• Information
  1. Types
  2. Prescribing Hormonal Contraception
  3. Benefits of OCPs
  4. Estrogens
  5. Progestins
  6. Toxicities
  7. Cardiovascular and Thromboembolic Risks of OCPs
  8. Contraindications to OCPs
  9. Management of Side Effects of OCPs
  10. Levonorgestrel
  11. Etonogestrel
  12. Medroxyprogesterone Acetate
  13. Contraceptive Patch
  14. Spermacide
  15. Intrauterine Devices
  16. Condoms
  17. Mifepristone
  18. Post-Coital Contraception

A. Types

1. Female - Hormonal [2,3]
   1. Oral Contraceptive Pills (OCP) [4]
   2. OCP - estrogen + progestin
   3. OCP - progestin only
   4. Transdermal estrogen/progestin patch - under evaluation (see below)
   5. Progesterone Injection IM (effective for 3 months)
   6. Subdermal Implants (Norplant®; 5 years; Implanon®, 3 years)
   7. Intrauterine progestin devices
2. Barrier Methods (including diaphragm)
   1. Spermicides usually added to diaphragm barrier method
   2. Condoms
3. Intrauterine Devices (IUD) [6]
   1. Copper based (including GynFix®, ParaGard®) [5]
   2. Progestin releasing (Mirena®)
4. Sterilization
   1. Male
   2. Female
5. Post-Coital Contraception [52]
6. There are 1.7 million unintended pregnancies and 0.8 million abortions annually in USA

B. Prescribing Hormonal Contraception [3]

1. Medical History
   1. Particular focus on thromboses, hypertension, smoking
   2. Family history of thrombosis should prompt specific genetic screening
   3. These genetic tests include Factor V Leiden and Prothrombin gene mutation screening [43]
2. Blood pressure measurement
3. Pelvic and breast examinations only with routine evaluations (not required for OCPs)
4. Screening for cervical neoplasia and sexually transmitted diseases (STDs) not required for OCPs but may be considered for routine health screening
5. Prolonged use of hormonal contraceptives may increase risk of cervical cancer[13,16]
   1. Unclear if this is a direct cause and effect
   2. Use for >5 years increases risk ~1.9X overall
   3. Once discontinued, risk normalizes after 10 years
   4. May be related to number of sexual partners
6. Progestins usually determine which "generation" an OCP belongs to
7. No significant clinical differences overall for monophasic versus multiphasic OCPs
8. Dosing with OCPs [14]
   1. Most older agents use 21 days of active pills with 7 days of placebo pills
   2. These 21/7 pills generally regulate monthly menstruation, resulting in 13 withdrawal bleeding episodes per year
   3. Loestrin 24®, Yaz® (24 active tablets, 4 intert) reduce withdrawal symptoms [14,17]
9. Extended Cycle Formulations [14,17]
   1. Seasonale®: 91 day cycle with 84 days active pills, 7 days inactive [53]
   2. Seasonique® (84 active + 7 days of 10µg ethinyl estradiol) reduced withdrawal bleeds [14]
   3. Lybrel®: low dose combination (ethyinyl estradiol 20µg+levonorgestrel 0.09mg) daily without any interruption (365 days/year); amenorrhea in most women within 1 year [17]
10. Hepatic Enzyme Inducing Anticonvulsants [23]
    1. Include phenytoin (Dilantin), carbamazepine, oxcarbazepine, phenobartibal, topiramate
    2. Increase clearance of certain drugs including oral contraceptive pills (OCP)
    3. If OCPs are to be used with these agents, at least 50µg ethinyl estradiol should be used
11. OCPs are safe in patients with stable systemic lupus erythematosus [8,9]
12. Overall mortality for long term users of OCPs same as general population [10]
13. Use associated with ~1-2 pregnancies per 100 person years in women <35 years [17]

C. Benefits of OCPs [2]

1. Daily, ease of use, generally well tolerated
2. OCPs (including 50µg estrogen pills) have no effect on mortality (25-30 year studies) [10]
3. >99% effective as contraceptives when taken regularly
4. Ovarian Cancer [10,11]
   1. Reduces overall risk of and death from ovarian cancer 30-80%
   2. Reduces overall rates of ovarian cancer from 1.2 to 0.8 per 100 users over 10 years [11]
   3. Reduce risk of ovarian cancer ~50% in patients with BRCA1 or BRCA2 mutations
5. Uterine Cancer - reduces overall risk of and death from uterine cancer >50% [2,10]
6. Acne
   1. OCPs reduce acne severity
   2. Combination OCPs raise sex hormone binding globulin and
   3. Decrease free testosterone combinations
7. Control Menstruation
   1. Reduce menorrhagia; reduce menstrual blood loss and incidence of anemia
   2. Reduces severity of dysfunctional uterine bleeding
   3. Improves predictibility of menstrual cycles
8. High doses can be used for emergency (post-coital) contraception (see below)
   1. Preven® - available with prescription
   2. Plan B® - awaiting full FDA approval for over the counter sales [52]
9. Probable reduced weight gain with Yasmin® [48]

