REVIEW

Helping Women Choose Appropriate Hormonal Contraception: Update on Risks, Benets, and Indications
Abby L. Spencer, MD, MS,a Rachel Bonnema, MD, MS,b Megan C. McNamara, MD, MScc
a

Department of Medicine, Section of General Internal Medicine, Allegheny General Hospital, Pittsburgh, Pa; bDepartment of Medicine, Section of General Internal Medicine, University of Nebraska Medical Center, Omaha; and cDepartment of Medicine, Section of General Internal Medicine, Case Western Reserve University, Cleveland, Ohio.

ABSTRACT Primary care physicians frequently provide contraceptive counseling to women who are interested in family planning, have medical conditions that may be worsened by pregnancy, or have medical conditions that necessitate the use of potentially teratogenic medications. Effective counseling requires up-to-date knowledge about hormonal contraceptive methods that differ in hormone dosage, cycle length, and hormone-free intervals and are delivered by oral, transdermal, transvaginal, injectable, or implantable routes. Effective counseling also requires an understanding of a womans preferences and medical history as well as the risks, benets, side effects, and contraindications of each contraceptive method. This article is designed to update physicians on this information. 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 497-506 KEYWORDS: Contraception; Contraception counseling; Contraceptive choice; Womens health

The rate of unintended pregnancies in the United States is nearly 1 in 5 for women of all ages and 1 in 10 for women aged 18-24 years.1 Because primary care physicians routinely provide treatment for a variety of medical conditions, including conditions that may be adversely affected by pregnancy and conditions that necessitate the use of potentially teratogenic drugs,2 it is important for them to have a thorough knowledge of contraceptive methods. Women today have the option of using new types of oral contraceptives that differ from traditional types in terms of hormone dosages, cycle length, and hormone-free intervals. They also have the option of using contraceptives with a variety of hormone delivery systems, including transdermal, transvaginal, injectable, and implantable devices. In this review, we discuss newer contraceptives and give special consideration to their use by women with medical disorders.
Funding: None. Conict of Interest: None. Authorship: Each author was involved in the conception, design, and the writing of the manuscript, and approved the submitted version of the manuscript. Requests for reprints should be addressed to Abby L. Spencer, MD, MS, Department of Medicine, Division of General Internal Medicine, Allegheny General Hospital, 320 East North Avenue, Pittsburgh, PA 15212. E-mail address: aspence1@wpahs.org

Intrauterine devices or systems may be appropriate for many women seeking effective long-term contraception but are beyond the scope of this article which focuses primarily on newer hormonal methods. We present 3 clinical vignettes and use the vignettes to discuss controversies about benets and risks associated with different contraceptive methods.

CASE 1
A 27-year-old woman presents to you for advice about contraception. She says she would be willing to take oral contraceptive pills on a daily basis. She typically experiences bloating and pain for 3 days before her menses and reports that her menstrual ow is heavy and lasts for 6 days. She smokes a pack of cigarettes a week, and her mother had breast cancer at the age of 65 years.

How Do Oral Contraceptive Pills Work?

Oral contraceptive pills are agents that contain estrogen (ethinyl estradiol) and a progestin. They work primarily by preventing the surge of luteinizing hormone and thereby preventing ovulation, but they also thicken the cervical mucus and alter the endometrial lining to help prevent fertilization or implantation. Failure rates of oral contraceptive pills vary from 0.3% with perfect use to 8%

0002-9343/$ -see front matter 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2009.01.016

498 with typical use.3 It is important to counsel patients about failure rates and to remind them that oral contraceptive pills do not offer protection against sexually transmitted diseases.

The American Journal of Medicine, Vol 122, No 6, June 2009

What Are the Noncontraceptive Benets of Oral Contraceptive Pills?

