systematic review.
        Contraception. 2012; 86: 606-621
        • Berenson A.B.
        • Radecki C.
        • Grady J.J.
        • et al.
        A prospective, controlled study of the effects of hormonal contraception on bone mineral density.
        Obstet Gynecol. 2001; 98: 576-582
        • Lindh I.
        • Ellstrom A.A.
        • Milsom I.
        The effect of combined oral contraceptives and age on dysmenorrhoea: an epidemiological study.
        Hum Reprod. 2012; 27: 676-682
        • Wong C.L.
        • Farquhar C.
        • Roberts H.
        • et al.
        Oral contraceptive pill for primary dysmenorrhoea.
        Cochrane Database Syst Rev. 2009; : CD002120
        • Kaunitz A.M.
        Clinical practice. Hormonal contraception in women of older reproductive age.
        N Engl J Med. 2008; 358: 1262-1270
        • Shargril A.A.
        Hormone replacement therapy in perimenopausal women with a triphasic contraceptive compound: a three year prospective study.
        Int J Fertility. 1985; 30: 18-28
        • Casper R.F.
        • Dodin S.
        • Reid R.L.
        The effect of 20mcg ethinyl estradiol/1 mg norethindrone acetate (Minestrin), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes, and quality of life in symptomatic perimenopausal women.
        Menopause. 1997; 4: 139-147
        • Arowojolu A.O.
        • Gallo M.F.
        • Lopez L.M.
        • et al.
        Combined oral contraceptive pills for treatment of acne.
        Cochrane Database Syst Rev. 2012; : CD004425
        • Thorneycroft H.
        • Gollnick H.
        • Schellschmidt I.
        Superiority of a combined contraceptive containing drospirenone to a triphasic preparation containing norgestimate in acne treatment.
        Cutis. 2004; 74: 23-30
        • Palli M.B.
        • Reyes-Habito C.M.
        • Lima X.T.
        • et al.
        A single-center, randomized double-blind, parallel-group study to examine the safety and efficacy of 3mg drospirenone/0.02 mg ethinyl estradiol compared with placebo in the treatment of moderate truncal acne vulgaris.
        J Drugs Dermatol. 2013; 12: 633-637
        • Kelly S.
        • Davies E.
        • Fearns S.
        • et al.
        Effects of oral contraceptives containing ethinylestradiol with either drospirenone or levonorgestrel on various parameters associated with well-being in healthy women: a randomized, single-blind, parallel-group, multicentre study.
        Clin Drug Investig. 2010; 30: 325-336
        • Dewis D.
        • Petsos M.
        • Anderson D.C.
        The treatment of hirsutism with a combination of desogestrel and ethinyl estradiol.
        Clin Endocrin. 1985; 22: 29-36
        • Cibula D.
        • Gompel A.
        • Mueck A.O.
        • et al.
        Hormonal contraception and risk of cancer.
        Hum Reprod Update. 2010; 16: 631-650
        • Dossus L.
        • Allen N.
        • Kaaks R.
        • et al.
        Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition.
        Int J Cancer. 2010; 127: 442-451
        • Collaborative Group on Epidemiological Studies on Endometrial Cancer
        Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies.
        Lancet Oncol. 2015; 16: 1061-1070
        • Hannaford P.C.
        • Iversen L.
        • Macfarlane T.V.
        • et al.
        Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study.
        BMJ. 2010; 340: c927
        • Vessey M.
        • Yeates D.
        • Flynn S.
        Factors affecting mortality in a large cohort study with special reference to oral contraceptive use.
        Contraception. 2010; 82: 221-229
        • Gierisch J.M.
        • Coeytaux R.R.
        • Urrutia R.P.
        • et al.
        Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review.
        Cancer Epidemiol Biomarkers Prev. 2013; 22: 1931-1943
        • Gross T.P.
        • Schlesselman J.J.
        The estimated effect of oral contraceptive use on the cumulative risk of epithelial ovarian cancer.
        Obstet Gynecol. 2003; 83: 419-424
        • Beral V.
        • Doll R.
        • Hermon C.
        • et al.
        • Collaborative Group on Epidemiological Studies of Ovarian Cancer
        Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls.
        Lancet. 2008; 371: 303-314
        • Havrilesky L.J.
        • Moorman P.G.
        • Lowery W.J.
        • et al.
        Oral contraceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis.
        Obstet Gynecol. 2013; 122: 139-147
        • Moorman P.G.
        • Havrilesky L.J.
        • Gierisch J.M.
        • et al.
        Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis.
        J Clin Oncol. 2013; 31: 4188-4198
        • Ness R.B.
        • Dodge R.C.
        • Edwards R.P.
        • et al.
        Contraception methods, beyond oral contraceptives and tubal ligation, and risk of ovarian cancer.
        Ann Epidemiol. 2011; 21: 188-196
        • Tsilidis K.K.
        • Allen N.E.
        • Key T.J.
        • et al.
        Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition.
        Br J Cancer. 2011; 105: 1436-1442
        • Ross R.K.
        • Pike M.C.
        • Vessey M.P.
        • et al.
        Risk factors for uterine fibroids: reduced risk associated with oral contraceptives.
        BMJ. 1986; 293: 359-362
        • Chiaffarino F.
        • Parazzini F.
        • La Vecchia C.
        • et al.
        Use of oral contraceptives and uterine fibroids: results from a case-control study.
        Br J Obstet Gynaecol. 1999; 106: 857-860
        • Qin J.
        • Yang T.
        • Kong F.
        • et al.
        Oral contraceptive use and uterine leiomyoma risk: a meta-analysis based on cohort and case-control studies.
        Arch Gynecol Obstet. 2013; 288: 139-148
        • Friedman A.J.
        • Thomas P.P.
        Does low-dose combination oral contraceptive use affect uterine size or menstrual flow in premenopausal women with leiomyomas?.
        Obstet Gynecol. 1995; 85: 631-635
        • Lanes S.F.
        • Birmann B.
        • Walker A.M.
        • et al.
        Oral contraceptive type and functional ovarian cysts.
        Am J Obstet Gynecol. 1992; 166: 956-961
        • Grimes D.A.
        • Jones L.B.
        • Lopez L.M.
        • et al.
        Oral contraceptives for functional ovarian cysts.
        Cochrane Database Syst Rev. 2014; : CD006134
        • Vessey M.
        • Yeates D.
        Oral contraceptives and benign breast disease: an update of findings in a large cohort study.
        Contraception. 2007; 76: 418-424
        • Hannaford P.
        • Elliott A.
        Use of exogenous hormones by women and colorectal cancer: evidence from the Royal College of General Practitioners’ Oral Contraception Study.
        Contraception. 2005; 71: 95-98
        • Bosetti C.
        • Bravi F.
        • Negri E.
        • et al.
        Oral contraceptives and colorectal cancer risk: a systematic review and meta-analysis.
        Hum Reprod Update. 2009; 15: 489-498
        • Nichols H.B.
        • Trentham-Dietz A.
        • Hampton J.M.
        • et al.
        Oral contraceptive use, reproductive factors, and colorectal cancer risk: findings from Wisconsin.
        Cancer Epidemiol Biomarkers Prev. 2005; 14: 1212-1218
        • Tsilidis K.K.
        • Allen N.E.
        • Key T.J.
        • et al.
        Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition.
        Br J Cancer. 2010; 103: 1755-1759
        • Cates Jr., W.
        • Steiner M.J.
        Dual protection against unintended pregnancy and sexually transmitted infections: what is the best contraceptive approach?.
        Sex Transm Dis. 2002; 29: 168-174
        • Burkman R.
        • Schlesselman J.J.
        • Zieman M.
        Safety concerns and health benefits associated with oral contraception.
        Am J Obstet Gynecol. 2004; 190: S5-S22
        • Walker A.
        • Bancroft J.
        Relationship between premenstrual symptoms and oral contraceptive use: a controlled study.
        Psychosom Med. 1990; 52: 86-96
        • Pearlstein T.B.
        • Bachmann G.A.
        • Zacur H.A.
        • et al.
        Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation.
        Contraception. 2005; 72: 414-421
        • Yonkers K.
        • Brown C.
        • Pearlstein T.B.
        • et al.
        Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder.
        Obstet Gynecol. 2005; 106: 492-501
        • Coffee A.L.
        • Kuehl T.J.
