Contraception Choices in Women with Underlying Medical Conditions

RACHEL A. BONNEMA; MEGAN C. McNAMARA; ABBY L. SPENCER

RACHEL A. BONNEMA, MD, MS, MEGAN C. MCNAMARA, MD, MSc, AND ABBY L. SPENCER, MD, MS

The online version of this article has been updated to clarify that it reviews hormonal contraceptives only. In addition, one contraceptive has been added to Table 1.

Am Fam Physician. 2010;82(6):621-628

Author disclosure: Nothing to disclose

Primary care physicians often prescribe contraceptives to women of reproductive age with comorbidities. Novel delivery systems (e.g., contraceptive patch, contraceptive ring, single-rod implantable device) may change traditional risk and benefit profiles in women with comorbidities. Effective contraceptive counseling requires an understanding of a woman's preferences and medical history, as well as the risks, benefits, adverse effects, and contraindications of each method. Noncontraceptive benefits of combined hormonal contraceptives, such as oral contraceptive pills, include regulated menses, decreased dysmenorrhea, and diminished premenstrual dysphoric disorder. Oral contraceptive pills may be used safely in women with a range of medical conditions, including well-controlled hypertension, uncomplicated diabetes mellitus, depression, and uncomplicated valvular heart disease. However, women older than 35 years who smoke should avoid oral contraceptive pills. Contraceptives containing estrogen, which can increase thrombotic risk, should be avoided in women with a history of venous thromboembolism, stroke, cardiovascular disease, or peripheral vascular disease. Progestin-only contraceptives are recommended for women with contraindications to estrogen. Depo-Provera, a long-acting injectable contraceptive, may be preferred in women with sickle cell disease because it reduces the frequency of painful crises. Because of the interaction between antiepileptics and oral contraceptive pills, Depo-Provera may also be considered in women with epilepsy. Implanon, the single-rod implantable contraceptive device, may reduce symptoms of dysmenorrhea. Mirena, the levonorgestrelcontaining intrauterine contraceptive system, is an option for women with menorrhagia, endometriosis, or chronic pelvic pain.

Nearly one half of all pregnancies in the United States are unplanned.¹ An unintended pregnancy can have serious health consequences in women with chronic medical conditions. Certain diseases can be worsened by pregnancy or are associated with adverse outcomes.² Moreover, medications used to treat many chronic conditions are potentially teratogenic.³

Clinical recommendation	Evidence rating	References
OCPs may be considered in healthy, nonsmoking women older than 35 years if there are no other contraindications to combined hormonal contraceptives.	C	⁶, ⁹, ³⁵, ³⁶
OCPs may be considered in women who have migraine headaches without aura if they do not have focal neurologic symptoms, do not smoke, are younger than 35 years, and are otherwise healthy.	C	⁶, ⁹, ⁴⁴, ⁴⁵
OCPs appear to be safe in women with stable or inactive systemic lupus erythematosus who do not have antiphospholipid antibodies.	C	⁶, ⁸, ⁹
Injectable long-acting progestin (depot medroxyprogesterone acetate [Depo-Provera]) is an appropriate contraceptive option for women with sickle cell disease and has been shown to reduce painful crises.	C	⁵⁸, ⁵⁹
Injectable long-acting progestin is associated with a loss in bone mineral density; however, the length of use does not need to be restricted because the loss is reversible with discontinuation.	C	⁶, ⁹, ^66–70
The single-rod implantable contraceptive device (Implanon) may be used to decrease symptoms of dysmenorrhea.	C	⁷², ⁷³

Despite this, women with comorbidities may not receive adequate counseling on contraceptive methods. For example, in a study at an urban epilepsy center, 50 percent of women experienced unplanned pregnancies.⁴ Almost 17 percent of these women were taking antiepileptic drugs that reduce the effectiveness of hormonal contraceptives. Additionally, women with diabetes mellitus rarely receive contraceptive counseling during ambulatory visits,⁵ even though poor preconception glycemic control can be associated with adverse outcomes.²

In 2006, the American College of Obstetricians and Gynecologists (ACOG) published guidelines for the use of hormonal contraceptives in women with comorbidities.⁶ Since its publication, new contraceptive products have been approved by the U.S. Food and Drug Administration, and new data about the risks of the contraceptive patch (Ortho Evra) and the long-acting injectable progestin, depot medroxyprogesterone acetate (Depo-Provera), have emerged.

