Contraception Update
Guide to Contraceptive Counseling for Women With Medical Comorbidities, Part 2
Bonnema R, McNamara MC, Spencer AL

When providing contraceptive counseling to women with medical conditions, clinicians should not only review a patient’s medical history but also consider her current medication regimen and its potential to affect contraceptive efficacy. Part 2 of this 2-part series focuses on progestin-only contraceptive options, with special consideration to women with medical comorbidities.

Among women who have chronic medical conditions, an unintended pregnancy can have serious health consequences. Certain diseases may be exacerbated by pregnancy and/or associated with adverse pregnancy outcomes. Moreover, medications used to treat many chronic medical conditions are teratogenic and/ or may interfere with the efficacy of various contraceptive methods. Despite the potential for such complications, women with medical comorbidities may not receive adequate contraceptive counseling.1,2

In last month's issue, part 1 of this 2-part series reviewed combined hormonal contraceptive (CHC) options for patients with medical comorbidities. In this issue, part 2 focuses on progestinonly contraceptive choices in this select group of patients.

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a 31-year-old patient with a history of a seizure disorder that has been well controlled with phenytoin presents to her clinician to discuss her current use of depot medroxyprogesterone acetate (DMPA) injectable suspension (Depo-Provera®;Pfizer Inc, New York, NY). This paitient states that she has been using DMPA for the past 3 years and has found it "works well" for her. She further expresses her preference for not having to take a pill daily and reports having significantly light menstrual cycles since initiatin DMPA. This patient, however, has concerns regarding continuation of DMPA based on an article she read regarding the effects of DMPA on bone density.

Depot Medroxyprogesterone Acetate
DMPA is a progestin-only contraception that is safe for use in women with a history of migraines with aura, thromboembolic disease, cerebrovascular disease, and coronary artery disease.3 Women with seizure disorder are particularly good candidated for DMPA. Unlike other forms of contraception, DMPA's efficacy is not affected by enzyme-inducing antiseizure drugs.4 In addition, there is some evidence that DMPA may also derease seizure frequency, thereby providing additional benefit for this group of patients.5 Therefore, DMPA is an appropriate contraceptive option for this patient.

What size effects are associated with DMPA?
Commonly reported side effects associated with DMPA include menstrual irrefularities, weight gain, and mood changes.6 Eventual amenorrhea is common, which is a desirable side effect for many users.7

DMPA reduces serum estradiol levels, which can adversely affect bone health.3 In 2004, the US Food and Drug Administration (FDA) issues a black box warning to DMPA package labeling, stating that women using DMPA may lose significant bone mineral density (BMD); this warning also recommends duration of DMPA use be limited to less than 2 years, unless other methods are inadequate.8

In 2006 and 2008, reviews of various studies showed that although there is a clear association between DMPA use and decreased BMD, BMD loss was reversible upon discontinuation of DMPA use.9,10 Most DMPA users have a low risk for fracture at baseline, and there are scant data linking DMPA use to an increased incidence of fractures.11

Should this patient continue to use DMPA?
The World Health Organization recommends no restriction on use of DMPA in women aged 18 to 45 years.12 Accodring to recent consensus guidelines, clinicians should advise patient about the risk for DMB loss as well as inform them of the reversibility of DMB loss upon discontinuation of DMPA.13 In addition, patients should be informed that calcium and vitamin D supplements are important for maintaining bone health and are not prescribed solely for patients using DMPA. There are currently no recommendations for BMD screening with dual-energy x-ray absorptiometry in patients using DMPA.13

In this case example, the clinician should discuss available progestin-only options with this paitient, along with the risks and benefits of each option. However, it is reasonable for this patient to continue using DMPA, as it may help control her seizure disorder and does not interact wiht her current antiseizure medication. The health care prodiver should review this paitient's contraceptive needs and medication regimen on an annual basis.

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A 33-year-old nulliparous patient presents to her clinician to discuss contraceptive options. This patient has a history of endometriosis that required 2 laparoscopies over 10 years ago. She is currently using an extended-cycle oral contraceptive (OC) but continues to experience severe menstrual pain during the hormone-free interval (HFI). This patient is seeking an alternate contraceptive to reduce dysmenorreha. She reports having taken DMPA in the past but discontined use based on personal dislike for regular injections.

Etonogestrel (ENG) Implant
The ENG Implant (Implnon®; NV Organon, OSS, The Netherlands) is a highly effective and long-term progestin-only single-rod, subdermal implant.14 The rod is implanted in the upper arm and remains active for 3 years. The ENG implant is unique to other progestin-onlu methods in that the initial decrease in estrogen levels is followed by a gradual rise in estradiol to normal endogenous levels.15,16

The ENG Implant is placed during a simple office procedure by a trained provider using a preloaded, displosable applicator. Prior to insertion, clinicians may administer a local anesthetic to minimize discomfort or pain. Post-removal, patients experience a quick return to both normal menstrual cycles and fertility; to date, there have been no reports of infertility post-removal.17

What are the common side effects associated with the ENG Implant? Are there any contraindications to its use?
Similar to other progestin-only contraceptives, irregular bleeding is the major side effect of the ENG implant, with the most common being infrequent bleeding.14 At 6 months post-insertion, approximately 30% to 40% of women become amenorrheic, 30% have infrequent bleeding, and the remainder experience frequent or prolonged bleeding.18 As there is no method to predict inidividual bleeding response in ENG implant users, health care providers should consel patients on these side effect-particularly because the highest rate of discontinuation is during the first 8 to 9 months of use and primarily due to frequent bleeding.18