        • Willis S.
        • et al.
        Oral contraceptives and premenstrual symptoms: comparison of a 21/7 and extended regimen.
        Am J Obstet Gynecol. 2006; 195: 1311-1319
        • Lopez L.M.
        • Kaptein A.A.
        • Helmerhorst F.M.
        Oral contraceptives containing drospirenone for premenstrual syndrome.
        Cochrane Database Syst Rev. 2012; : CD006586
        • Zorbas K.A.
        • Economopoulos K.P.
        • Vlahos N.F.
        Continuous versus cyclic oral contraceptives for the treatment of endometriosis: a systematic review.
        Arch Gynecol Obstet. 2015; 292: 37-43
        • Harada T.
        • Momoeda M.
        • Taketani Y.
        • et al.
        Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial.
        Fertil Steril. 2008; 90: 1583-1588
        • Seracchioli R.
        • Mabrouk M.
        • Frasca C.
        • et al.
        Long-term oral contraceptive pills and postoperative pain management after laparoscopic excision of ovarian endometrioma: a randomized controlled trial.
        Fertil Steril. 2010; 94: 464-471
        • Rosenberg M.J.
        • Meyers A.
        • Roy V.
        Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives: a randomized trial of 20 [mu]g and 35 [mu]g estrogen preparations.
        Contraception. 1999; 60: 321-329
        • Rosenberg M.J.
        • Waugh M.S.
        Oral contraceptive discontinuation: a prospective evaluation of frequency and reasons.
        Am J Obstet Gynecol. 1998; 179: 577-582
        • Halpern V.
        • Lopez L.M.
        • Grimes D.A.
        • et al.
        Strategies to improve adherence and acceptability of hormonal methods of contraception.
        Cochrane Database Syst Rev. 2013; : CD004317
        • Clark L.R.
        Will the pill make me sterile? Addressing reproductive health concerns and strategies to improve adherence to hormonal contraceptive regimens in adolescent girls.
        J Ped Adolesc Gynecol. 2001; 14: 153-162
        • Thorneycroft I.H.
        Cycle control with oral contraceptives: a review of the literature.
        Am J Obstet Gynecol. 1999; 180: 280-287
        • Saleh W.A.
        • Burkman R.T.
        • Zacur H.A.
        • et al.
        A randomized trial of three oral contraceptives: comparison of bleeding patterns by contraceptive types and steroid levels.
        Am J Obstet Gynecol. 1993; 168: 1745-1747
        • Bachmann G.
        • Korner P.
        Bleeding patterns associated with oral contraceptive use: a review of the literature.
        Contraception. 2007; 76: 182-189
        • Gallo M.F.
        • Nanda K.
        • Grimes D.A.
        • et al.
        20 microg versus >20 microg estrogen combined oral contraceptives for contraception.
        Cochrane Database Syst Rev. 2013; : CD003989
        • Endrikat J.
        • Hite R.
        • Bannemerschult R.
        • et al.
        Multicenter, comparative study of cycle control, efficacy and tolerability of two low-dose oral contraceptives containing 20 microg ethinylestradiol/100 microg levonorgestrel and 20 microg ethinylestradiol/500 microg norethisterone.
        Contraception. 2001; 64: 3-10
        • Endrikat J.
        • Dusterberg B.
        • Ruebig A.
        • et al.
        Comparison of efficacy, cycle control, and tolerability of two low-dose oral contraceptives in a multicenter clinical study.
        Contraception. 1999; 60: 269-274
        • Halbe H.W.
        • de Melo N.R.
        • Bahamondes L.
        • et al.
        Efficacy and acceptability of two monophasic oral contraceptives containing ethinylestradiol and either desogestrel or gestodene.
        Eur J Contracept Reprod Health Care. 1998; 3: 113-120
        • Archer D.F.
        • Maheux R.
        • Delconte A.
        • et al.
        Efficacy and safety of a low-dose monophasic combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol (Alesse).
        Am J Obstet Gynecol. 1999; 181: 39-44
        • Westhoff C.
        • Jones K.
        • Robilotto C.
        • et al.
        Smoking and oral contraceptive continuation.
        Contraception. 2009; 79: 375-378
        • Rosenberg M.J.
        • Waugh M.S.
        Smoking and cycle control among oral contraceptive users.
        Am J Obstet Gynecol. 1996; 174: 628-632
        • Rosenberg M.J.
        • Waugh M.S.
        • Higgens J.E.
        The effect of desogestrel, gestodene, and other factors on spotting and bleeding.
        Contraception. 1996; 53: 85-90
        • Krettek J.E.
        • Arkin S.I.
        • Chaisilwattana P.
        • et al.
        Chlamydia trachomatis in patients who used oral contraceptives and had intermenstrual spotting.
        Obstet Gynecol. 1993; 81: 728-731
        • Van Vliet H.A.
        • Grimes D.A.
        • Helmerhorst F.M.
        • et al.
        Biphasic versus monophasic oral contraceptives for contraception.
        Cochrane Database Syst Rev. 2006; : CD002032
        • Archer D.F.
        • Nakajima S.T.
        • Sawyer A.T.
        • et al.
        Norethindrone acetate 1.0 milligram and ethinyl estradiol 10 micrograms as an ultra low-dose oral contraceptive.
        Obstet Gynecol. 2013; 122: 601-607
        • Kaunitz A.M.
        • Burkman R.T.
        • Fisher A.C.
        • et al.
        Cycle control with a 21-day compared with a 24-day oral contraceptive pill: a randomized controlled trial.
        Obstet Gynecol. 2009; 114: 1205-1212
        • Ahrendt H.J.
        • Makalova D.
        • Parke S.
        • et al.
        Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.
        Contraception. 2009; 80: 436-444
        • Redmond G.
        • Godwin A.J.
        • Olson W.
        • et al.
        Use of placebo controls in an oral contraceptive trial: methodological issues and adverse event incidence.
        Contraception. 1999; 60: 81-85
        • Gallo M.F.
        • Lopez L.M.
        • Grimes D.A.
        • et al.
        Combination contraceptives: effects on weight.
        Cochrane Database Syst Rev. 2014; : CD003987
        • Coney P.
        • Washenik K.
        • Langley R.G.B.
        • et al.
        Weight change and adverse event incidence with a low-dose oral contraceptive: two randomized, placebo-controlled trials.
        Contraception. 2001; 63: 297-302
        • Moreau C.
        • Cleland K.
        • Trussell J.
        Contraceptive discontinuation attributed to method dissatisfaction in the United States.
        Contraception. 2007; 76: 267-272
        • Wiebe E.R.
        • Brotto L.A.
        • MacKay J.
        Characteristics of women who experience mood and sexual side effects with use of hormonal contraception.
        J Obstet Gynaecol Can. 2011; 33: 1234-1240
        • Oinonen K.A.
        • Mazmanian D.
        To what extent do oral contraceptives influence mood and affect?.
        J Affect Disord. 2002; 70: 229-240
        • Keyes K.M.
        • Cheslack-Postava K.
        • Westhoff C.
        • et al.
        Association of hormonal contraceptive use with reduced levels of depressive symptoms: a national study of sexually active women in the United States.
        Am J Epidemiol. 2013; 178: 1378-1388
        • Davis A.R.
        • Castano P.M.
        Oral contraceptives and libido in women.
        Ann Rev Sex Res. 2004; 15: 297-320
        • Pastor Z.
        • Holla K.
        • Chmel R.
        The influence of combined oral contraceptives on female sexual desire: a systematic review.
        Eur J Contracept Reprod Health Care. 2013; 18: 27-43
        • Graham C.A.
        • Bancroft J.
        • Doll H.A.
        • et al.
        Does oral contraceptive-induced reduction in free testosterone adversely affect the sexuality or mood of women?.
        Psychoneuroendocrinology. 2007; 32: 246-255
        • Strufaldi R.
        • Pompei L.M.
        • Steiner M.L.
        • et al.
        Effects of two combined hormonal contraceptives with the same composition and different doses on female sexual function and plasma androgen levels.
        Contraception. 2010; 82: 147-154
        • Elaut E.
        • Buysse A.
        • De Sutter P.
        • et al.
        Cycle-related changes in mood, sexual desire, and sexual activity in oral contraception-using and nonhormonal-contraception-using couples.