D. Estrogens
[Figure]: "Estrogen and Progesterone"

1. Natural
   1. Estradiol
   2. Estrone
   3. Estriol
2. Synthetic (Good Gastrointestinal Absorbtion)
   1. Ethinyl Estradiol (can improve acne symptoms in Ortho Tri-Cyclen)
   2. Mestranol
3. A complete listing of agents is provided elsewhere [4]

E. Progestins
[Figure]: "Estrogen and Progesterone"

1. Progesterone
2. Norethynodrel
3. Norethynodrone
4. Norethynodrone acetate
5. Norgestrel / Levonorgestrel / Norgestimate
6. Ethinodiol diacetate
7. Desogestrel / Gestodene (third generation)
8. Etonogestrel (Implanon®) - implantable, progestin only for up to 3 years [55]
9. Drospirinone (in Yasmin®) [48]
10. A complete listing of agents is provided elsewhere [4]

F. Toxicities

1. Thromboembolic Risks (see below)
   1. Cardiovascular events and Stroke - mainly in smokers age >34
   2. Coagulation factor polymorphisms contribute to risk of OCP induced thromboembolism
   3. Increased thromboembolic risks in patients with anti-phospholipid antibodies (APLA)
   4. Increased risk of initial and recurrent deep vein thrombosis (DVT) [38]
2. Menstrual Disorders - mainly menstrual irregularities
3. Neurologic Disorders
   1. No clear increased risk for stroke
   2. Possible that OCP's effective for stroke protection
   3. Exacerbation of migraines
4. Dermatologic Disorders
   1. Eczema, Dermatitis
   2. Rosacea
   3. Erythema nodosum
5. Elevated Serum Triglycerides
   1. Unclear effect overall on cholesterol, coronary artery disease risk
   2. Added risk in patients with already low HDL (<35mg/dL)
6. Breast Cancer Risk [2]
   1. Older studies of OCPs show risk of breast cancer in current or past users is <1.3X [12]
   2. Second and third generation OCP have lower or no increased risk in women with family history
   3. Case control study confirms no increase risk of breast cancer with OCPs [49]
7. Cervical Cancers [2,10]
   1. Long term use probably increases overall risk of cervical cancer
   2. Risk increase only in women who have human pappilomavirus (high risk forms)
8. Likely increases frequency of migraine headaches
9. Increased risk of death in smokers who use OCPs [10]
   1. Death increased 1.2X for smokers 1-14 cigarettes per day
   2. Death increased 2.1X for smokers 15 or more per day