[ corrected] Although women of reproductive age with comorbidities may prefer, or be more appropriate for, nonpharmacologic family planning options, such as fertility awareness-based methods or barrier contraceptives, this article focuses on the prescription of hormonal contraceptives. Understanding the indications, benefits, and risks of these products, as well as patient preferences, will help physicians match patients with the contraceptive method best for them. Table 1 provides a summary of hormonal contraceptive options.⁷ Table 2 lists contraceptive methods to consider and those to avoid in women with comorbidities.^6,8–13

Contraceptive	Duration	Reversibility	Cost of generic (brand)*	Failure rate (%)	Adverse effects	Candidates
Combination estrogen-progestin†
Traditional OCPs	Daily pill	Immediate	$30 ($62) per month‡	3 to 8	Spotting, nausea, headache, breast tenderness, breakthrough bleeding, VTE, stroke, MI	Women with dysmenorrhea, menorrhagia, irregular menstrual periods, acne, hirsutism, or polycystic ovary syndrome
Traditional OCPs	Daily pill	Immediate	$30 ($62) per month‡	3 to 8		Drospirenone-containing OCPs may offer enhanced benefit to women with acne, hirsutism, or evidence of polycystic ovary syndrome
Extended-cycle OCPs	Daily pill	Immediate	NA ($42) per month	3 to 8	Spotting, increased unscheduled bleeding, nausea, VTE, stroke, MI	Women who do not want monthly periods
Extended-cycle OCPs	Daily pill	Immediate	NA ($42) per month	3 to 8		Fewer withdrawal bleeds per year and shorter hormone-free interval may benefit women with estrogen withdrawal symptoms, dysmenorrhea, or endometriosis
Contraceptive patch (Ortho Evra)	Weekly application	Immediate	NA ($82) per month	3 to 8§	Site reaction, VTE, stroke, MI	Women unable to take OCPs
Contraceptive ring (Nuvaring)	Monthly insertion	Immediate	NA ($83) per month	3 to 8	Vaginal discharge, vaginal discomfort, VTE, stroke, MI	Women unable to take OCPs; women who are obese
Progestin-only
Norethindrone (Micronor) [ corrected]	Daily pill	Immediate	$36 ($50)	3 to 10\|\|	Irregular bleeding	Women with contraindication to estrogen, seizure disorder, hypercoagulable states, dysmenorrhea, or migraine headaches with aura; women who want long-term contraception
Long-acting injectable (depot medroxyprogesterone acetate [Depo-Provera])	14 weeks	May be delayed	$50 ($95) per injection	3	Irregular bleeding, decreased bone mineral density
Single-rod implantable device (Implanon)	Up to three years	Immediate	NA ($500 to 750)	0.05	Irregular bleeding
Levonorgestrel-containing intrauterine system (Mirena)	Up to five years	Immediate	NA ($400 to 750)	0.8	Irregular bleeding