        J Sex Res. 2014; 53: 1-12
        • Graham C.A.
        • Ramos R.
        • Bancroft J.
        • et al.
        The effects of steroidal contraceptives on the well-being and sexuality of women: a double-blind, placebo-controlled, two-centre study of combined and progestogen-only methods.
        Contraception. 1995; 52: 363-369
        • Sabatini R.
        • Cagiano R.
        Comparison profiles of cycle control, side effects and sexual satisfaction of three hormonal contraceptives.
        Contraception. 2006; 74: 220-223
        • Li D.
        • Wilcox A.J.
        • Dunson D.B.
        Benchmark pregnancy rates and the assessment of post-coital contraceptives: an update.
        Contraception. 2015; 91: 344-349
        • Davis S.R.
        • Bitzer J.
        • Giraldi A.
        • et al.
        Change to either a nonandrogenic or androgenic progestin-containing oral contraceptive preparation is associated with improved sexual function in women with oral contraceptive-associated sexual dysfunction.
        J Sex Med. 2013; 10: 3069-3079
        • Zimmerman Y.
        • Foidart J.M.
        • Pintiaux A.
        • et al.
        Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: I. Endocrine effects.
        Contraception. 2015; 91: 127-133
        • Vetvik K.G.
        • MacGregor E.A.
        • Lundqvist C.
        • et al.
        Contraceptive-induced amenorrhoea leads to reduced migraine frequency in women with menstrual migraine without aura.
        J Headache Pain. 2014; 15: 30
        • Coffee A.L.
        • Sulak P.J.
        • Hill A.J.
        • et al.
        Extended cycle combined oral contraceptives and prophylactic frovatriptan during the hormone-free interval in women with menstrual-related migraines.
        J Womens Health (Larchmt). 2014; 23: 310-317
        • Nierenburg Hdel C.
        • Ailani J.
        • Malloy M.
        • et al.
        Systematic review of preventive and acute treatment of menstrual migraine.
        Headache. 2015; 55: 1052-1071
        • De Leo V.
        • Scolaro V.
        • Musacchio M.C.
        • et al.
        Combined oral contraceptives in women with menstrual migraine without aura.
        Fertil Steril. 2011; 96: 917-920
        • World Health Organization
        Medical eligibility for contraceptive use.
        (Executive summary)ed 5. WHO, Geneva, Switzerland2015: i-xiii
        • Nappi R.E.
        • Merki-Feld G.S.
        • Terreno E.
        • et al.
        Hormonal contraception in women with migraine: is progestogen-only contraception a better choice?.
        J Headache Pain. 2013; 14: 66
        • Merki-Feld G.S.
        • Imthurn B.
        • Langner R.
        • et al.
        Positive effects of the progestin desogestrel 75 mug on migraine frequency and use of acute medication are sustained over a treatment period of 180 days.
        J Headache Pain. 2015; 16: 522
        • Morotti M.
        • Remorgida V.
        • Venturini P.L.
        • et al.
        Progestin-only contraception compared with extended combined oral contraceptive in women with migraine without aura: a retrospective pilot study.
        Eur J Obstet Gynecol Reprod Biol. 2014; 183: 178-182
        • Handel A.C.
        • Lima P.B.
        • Tonolli V.M.
        • et al.
        Risk factors for facial melasma in women: a case-control study.
        Br J Dermatol. 2014; 171: 588-594
        • Guinot C.
        • Cheffai S.
        • Latreille J.
        • et al.
        Aggravating factors for melasma: a prospective study in 197 Tunisian patients.
        J Eur Acad Dermatol Venereol. 2010; 24: 1060-1069
      6. Hatcher R.A. Trussell J. Nelson A. Contraceptive technology. ed 20. Ardent Media, New York2011
        • Dinger J.C.
        • Heinemann L.A.
        • Kuhl-Habich D.
        The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation.
        Contraception. 2007; 75: 344-354
        • Dinger J.
        • Bardenheuer K.
        • Heinemann K.
        Cardiovascular and general safety of a 24-day regimen of drospirenone-containing combined oral contraceptives: final results from the International Active Surveillance Study of Women Taking Oral Contraceptives.
        Contraception. 2014; 89: 253-263
        • Peragallo Urrutia R.
        • Coeytaux R.R.
        • McBroom A.J.
        • et al.
        Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis.
        Obstet Gynecol. 2013; 122: 380-389
        • Salonen Ros H.
        • Lichtenstein P.
        • Bellocco R.
        • et al.
        Increased risks of circulatory diseases in late pregnancy and puerperium.
        Epidemiology. 2001; 12: 456-460
        • Sidney S.
        • Cheetham T.C.
        • Connell F.A.
        • et al.
        Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users.
        Contraception. 2013; 87: 93-100
        • van Hylckama Vlieg A.
        • Helmerhorst F.M.
        • Vandenbroucke J.P.
        • et al.
        The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study.
        BMJ. 2009; 339: b2921
        • Lidegaard O.
        • Lokkegaard E.
        • Svendsen A.L.
        • et al.
        Hormonal contraception and risk of venous thromboembolism: national follow-up study.
        BMJ. 2009; 339: b2890
        • Parkin L.
        • Sharples K.
        • Hernandez R.K.
        • et al.
        Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database.
        BMJ. 2011; 342: d2139
        • Jick S.S.
        • Hernandez R.K.
        Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data.
        BMJ. 2011; 342: d2151
        • Farley T.M.
        • Collins J.
        • Schlesselman J.J.
        Hormonal contraception and risk of cardiovascular disease. An international perspective.
        Contraception. 1998; 57: 211-230
      7. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study.
        Lancet. 1997; 349: 1202-1209
        • Roach R.E.
        • Helmerhorst F.M.
        • Lijfering W.M.
        • et al.
        Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke.
        Cochrane Database Syst Rev. 2015; : CD011054
        • Dunn N.R.
        • Arscott A.
        • Thorogood M.
        • et al.
        Regional variation in incidence and case fatality of myocardial infarction among young women in England, Scotland and Wales.
        J Epidemiol Community Health. 2000; 54: 293-298
        • Farley T.M.
        • Meirik O.
        • Chang C.L.
        • et al.
        Combined oral contraceptives, smoking, and cardiovascular risk.
        J Epidemiol Community Health. 1998; 52: 775-785
      8. Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives: results of an international, multicenter, case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
        Contraception. 1998; 57: 315-324
        • Poulter N.R.
        Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
        Lancet. 1996; 348: 498-505
        • Bennion L.J.
        • Ginsberg R.L.
        • Gernick M.B.
        • et al.
        Effects of oral contraceptives on the gallbladder bile of normal women.
        New Engl J Med. 1976; 294: 189-192
      9. Benign gallbladder disease: newer data suggest little or no excess risk with oral contraceptive use.
        Contracept Rep. 1997; 8: 9-11
        • Jick S.
        • Pennap D.
        Drospirenone- and levonorgestrel-containing oral contraceptives and the risk of gallbladder disease.
        Contraception. 2012; 86: 220-223
        • Grodstein F.
        • Colditz G.A.
        • Hunter D.J.
        • et al.
        A prospective study of symptomatic gallstones in women: relation with oral contraceptives and other risk factors.
        Obstet Gynecol. 1994; 84: 207-214
        • Etminan M.
        • Delaney J.A.
        • Bressler B.
        • et al.
        Oral contraceptives and the risk of gallbladder disease: a comparative safety study.
        CMAJ. 2011; 183: 899-904
      10. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Collaborative Group on Hormonal Factors in Breast Cancer.
        Lancet. 1996; 347: 1713-1727
        • Kahlenborn C.
        • Modugno F.
        • Potter D.M.
        • et al.
        Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis.
        Mayo Clin Proc. 2006; 81: 1290-1302
        • Hunter D.J.
        • Colditz G.A.
        • Hankinson S.E.
        • et al.
        Oral contraceptive use and breast cancer: a prospective study of young women.
        Cancer Epidemiol Biomarkers Prev. 2010; 19: 2496-2502
      11. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics. Special Topic: Predictions of the Future Burden of Cancer in Canada. Available at: https://www.cancer.ca/∼/media/cancer.ca/CW/cancer information/cancer 101/Canadian cancer statistics/Canadian-Cancer-Statistics-2015-EN.pdf. Accessed on January 2, 2015.

        • Beaber E.F.