G. Cardiovascular and Thromboembolic Risks of OCPs

1. OCPs and progestin only agents are generally safe
2. Cardiovascular problems occur primarily when agents are used in patients in risk factors
3. Major interaction is between OCPs and smoking cigarettes [25]
   1. This is particularly true in women age >35
   2. Serious cardiovascular disease risk: 29.4/100,000 annually in smokers >34 on OCPs
   3. Compares with 3.3/100,000 annually in women 15-34 who smoke while on OCPs
4. Acute Myocardial Infarction (MI)
   1. Older agents with high estrogen increased MI risk in general
   2. Newer OCPs increase risk of MI only in persons with concommitant risk factors
   3. Blood pressure must be assessed before and during OCP use
   4. Combination of hypertension (HTN) and OCP use increases risk of acute MI
   5. In nonsmokers, increased risk of acute MI with OCP is <3 per million women-years
   6. In older smokers on OCPs, increased risk of acute MI is ~400 per million women-years
5. Cerebrovascular Disease (Stroke) [18]
   1. Low (<2 fold) or no increase with low dose estrogen OCP's [19,20,21]
   2. Moderate and high dose estrogen containing OCP's have <2.8 fold increased risk
   3. Meta-analysis risk of stroke was 1 per year per 24,000 nonsmoking, normotensive women [18]
   4. Smoking increases risk of stroke with OCPs by >10 fold
   5. HTN prior to starting OCPs causes a 10-14X increase in stroke risk (mainly hemorrhagic)
   6. Age >35 was a major risk factor for all types of strokes
   7. Hemorrhagic stroke had no or slight increase in risk in non-smoking OCP users [21,22]
   8. Some concern with increased hemorrhagic strokes with norgestrel or levonorgestrel [21]
   9. Migraine was also a risk factor for stroke with low dose OCP
6. Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) [38,43]
   1. Overall risk of DVT and PE in persons on OCPs is 2-6 per million per year [43]
   2. There is a 2-6X increased risk of DVT with low estrogen OCP's [24,43]
   3. Venous thromboembolism risk may also be related to type of progestin [2,24]
   4. Third generation progestins have ~2.5X increased risk versus second generation
   5. These risks are increased >10 fold if patient is smoking tobacco
   6. Age and obesity are independent risk factors for OCP associated DVT [19]
   7. Risks also increased in patients with Factor V Leiden or Prothrombin G20210A
   8. OCPs cause an increase in resistance to activated protein C (APC) [26]
   9. Third generation agents (such as desogestrel) are strong inhibitors of APC [26]
   10. Unclear if this acquired APC resistance can explain increased risk of DVT in OCP users
   11. OCPs increase risk of recurrence of venous thromboemolism [38]
7. Risk Factors for Thrombosis on OCPs
   1. Smoking is greatest single risk factor for DVT on OCP
   2. Factor V Leiden with hyperhomocysteinemia has >10 fold increase DVT risk [27]
   3. Factor V Leiden alone has 3-5 fold increased risk for DVT
   4. Combination of FV Leiden and OCP may have even higher risk
   5. Prothrombin gene mutation G20210A increases risk of DVT [43] and cerebral vein thrombosis [28] in OCP users
   6. May be reasonable to screen patients, particularly smokers and patients with family history of venous thrombosis, for these risk factors [29]
   7. Third generation OCPs have increased risk for DVT [26]
8. OCPs can exacerbate essential hypertension
9. OCPs must be avoided in persons who smoke tobacco due to high vascular risks

H. Contraindications to OCPs [2,3,4]

1. Absolute
   1. Thromboembolic Disease (MI, DVT, PE)
   2. Cerebrovascular Accident (Stroke)
   3. Smoking and age >35 years
   4. Breast or Reproductive System Malignancy
   5. Pregnancy
   6. Antiphospholipid Syndrome
   7. Unexplained vaginal bleeding
   8. Decompensated Cirrhosis
   9. Liver tumor
2. Relative (Strong)
   1. Uncontrolled Hypertension
   2. Full term gestation within last 4 weeks
   3. Pre- or true Diabetes
   4. Gall Bladder Disease
   5. Acute mononucleosis
   6. Sickle Cell Anemia
   7. Migraine headache with neurological changes or Age >34
   8. Breastfeeding, particularly <6 weeks post-partum
   9. Liver dysfunction
3. Genetic Factors and Thromboembolic Risks
   1. DVT risk increased >5 fold with OCP and Factor V Leiden [24]
   2. Prothrombin mutations increase risk of DVT and cerebral vein thrombosis with OCP [2]
   3. Hyperhomocysteinemia also increases risk >10 fold [27]
   4. General screening for mutations in any potential OCP user has not yet been adopted
4. OCPs can safely be given to most women age >34 until menopause [25]
   1. Acceptable in persons with family history of breast or ovarian cancer
   2. Acceptable in hypercholesterolemia
   3. Acceptable in diabetes mellitus if no other cardiac risk factors or end organ damage

I. Management of Side Effects of OCPs

1. Reduce Estrogen Dose For:
   1. Nausea and Vomiting
   2. Weight gain
   3. Edema
   4. Headache
   5. Nervousness
   6. Chlorasma (Melasma, Melanoderma)
   7. Mucorrhea and Leukorrhea
   8. Cystic Breast Changes
   9. Fibroid Enlargement
   10. Hypermenorrhea
   11. Clotting Abnormalities (contraindication - stop agent)
2. Increase Estrogen Dose For:
   1. Early Cycle Spotting
   2. Breakthrough Bleeding
   3. Hypomenorrhea
   4. Vasomotor Symptoms - flushing
   5. Dyspareunia (painful sexual intercourse)
   6. Malaise
   7. Amenorrhea
3. Reduce Progestin Dose For:
   1. Depression
   2. Weight Gain - anabolic effects (reduced weight gain with drospirenone in Yasmin®) [48]
   3. Oligomenorrhea, Amenorrhea
   4. Monilia (yeast)
   5. Acne
   6. Hirsutism
   7. Pruritus
4. Increase Progestin Dose For:
   1. Late Cycle Spotting and Breakthrough Bleeding
   2. Hypermenorrhea
   3. Dysmenorrhea