Comorbidity or risk factor		Methods to consider	Methods to avoid
Depression		Combination OCPs; Depo-Provera (long-acting injectable); Implanon (single-rod implantable device); Mirena (levonorgestrel-containing intrauterine system); Nuvaring (ring); Ortho Evra (patch); progestin-only OCPs	—
Diabetes mellitus with complications		Depo-Provera; Implanon; Mirena; progestin-only OCPs	Combination OCPs; Nuvaring; Ortho Evra
Epilepsy treated with medications that induce hepatic enzymes:		Depo-Provera; Mirena	Combination OCPs; Implanon; Nuvaring; Ortho Evra; progestin-only OCPs
	Carbamazepine (Tegretol); lamotrigine* (Lamictal); oxcarbazepine (Trileptal); phenobarbital; phenytoin (Dilantin); primidone (Mysoline); topiramate (Topamax; more than 200 mg per day)	Depo-Provera; Mirena
Epilepsy treated with medications that do not induce hepatic enzymes:		Combination OCPs; Depo-Provera; Implanon; Mirena; Nuvaring; Ortho Evra; progestin-only OCPs	—
	Acetazolamide; benzodiazepines; ethosuximide (Zarontin); gabapentin (Neurontin); levetiracetam (Keppra); pregabalin (Lyrica); tiagabine (Gabitril); valproic acid† (Depakene); vigabatrin (Sabril); zonisamide (Zonegran)		—
History of bariatric surgery (malabsorptive procedure)		Depo-Provera; Implanon; Mirena; Nuvaring; Ortho Evra	Combination OCPs; progestin-only OCPs
History of bariatric surgery (restrictive procedure)		Combination OCPs; Depo-Provera; Implanon; Mirena; Nuvaring; Ortho Evra; progestin-only OCPs	—
History of VTE/pulmonary embolism		Depo-Provera; Implanon; Mirena; progestin-only OCPs	Combination OCPs; Nuvaring; Ortho Evra
Inflammatory bowel disease (mild)‡		Combination OCPs; Depo-Provera; Implanon; Mirena; Nuvaring; Ortho Evra; progestin-only OCPs	—
Migraine headaches with aura		Depo-Provera; Implanon; Mirena; progestin-only OCPs	Combination OCPs; Nuvaring; Ortho Evra
Poorly controlled hypertension		Depo-Provera; Implanon; Mirena; progestin-only OCPs	Combination OCPs; Nuvaring; Ortho Evra
Rheumatoid arthritis (in patients taking immunosuppressants)		Combination OCPs; Implanon; Mirena; Nuvaring; Ortho Evra; progestin-only OCPs	Depo-Provera§
Smoking and age older than 35 years		Depo-Provera; Implanon; Mirena; progestin-only OCPs	Combination OCPs; Nuvaring; Ortho Evra
Stroke		Depo-Provera; Implanon; Mirena; progestin-only OCPs	Combination OCPs; Nuvaring; Ortho Evra
Systemic lupus erythematosus with antiphospholipid antibodies		Depo-Provera; Implanon; Mirena; progestin-only OCPs	Combination OCPs; Nuvaring; Ortho Evra

Combined Hormonal Contraceptives

Oral contraceptive pills (OCPs) have been widely used in the United States for decades because of the contraceptive and noncontraceptive benefits of combined hormonal contraceptives. Many women want the noncontraceptive benefits of combined hormonal contraceptives, such as regulated menses, decreased dysmenorrhea, and diminished premenstrual dysphoric disorder. However, combined hormonal contraceptives are not appropriate for every patient. Before prescribing OCPs, physicians should obtain a complete medical history to determine whether OCPs may benefit patients or put them at increased risk of adverse events, such as stroke or venous thromboembolism (VTE). Most contraindications to OCPs can be ruled out during the history. Although a pelvic examination is not necessary before prescribing combined hormonal contraceptives,¹⁴ a focused physical examination that includes blood pressure measurement and evaluation for signs of hyperandrogenism, such as hirsutism or acne, may guide the contraceptive decision.

The noncontraceptive benefits of OCPs, as well as the established cardiovascular risks and common adverse effects, have been discussed elsewhere.^15,16 Some risks of OCPs may be enhanced and some benefits may be negated in women with comorbidities. For example, OCPs containing 35 mcg of estrogen or less are optimal in most women to reduce the risks and adverse effects of estrogen. However, women with seizure disorders are an exception. The World Health Organization (WHO) recommends that women taking antiepileptic medications not be prescribed OCPs containing less than 30 mcg of estrogen because certain anticonvulsants can decrease the effectiveness of combined hormonal contraceptives.⁹

Many contraindications to combined hormonal contraceptives are caused by the estrogen component. Although the estrogen schedule may differ depending on the delivery (i.e., oral, transdermal, or intravaginal), the risks and benefits are grouped together in the WHO's updated 2009 medical eligibility criteria for contraceptive use.⁹ Several extended-cycle OCPs that shorten or eliminate the hormone-free interval have been developed to better manage common menstrual symptoms (e.g., headaches, tiredness, bloating, excessive bleeding, menstrual pain), as well as to improve OCP compliance through better symptom management.^17–33 However, a systematic review of extended-cycle versus traditional 28-day–cycle OCPs found similar effectiveness and safety, and no difference in adherence.²⁴ For the purpose of this article, unless otherwise stated, the risks and benefits of traditional OCPs can be extrapolated to extended-cycle OCPs, the contraceptive patch, and the contraceptive ring (Nuvaring).