        • Malone K.E.
        • Tang M.T.
        • et al.
        Oral contraceptives and breast cancer risk overall and by molecular subtype among young women.
        Cancer Epidemiol Biomarkers Prev. 2014; 23: 755-764
        • Ritte R.
        • Tikk K.
        • Lukanova A.
        • et al.
        Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study.
        BMC Cancer. 2013; 13: 584
        • Poosari A.
        • Promthet S.
        • Kamsa-ard S.
        • et al.
        Hormonal contraceptive use and breast cancer in Thai women.
        J Epidemiol. 2014; 24: 216-220
        • Beaber E.F.
        • Buist D.S.
        • Barlow W.E.
        • et al.
        Recent oral contraceptive use by formulation and breast cancer risk among women 20 to 49 years of age.
        Cancer Res. 2014; 74: 4078-4089
        • Marchbanks P.A.
        • McDonald J.A.
        • Wilson H.G.
        • et al.
        Oral contraceptives and the risk of breast cancer.
        New Engl J Med. 2002; 346: 2025-2032
        • Hankinson S.E.
        • Colditz G.A.
        • Manson J.E.
        • et al.
        A prospective study of oral contraceptive use and risk of breast cancer (Nurses’ Health Study, United States).
        Cancer Causes Control. 1997; 8: 65-72
        • Vessey M.
        • Yeates D.
        Oral contraceptive use and cancer: final report from the Oxford-Family Planning Association contraceptive study.
        Contraception. 2013; 88: 678-683
        • Narod S.A.
        • Dube M.P.
        • Klijn J.
        • et al.
        Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
        J Natl Caner Inst. 2002; 94: 1773-1779
        • Brohet R.M.
        • Goldgar D.E.
        • Easton D.F.
        • et al.
        Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group.
        J Clin Oncol. 2007; 25: 3831-3836
        • Iodice S.
        • Barile M.
        • Rotmensz N.
        • et al.
        Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis.
        Eur J Cancer. 2010; 46: 2275-2284
        • Franco E.L.
        • Duarte-Franco E.
        • Ferenczy A.
        Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection.
        CMAJ. 2001; 164: 1017-1025
        • Chih H.J.
        • Lee A.H.
        • Colville L.
        • et al.
        Condom and oral contraceptive use and risk of cervical intraepithelial neoplasia in Australian women.
        J Gynecol Oncol. 2014; 25: 183-187
        • Schiff M.
        • Miller J.
        • Masuk M.
        • et al.
        Contraceptive and reproductive risk factors for cervical intraepithelial neoplasia in American Indian women.
        Int J Epidemiol. 2000; 29: 983-990
        • Oh H.Y.
        • Kim M.K.
        • Seo S.S.
        • et al.
        Association of combined tobacco smoking and oral contraceptive use with cervical intraepithelial neoplasia 2 or 3 in Korean women.
        J Epidemiol. 2016; 26: 22-29
        • Moreno V.
        • Bosch F.X.
        • Munoz N.
        • et al.
        Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study.
        Lancet. 2002; 359: 1085-1092
        • Smith J.S.
        • Green J.
        • Berrington de Gonzalez A.
        • et al.
        Cervical cancer and use of hormonal contraceptives: a systematic review.
        Lancet. 2003; 361: 1159-1167
        • Appleby P.
        • Beral V.
        • Berrington de Gonzalez A.
        • et al.
        • International Collaboration of Epidemiological Studies of Cervical Cancer
        Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies.
        Lancet. 2007; 370: 1609-1621
      12. Public Health Agency of Canada. Cervical Cancer. Available at: http://www.phac-aspc.gc.ca/cd-mc/cancer/cervical_cancer-cancer_du_col_uterus-eng.php. Accessed on February 29, 2016.

        • Shulman L.P.
        Oral contraceptives: risks.
        Obstet Gynecol Clin N Am. 2000; 27: 695-704
        • Borgelt-Hansen L.
        Oral contraceptives: An update on health benefits and risks.
        J Am Pharm Assoc. 2001; 41: 875-886
        • Mikkelsen E.M.
        • Riis A.H.
        • Wise L.A.
        • et al.
        Pre-gravid oral contraceptive use and time to pregnancy: a Danish prospective cohort study.
        Hum Reprod. 2013; 28: 1398-1405
        • Mansour D.
        • Gemzell-Danielsson K.
        • Inki P.
        • et al.
        Fertility after discontinuation of contraception: a comprehensive review of the literature.
        Contraception. 2011; 84: 465-477
        • Farrow A.
        • Hull M.G.
        • Northstone K.
        • et al.
        Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception.
        Hum Reprod. 2002; 17: 2754-2761
        • Gold E.B.
        • Bromberger J.
        • Crawford S.
        • et al.
        Factors associated with age at natural menopause in a multiethnic sample of midlife women.
        Am J Epidemiol. 2001; 153: 865-874
        • Palmer J.R.
        • Rosenberg L.
        • Wise L.A.
        • et al.
        Onset of natural menopause in African American women.
        Am J Public Health. 2003; 93: 299-306
        • Briggs G.C.
        • Freeman R.K.
        Drugs in pregnancy and lactation.
        ed 10. Wolters Kluwer Health, Philadelphia, PA2014
        • Charlton B.M.
        • Molgaard-Nielsen D.
        • Svanstrom H.
        • et al.
        Maternal use of oral contraceptives and risk of birth defects in Denmark: prospective, nationwide cohort study.
        BMJ. 2016; 352: h6712
        • ESHRE Capri Workshop Group
        Female contraception over 40.
        Hum Reprod Update. 2009; 15: 599-612
        • Baldwin M.K.
        • Jensen J.T.
        Contraception during the perimenopause.
        Maturitas. 2013; 76: 235-242
        • Allen R.H.
        • Cwiak C.A.
        • Kaunitz A.M.
        Contraception in women over 40 years of age.
        CMAJ. 2013; 185: 565-573
      13. FFPRHC Guidance (January 2005) contraception for women aged over 40 years.
        J Fam Plann Reprod Health Care. 2005; 31 (quiz 63–4): 51-63
        • Koltun W.
        • Maloney J.M.
        • Marr J.
        • et al.
        Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 mug plus drospirenone 3mg administered in a 24/4 regimen: a pooled analysis.
        Eur J Obstet Gynecol Reprod Biol. 2011; 15: 171-175
        • van der Vange N.
        • Blankenstein M.A.
        • Kloosterboer H.J.
        • et al.
        Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone.
        Contraception. 1990; 41: 345-352
        • Vessey M.
        • Painter R.
        Oral contraceptive use and cancer. Findings in a large cohort study, 1968-2004.
        Br J Cancer. 2006; 95: 385-389
        • Braem M.G.
        • Onland-Moret N.C.
        • van den Brandt P.A.
        • et al.
        Reproductive and hormonal factors in association with ovarian cancer in the Netherlands cohort study.
        Am J Epidemiol. 2010; 172: 1181-1189
        • Mueck A.O.
        • Seeger H.
        • Rabe T.
        Hormonal contraception and risk of endometrial cancer: a systematic review.
        Endocr Relat Cancer. 2010; 17: R263-R271
        • Jatoi A.
        • Foster N.R.
        • Kalli K.R.
        • et al.
        Prior oral contraceptive use in ovarian cancer patients: assessing associations with overall and progression-free survival.
        BMC Cancer. 2015; 15: 711
        • Curtis K.M.
        • Jatlaoui T.C.
        • Tepper N.K.
        • et al.
        U.S. selected practice recommendations for contraceptive use, 2016.
        MMWR Recomm Rep. 2016; 65: 1-66
        • Heinemann L.A.J.
        • Lewis M.A.
        • Spitzer W.O.
        • Guggenmoos-Holzmann I.
        • Bruppacher R.
        • et al.
        Thromboembolic stroke in young women: a European case-control study on oral contraceptives.
        Contraception. 1998; 57: 29-37
        • Dunn N.
        • Thorogood M.
        • Faragher N.
        • et al.
        Oral contraceptives and myocardial infarction: results of the MICA case-control study.
        BMJ. 1999; 318: 1579-1583
      14. Public Health Agency of Canada. Canadian Guidelines on Sexually Transmitted Infections 2015. Available at: http://www.phac-aspc.gc.ca/std-mts/sti-its/index-eng.php. Accessed on June 25, 2015.

