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Women who have survived cancer may need guidance in choosing a method of contraception. This paper reviews the evidence supporting the safety and efficacy of available methods of contraception for cancer survivors and concludes that the Copper T380A intrauterine device (IUD), a highly effective, reversible, long-acting, hormone-free method should be considered a first-line contraceptive option for women with a history of a hormonally mediated cancer. However, the levonorgestrel-containing IUD may be preferable for women being treated with tamoxifen and women who have survived non-hormonally mediated cancers. Women with IUDs can undergo all forms of imaging, including computed tomography and magnetic resonance imaging.
Ovarian failure is a common consequence of chemotherapy.1 However, some women remain fertile despite undergoing chemotherapy.2,3 Identification of fertility after chemotherapy is challenging and remains an area of active research. New data suggest that anti-Mullerian hormone levels may be the best predictor of future fertility,4 as pregnancy has been reported in cancer survivors despite amenorrhea and follicle stimulating hormone (FSH) levels suggestive of menopause.5 Women who are amenorrheic during treatment with gonadotropin-releasing hormone (GnRH) agonists are not at risk of pregnancy. However, when treatment stops, women who ceased menstruation during chemotherapy may find that fertility returns. In a study of young survivors of breast cancer, 67% remained premenopausal.3 Among childhood cancer survivors, treatment is thought to reduce fertility by 10% to 25% depending on type of treatment.6 Norwegian data suggest that in the 10 years after a cancer diagnosis women are about half as likely as women without cancer diagnoses to become pregnant.7
In general, women are advised to avoid pregnancy during chemotherapy or radiation treatments that may be teratogenic. In addition, women with hormonally sensitive cancers (e.g., breast cancer) are advised to avoid pregnancy until they have passed the period of peak recurrence, 3 years after treatment.8 After treatment, fertile cancer survivors can be reassured that existing data suggest no subsequent increased risk of birth defects9,10 or that pregnancy increases the risk of cancer recurrence.11,12 However, some cancer treatments (e.g., pelvic and ovarian irradiation, central nervous system irradiation, and nonalkylating chemotherapy) do increase the risk of pregnancy loss and low birth weight babies.9 Contraception may, therefore, be desired to allow women to ensure their pregnancies coincide with a period of optimum health. Alternatively, women may desire to avoid pregnancy indefinitely.
Broadly speaking, there are 6 classes of contraceptive methods: (1) behavioral methods, (2) barrier methods, (3) estrogen-containing methods, (4) progestin-only methods, (5) intrauterine devices (IUDs), and (6) surgical sterilization. There are pros and cons to each of these methods (Table 1) including marked differences in efficacy during typical use. Although contraceptive efficacy is frequently discussed in the context of 1-year failure rates, for women requiring longer term contraception, it is important to consider cumulative rates of failure over more extended periods of time. Over the long term, IUDs, contraceptive implants, and sterilization are dramatically more effective than barrier methods or birth control pills. Unfortunately, birth control pills remain the most widely used form of reversible contraception in the United States.13,14 Unintended pregnancy remains common in the United States; it is estimated that half of all pregnancies in the United States are unintended.15 During a lifetime of use of reversible contraceptive methods, the typical woman will experience 1.8 contraceptive failures.16 Moreover, unintended pregnancy is more common among women with chronic medical conditions,17,18 perhaps because women with chronic conditions receive less contraceptive counseling.19,20 In the United States, cancer survivors between the ages of 15 and 30 years were more likely to terminate a pregnancy than age-matched control subjects.9 Similarly, a recent Danish study found that cancer survivors were slightly more likely to terminate a pregnancy.21 Other studies have also found that cancer survivors have limited awareness of available contraceptives.22
Without clear guidance from a healthcare provider, women with chronic conditions or complex medical histories who wish to preserve their fertility may limit themselves to barrier and behavioral methods.23 Unfortunately, with typical use, these methods leave women at high risk of unintended pregnancy (1-year failure rates typically range from 15% to 32%).24 Alternatively, women may feel that surgical sterilization, either through tubal ligation or partner vasectomy, is their only highly effective option. Worldwide, sterilization is used by more people than any other method of contraception.25 However, women who undergo sterilization may later regret this decision. There appears to be a consistent inverse relationship between a woman’s age at sterilization and the likelihood of regretting having been sterilized, with women less than 30 years of age expressing regret nearly twice as often. They were also from 3.5 to 18 times as likely to request information about reversing the procedure and about 8 times as likely to undergo an evaluation for in vitro fertilization.26