Combined hormonal contraceptives can be used safely in women with a range of medical conditions, including well-controlled hypertension, uncomplicated diabetes, depression, uncomplicated valvular heart disease, migraine headaches without aura, systemic lupus erythematosus without antiphospholipid antibodies, human immunodeficiency virus (HIV) infection, thyroid disease, anemia, and uncomplicated liver disease.^6,9

Table 3 lists selected contraindications to combined hormonal contraceptives.^6,8,9,34 The contraindications in the WHO medical eligibility criteria for OCPs differ from those in the Physicians' Desk Reference³⁴; according to the WHO, women who have systemic lupus erythematosus with antiphospholipid antibodies or unknown antibody results should avoid using combined hormonal contraceptives.⁹ Instead of listing contraindications, ACOG designates patients in whom progestin-only methods may be appropriate, such as in women older than 35 years who smoke or are obese.⁶

AGE

Combined hormonal contraceptives are generally safe in healthy women older than 35 years who do not smoke, provided that there are no other contraindications.⁶ Data from U.S. trials suggest that stroke and myocardial infarction risks for OCP users compared with nonusers are similar in younger and older nonsmoking women.^35,36

HYPERTENSION

Many risks of combined hormonal contraceptives, such as VTE and, less commonly, myocardial infarction or stroke, are related to the effects of estrogen on the cardiovascular system. These risks are increased in women older than 35 years who smoke. OCPs have been shown to elevate systolic and diastolic blood pressures by about 8 and 6 mm Hg, respectively.³⁷ Caution should be used in women with elevated blood pressures, especially those older than 35 years. Guidelines from the WHO and ACOG suggest that the risks of OCPs outweigh the benefits in patients with poorly controlled hypertension.^6,9

The risks of myocardial infarction and stroke in women with medically controlled hypertension who use OCPs are not known. However, ACOG and WHO guidelines recommend a trial of OCPs in women with well-controlled hypertension who are otherwise healthy and who do not have other contraindications to combined hormonal contraceptives. ^6,9 Drospirenone-containing hormone combinations have been shown to modestly lower systolic and diastolic blood pressures in postmenopausal women,^38–40 but these effects have not been shown in women of reproductive age. A third-generation OCP or progestin-only contraceptives may lower cardiovascular risk in women with hypertension.^41–43 The relative risk of myocardial infarction and stroke remains high in women with hypertension who use OCPs and smoke, or who have uncontrolled diabetes or hypercholesterolemia. Progestin-only methods may be more appropriate in these women.^6,44,45

DIABETES

ACOG recommends that the use of OCPs in women with diabetes be limited to women younger than 35 years who do not smoke; are otherwise healthy; and show no evidence of hypertension, nephropathy, retinopathy, or other vascular disease.⁶

MIGRAINE HEADACHES

There does not appear to be an increased risk of stroke in healthy, nonsmoking women taking OCPs containing 35 mcg of estrogen or less.⁶ However, migraine headaches with aura have been associated with up to a twofold increased risk of stroke in otherwise healthy women taking OCPs.^46,47 Smoking further increases this risk.⁴⁶

For this reason, migraine headache with aura is a contraindication to combined hormonal contraceptives. Stroke risk is not increased in patients with migraine without aura; therefore, combined hormonal contraceptives is not contraindicated unless the patient has other major risk factors for stroke (e.g., smoking, hypertension, diabetes) or unless the patient's headaches are exacerbated when OCPs are started.^6,9,47 In general, OCPs may be cautiously considered in women who have migraine headaches if they do not have focal neurologic symptoms (such as aura), do not smoke, are younger than 35 years, and are otherwise healthy.^6,9,44,45

OBESITY

Obesity can complicate the choice of contraceptives for several reasons. For example, data suggest that certain OCPs and the contraceptive patch may have limited effectiveness in women who are obese.^48,49 Additionally, obesity is an independent risk factor for cardiovascular disease and VTE, and exposure to excess estrogen in these women may further increase their risk.^49,50 The WHO considers the benefits of OCPs in this population to be greater than the harms,⁹ although ACOG suggests that a progestin-only method may be safer.⁶ Weight has not been shown to change the effectiveness of the contraceptive ring⁵¹ or extended-cycle OCPs.²⁸ If the decision is made to prescribe OCPs to a patient who is obese, the physician should assess for comorbidities that would preclude her from using OCPs, such as severe hypertension or uncontrolled diabetes.