Oral contraceptive pills are often considered the rst-line treatment for women with dysfunctional uterine bleeding. In case 1, oral contraceptive pill use may minimize the patients dysmenorrhea and menorWhat Are the Side Effects rhagia, offer her improved cycle of and Contraindications control and regularity, and thereby CLINICAL SIGNIFICANCE for Oral Contraceptive reduce the risk of iron-deciency Combination contraceptives are availanemia. Indeed, oral contraceptive Pills? able in low estrogen dosages, new forpills provide several noncontraThe most common side effects of ceptive benets.12 For example, mulations (transdermal patch and intraoral contraceptive pills are nauthey reduce the risks for endomesea, headache, breast tenderness, vaginal ring), and with new progestin triosis, ovulatory pain, ovarian and breakthrough bleeding. A types, taken in cycles ranging from 21-84 cysts, benign breast disease, premore serious but less common days for improved efcacy and managemenstrual syndrome, premenstrual side effect is venous thromboemment of cycles/side effects. dysphoric disorder,13 and ovarian bolism. On the one hand, the risk Depo-Provera is a safe method of conand endometrial cancer.14,15 They of venous thromboembolism astraception for women with medical coalso might improve acne, hirsutism, sociated with oral contraceptive and other manifestations of polymorbidities, although it may result in a pill use is lower than the risk of cystic ovary syndrome. The imvenous thromboembolism assoreversible decrease in bone mineral provement occurs secondary to an ciated with pregnancy, and the density. increase in the level of sex-horabsolute risk of venous thrombo Implanon is a new, highly effective immone-binding globulin, which reembolism among oral contracepplantable progestin-only contraceptive. duces circulating free testosterone tive pill users is small. On the and ameliorates many androgenic other hand, the risk of venous effects. thromboembolism is 4 times as 4 high in oral contraceptive pill users as in nonusers. What are Appropriate Contraceptive Options Among oral contraceptive pill users, venous thromboem4 for Her Based on Her Symptoms and bolism risk is higher in women who are obese and in women who use oral contraceptive pill formulas that Contraceptive Needs? Would You Choose an contain specic third-generation progestins, such as Extended-cycle or Conventional Oral desogestrel and gestodene.5 Contraceptive Pill? Oral contraceptive pill use is contraindicated in Table 1 describes numerous oral contraceptive pill and women who have a history of migraine headache with nonoral contraceptive pill options and compares hormone aura and are therefore at increased risk of stroke.6-8 It is contents, delivery systems, failure rates, costs, side effects, contraindicated in women who have a systolic blood and contraindications. pressure above 160 mm Hg, have a diastolic blood presIndividual oral contraceptive pills differ in terms of their sure above 90 mm Hg, or smoke after the age of 35 years estrogen dosage, progestin type and dosage, and hormoneand are therefore at increased risk of an adverse cardiofree interval. Traditional oral contraceptive pill regimens vascular event.6,7,9 Other contraindications to oral conconsist of a 21-day course of hormones followed by a 7-day traceptive pill use include diabetes with end-organ damhormone-free interval. Newer oral contraceptive pills inage, breastfeeding within 6 weeks of delivery (relative clude Yasmin (Bayer Healthcare Pharmaceuticals, Montville, contraindication), and a personal history of the following: NJ), which is unique for its novel progestin, and several breast cancer, an estrogen-dependent tumor, unexplained extended-cycle regimens that offer shorter hormone-free vaginal bleeding, stroke, known thromboembolic disorintervals (Yaz [Bayer Healthcare Pharmaceuticals], der, and venous thromboembolism.6,10 Active liver disLoestrin 24 [Warner Chilcott, Rockaway, NJ], Seasonale ease is a contraindication, but it is not necessary to [Duramed Pharmaceuticals, Pomona, NY], Seasonique [Duperform liver function tests before initiating oral contraramed Pharmaceuticals], and Lybrel [Wyeth Pharmaceuticeptive pill use. Family history of breast cancer is not a cals, Philadelphia, Penn]). Women with hormone withcontraindication for prescribing oral contraceptive pills11 drawal symptoms or severe dysmenorrhea may benet from to the patient in case 1, and according to the American the fewer periods per year and shorter hormone-free interCollege of Obstetricians and Gynecologists (ACOG) vals provided by extended-cycle regimens as outlined in Practice Bulletin,6 family history of BRCA 1 or 2 mutaTable 1.13,16-19 tions should not preclude provision of oral contraceptive Yasmin contains drospirenone, a synthetic progestin that is chemically related to spironolactone. The antiandrogen pills.