Intrauterine contraception is reversible, but offers efficacy similar (or greater) than sterilization.24 The cumulative pregnancy rate at 5 years for the levonorgestrel-releasing intrauterine system is less than 0.5% and between 0.3% and 0.6% for the Copper T380A IUD.27 As a result of high levels of user satisfaction,28 and cost-effectiveness,29 the IUD is the most widely used reversible method of contraception outside the United States.30 Women with IUDs can undergo all forms of imaging, including computed tomograph (CT) and magnetic resonance imaging (MRI).31 Infection after IUD insertion is rare32 and IUDs can be safely used even by women who are immunocompromised.33 IUDs can be used by women who have previously had sexually transmitted infections or multiple sexual partners, provided that they have no evidence of infection at the time of insertion.33 Insertion of an IUD is a simple office procedure and uterine perforation with IUD insertion is rare.34 IUDs can be successfully used by both nulliparous and parous women,35 with rapid return of fertility upon removal of the IUD. IUDs do not increase the risk of clotting33 or osteoporosis,36 and the levonorgestrel-IUD reduces menstrual blood loss and risk of anemia.37 While some people worry that IUDs are effective because they destroy embryos that arrive in a woman’s uterus, detailed study of the IUD’s mechanism of action does not support these concerns.38 The primary disadvantages of IUDs are the need to have a trained provider insert the device and a one-time out-of-pocket cost of $400 to $800 if a woman’s insurance does not cover the cost of IUDs.
There are currently two types of IUDs available in the United States: the copper T 380A (Paragard) and levonorgestrel-containing IUD (Mirena). The copper-containing IUD contains no hormones, which may make it a preferred option for some women who have survived cancer. The copper T 380A IUD is labeled for use for 10 years, but studies have shown good efficacy of a single IUD used for 12 years39 to 20 years.40 While generally well tolerated, some women who have a copper-containing IUD inserted experience increased menstrual cramping and vaginal bleeding.
To reduce this cramping, the levonorgestrel-IUD was developed. This IUD is effective for 5 to 7 years, after which time a new IUD can be safely inserted.41 With this IUD, women experience less cramping and vaginal bleeding. However, the bleeding that does occur with the levonorgesterel-IUD (as with all progestin-only contraceptive methods) is irregular, and some women may find this bleeding pattern unacceptable. The levels of progestin contained in this IUD are so low that many women continue to ovulate.42 However, the levonorgestrel-IUD does produce detectable serum levels of levonorgestrel.43 While women with cancers such as breast cancer are cautioned about the potential for hormonal stimulation of residual disease,44 several studies (Table 2) have examined the use of the levonorgestrel-IUD by women with histories of breast cancer who are being treated with tamoxifen. One recent study found no higher recurrence risk in breast cancer patients using a levonorgestrel-IUD.45 However, a subgroup of patients who were using a levonorgestrel-IUD at the time of diagnosis and who continued using it, experienced an increased risk of breast cancer recurrence.45 More research is, therefore, needed to determine the long-term safety of use of a levonorgestrel-IUD by women at risk of hormonally mediated cancers. For breast cancer survivors treated with tamoxifen, which can cause proliferative changes of the endometrium and even endometrial cancer, the levonorgestrel-IUD, which reduces endometrial proliferation, may be preferred because it decreases the need for investigation of vaginal bleeding.48
The third form of highly effective reversible contraception available in the United States is a contraceptive implant, Implanon, which is effective for 3 years after subcutaneous placement.46 Similar to all progesterone-only methods, women using this method experience irregular vaginal bleeding. Data on whether the use of Implanon contraceptive implants affects the risk of breast cancer in the general population, or the risk of recurrence among breast cancer survivors, are not yet available. Limited data on the Norplant contraceptive implant, which is no longer available in the United States, did not raise concern about increased rates of breast cancer.47 However, use of this method is not advised for women who have survived a hormonally mediated cancer, or who have received thoracic radiation which may increase their risk of breast cancer.
For women who desire pregnancy within 2 to 5 years, a contraceptive pill, patch, or ring may be more cost-effective than an IUD or implant.48 Estrogen-containing contraceptives are effective because they contain a progestin that suppresses ovulation. However, the combination of estrogen and progestin provides better control of vaginal bleeding, which makes these methods more popular. Women at low risk of breast cancer may choose to use an estrogen-containing contraceptive if they do not have significant risk factors for thrombosis or vascular disease. Concern has been raised that the contraceptive patch may increase the relative risk of thrombosis beyond that of oral contraceptives.49 However, it is important to remember that the absolute risk of venous thromboembolism while using any form of estrogen-containing contraception remains less than that during pregnancy (when it is estimated to be 57 per 100,000 women-years).