J. Levonorgestrel (LNG, Norplant®) [6]

1. LNG, a progesterone, embedded in silicone implantable sticks
   1. Usually placed under medial aspect of arm
   2. Procedure done in office under local anesthesia
   3. Original Norplant® used 6 sticks containing levonorgestrel
   4. Norplant® 2, now available, uses 2 sticks
2. Implant subscutaneously, followup in one week
3. Side effects typical of progesterone-only agents
   1. Breakthrough bleeding, spotting, hypomenorrhea are common
   2. Hair loss relatively uncommon
   3. May also have transient headaches, nausea
4. Contraindications are very few
   1. DVT is not a strong contraindication
   2. History of breast cancer is likely only absolute contraindication
5. LNG pills are very effective "emergency" contraceptives [31]
   1. Dose of LNG is 0.75mg given twice 12 hours apart
   2. Crude pregnancy rate 1.1% with LNG
   3. Crude pregnancy rate with typical OCP (100µg ethinylestradiol + 0.5mg LNG) 3.2%
   4. Thus, LNG appears to be considerably more effective than high dose OCP
   5. Single 1.5mg dose LNG is clearly as effective as split dosing [30]
   6. LNG is as effective as single 10mg dose mifepristone [30]
   7. Nausea and vomiting occurred 50-70% less with LNG than with with high dose OCP

K. Etonogestrel (3-Ketodesogestrel, Implanon®) [1,55]

1. Very high efficacy, single 3-year stick implant
2. Much easier to insert than Norplant® or Norplant® 2
3. Fertility returns rapidly on removal
4. Metabolized by CYP3A4; caution with inducers of metabolism
5. Now FDA approved

L. Medroxyprogesterone Acetate (Depo-Provera®) [6]

1. Progestrin
2. IM injection of 150mg, lasts 3 months in most patients
3. Side effect profile similar to other progesterone-only agents (above)

M. Contraceptive Patch (Ortho Evra®) [50]

1. Patch delivers 150µg norelgestromin and 20µg estradiol daily
2. Patch is applied weekly and hormones released bypass liver (no first pass effects)
3. Active patch used for 3 out of every 4 weeks on abdomen, buttocks or upper torso
4. Patch should not be worn on breasts
5. Breast discomfrot, headache, nausea, menstrual cramps may occur
6. Improved compliance relative to OCPs, with possible improved contraceptive rate

N. Spermacide

1. Contraceptive sponge is no longer available - concern for bacterial contamination
2. Major method is diaphragm which fits over the cervix
3. Diaphragm should be fitted to cervical/pelvic size by properly trained person
4. Usually fill diaphragm with spermacide
5. Most commonly used sperimicide is nonoxynol 9
6. Nonoxynol 9 film or gel does not affect transmission of STDs [32,47] including HIV [51]

O. Intrauterine Devices (IUD) [5,6]

1. Barrier method, one of the most effective, semi-permanent contraceptive methods
   1. Copper IUD likely works due to copper's adverse on sperm, preventing fertilization
   2. Progestin releasing IUD (Mirena®) is approved in USA for use over a 5-year period [6,35]
2. Used by ~160 million worldwide, but only 2% of women using contraception in USA
3. IUD use generally only for women at low risk for sexually transmitted diseases (STD)
4. IUD is inserted by a professional
   1. May be used in combination with spermacides
   2. There is some risk of bacterial infection following insertion of IUD
   3. Prophylactic azithromycin prior to IUD insertion does not reduce risk of infection [33]
   4. Overall rate of IUD removal for reasons other than (partial) expulsion is <4% [33]
   5. Explusion rate depends primarily on insertion technique
   6. In general, rates are 1.8-2.9 per 100 yeras of use
5. IUD does NOT increase the risk of upper genital-tract infection [34]
6. IUD does NOT increase the risk of tubal infertility [45]
7. Pregnancy while using an IUD carries increased risk of complications (device usually removed)
8. Main side effects are menstrual abnormalities
   1. Heavy menstruation and intermenstrual spotting occur with copper IUDs
   2. Amenorrhea more common with levonorgestrel releasing IUD