        • Vandenbroucke J.P.
        • van der Meer F.J.
        • Helmerhorst F.M.
        • et al.
        Factor V Leiden: should we screen oral contraceptive users and pregnant women?.
        BMJ. 1996; 313: 1127-1130
        • Wu O.
        • Greer I.A.
        Is screening for thrombophilia cost-effective?.
        Curr Opin Hematol. 2007; 14: 500-503
        • Wu O.
        • Robertson L.
        • Twaddle S.
        • et al.
        Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study.
        Health Technol Assess. 2006; 10: 1-110
        • Lopez L.M.
        • Tolley E.E.
        • Grimes D.A.
        • et al.
        Theory-based interventions for contraception.
        Cochrane Database Syst Rev. 2013; : CD007249
        • Westhoff C.
        • Kerns J.
        • Morroni C.
        • et al.
        Quick Start: a novel oral contraceptive initiation method.
        Contraception. 2002; 66: 141-145
        • Westhoff C.
        • Morroni C.
        • Kerns J.
        • et al.
        Bleeding patterns after immediate vs. conventional oral contraceptive initiation: a randomized, controlled trial.
        Fertil Steril. 2003; 79: 322-329
        • Westhoff C.
        • Heartwell S.
        • Dwards S.
        • et al.
        Initiation of oral contraceptives using a Quick Start compared with a conventional start: a randomized controlled trial.
        Obstet Gynecol. 2007; 109: 1270-1276
        • Lara-Torre E.
        Quick Start: an innovative approach to the combination oral contraceptive pill in adolescents. Is it time to make the switch?.
        J Pediatric Adolesc Gynecol. 2004; 17: 65-67
        • Brahmi D.
        • Curtis K.M.
        When can a woman start combined hormonal contraceptives (CHCs)? A systematic review.
        Contraception. 2013; 87: 524-538
        • Steenland M.W.
        • Rodriguez M.I.
        • Marchbanks P.A.
        • et al.
        How does the number of oral contraceptive pill packs dispensed or prescribed affect continuation and other measures of consistent and correct use? A systematic review.
        Contraception. 2013; 87: 605-610
      15. Health Canada. Non-Insured Health Benefits: First Nations and Health Benefits. Drug Benefit List. Available at: http://www.healthycanadians.gc.ca/publications/health-system-systeme-sante/nihb-drug-list-2016-liste-medicaments-ssna/index-eng.php. Accessed on December 6, 2016.

      16. Reproductive Health Access Project. Available at: http://www.reproductiveaccess.org. Accessed on June 6, 2016.

      17. Institut National de Santé Publique du Quebec. Ordonnance Collective de Contraception Hormonale et du Stérilet 2016. Available at: https://www.inspq.qc.ca/contraception. Accessed on November 3, 2016.

        • Moreau C.
        • Trussell J.
        • Gilbert F.
        • et al.
        Oral contraceptive tolerance: does the type of pill matter?.
        Obstet Gynecol. 2007; 109: 1277-1285
        • Anderson F.D.
        • Gibbons W.
        • Portman D.
        Long-term safety of an extended-cycle oral contraceptive (Seasonale): a 2-year multicenter open-label extension trial.
        Am J Obstet Gynecol. 2006; 195: 92-96
        • Anttila L.
        • Neunteufel W.
        • Petraglia F.
        • et al.
        Cycle control and bleeding pattern of a 24/4 regimen of drospirenone 3 mg/ethinylestradiol 20 mug compared with a 21/7 regimen of desogestrel 150 mug/ethinylestradiol 20 mug: a pooled analysis.
        Clin Drug Investig. 2011; 31: 519-525
        • Audet M.C.
        • Moreau M.
        • Koltun W.D.
        • et al.
        Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial.
        JAMA. 2001; 285: 2347-2354
        • Rosenberg M.
        • Waugh M.S.
        Causes and consequences of oral contraceptive noncompliance.
        Am J Obstet Gynecol. 1999; 180: S276-S279
      18. Approach to oral contraceptive nuisance side effects.
        Contracept Rep. 2004; 14: 13-15
        • Kulier R.
        • Helmerhorst F.M.
        • Maitra N.
        • et al.
        Effectiveness and acceptability of progestogens in combined oral contraceptives - a systematic review.
        Reprod Health. 2004; 1: 1
      19. Trends in oral contraceptive development and utilization: looking to the future.
        Contracept Rep. 1997; 7: 4-13
        • Grossman M.P.
        • Nakajima S.T.
        Menstrual cycle bleeding patterns in cigarette smokers.
        Contraception. 2006; 73: 562-565
        • Murphy P.A.
        • Kern S.E.
        • Stanczyk F.Z.
        • et al.
        Interaction of St. John’s Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding.
        Contraception. 2005; 71: 402-408
        • Schindler A.E.
        • Campagnoli C.
        • Druckmann R.
        • et al.
        Classification and pharmacology of progestins.
        Maturitas. 2003; 46: S7-S16
        • Guerra J.A.
        • López-Muñoz F.
        • Álamo C.
        • et al.
        Progestins in combined contraceptives.
        J Exp Clin Med. 2013; 5: 51-55
        • Godfrey E.M.
        • Whiteman M.K.
        • Curtis K.M.
        Treatment of unscheduled bleeding in women using extended- or continuous-use combined hormonal contraception: a systematic review.
        Contraception. 2013; 87: 567-575
        • Sulak P.J.
        • Smith V.
        • Coffee A.
        • et al.
        Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial.
        Obstet Gynecol. 2008; 112: 563-571
        • Guilbert E.
        • Black A.
        • Dunn S.
        Missed hormonal contraceptives: new recommendations.
        J Obstet Gynaecol Can. 2008; 30 (63–77): 1050-1062
        • Guilbert E.
        • Dunn D.
        • Black A.
        Addendum to the Canadian Consensus on Contraception e Emergency Contraception: 1) Excluding pre-existing pregnancy when inserting copper IUD and 2) Initiation of hormonal contraception after emergency contraception.
        J Obstet Gynaecol Can. 2016; 38: 1150-1151
        • Zapata L.B.
        • Steenland M.W.
        • Brahmi D.
        • et al.
        Patient understanding of oral contraceptive pill instructions related to missed pills: a systematic review.
        Contraception. 2013; 87: 674-684
        • Coutinho E.M.
        • de Souza J.C.
        • da Silva A.R.
        • et al.
        Comparative study on the efficacy and acceptability of two contraceptive pills administered by the vaginal route: an international multicenter clinical trial.
        Clin Pharmacol Ther. 1993; 53: 66-75
        • Coutinho E.M.
        • Mascarenhas I.
        • de Acosta O.M.
        • et al.
        Comparative study on the efficacy, acceptability, and side effects of a contraceptive pill administered by the oral and the vaginal route: an international multicenter clinical trial.
        Clin Pharmacol Ther. 1993; 54: 540-545
        • Coutinho E.M.
        • O’Dwyer E.
        • Barbosa I.C.
        • et al.
        Comparative study on intermittent versus continuous use of a contraceptive pill administered by vaginal route.
        Contraception. 1995; 51: 355-358
        • Kives S.
        • Hahn P.M.
        • White E.
        • et al.
        Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration.
        Contraception. 2005; 71: 197-201
        • Zichella L.
        • Sbrignadello C.
        • Tomassini A.
        • et al.
        Comparative study on the acceptability of two modern monophasic oral contraceptive preparations: 30 microgram ethinyl estradiol combined with 150 microgram desogestrel or 75 microgram gestodene.
        Adv Contracept. 1999; 15: 191-200
        • Iddon J.
        • Dixon J.M.
        Mastalgia.
        BMJ. 2013; 347: f3288
        • Lopez L.M.
        • Grimes D.A.
        • Gallo M.F.
        • et al.
        Skin patch and vaginal ring versus combined oral contraceptives for contraception.
        Cochrane Database Syst Rev. 2013; : CD003552
        • Lawrie T.A.
        • Helmerhorst F.M.
        • Maitra N.K.
        • et al.
        Types of progestogens in combined oral contraception: effectiveness and side-effects.
        Cochrane Database Syst Rev. 2011; : CD004861
        • Zhang H.
        • Cui D.
        • Wang B.
        • et al.
        Pharmacokinetic drug interactions involving 17alpha-ethinylestradiol: a new look at an old drug.