There is mixed data on the effects of combined hormonal contraception on risk of malignancies (Table 3). The large Royal College of General Practitioners’ oral contraception study,50 found an absolute rate reduction of any cancer of 45 per 100,000 years of use among ever-users of oral contraception. Specific tumor types reduced included cancer of the large bowel or rectum, uterus, ovaries, and tumors of unknown site. For ovarian cancer, there is good evidence that the use of combined hormonal contraceptives confers long-term protection.51 It has been estimated that 10 years use of combined hormonal contraceptives reduces ovarian cancer incidence before the age of 75 years from 1.2 to 0.8 per 100 users and mortality from 0.7 to 0.5 per 100.51 This reduction in risk was seen for many years after oral contraception was discontinued for both ovarian and uterine cancer.50 However, combined hormonal contraceptives do appear to increase the risk of being diagnosed with breast cancer. A collaborative reanalysis of 54 studies found that women who were taking combined oral contraceptives (or who had used oral contraceptives in the last 10 years) had a relative risk of 1.24 [95% CI 1.15–1.33].52 However, use of oral contraceptives before diagnosis of breast cancer has not been shown to have either a harmful or a beneficial effect on breast cancer mortality.53 Recently, another large study was conducted in China54 that examined incidence rates for 12 types of cancers in users of oral contraceptives; no associations were observed between oral contraceptives and the risk of breast cancer or all cancers combined.
For women with a history of hormonally mediated cancer, such as breast cancer, and women who received thoracic radiation, which may increase risk of breast cancer, nonhormonal contraceptive methods should be considered as a first-line method.44,55 Women who do not find any of these methods acceptable may wish to consider a progestin-only method (e.g., pill, injection, or implant). Studies have shown that progestins can have a proliferative, antiproliferative, or neutral effect on breast tissue, depending on the type, timing, and dose of progestin used.55 Depot medroxyprogesterone (DMPA) injections do not increase the risk of breast cancer.56 High-dose DMPA has been used as adjunctive treatment for advanced or recurrent breast cancer with significant prolongation of the time to progression.57 Although not as well-studied as the combined contraceptive pill, neither progestin-only pills52,58,59, progestin-only implants, or the levonorgestrel-releasing intrauterine system appear to increase the risk of breast cancer in the general population.55,60 However, one study recently suggested an increase in breast cancer recurrence among women who had a levonorgestrel-IUD in place at the time of diagnosis (although an increase in recurrence was not seen among women who had a levonorgestrel-IUD placed after their diagnosis of breast cancer).45 Further studies of the use of progestin-only methods by cancer survivors are therefore needed.
Women who opt for behavioral or barrier methods of contraception should be advised that emergency contraception can decrease the risk of unintended pregnancy if unprotected intercourse occurs. For women who should avoid exposure to exogenous hormones, insertion of a copper-containing IUD is a highly effective way of preventing pregnancy up to 7 days after a contraceptive emergency.61 Alternatively, emergency contraceptive pills, marketed in the United States under the trade name Plan B, are available to women (and men) ages 17 years or over without a physician’s prescription.62 While these progestin-only pills have been shown to have some efficacy up to 5 days after unprotected intercourse,63,64, they are more effective the sooner they are used. A number of professional organizations recommend that women be provided emergency contraception in advance of need.65–67 Studies have shown that women provided a supply of emergency contraception in advance of need are more likely to use it should unprotected intercourse occur, and that easy access to emergency contraception does not increase sexual risk-taking behavior.68 Detailed study of the mechanism of action of emergency contraception indicates that it does not disrupt implantation or induce abortion.62
In conclusion, contraception is an important issue to discuss with female cancer survivors. Given the prevalence of ovarian failure after chemotherapy, this topic should be broached carefully. As up to one third of women may be ambivalent towards pregnancy,69 open-ended questions should be used to explore women’s intentions to become pregnant. For women who desire contraception and have a history of a hormonally mediated cancer or thoracic radiation, the Copper T 380 A IUD, a highly effective and cost-effective, reversible, long-acting, hormone-free method should be considered a first-line method. However, the levonorgestrel-IUD may be preferred for women being treated with tamoxifen. Prior work has shown that that in many clinical settings, awareness of the benefits of IUDs is limited.70 This makes comprehensive counseling about contraceptive options an essential part of comprehensive care of cancer survivors.
Dr. Schwarz was supported by NICHD K23HD051585. Dr. Hess was supported by NIA K23AG024254.
Conflict of Interest None disclosed.