Spencer et al

Table 1 Method

Characteristics of Contraceptive Methods Description Packet of 21 tabs containing ethinyl estradiol (20-50 g) and progestin; 7 placebo tabs. Average Cost per Month $20-$60 Failure Rate 0.3% with perfect use; 3%-8% with typical use. Side Effects and Drawbacks Spotting; nausea; headache; breast tenderness; breakthrough bleeding; venous thromboembolism (VTE); stroke; myocardial infarction (MI). Special Considerations Consider for women with dysmenorrhea, menorrhagia, irregular menstrual periods, acne, hirsutism, or polycystic ovary syndrome (PCOS). Women can expect rapid resolution of fertility after stopping OCPs. Contraindications Systolic blood pressure (SBP) 160 mmHg; diastolic BP 90 mm Hg; smoking after the age of 35 years; breastfeeding within 6 weeks of delivery; active liver disease; contraindication to estrogen; or history of the following: migraine headache with aura, diabetes with end-organ damage, breast cancer, estrogen-dependent tumor, unexplained vaginal bleeding, stroke, VTE, and known thromboembolic disorder.

Traditional oral contraceptive pills (OCPs)

Update on Contraception

Extended-cycle OCPs Yasmin

Packet of 28 tabs containing ethinyl estradiol (20 g) and drospirenone (3 mg); 7 placebo tabs.

$60

Similar to rates of traditional OCPs.

Spotting; nausea; VTE; stroke; MI.

Yaz

Packet of 24 tabs containing ethinyl estradiol (20 g) and drospirenone (3 mg); 4 placebo tabs.

$60

Similar to rates of traditional OCPs.

Spotting; nausea; VTE; stroke; MI.

Loestrin 24

Packet of 24 tabs containing ethinyl estradiol (20 g) and norethindrone (1 mg); 4 placebo tabs.

$60

Similar to rates of traditional OCPs.

Spotting; nausea; VTE; stroke; MI.

Same as traditional OCPs. Might be safer for women with mild hypertension given modest reductions in SBP seen with drospirenone. Might offer particular benet to women with acne, hirsutism, and evidence of PCOS. Same as Yasmin. Shorter HFI may offer particular benet for women with estrogen withdrawal symptoms. Particular benet in women with premenstrual dysphoric disorder. Same as traditional OCPs. Shorter HFI may offer particular benet for women with estrogen withdrawal symptoms.

Same as above but also renal, hepatic, or adrenal insufciency.

Same as Yasmin.

Same as traditional OCPs.

499

500

Table 1 Method

Continued Description Packet of 84 tabs containing ethinyl estradiol (30 g) and levonorgestrel (0.15 mg); 7 placebo tabs. Average Cost per Month $60 Failure Rate Similar to rates of traditional OCPs. Side Effects and Drawbacks Spotting; nausea; VTE; stroke; MI. Unknown if additional days of estrogen exposure increases risk. Special Considerations Same as traditional OCPs. Fewer withdrawal bleeds per year and shorter HFI may offer particular benet for women with estrogen withdrawal symptoms, dysmenorrhea or endometriosis. Withdrawal bleed is once every 3 months or once/season. Same as Seasonale. Might be more helpful for women with dysmenorrhea or endometriosis. Withdrawal bleed is once every 3 months or once/season, shorter HFI than Seasonale. Same as traditional OCPs. Shorter HFI can offer particular benet for women with estrogen withdrawal symptoms, dysmenorrhea, or endometriosis. Option for women who do not desire monthly periods. Consider for women who are unable to take pills on a daily basis but would benet from combined estrogen and progestin contraceptive. Might have increased risk of VTE as compared with OCPs. Contraindications Same as traditional OCPs.

Seasonale

Seasonique

Packet of 84 tabs containing ethinyl estradiol (30 g) and levonorgestrel (0.15 mg); 7 tabs containing ethinyl estradiol (10 g); 0 placebo tabs.

$60

Similar to rates of traditional OCPs.

Spotting; nausea; VTE; stroke; MI. Unknown if additional days of estrogen exposure increases risk.

Same as traditional OCPs.

The American Journal of Medicine, Vol 122, No 6, June 2009

Lybrel

Packet of 28 tabs containing ethinyl estradiol (20 g) and levonorgestrel (0.09 mg); 0 placebo tabs.

$60

Similar to rates of traditional OCPs.

Spotting; nausea; VTE; stroke; MI.

Same as traditional OCPs.