VENOUS THROMBOEMBOLISM

Although OCPs can increase the risk of VTE in all users, risk is especially high in women with a history of VTE, women with antiphospholipid antibodies, or women who are undergoing major surgery with an anticipated period of prolonged immobilization.⁹ The risk of VTE may also be higher in women who use OCPs that contain specific third-generation progestins, such as desogestrel and gestodene.^52–54 There have been conflicting data about an increased risk of VTE in women who use the contraceptive patch; the risk may be slightly increased or equivalent to the risk of VTE in women who use OCPs.^55–57 Although there are no recommendations to alter prescribing habits at this time, these risks should be balanced with the risk of pregnancy and pregnancy-related complications.

SYSTEMIC LUPUS ERYTHEMATOSUS

Use of OCPs in women with stable or inactive systemic lupus erythematosus does not appear to increase mild or severe flare-ups.⁸ If vascular disease, nephritis, or antiphospholipid antibodies are present, progestin-only methods are more appropriate.⁶

Progestin-Only Methods

LONG-ACTING INJECTABLE CONTRACEPTIVE

Depo-Provera is a highly effective, injectable, progestinonly contraceptive that is safe in women with a contraindication to estrogen (e.g., a history of cardiovascular disease, stroke, VTE, peripheral vascular disease).^2,6 Women with sickle cell disease may note a decrease in sickling or painful crises with Depo-Provera use.^58,59 Certain antiepileptic drugs (e.g., carbamazepine [Tegretol], oxcarbazepine [Trileptal], phenobarbital, phenytoin [Dilantin], topiramate [Topamax]) induce hepatic metabolism of estrogen and progestin, potentially leading to contraceptive failure in women taking OCPs.¹⁰ Conversely, lamotrigine (Lamictal) levels are reduced in patients taking OCPs, which may lead to an increase in seizures.^11,60 Depo-Provera is effective in women taking enzyme-inducing antiepileptics, although there are some recommendations that the injection frequency be increased to every 10 weeks.^10,11 Additionally, progestins may decrease seizure frequency.⁶¹

Data are conflicting regarding the effects of Depo-Provera on depression.^62,63 ACOG has concluded that Depo-Provera does not worsen depressive symptoms.⁶ Depo-Provera reduces serum estradiol levels, which can adversely affect bone health.⁶⁴ In 2004, the U.S. Food and Drug Administration issued a boxed warning associating

Depo-Provera use with loss of bone mineral density, and recommended that its use be limited to less than two years.⁶⁵ In 2006, a seven-year, prospective matched cohort study in young women showed that those who used Depo-Provera had substantial bone mineral density loss, but the loss was reversible with discontinuation of use.⁶⁶ Systematic reviews in 2006 and 2008 reached the same conclusion about the reversibility of bone mineral density loss.^67,68

The WHO has recommended that there be no restriction on the use of Depo-Provera in women 18 to 45 years of age, and that the benefits likely outweigh the harms in women outside that age group.⁶⁹ Physicians should counsel patients about the risk of bone mineral density loss, but reassure them about reversibility with discontinuation. No evidence exists to support routine bone mineral density assessment in women who use Depo-Provera.^6,70

SINGLE-ROD IMPLANTABLE CONTRACEPTIVE DEVICE

The single-rod implantable contraceptive device containing etonogestrel (Implanon) is inserted subdermally in the upper arm and remains active for three years.⁷¹ It has been available for more than 10 years, but has been widely marketed in the United States only since 2007. Insertion and removal of the implant requires specific training by the manufacturer.

Implanon has been shown to be beneficial in women with dysmenorrhea. One study found that it is associated with a decrease in symptoms in 80 percent of women.⁷² ACOG has suggested that the contraceptive implant may be used for dysmenorrhea.⁷³

WHO guidelines consider Implanon to be a contraceptive option in women with a history of hypertension, diabetes, VTE, cardiovascular disease or stroke, migraine headaches (with or without aura), seizure disorder, sickle cell disease, or HIV infection.⁹

LEVONORGESTREL-CONTAINING INTRAUTERINE CONTRACEPTIVE SYSTEM

The levonorgestrel-containing intrauterine contraceptive system (Mirena) has been reviewed previously,⁷⁴ but is another option for women with contraindications to estrogen who want long-term contraception.^6,9 It may be considered specifically in women with menorrhagia, endometriosis, or chronic pelvic pain.⁷⁴

Finer LB, Henshaw SK. Disparities in rates of unintended pregnancy in the United States, 1994 and 2001. Perspect Sex Reprod Health. 2006;38(2):90-96.