In addition to irregular bleeding, the ENG implant has other side effect to consider. In one study, approximately 80% of women with dysmenorrhea at base lines reported a decrease in symptoms.18 Thus, the ENG implant would be a good contraceptive option for the patient in this case example. Unlike DMPA, weight gain is only rarely associated with the ENG implant.15 There are no longer-term studies assessing DMB or fracture risk post-ENG implant use. However, because the ENG implant does not cause a hypoestreogenic state, it is not considered to have any signiciant effect on BMD.15

The ENG implant is contraindindicated in women taking cytochrome P4503A-(CY-P3A) inducing (eg, carbamazepine, phenytoin) or CYP3A-inhibiting (eg, ketoconazole, erythromycin) medication.14

Active venous thromboelism (VTE) is a contraindication listed in the packaging information of several progestin-only methods, including the ENG implant; however, use of progestin-only contraceptives has been considered safe in women at increased risk for VTE.3,19,20 Therefore, despite this listed contraindications, in clinical practive, women's health care prodivers consider the ENG implant an acceptable contraceptive agent in cases where a combind progrestin/estrogen option is contrainidicated.3,15

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A 35-year-old patient with a medical history of iterine fibroids presents to her clinician for evaluation. For the past 2 years, she has experienced very heavy monthly menses that last for about 7 days and are associated with significant blood clots and cramping. She states she has been taking iron supplements to treat symptomatic aanemia for approximately 1 year. She also reports past OC use to reduce menorrhagia but had difficulty remembering to take pills on a dily basis. This patient is not interested in surgical options to treat her frbroids and does not plan on becoming pregnant in the next several years.

Levonogestrel-Releasing Intrauterine System (LNG-IUS)
The LNG-IUS (Mirena®; Bayer Health-Care Pharmaceuticals Inc, Wayne, NJ) is an intrauterine device (IUD) that releases approximately 20mcg of LNG daily. The LNG-IUS is a highly effective contraceptive and is considered to be a reversible method of sterilization due to its excellent efficacy in preventing pregnancy and rapid return to fertility post-removal.21 It is a particulary beneficial and cost-effective option for patients requiring a progestin-only therapy.3

Within the first year of use, the LNG-IUS reduces menstrual blood loss by 90%, though in the first 6 months of use, irregular spotting is common.22 Based on her history of menorrhagia, the patient in this case example may benefit from the LNG-IUS.

Several studies have confirmed the effectiveness of the LNG-IUS for reduction of menstrual blood loss in idiopathic menorrahagia and leiomyoma-associated menorrahagia, as well as amelioration of endometriosis-associated pain.23,24 The LNG-IUS recently received FDA approval for the indication of menorrahagia and has been shown to decrease menorrhagia in women on anticoagulation therapy.25,26 Use of the LNG-IUS to manage heavy menstrual bleeding appears to have therapeutic effects comparable to those of endometrial ablation up to 2 years after treatment.26

Fibroids rarely distort the uterine cavity to the extent that placing the LNG-IUS becomes techincally too difficult. Depending on physical examniation findings, clinicians may choose to perform a transvaginal ultrasound prior to placement to assess for distortion of the endometrial cavity.

What are common side effect and contrainidications to LNG-IUS use?
The LNG-IUS must be iserted by a trained clinician. At the time of placement, patients may experience cramping and pain. Uterine-wall rupture is a rare complication of LNG-IUS placement.21 Though patients will likely develop amenorreha, they should be counseled about inital irregular bleeding and spotting, and should be advised of the development of ovarian cysts, of which most are asymptomatic.

The LNG-IUS may be used in both nulliparous and multiparous women but should not be placed in women with suspected pregnancy or in those with an active infection, such as acute cevicitis or vaginitis.21 Although risk of pregnancy is extremely low in IUD users, there is an increased risk of ectopic pregnancy when it does occur.21 Most data concerning IUD use and ectopic pregnancies are related to the copper IUD. In a 5-year, international study comparing the LNG-IUS and the copper IUD, none of the 6 pregnancies in 1,124 women who had the LNG-IUS were ectopic.27

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A comprehensive understanding of available progestin-only contraceptive options for women's health care provider, particularly those caring for reproductive-aged women with medical comorbidities. Clinicians should carefull review a patient's medical history and current medication regimen to determine if contraindications to any of the progestin-only options exist, as well as consider patient's individual preferences, including acceptable side effects and reversibility.

DMPA is a safe option for use in women with seizure disorders, and associated BMD loss has been shown to be reversible with discontinuation of use.9,10 The ENG implant offers the unique feature of returning estradiol to normal endogenous levels during use,15,16 while the high efficacy, reversibility, and low cost of the implant make it an attractive option for many patients. The reduction of menstrual blood loss associated with the LNG-IUS is an excellent option for patients suffering from menorrhagia (Table).

When counseling patients with medical comorbidities on combined estrogen-progestin and progestin-only contraceptive options, health care providers must be knowledgeable of the risks and benefits of each method, consider the patient's personal preferences, and take into account her personal medical history.

The authors report no actual or potential conflicts of interest in relation to this article

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Rachel A. Bonnema, MD, MS, is Associate Program Director, Internal Medicine Residency Program, and Assistant Professor of Medicine, University of Nebraska, Omaha, NE. Megan C. McNamara, MD, MSc, is Assistant Professor of Medicine, Case Western Reserve University, Cleveland, OH. Abby L. Spencer, MD, MS, is Associate Program Director and Site Director, Internal Medicine Residency Program, Allegheny General Hospital; and Assistant Professor of Medicine, Temple University School of Medicine, both in Pittsburgh, PA.


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