P. Condoms

1. Both Male and Female Barrier Methods are now available and FDA approved [5,36]
2. Only acceptable method besides abstinance for prevention of sexually transmitted diseases including herpes simplex type 2 (HSV-2) transmission [44,54]
3. Latex Condoms
   1. These provide very reliable protection against disease transmission
   2. Natural (such as lamb's intestine) condoms do not provide reliable barriers to organisms
4. Regular condom use associated with about 70% reduction in new HPV infections [15]
5. Polyurethane condoms are being developed and may be stronger than latex

Q. Mifepristone (RU 486, Mifeprex®) [37]

1. FDA approved progesterone analog
2. Activity as Abortion Induction Agent
   1. Combination with prostaglandin (PG) such as Misoprostal (Cytotec®), a PGE1 analog
   2. Misoprostal (800µg) given intravaginally is more effective than orally
   3. Combination mifepristone and misoprostal Intravaginally is >95% effective
3. Post-Coital Emergency Contraception [39]
   1. Very effective for post-coital contraception when used within 72-120 hours
   2. Dose as low as 10mg x 1 was as effective as single 600mg dose
   3. Low dose (10mg) associated with more rapid return of normal menses
   4. Single 10mg dose mifepristone as effective any LNG regimen, similar side effects [50]
4. Investigational for induction of labor

R. Post-Coital Contraception [7]

1. Average risk of conception following intercourse is 10-33%
2. Most methods prevent initiation of a pregnancy
3. Efficacy is 60-80% for estrogen-progestin; 100% for mefepristone
4. Methods of Post-Coital Contraception [40]
   1. FDA approved Preven® emergency contraceptive kit now available
   2. This kit has 4 pills each containing 50µg ethenyl estradiol and 0.25mg levonorgestrel
   3. First dose of each medication should be given within 72 hours of intercourse
   4. Estrogen (100µg ethinyl estradiol) + L-norgestrel (0.5mg) given twice 12 hours apart
   5. Pregnancy test should be performed BEFORE using this emergency contraceptive method
   6. Two doses of 0.75mg levonorgestrel (Plan B®) taken 12 hours part more effective than combination pills (1.1% versus 3.2% pregnancy rates) [41,52]
   7. Plan B® has received FDA advisory approval for over the counter sales but awaits full FDA marketing approval [52]
   8. Single dose of 4 pills (50µg ethinyl estradiol + 0.25mg L-norgestrel each pill) reduced doctor's visits, emergency room visits, and number of unwanted pregnancies [42]
   9. This single dose of 4 pills was safe as well as effective
   10. Single dose 600mg mifepristone may be effective
   11. Copper intrauterine device may be inserted within 5 days of intercourse
5. For patients on OCPs who miss a pill:
   1. If pill missed <12 hours prior to intercourse, take missed pill and continue normally
   2. If pill missed >12 hours prior to intercourse, take most recent pill, discard any earlier missed pills, use extra precautions (such as a condom) for one week
   3. For case (b), if 7 or more pills left in packet, maintain usual break before next packet
   4. For case (b), if fewer than 7 pills left, skip the break and start next packet next day
6. Estimated that these methods could prevent up to 2 million unwanted conceptions
7. These methods do not affect an already developing fetus
8. No medical contraindications to use of emergency (post-coital) contraception
9. Mifepristone is also highly effective when used within 120 hours [39]
10. Making emergency contraception packets available over the counter being considered [7]