Frederiksen MC. Depot medroxyprogesterone acetate contraception in women with medical problems. J Reprod Med. 1996;41(5 suppl):414-418.

Schwarz EB, Postlethwaite DA, Hung YY, Armstrong MA. Documentation of contraception and pregnancy when prescribing potentially teratogenic medications for reproductive-age women. Ann Intern Med. 2007;147(6):370-376.

Davis AR, Pack AM, Kritzer J, Yoon A, Camus A. Reproductive history, sexual behavior and use of contraception in women with epilepsy. Contraception. 2008;77(6):405-409.

Schwarz EB, Maselli J, Gonzales R. Contraceptive counseling of diabetic women of reproductive age. Obstet Gynecol. 2006;107(5):1070-1074.

ACOG Committee on Practice Bulletins-Gynecology. ACOG practice bulletin. No. 73: Use of hormonal contraception in women with coexisting medical conditions. Obstet Gynecol. 2006;107(6):1453-1472.

Trussell J. Contraceptive efficacy. In: Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart FH, Kowal D. Contraceptive Technology. 19th ed. New York, NY: Ardent Media; 2007.

Petri M, Kim MY, Kalunian KC, et al.; OC-SELENA Trial. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. 2005;353(24):2550-2558.

Department of Reproductive Health, World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 4th ed. 2009, http://www.who.int/reproductivehealth/publications/family_planning/9789241563888/en/index.html. Accessed June 7, 2010.

Crawford PM. Managing epilepsy in women of childbearing age. Drug Saf. 2009;32(4):293-307.

Crawford P. Best practice guidelines for the management of women with epilepsy. Epilepsia. 2005;46(suppl 9):117-124.

Sánchez-Guerrero J, Uribe AG, Jiménez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med. 2005;353(24):2539-2549.

Centers for Disease Control and Prevention. U.S. medical eligibility criteria for contraceptive use, 2010. MMWR2010;59:1–88. http://www.cdc.gov/mmwr/pdf/rr/rr59e0528.pdf. Accessed June 7, 2010.

Stewart FH, Harper CC, Ellertson CE, Grimes DA, Sawaya GF, Trussell J. Clinical breast and pelvic examination requirements for hormonal contraception: Current practice vs evidence. JAMA. 2001;285(17):2232-2239.

ESHRE Capri Workshop Group. Noncontraceptive health benefits of combined oral contraception. Hum Reprod Update. 2005;11(5):513-525.

Cerel-Suhl SL, Yeager BF. Update on oral contraceptive pills. Am Fam Physician. 1999;60(7):2073-2084.

Yonkers KA, Brown C, Pearlstein TB, Foegh M, Sampson-Landers C, Rapkin A. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol. 2005;106(3):492-501.

Pearlstein TB, Bachmann GA, Zacur HA, Yonkers KA. Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation. Contraception. 2005;72(6):414-421.

Willis SA, Kuehl TJ, Spiekerman AM, Sulak PJ. Greater inhibition of the pituitary-ovarian axis in oral contraceptive regimens with a shortened hormone-free interval. Contraception. 2006;74(2):100-103.

Schlaff WD, Lynch AM, Hughes HD, Cedars MI, Smith DL. Manipulation of the pill-free interval in oral contraceptive pill users: the effect on follicular suppression. Am J Obstet Gynecol. 2004;190(4):943-951.

Baerwald AR, Olatunbosun OA, Pierson RA. Ovarian follicular development is initiated during the hormone-free interval of oral contraceptive use. Contraception. 2004;70(5):371-377.

Coffee AL, Kuehl TJ, Willis SA, Sulak PJ. Oral contraceptives and premenstrual symptoms: comparison of a 21/7 and extended regimen. Am J Obstet Gynecol. 2006;195(5):1311-1319.

Vandever MA, Kuehl TJ, Sulak PJ, et al. Evaluation of pituitary-ovarian axis suppression with three oral contraceptive regimens. Contraception. 2008;77(3):162-170.

Edelman AB, Gallo MF, Jensen JT, Nichols MD, Schulz KF, Grimes DA. Continuous or extended cycle vs. cyclic use of combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2005(3):CD004695.