Ortho Evra

Transdermal patch that is applied once a week and releases ethinyl estradiol (75 g) and norelgestromin (6 mg) during the week.

$50-$60

0.3% with perfect use; 8% with typical use. Efcacy may be reduced in obese women.

VTE; stroke; MI; reaction at site of application.

Same as traditional OCPs. Has decreased effectiveness and should not be used by women weighing 90 kg.

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Table 1 Method NuvaRing

Continued Description Soft plastic ring that is inserted vaginally and releases ethinyl estradiol (15 g) and etonogestrel (0.12 mg) each day for at least 3 weeks. Injectable formula of medroxyprogesterone acetate that is administered intramuscularly (150 mg) or subcutaneously (104 mg) every 12 weeks. Average Cost per Month $50-$60 Failure Rate 0.3% with perfect use; 8% with typical use. Side Effects and Drawbacks Leukorrhea; VTE; stroke; MI; vaginal discomfort. Rare risk of ring falling out. Special Considerations Consider for women who would benet from a combined estrogen and progestin contraceptive but who are either obese or unable to take pills on a daily basis. Consider for women who have dysmenorrhea, seizure disorder, hemoglobinopathies, migraine headache with aura, or a history of cardiovascular disease, stroke, thromboembolism, or peripheral vascular disorder. Consider for women who are unable to use products containing estrogen or have a desire for longterm contraception. Does not increase the risk of VTE, stroke, MI, breast cancer, or bone fracture. Consider for women who have dysmenorrhea, are unable to use products containing estrogen, or have a desire for long-term contraception. Is safe for women who are breastfeeding. Contraindications Same as traditional OCPs.

Update on Contraception

Depo-Provera

$16-$20 ($50$90 per injection)

0.3% with perfect use; 3% with typical use.

Irregular bleeding; transient decrease in bone mineral density; may have delayed reversibility.

None.

Implanon

Single-rod device that is implanted subdermally in the upper arm, releases etonogestrel, active for 3 years.

$15 ($500-$750 per implant)

0.05% with perfect or typical use.

Irregular bleeding.

Use of CYP3A inducers, such as carbamazepine, phenobarbital, phenytoin, rifampin and St. Johns wort, may decrease effectiveness; active liver disease.

501

502 and antimineralocorticoid activity of Yasmin causes less weight gain and water retention and may offer a greater reduction in acne and hirsutism than that offered by traditional oral contraceptive pills.20 Additionally, Yasmin can lower systolic and diastolic blood pressure up to 4 mm Hg.20,21 Although potassium retention is a potential side effect of Yasmin use, this problem has not been found in clinical trials. Nevertheless, Yasmin is contraindicated in patients with renal, hepatic, or adrenal insufciency.22 During the standard 7-day hormone-free interval that occurs with use of low-dose estrogen formulations, the function of the hypothalamic-pituitary-ovarian axis recovers rapidly, and this increases the risk of ovarian follicle development, ovulation with unintended pregnancy, and increased spotting due to endogenous estradiol production.23-27 Fluctuating hormone levels allow endometrial buildup and can exacerbate premenstrual symptoms and menstrual headaches by creating hormone excess and withdrawal states.24-27 The newer extended-cycle oral contraceptive pills with a shorter or eliminated hormone-free interval reduce the risk of these unwanted effects by preventing endogenous estradiol production while still providing highly effective and safe contraception.13,16-18,27 Discussing a patients preferences for menstrual frequency and tolerance for scheduled and unscheduled bleeding will be important in deciding which contraceptive will best t her needs. For example, Lybrel, the rst Food and Drug Administration (FDA)-approved oral contraceptive pill taken 365 days per year, is an option for women with hormone withdrawal symptoms who do not desire scheduled monthly periods, as there is no hormone-free interval. Safety, efcacy, and resolution of fertility are similar to other oral contraceptive pills.18,19 If a woman is having difculty remembering to take a daily pill but would like to have the benets of a combined estrogen-progestin contraceptive, there are two options available: the Ortho Evra patch and the NuvaRing. The Ortho Evra patch is a thin transdermal patch containing 75 g of ethinyl estradiol and 6 mg of norelgestromin. Although the patch is generally as effective as oral contraceptive pills (Table 1), studies have shown that it has decreased efcacy in women who are obese (90 kg).28 Most of the side effects, cardiovascular risks, and contraindications are similar to those of other combinedhormone contraceptives. While one study showed no difference in the risk of venous thromboembolism with use of the patch versus oral contraceptive pills, other studies showed that the risk was twice as high with the patch as compared with oral contraceptive pills containing norgestimate or levonorgestrel.29 These studies were the basis for updating the Ortho Evra label to indicate a higher risk of venous thromboembolism.29 Of note, the venous thromboembolism risk associated with patch use is lower than the venous thromboembolism risk associated with pregnancy.30 NuvaRing is a soft plastic ring that is inserted vaginally, usually for 3 weeks, and then removed for 1 week (the hormone-free interval). The ring releases 15 g of ethinyl