References

1. Kubba A, Guillebaud J, Anderson RA, MacGregor EA. 2000. Lancet. 356(9245):1913
2. Petitti DB. 2003. NEJM. 349(15):1443
3. Stewart FH, Harper CC, Ellertson CE, et al. 2001. JAMA. 285(17):2232
4. Oral Contraceptives. 2000. Med Let. 42(1078):42
5. Barrier Contraceptive Methods. 1995. Med Let. 37(941):9
6. Peterson HB and Curtis KM. 2005. NEJM. 353(20):2169
7. Grimes DA and Raymond EG. 2002. Ann Intern Med. 137(3):180
8. Sanchez-Guerrero J, Uribe AG, Jimenez-Santana L, et al. 2005. NEJM. 353(24):2539
9. Petri M, Kim MY, Kalunian KC, et al. 2005. NEJM. 353(24):2550
10. Vessey M, Painter R, Yeates D, et al. 2003. Lancet. 362(9379):185
11. Collaborative Group on Epidemiological Studies of Ovarian Cancer. 2008. Lancet. 371(9609):303
12. Grabrick DM, Hartmann LC, Cerhan JR, et al. 2000. JAMA. 284(14):1791
13. Smith JS, Green J, de Gonzalez AB, et al. 2003. Lancet. 361(9364):1159
14. New Oral Contraceptives. 2006. Med Let. 48(1244):77
15. Winer RL, Hughes JP, Feng Q, et al. 2006. NEJM. 354(25):2645
16. International Collab of Epidemiol Studies in Cervical Cancer. 2007. Lancet. 370(9599):1609
17. Lybrel Continuous Oral Contraceptive. 2007. Med Let. 49(1266):61
18. Gillum LA, Mamidipudi SK, Johnston SC. 2000. JAMA. 284(1):72
19. Kaunitz AM. 2008. NEJM. 358(12):1262
20. WHO Collaborative Study. 1996. Lancet. 348:498
21. Schwartz SM, Siscovick DS, Longstreth WT Jr, et al. 1997. Ann Intern Med. 127(8):596
22. WHO Collaborative Study. 1996. Lancet. 348:505
23. French JA and Pedley TA. 2008. NEJM. 359(2):166
24. Farmer RDT, Lawrenson RA, Thompson CR, et al. 1997. Lancet. 349:83
25. Seibert C, Barbouche E, Fagan J, et al. 2003. Ann Intern Med. 138(1):54
26. Rosing J, Middeldorp S, Curvers J, et al. 1999. Lancet. 354(9195):2036
27. Mandel H, Brenner B, Berant M, et al. 1996. NEJM. 334(12):763
28. Martinelli I, Sacchi E, Landi G, et al. 1998. NEJM. 338(25):1793
29. Middeldorp S, Henkens CMA, Koopman MMW, et al. 1998. Ann Intern Med. 128(1):15
30. Von Hertzen H, Piaggio G, Ding J, et al. 2002. Lancet. 360(9348):1803
31. Task Force on Postovulatory Methods of Fertility Regulation. 1998. Lancet. 352(9126):428
32. Roddy RE, Zekeng L, Ryan KA, et al. 1998. NEJM. 339(8):504
33. Walsh T, Grimes D, Frezieres R, et al. 1998. Lancet. 351(9108):1005
34. Grimes DA. 2000. Lancet. 356(9234):1013
35. Progesterone Releasing Intrauterine Device. 2001. Med Let. 43(1096):7
36. Female Condom. 1993. Med Let. 35(912):123
37. Mifepristone (RU 486). 2000. Med Let. 42(1091):101
38. Christiansen SC, Cannegieter SC, Koster T, et al. 2005. JAMA. 293(19):2352
39. Task force on Postovulatory Methods of Fertility Regulation. 1999. Lancet. 353(9154):697
40. Emergency Contraceptive Kit. 1998. Med Let. 40(1038):101
41. Plan B: Progestin-Only Emergency Contraceptive. 2000. Med Let. 42(1070):10
42. Glasier A and Baird D. 1998. NEJM. 338(1):1
43. Vandenbroucke JP, Rosing J, Bloemenkamp KWM, et al. 2001. NEJM. 344(20):1527
44. Wald A, Langenberg AGM, Link K, et al. 2001. JAMA. 285(24):3100
45. Hubacher D, Lara-Ricalde R, Taylor DJ, et al. 2001. NEJM. 345(8):561
46. Ortho Evra Contraceptive Patch. 2002. Med Let. 44(1122):8
47. Roddy RE, Zekeng L, Ryan KA, et al. 2002. JAMA. 287(9):1117
48. Yasmin. 2002. Med Let. 44(1133):55
49. Marchbanks PA, McDonald JA, Wilson HG, et al. 2002. NEJM. 346(26):2025
50. Audet MC, Moreau M, Koltun WD, et al. 2001. JAMA. 285(18):2347
51. Van Damme L, Ramjee G, Alary M, et al. 2002. Lancet. 360(9338):971
52. Emergency Contraception Over the Counter. 2004. Med Let. 46(1175):11
53. Seasonale Extended Cycle OCP. 2004. Med Let. 46(1175):9
54. Wald A, Langenberg AGM, Krantz E, et al. 2005. Ann Intern Med. 145(10):707
55. Progestin Implant (Implanon). 2006. Med Let. 48(1245):83