        Clin Pharmacokinet. 2007; 46: 133-157
        • Wilbur K.
        • Ensom M.H.
        Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants.
        Clin Pharmacokinet. 2000; 38: 355-365
        • Nelson A.
        • Cwiak C.
        Combined oral contraceptives.
        in: Hatcher R.A. Trussel J. Nelson A.L. Cates W. Kowal D. Pelicar M.S. Contraceptive technology. ed 20. Ardent Media, New York2011: 249-319
        • Shenfield G.M.
        • Griffin J.M.
        Clinical pharmacokinetics of contraceptive steroids. An update.
        Clin Pharmacokinet. 1991; 20: 15-37
        • D’Arcy P.F.
        Drug interactions with oral contraceptives.
        Drug Intell Clin Pharm. 1986; 20: 353-362
        • Fotherby K.
        Interactions with oral contraceptives.
        Am J Obstet Gynecol. 1990; 163: 2153-2159
        • Oesterheld J.R.
        • Cozza K.L.
        • Armstrong S.C.
        Gynecology: oral contraceptives. The cytochrome P450 system drug interaction principles for medical practice.
        American Psychiatric Publishing Inc, Washington, DC2001: 103-114
        • Reddy D.S.
        Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives.
        Expert Rev Clin Pharmacol. 2010; 3: 183-192
        • Johannessen S.I.
        • Landmark C.J.
        Antiepileptic drug interactions - principles and clinical implications.
        Curr Neuropharmacol. 2010; 8: 254-267
        • Crawford P.
        • Chadwick D.J.
        • Martin C.
        • et al.
        The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids.
        Br J Clin Pharmacol. 1990; 30: 892-896
        • Crawford P.
        Interactions between antiepileptic drugs and hormonal contraception.
        CNS Drugs. 2002; 16: 263-272
        • Sabers A.
        • Ohman I.
        • Christensen J.
        • et al.
        Oral contraceptives reduce lamotrigine plasma levels.
        Neurology. 2003; 61: 570-571
        • Christensen J.
        • Petrenaite V.
        • Atterman J.
        • et al.
        Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial.
        Epilepsia. 2007; 48: 484-489
        • Hall S.D.
        • Wang Z.
        • Huang S.M.
        • et al.
        The interaction between St John’s wort and an oral contraceptive.
        Clin Pharmacol Ther. 2003; 74: 525-535
        • Pfrunder A.
        • Schiesser M.
        • Gerber S.
        • et al.
        Interaction of St John’s wort with low-dose oral contraceptive therapy: a randomized controlled trial.
        Br J Clin Pharmacol. 2003; 56: 683-690
      20. Berry-Bibee EN, Kim MJ, Tepper NK, et al. Co-administration of St. John’s wort and hormonal contraceptives: a systematic review [e-pub ahead of print]. Contraception http://dx.doi.org/10.1016/j.contraception.2016.07.010, accessed November 3, 2016.

        • Landolt N.K.
        • Phanuphak N.
        • Ubolyam S.
        • et al.
        Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when coadministered with combined oral contraceptives.
        J Acquir Immune Defic Syndr. 2013; 62: 534-539
        • Sevinsky H.
        • Eley T.
        • Persson A.
        • et al.
        The effect of efavirenz on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy HIV-negative women.
        Antivir Ther. 2011; 16: 149-156
        • Tittle V.
        • Bull L.
        • Boffito M.
        • et al.
        Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.
        Clin Pharmacokinet. 2015; 54: 23-34
        • Dickinson B.D.
        • Altman R.D.
        • Nielsen H.
        • et al.
        Drug interactions between oral contraceptives and antibiotics.
        Am J Obstet Gynecol. 2001; 98: 853-860
        • Toh S.
        • Mitchell A.A.
        • Anderka M.
        • National Birth Defects Prevention Study
        • et al.
        Antibiotics and oral contraceptive failure - a case-crossover study.
        Contraception. 2011; 83: 418-425
        • Baciewicz A.M.
        • Chrisman C.R.
        • Finch C.K.
        • Self T.H.
        Update on rifampin, rifabutin, and rifapentine drug interactions.
        Curr Med Res Opin. 2013; 29: 1-12
        • Hachad H.
        • Ragueneau-Majlessi I.
        • Levy R.H.
        New antiepileptic drugs: review on drug interactions.
        Ther Drug Monit. 2002; 24: 91-103
        • Schwarz U.I.
        • Buschel B.
        • Kirch W.
        Unwanted pregnancy on self-medication with St John’s wort despite hormonal contraception.
        Br J Clin Pharmacol. 2003; 55: 112-113
      21. Janssen Inc. Product Monograph: EVRA 6.0 mg Norelgestromin and 0.60 mg Ethinyl Estradiol Transdermal System 2013. Available at: http://www.janssen.com/canada/sites/www_janssen_com_canada/files/product/pdf/evr05162013cpm.pdf. Accessed on November, 15, 2015.

        • Devineni D.
        • Skee D.
        • Vaccaro N.
        • et al.
        Pharmacokinetics and pharmacodynamics of a transdermal contraceptive patch and an oral contraceptive.
        J Clin Pharmacol. 2007; 47: 497-509
        • van den Heuvel M.W.
        • van Bragt A.
        • Alnabawy A.K.M.
        • et al.
        Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive.
        Contraception. 2005; 72: 168-174
        • Smallwood G.H.
        • Meador M.L.
        • Lenihan J.P.
        • et al.
        ORTHO EVRA/EVRA 002 Study Group. Efficacy and safety of a transdermal contraceptive system.
        Obstet Gynecol. 2001; 98: 799-805
        • Urdl W.
        • Apter D.
        • Alperstein A.
        • et al.
        Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception.
        Eur J Obstet Gynecol Reprod Biol. 2005; 121: 202-210
        • Zieman M.
        • Guillebaud J.
        • Weisberg E.
        • et al.
        Contraceptive efficacy and cycle control with Ortho Evra/Evra transdermal system: the analysis of pooled data.
        Fertil Steril. 2002; 77: S13-S18
        • Lopez L.M.
        • Grimes D.A.
        • Chen M.
        • et al.
        Hormonal contraceptives for contraception in overweight or obese women.
        Cochrane Database Syst Rev. 2013; : CD008452
        • Archer D.F.
        • Bigrigg A.
        • Smallwood G.H.
        • et al.
        Assessment of compliance with a weekly contraceptive patch among North American women.
        Fertil Steril. 2002; 77: S27-S31
        • Kluft C.
        • Meijer P.
        • LaGuardia K.D.
        • et al.
        Comparison of a transdermal contraceptive patch vs. oral contraceptives on hemostasis variables.
        Contraception. 2008; 77: 77-83
        • Centers for Disease Control and Prevention
        U.S. medical eligibility criteria for contraceptive use, 2010.
        MMWR. 2010; 59: 1-85
        • Vercellini P.
        • Barbara G.
        • Somigliana E.
        • et al.
        Comparison of contraceptive ring and patch for the treatment of symptomatic endometriosis.
        Fertil Steril. 2010; 93: 2150-2161
        • White T.
        • Jain J.K.
        • Stanczyk F.Z.
        Effect of oral versus transdermal steroidal contraceptives on androgenic markers.
        Am J Obstet Gynecol. 2005; 192: 2055-2059
        • Sibai B.M.
        • Odlind V.
        • Neador M.L.
        • et al.
        A comparative and pooled analysis of the safety and tolerability of the contraceptive patch.
        Fertil Steril. 2002; 77: S19-S26
        • Dittrich R.
        • Parker L.
        • Rosen J.B.
        • et al.
        Ortho Evra/Evra 001 Study Group. Transdermal contraception: evaluation of three transdermal norelgestromin/ethinyl estradiol doses in a randomized, multicenter, dose-response study.
        Am J Obstet Gynecol. 2002; 186: 15-20
        • Johnson J.V.
        • Lowell J.
        • Badger G.J.
        • et al.
        Effects of oral and transdermal hormonal contraception on vascular risk markers: a randomized controlled trial.
        Obstet Gynecol. 2008; 111: 278-284
        • Jick S.S.
        • Kaye J.A.
        • Russmann S.
        • et al.
        Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 [mu]g of ethinyl estradiol.
        Contraception. 2006; 73: 223-228
        • Jick S.