The American Journal of Medicine, Vol 122, No 6, June 2009 estradiol and 0.12 mg of etonogestrel daily for 3-5 weeks, so it can be kept in longer than 3 weeks. Each ring releases about half the level of hormones as the average oral contraceptive pill without affecting efcacy. If the ring falls out (as occurs in 2.5% of women per year), it can be rinsed and reinserted without a change in efcacy. Unlike the patch, the ring is not affected by excess weight. Most women nd the ring easy to insert and remove and comfortable to retain during intercourse.31 NuvaRing has been associated with an increase in leukorrhea. Otherwise, its side effects, cardiovascular risks, and contraindications are similar to those of other combined-hormone contraceptives (Table 2).

CASE 2
A 31-year-old woman with a history of seizure disorder presents to your ofce to discuss Depo-Provera (Pzer, New York, NY). She has been using this injectable contraceptive for 2 years. She likes not having to take a daily pill and is pleased that her menstrual cycles have lightened substantially. However, she read some recent reports about the effects of Depo-Provera on bone strength and wonders if it is still safe for her to use.

How Does Depo-Provera Work?

Depo-Provera (depot medroxyprogesterone acetate) is a progestin-only contraceptive that was approved by the FDA more than 15 years ago.32 Depo-Provera can be given intramuscularly (150-mg dose) or subcutaneously (104-mg

Table 2

Take-Home Points: Case 1

Oral contraceptive pills (OCPs) are comprised of varying doses of estrogen and progesterone, which prevent pregnancy by inhibiting ovulation, thickening cervical mucus, and altering the endometrial lining. Common side effects of OCPs include nausea, headaches, breast tenderness, and breakthrough bleeding. More rare but serious side effects include VTE, stroke, and myocardial infarction. These risks are increased in women with migraines with aura, uncontrolled hypertension, diabetes with complications, and in women aged 35 years who smoke. Drosperinone-containing OCPs or progestin-only contraceptives may be safer options for women with mild hypertension. OCPs are not associated with an increased risk of breast cancer in non-mutation carriers. Extended-cycle OCPs may reduce unwanted menstrual symptoms by preventing endogenous estradiol production with shorter hormone-free intervals. Discussing your patients preferences for menstrual frequency and tolerance for scheduled and unscheduled bleeding will be important in deciding whether a traditional or extended-cycle OCP will best t her needs. Ortho Evra patch and NuvaRing are combined-hormonal options if a woman can not take a daily pill; OrthoEvra may be less effective in obese women (90 kg).
OCPs oral contraceptive pills; VTE venous thromboembolism.

Spencer et al

Update on Contraception

503 various studies reached the same conclusion about reversibility of bone mineral density loss.40,41 The authors of the 2006 review identied only one study that evaluated the risk of fracture among Depo-Provera users, and this study suggested no association between stress fracture occurrence and Depo-Provera use.40 The WHO has recommended that there be no restriction on the use of Depo-Provera.42 Practitioners should advise patients about the risk of bone mineral density loss but reassure them about reversibility with discontinuation. They also should recommend that Depo-Provera users exercise regularly and increase their intake of calcium and vitamin D (Table 3).

dose). It is highly effective and works by thickening the cervical mucus, preventing ovulation through suppression of the luteinizing hormone surge, and altering the endometrial lining.33 Its slow absorption through the subcutaneous tissues provides adequate systemic levels of progesterone for at least 14 weeks, although women are instructed to return in 12 weeks to ensure timely administration.33

Who Are Good Candidates for Depo-Provera?