Yonkers KA, Brown C, Pearlstein TB, Foegh M, Sampson-Landers C, Rapkin A. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol. 2005;106(3):492-501.

Fenton C, Wellington K, Moen MD, Robinson DM. Drospirenone/ethinylestradiol 3mg/20microg (24/4 day regimen): a review of its use in contraception, premenstrual dysphoric disorder and moderate acne vulgaris. Drugs. 2007;67(12):1749-1765.

Nakajima ST, Archer DF, Ellman H. Efficacy and safety of a new 24-day oral contraceptive regimen of norethindrone acetate 1 mg/ethinyl estradiol 20 micro g (Loestrin 24 Fe). Contraception. 2007;75(1):16-22.

Anderson FD, Hait H. A multicenter, randomized study of an extended cycle oral contraceptive [published correction appears in Contraception. 2004;69(2):175]. Contraception. 2003;68(2):89-96.

Wilson SA, Kudis HA. Ethinyl estradiol/levonorgestrel (Seasonale) for oral contraception [published correction appears in Am Fam Physician. 2005;72(12):2436]. Am Fam Physician. 2005;71(8):1581-1582.

Anderson FD, Gibbons W, Portman D. Safety and efficacy of an extended-regimen oral contraceptive utilizing continuous low-dose ethinyl estradiol. Contraception. 2006;73(3):229-234.

Archer DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006;74(6):439-445.

Davis AR, Kroll R, Soltes B, Haudiquet V, Constantine G, Grubb G. Return to menses after continuous use of a low-dose oral contraceptive. Obstet Gynecol. 2006;107(suppl 4):3S.

McCarthy L, Brar H. Levonorgestrel/ethinyl estradiol (Lybrel) for continuous contraception. Am Fam Physician. 2008;77(2):222-225.

Physicians' Desk Reference. 61st ed. Montvale, N.J.: Thomson PDR; 2007.

Sidney S, Siscovick DS, Petitti DB, et al. Myocardial infarction and use of low-dose oral contraceptives: a pooled analysis of 2 US studies. Circulation. 1998;98(11):1058-1063.

Schwartz SM, Petitti DB, Siscovick DS, et al. Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies. Stroke. 1998;29(11):2277-2284.

Cardoso F, Polónia J, Santos A, Silva-Carvalho J, Ferreira-de-Almeida J. Low-dose oral contraceptives and 24-hour ambulatory blood pressure. Int J Gynaecol Obstet. 1997;59(3):237-243.

Oelkers W, Foidart JM, Dombrovicz N, Welter A, Heithecker R. Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism. J Clin Endocrinol Metab. 1995;80(6):1816-1821.

White WB, Pitt B, Preston RA, Hanes V. Antihypertensive effects of drospirenone with 17beta-estradiol, a novel hormone treatment in postmenopausal women with stage 1 hypertension. Circulation. 2005;112(13):1979-1984.

Shulman LP. A review of drospirenone for safety and tolerability and effects on endometrial safety and lipid parameters contrasted with medroxyprogesterone acetate, levonorgestrel, and micronized progesterone. J Womens Health (Larchmt). 2006;15(5):584-590.

Cardiovascular disease and steroid hormone contraception. Report of a WHO Scientific Group. World Health Organ Tech Rep Ser. 1998;877:i-vii.

Heinemann LA, Assmann A, DoMinh T, Garbe E. Oral progestogen-only contraceptives and cardiovascular risk: results from the Transnational Study on Oral Contraceptives and the Health of Young Women. Eur J Contracept Reprod Health Care. 1999;4(2):67-73.

Tanis BC, van den Bosch MA, Kemmeren JM, et al. Oral contraceptives and the risk of myocardial infarction. N Engl J Med. 2001;345(25):1787-1793.

Kaunitz AM. Clinical practice. Hormonal contraception in women of older reproductive age. N Engl J Med. 2008;358(12):1262-1270.

Petitti DB. Clinical practice. Combination estrogen-progestin oral contraceptives [published correction appears in N Engl J Med. 2004;350(1):92]. N Engl J Med. 2003;349(15):1443-1450.

MacClellan LR, Giles W, Cole J, et al. Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study. Stroke. 2007;38(9):2438-2445.

Becker WJ. Use of oral contraceptives in patients with migraine. Neurology. 1999;53(4 suppl 1):S19-S25.