        • Kaye J.A.
        • Li L.
        • et al.
        Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol.
        Contraception. 2007; 76: 4-7
        • Jick S.S.
        • Hagberg K.W.
        • Kaye J.A.
        ORTHO EVRA and venous thromboembolism: an update.
        Contraception. 2010; 81: 452-453
        • Dore D.D.
        • Norman H.
        • Loughlin J.
        • et al.
        Extended case-control study results on thromboembolic outcomes among transdermal contraceptive users.
        Contraception. 2010; 81: 408-413
        • Lidegaard O.
        • Lokkegaard E.
        • Jensen A.
        • et al.
        Thrombotic stroke and myocardial infarction with hormonal contraception.
        N Engl J Med. 2012; 366: 2257-2266
        • Zacur H.A.
        • Hedon B.
        • Mansour D.
        • et al.
        Integrated summary of Ortho Evra/Evra contraceptive patch adhesion in varied climates and conditions.
        Fertil Steril. 2002; 77: S32-S35
        • Creasy G.W.
        • Fisher A.C.
        • Hall N.
        • et al.
        Transdermal contraceptive patch delivering norelgestromin and ethinyl estradiol. Effects on the lipid profile.
        J Reprod Med. 2003; 48: 179-186
        • Abrams L.S.
        • Skee D.M.
        • Natarajan J.
        • et al.
        Pharmacokinetics of a contraceptive patch (Evra/Ortho Evra) containing norelgestromin and ethinyloestradiol at four application sites.
        Br J Clin Pharmacol. 2002; 53: 141-146
        • Stewart F.H.
        • Kaunitz A.M.
        • LaGuardia K.D.
        • et al.
        Extended use of transdermal norelgestromin/ethinyl estradiol: a randomized trial.
        Obstet Gynecol. 2005; 105: 1389-1396
        • Benson L.S.
        • Micks E.A.
        Why stop now? Extended and continuous regimens of combined hormonal contraceptive methods.
        Obstet Gynecol Clin North Am. 2015; 42: 669-681
        • Abrams L.S.
        • Skee D.M.
        • Wong F.A.
        • et al.
        Pharmacokinetics of norelgestromin and ethinyl estradiol from two consecutive contraceptive patches.
        J Clin Pharmacol. 2001; 41: 1232-1237
        • Abrams L.S.
        • Skee D.M.
        • Natarajan J.
        • et al.
        Pharmacokinetic overview of Ortho Evra/Evra.
        Fertil Steril. 2002; 77: S3-S12
      22. Merck Canada Inc. Product Monograph. NUVARING: Etonogestrel/Ethunyl Estradiol Slow Release Vaginal Ring (11.4 mg/2.6 mg) to Deliver 120 mcg Etonogestrel/15 mcg Ethinyl Estradiol per Day. Contraceptive Vaginal Ring. Available at: http://www.merck.ca/assets/en/pdf/products/NUVARING-PM_E.pdf. Accessed on November 3, 2016.

        • Timmer C.J.
        • Mulders T.M.
        Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring.
        Clin Pharmacokinet. 2000; 39: 233-242
        • Alexander N.J.
        • Baker E.
        • Kaptein M.
        • et al.
        Why consider vaginal drug administration?.
        Fertil Steril. 2004; 82: 1-12
        • Roumen F.J.
        • Apter D.
        • Mulders T.M.
        • et al.
        Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol.
        Hum Reprod. 2001; 16: 469-475
        • Dieben T.O.
        • Roumen F.J.
        • Apter D.
        Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring.
        Obstet Gynecol. 2002; 100: 585-593
        • Roumen F.J.
        Review of the combined contraceptive vaginal ring, NuvaRing.
        Ther Clin Risk Manag. 2008; 4: 441-451
        • Oddsson K.
        • Leifels-Fischer B.
        • de Melo N.R.
        • et al.
        Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial.
        Contraception. 2005; 71: 176-182
        • Ahrendt H.J.
        • Nisand I.
        • Bastianelli C.
        • et al.
        Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone.
        Contraception. 2006; 74: 451-457
        • Mulders T.M.
        • Dieben T.O.
        Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation inhibition.
        Fertil Steril. 2001; 75: 865-870
        • Mulders T.M.
        • Dieben T.O.
        • Bennink H.J.
        Ovarian function with a novel combined contraceptive vaginal ring.
        Hum Reprod. 2002; 17: 2594-2599
        • Killick S.
        Complete and robust ovulation inhibition with NuvaRing.
        Eur J Contracept Reprod Health Care. 2002; 7: 13-18
        • Petrie K.A.
        • Torgal A.H.
        • Westhoff C.L.
        Matched-pairs analysis of ovarian suppression during oral vs. vaginal hormonal contraceptive use.
        Contraception. 2011; 84: e1-e4
        • Abu Hashim H.
        • Alsherbini W.
        • Bazeed M.
        Contraceptive vaginal ring treatment of heavy menstrual bleeding: a randomized controlled trial with norethisterone.
        Contraception. 2012; 85: 246-252
        • Brucker C.
        • Karck U.
        • Merkle E.
        Cycle control, tolerability, efficacy and acceptability of the vaginal contraceptive ring, NuvaRing: results of clinical experience in Germany.
        Eur J Contracept Reprod Health Care. 2008; 13: 31-38
        • Merki-Feld G.S.
        • Hund M.
        Clinical experience with NuvaRing in daily practice in Switzerland: cycle control and acceptability among women of all reproductive ages.
        Eur J Contracept Reprod Health Care. 2007; 12: 240-247
        • Roumen F.J.
        • op ten Berg M.M.
        • Hoomans E.H.
        The combined contraceptive vaginal ring (NuvaRing): first experience in daily clinical practice in The Netherlands.
        Eur J Contracept Reprod Health Care. 2006; 11: 14-22
        • Milsom I.
        • Lete I.
        • Bjertnaes A.
        • et al.
        Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone.
        Hum Reprod. 2006; 21: 2304-2311
        • Barreiros F.A.
        • Guazzelli C.A.
        • Barbosa R.
        • et al.
        Extended regimens of the contraceptive vaginal ring: evaluation of clinical aspects.
        Contraception. 2010; 81: 223-225
        • Merki-Feld G.S.
        • Hund M.
        Clinical experience with the combined contraceptive vaginal ring in Switzerland, including a subgroup analysis of previous hormonal contraceptive use.
        Eur J Contracept Reprod Health Care. 2010; 15: 413-422
        • Calhoun A.
        • Ford S.
        • Pruitt A.
        The impact of extended-cycle vaginal ring contraception on migraine aura: a retrospective case series.
        Headache. 2012; 52: 1246-1253
        • Battaglia C.
        • Mancini F.
        • Fabbri R.
        • et al.
        Polycystic ovary syndrome and cardiovascular risk in young patients treated with drospirenone-ethinylestradiol or contraceptive vaginal ring. A prospective, randomized, pilot study.
        Fertil Steril. 2010; 94: 1417-1425
        • Leone Roberti Maggiore U.
        • Remorgida V.
        • Scala C.
        • et al.
        Desogestrel-only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open-label comparative study.
        Acta Obstet Gynecol Scand. 2014; 93: 239-247
        • Mohamed A.M.
        • El-Sherbiny W.S.
        • Mostafa W.A.
        Combined contraceptive ring versus combined oral contraceptive (30-mug ethinylestradiol and 3-mg drospirenone).
        Int J Gynaecol Obstet. 2011; 114: 145-148
        • Bjarnadottir R.I.
        • Tuppurainen M.
        • Killick S.R.
        Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol.
        Am J Obstet Gynecol. 2002; 186: 389-395
        • O’Connell K.J.
        • Osborne L.M.
        • Westhoff C.
        Measured and reported weight change for women using a vaginal contraceptive ring vs. a low-dose oral contraceptive.
        Contraception. 2005; 72: 323-327
        • Bruni V.
        • Pontello V.
        • Luisi S.
        • et al.
        An open-label, multicentre trial to evaluate the vaginal bleeding pattern of the combined contraceptive vaginal ring NuvaRing.
        Eur J Obstet Gynecol Reprod Biol. 2008; 139: 65-71
        • Oddsson K.
        • Leifels-Fischer B.
        • Wiel-Masson D.
        • et al.