Depo-Provera is safe for women with a history of cardiovascular disease, stroke, thromboembolism, or peripheral vascular disease.6 It is ideal for women with hemoglobinopathies, such as sickle cell disease, because these women will likely notice a decrease in painful hemolytic crises.34 Women with seizure disorder are especially good candidates for DepoProvera. Anticonvulsants can increase hepatic metabolism of estrogen and progesterone in oral contraceptive pills, thereby lowering contraceptive efcacy.6,32,33 However, Depo-Provera is effective in women taking these medications, presumably secondary to its high progesterone levels;33,35 moreover, DepoProvera can decrease the frequency of seizures.35

CASE 3
A 31-year-old woman presents to your ofce to establish care. She underwent 2 laparoscopies to treat severe endometriosis more than 10 years ago. She is currently using an extended-cycle oral contraceptive pill but has severe symptoms every 3 months with menses. She previously tried Norplant, which best controlled her symptoms but is no longer available. She also tried Depo-Provera, which she did not tolerate well. She is currently sexually active and in a monogamous relationship. Results of her annual Pap smears have been normal. You counsel her about various methods of contraception, including Implanon (Organon USA Inc., Roseland, NJ).

What Are the Side Effects of and Contraindications for Depo-Provera?

Commonly reported side effects associated with DepoProvera include menstrual irregularities, weight gain, and mood changes.32,33 Approximately 40% of women receiving Depo-Provera will experience amenorrhea within the rst 3 months of use;33 this may be considered a desirable side effect for many users.32 About 2% of women will discontinue Depo-Provera within the rst 2 years due to weight gain, although studies are conicting about whether there is a true causal relationship.32 Several studies also have examined the risk of more serious health consequences associated with Depo-Provera use. According to the ndings of an international, multicenter, case-control study published by the World Health Organization (WHO),36 Depo-Provera users were not more likely than nonusers to experience stroke, acute myocardial infarction, or venous thromboembolism, and the overall combined risk for cardiovascular disease was similar in users and nonusers. Pooled results from the WHO trial and a similar trial conducted in New Zealand indicated that the relative risk for breast cancer among women who used Depo-Provera sometime during their life was 1.1 (condence interval 0.97-1.40) and there was no increased risk with longer durations of use.37 Depo-Provera reduces serum estradiol levels, and this can adversely affect bone health. In 2004, the FDA issued a black box warning that women who use Depo-Provera may lose signicant bone mineral density and recommended that use be limited to 2 years.38 In 2006, a 7-year, prospective, matched cohort study among young women showed that Depo-Provera users had substantial bone mineral density loss but that the loss was reversible with discontinuation of use.39 In 2006 and again in 2008, systematic reviews of

How Does Implanon Work?

Implanon is a contraceptive device that is implanted subdermally in the upper arm and remains active for 3 years. It consists of a single rod that contains etonogestrel, which is the same progestin used in the NuvaRing. Implanon has been available for more than 10 years but has been widely marketed in the United States only since 2007. Like other progestin-only contraceptives, Implanon works by blocking the luteinizing hormone surge and thereby preventing ovulation. It also thickens the cervical mucus and thins the endometrial lining. Unlike other progestinonly methods, Implanon causes estradiol to gradually increase to normal endogenous levels after an initial decrease.43,44 Implanon is extremely effective in preventing pregnancy and has an efcacy rate similar to that associated with sterilization or use of an intrauterine device.43,45

Table 3

Take-Home Points: Case 2

Depo-Provera is a progesterone-only contraceptive method that is safe in women with a variety of medical conditions Depo-Provera does not increase the risk of stroke, myocardial infarction, VTE, or breast cancer Users of Depo-Provera may experience a decrease in bone mineral density that is reversible with discontinuation and is not associated with increased fracture risk
VTE venous thromboembolism.

504 Women experience a quick return to normal cycles after implant removal, and there have been no reports of infertility after removal.46 The cost of implantation is typically $500-$750 and is often covered by health insurance. Implantation and removal of Implanon require training but can be performed as simple ofce procedures. For implantation, the clinician gives the patient a local anesthetic and then uses a preloaded, disposable applicator supplied by the manufacturer to insert the rod about 3 ngerbreadths above the medial epicondyle of the humerus. The correct placement is conrmed by palpation. Difculty with removal is experienced in only 2%-3% of patients, and the usual cause is that the implant was placed too deep in the arm.47

The American Journal of Medicine, Vol 122, No 6, June 2009

What Are the Contraindications for Implanon?