Holt VL, Scholes D, Wicklund KG, Cushing-Haugen KL, Daling JR. Body mass index, weight, and oral contraceptive failure risk. Obstet Gynecol. 2005;105(1):46-52.

Zieman M, Guillebaud J, Weisberg E, Shangold GA, Fisher AC, Creasy GW. Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data. Fertil Steril. 2002;77(2 suppl 2):S13-S18.

Nightingale AL, Lawrenson RA, Simpson EL, Williams TJ, MacRae KD, Farmer RD. The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives. Eur J Contracept Reprod Health Care. 2000;5(4):265-274.

Westhoff C. Higher body weight does not affect NuvaRing's efficacy. Obstet Gynecol. 2005;105(suppl 4):56S.

Walker AM. Newer oral contraceptives and the risk of venous thromboembolism. Contraception. 1998;57(3):169-181.

Hennessy S, Berlin JA, Kinman JL, Margolis DJ, Marcus SM, Strom BL. Risk of venous thromboembolism from oral contraceptives containing gestodene and desogestrel versus levonorgestrel: a meta-analysis and formal sensitivity analysis. Contraception. 2001;64(2):125-133.

Kemmeren JM, Algra A, Grobbee DE. Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. BMJ. 2001;323(7305):131-134.

Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception. 2006;73(3):223-228.

Jick S, Kaye JA, Li L, Jick H. 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(1):4-7.

Cole JA, Norman H, Doherty M, Walker AM. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users [published correction appears in Obstet Gynecol. 2008;111(6)1449]. Obstet Gynecol. 2007;109(2 pt 1):339-346.

Manchikanti A, Grimes DA, Lopez LM, Schulz KF. Steroid hormones for contraception in women with sickle cell disease. Cochrane Database Syst Rev. 2007(2):CD006261.

de Abood M, de Castillo Z, Guerrero F, Espino M, Austin KL. Effect of Depo-Provera or Microgynon on the painful crises of sickle cell anemia patients. Contraception. 1997;56(5):313-316.

Schwenkhagen AM, Stodieck SR. Which contraception for women with epilepsy?. Seizure. 2008;17(2):145-150.

Mattson RH, Rebar RW. Contraceptive methods for women with neurologic disorders. Am J Obstet Gynecol. 1993;168(6 pt 2):2027-2032.

Westhoff C, Truman C, Kalmuss D, et al. Depressive symptoms and Depo-Provera. Contraception. 1998;57(4):237-240.

Civic D, Scholes D, Ichikawa L, et al. Depressive symptoms in users and non-users of depot medroxyprogesterone acetate. Contraception. 2000;61(6):385-390.

Haider S, Darney PD. Injectable contraception. Clin Obstet Gynecol. 2007;50(4):898-906.

Kaunitz AM. Depo-Provera's black box: time to reconsider?. Contraception. 2005;72(3):165-167.

Kaunitz AM, Miller PD, Rice VM, Ross D, McClung MR. Bone mineral density in women aged 25–35 years receiving depot medroxyprogesterone acetate: recovery following discontinuation. Contraception. 2006;74(2):90-99.

Curtis KM, Martins SL. Progestogen-only contraception and bone mineral density: a systematic review. Contraception. 2006;73(5):470-487.

Kaunitz AM, Arias R, McClung M. Bone density recovery after depot medroxyprogesterone acetate injectable contraception use. Contraception. 2008;77(2):67-76.

WHO statement on hormonal contraception and bone health. Geneva: WHO; July 2005. http://www.who.int/reproductivehealth/publications/family_planning/hc_bone_health/en/index.html. Accessed July 7, 2010.

Guilbert ER, Brown JP, Kaunitz AM, et al. The use of depotmedroxyprogesterone acetate in contraception and its potential impact on skeletal health. Contraception. 2009;79(3):167-177.

A new progestin implant (Implanon) for long-term contraception. Obstet Gynecol. 2007;109(4):990-991.

Funk S, Miller MM, Mishell DR, et al.; Implanon US Study Group. Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel. Contraception. 2005;71(5):319-326.

ACOG Practice Bulletin No. 110: noncontraceptive uses of hormonal contraceptives. Obstet Gynecol. 2010;115(1):206-218.

McCarthy L. Levonorgestrel-releasing intrauterine system (Mirena) for contraception. Am Fam Physician. 2006;73(10):1799-1806.