        Superior cycle control with a contraceptive vaginal ring compared with an oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel: a randomized trial.
        Hum Reprod. 2005; 20: 557-562
        • Creinin M.D.
        • Meyn L.A.
        • Borgatta L.
        • et al.
        Multicenter comparison of the contraceptive ring and patch: a randomized controlled trial.
        Obstet Gynecol. 2008; 111: 267-277
        • Veres S.
        • Miller L.
        • Burington B.
        A comparison between the vaginal ring and oral contraceptives.
        Obstet Gynecol. 2004; 104: 555-563
        • Lete I.
        • Cuesta M.C.
        • Marin J.M.
        • et al.
        Vaginal health in contraceptive vaginal ring users - A review.
        Eur J Contracept Reprod Health Care. 2013; 18: 234-241
        • De Seta F.
        • Restaino S.
        • De Santo D.
        • et al.
        Effects of hormonal contraception on vaginal flora.
        Contraception. 2012; 86: 526-529
        • Camacho D.P.
        • Consolaro M.E.
        • Patussi E.V.
        • et al.
        Vaginal yeast adherence to the combined contraceptive vaginal ring (CCVR).
        Contraception. 2007; 76: 439-443
        • Novak A.
        • de la Loge C.
        • Abetz L.
        • et al.
        The combined contraceptive vaginal ring, NuvaRing: an international study of user acceptability.
        Contraception. 2003; 67: 187-194
        • Guida M.
        • Di Spiezio Sardo A.
        • Bramante S.
        • et al.
        Effects of two types of hormonal contraception—oral versus intravaginal—on the sexual life of women and their partners.
        Hum Reprod. 2005; 20: 1100-1106
        • Caruso S.
        • Cianci S.
        • Malandrino C.
        • et al.
        Quality of sexual life of women using the contraceptive vaginal ring in extended cycles: preliminary report.
        Eur J Contracept Reprod Health Care. 2014; 19: 307-314
        • Guida M.
        • Cibarelli F.
        • Troisi J.
        • et al.
        Sexual life impact evaluation of different hormonal contraceptives on the basis of their methods of administration.
        Arch Gynecol Obstet. 2014; 290: 1239-1247
        • Gracia C.R.
        • Sammel M.D.
        • Charlesworth S.
        • et al.
        Sexual function in first-time contraceptive ring and contraceptive patch users.
        Fertil Steril. 2010; 93: 21-28
        • Battaglia C.
        • Morotti E.
        • Persico N.
        • et al.
        Clitoral vascularization and sexual behavior in young patients treated with drospirenone-ethinyl estradiol or contraceptive vaginal ring: a prospective, randomized, pilot study.
        J Sex Med. 2014; 11: 471-480
        • Lidegaard O.
        • Nielsen L.H.
        • Skovlund C.W.
        • et al.
        Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10.
        BMJ. 2012; 344: e2990
        • Dinger J.
        • Mohner S.
        • Heinemann K.
        Cardiovascular risk associated with the use of an etonogestrel-containing vaginal ring.
        Obstet Gynecol. 2013; 122: 800-808
        • Duijkers I.
        • Killick S.
        • Bigrigg A.
        • et al.
        A comparative study on the effects of a contraceptive vaginal ring NuvaRing and an oral contraceptive on carbohydrate metabolism and adrenal and thyroid function.
        Eur J Contracept Reprod Health Care. 2004; 9: 131-140
        • Guazzelli C.A.
        • Barreiros F.A.
        • Torloni M.R.
        • et al.
        Effects of extended regimens of the contraceptive vaginal ring on carbohydrate metabolism.
        Contraception. 2012; 85: 253-256
        • Grodnitskaya E.E.
        • Grigoryan O.R.
        • Klinyshkova E.V.
        • et al.
        Effect on carbohydrate metabolism and analysis of acceptability (menstrual cycle control) of extended regimens of the vaginally inserted hormone-releasing system ‘NuvaRing’ as compared with the standard 21/7 regime in reproductive-age women with type 1 diabetes mellitus.
        Gynecol Endocrinol. 2010; 26: 663-668
        • Cagnacci A.
        • Ferrari S.
        • Tirelli A.
        • et al.
        Route of administration of contraceptives containing desogestrel/etonorgestrel and insulin sensitivity: a prospective randomized study.
        Contraception. 2009; 80: 34-39
        • Elkind-Hirsch K.E.
        • Darensbourg C.
        • Ogden B.
        • et al.
        Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive.
        Contraception. 2007; 76: 348-356
        • Tuppurainen M.
        • Klimscheffskij R.
        • Venhola M.
        • et al.
        The combined contraceptive vaginal ring (NuvaRing) and lipid metabolism: a comparative study.
        Contraception. 2004; 69: 389-394
        • Guazzelli C.A.
        • Barreiros F.A.
        • Barbosa R.
        • et al.
        Extended regimens of the contraceptive vaginal ring versus hormonal oral contraceptives: effects on lipid metabolism.
        Contraception. 2012; 85: 389-393
        • Magnusdottir E.M.
        • Bjarnadottir R.I.
        • Onundarson P.T.
        • et al.
        The contraceptive vaginal ring (NuvaRing) and hemostasis: a comparative study.
        Contraception. 2004; 69: 461-467
        • Fleischer K.
        • van Vliet H.A.
        • Rosendaal F.R.
        • et al.
        Effects of the contraceptive patch, the vaginal ring and an oral contraceptive on APC resistance and SHBG: a cross-over study.
        Thromb Res. 2009; 123: 429-435
        • Piltonen T.
        • Puurunen J.
        • Hedberg P.
        • et al.
        Oral, transdermal and vaginal combined contraceptives induce an increase in markers of chronic inflammation and impair insulin sensitivity in young healthy normal-weight women: a randomized study.
        Hum Reprod. 2012; 27: 3046-3056
        • Jensen J.T.
        • Burke A.E.
        • Barnhart K.T.
        • et al.
        Effects of switching from oral to transdermal or transvaginal contraception on markers of thrombosis.
        Contraception. 2008; 78: 451-458
        • Westhoff C.L.
        • Torgal A.H.
        • Mayeda E.R.
        • et al.
        Pharmacokinetics and ovarian suppression during use of a contraceptive vaginal ring in normal-weight and obese women.
        Am J Obstet Gynecol. 2012; 207: 39.e1-39.e6
        • Dragoman M.
        • Petrie K.
        • Torgal A.
        • et al.
        Contraceptive vaginal ring effectiveness is maintained during 6 weeks of use: a prospective study of normal BMI and obese women.
        Contraception. 2013; 87: 432-436
        • Roumen F.J.
        The contraceptive vaginal ring compared with the combined oral contraceptive pill: a comprehensive review of randomized controlled trials.
        Contraception. 2007; 75: 420-429
        • Verhoeven C.H.
        • Dieben T.O.
        The combined contraceptive vaginal ring, NuvaRing, and tampon co-usage.
        Contraception. 2004; 69: 197-199
        • Verhoeven C.H.
        • van den Heuvel M.W.
        • Mulders T.M.
        • et al.
        The contraceptive vaginal ring, NuvaRing, and antimycotic co-medication.
        Contraception. 2004; 69: 129-132
        • Haring T.
        • Mulders T.M.
        The combined contraceptive ring NuvaRing and spermicide co-medication.
        Contraception. 2003; 67: 271-272
        • Westhoff C.
        • Osborne L.M.
        • Schafer J.E.
        • et al.
        Bleeding patterns after immediate initiation of an oral compared with a vaginal hormonal contraceptive.
        Obstet Gynecol. 2005; 106: 89-96
        • Schafer J.E.
        • Osborne L.M.
        • Davis A.R.
        • et al.
        Acceptability and satisfaction using Quick Start with the contraceptive vaginal ring versus an oral contraceptive.
        Contraception. 2006; 73: 488-492
        • Miller L.
        • Verhoeven C.H.J.
        • Hout J.
        Extended regimens of the contraceptive vaginal ring: a randomized trial.
        Obstet Gynecol. 2005; 106: 473-482
        • Barreiros F.A.
        • Guazzelli C.A.
        • de Araujo F.F.
        • et al.
        Bleeding patterns of women using extended regimens of the contraceptive vaginal ring.
        Contraception. 2007; 75: 204-208
        • Dogterom P.
        • van den Heuvel M.W.
        • <