Implanon is contraindicated in women being treated with CYP3A-inducing or CYP3A-inhibiting medications. While inducers of CYP3A might decrease the efcacy of Implanon and lead to unintended pregnancy, inhibitors of CYP3A might increase serum etonogestrel levels and cause toxicity.6 Implanon is contraindicated in women with active liver disease or active venous thromboembolism, but these contraindications are controversial. Some studies indicate that etonogestrel causes mild abnormalities in results of liver function tests, but the abnormalities are thought to be of minimal clinical signicance.43,49 Progestin-only methods of contraception have long been considered safe to use in women with an increased risk of venous thromboembolism (eg, women who smoke or have hypertension, diabetes mellitus, migraine headaches, or a history of venous thromboembolism).6,51,52 However, active venous thromboembolic disease is listed as a contraindication in the packaging information for several progestin-only methods, including Implanon. Unfortunately, there are no data available on the association between Implanon use and venous thromboembolism, and only one small study has examined the effect of Implanon on hemostatic elements. In this open-label study, there was no change in prothrombin time, partial prothrombin time, or levels of brinogen or other coagulation variables over a 6-month period.53 Therefore, most experts consider Implanon to be an acceptable choice for women who have venous thromboembolism and cannot use contraceptives that contain estrogen (Table 4).43

How Does Implanon Differ from Norplant?

Norplant was a highly effective implant system that consisted of 6 rods containing levonorgestrel.43 In 2002, Norplant production was halted in the United States after clinicians and patients complained about difculty in removing the device and after the manufacturer found it necessary to recall a single lot of the implant devices because they released lower-than-expected levels of hormone. Serum etonogestrel levels in Implanon users have been shown to have less variability than levonorgestrel levels in Norplant users.48 After removal of the etonogestrel implant, etonogestrel levels fall quickly. Within a week, etonogestrel becomes undetectable and ovulation quickly follows.45

What Are the Side Effects and Benecial Noncontraceptive Effects of Implanon?
Like other progestin-only contraceptives, Implanon may cause irregular bleeding. During the rst 3 months of use, about 50% of women experience infrequent bleeding. At 6 months, about 30%-40% have amenorrhea, 30% have infrequent bleeding, and the remainder experience frequent or prolonged bleeding.49 Discontinuation of use usually occurs during the rst 8-9 months and is generally due to frequent or prolonged bleeding.49 Implanon has other effects to consider. One study indicated that its use was associated with a decrease in symptoms of dysmenorrhea in 80% of women with a history of this disorder. Although many progestin-only contraceptives are associated with an increase in weight, the increase with Implanon is relatively low (about 0.7 kg/m2) and only about 3%-7% of Implanon users have their implant removed because of weight gain.43 Implanon has mixed effects on acne, but about 70% of women with acne experience no change in their condition.50 There have been no long-term studies about Implanon, bone mineral density, and fractures. However, a study that followed Implanon users and nonhormonal intrauterine device users for 2 years showed no clinically signicant difference in the bone mineral density levels of these 2 groups.44

SUMMARY
Physicians need up-do-date information to help each patient choose a contraceptive that is appropriate based on her medical history and preferences for a pill, implant, or other method. If a womans medical condition requires treatment with a potentially teratogenic drug, it is imperative that her physician counsel her about the wide range of contraceptive methods that are available. If estrogen is contraindicated, progestin-only methods can be used in most cases. The newer formulations and extended-cycle regimens reviewed
Table 4 Take-Home Points: Case 3

Implanon is a highly effective, quickly reversible, long-term contraceptive using a single rod subdermal implant containing the progestin etonogestrel. Implanon is an alternative for women who cannot use estrogenbased contraceptives and is safe to use during breastfeeding. Most important preimplantation counseling point is the possibility of irregularly irregular bleeding patterns, although many women experience infrequent bleeding or amenorrhea. 80% of women with dysmenorrhea at baseline will have an improvement in symptoms with no major effects on weight, acne, or bone mineral density.

Spencer et al

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here are attractive options that offer both contraceptive and noncontraceptive benets.

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