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GYNECOLOGY
Combined hormonal contraception use in reproductive-age
women with contraindications to estrogen use
Julianne R. Lauring, MD; Erik B. Lehman, MS; Timothy A. Deimling, MD; Richard S. Legro, MD;
Cynthia H. Chuang, MD, MSc
BACKGROUND: The Centers for Disease Control and Prevention’s US sociodemographic data in women with and without contraindications to
Medical Eligibility Criteria for Contraceptive Use recommends that com- estrogen use.
bined hormonal contraceptives (ie, birth control pills, contraceptive patch, RESULTS: The MyNewOptions baseline study sample included 987 adult
vaginal ring) should be avoided in women with specific medical conditions women who were mostly young (46% were 18e25 years), white (94%),
because of the increased risk of cardiovascular events associated with employed (70%), and married or cohabiting (54%). Thirteen percent (n ¼
estrogen use. Whether women with category 3 (theoretical or proven risk 130) of the sample had a medical contraindication to estrogen-containing
usually outweigh the advantages) or category 4 (unacceptable health risk) contraceptive use: migraine with aura (81%) was the most common
contraindications are appropriately avoiding estrogen-containing com- contraindication, followed by smokers older than age 35 years (7%), hy-
bined hormonal contraceptives is unknown. pertension (11%), history of venous thromboembolism (4%), and diabetes
OBJECTIVE: We describe the prevalence of combined hormonal con- with complications (2%). High use of combined hormonal contraceptives
traceptive use among a sample of reproductive-age women with medical was reported among the women with medical contraindications to estrogen
contraindications to estrogen use. Our hypothesis was that women with at 39% (n ¼ 51). This was not statistically different from women without a
categories 3 and 4 contraindications would use estrogen-containing medical contraindication (47%, P ¼ .1). Among the 130 women with a
contraception less often than women without medical contraindications. contraindication, whether they did or did not use an estrogen-containing
We also explored whether inappropriate estrogen-containing contracep- contraceptive did not vary by education level, income, or weight category.
tive use is related to contraceptive provider characteristics. With respect to their contraceptive prescribers, there were no differences in
STUDY DESIGN: Data are from the baseline survey of the MyNe- prescriber specialty, provider type, or clinic type comparing women using
wOptions study, which included privately insured women residing in and not using an estrogen-containing contraceptive.
Pennsylvania aged 18e40 years, who were sexually active and not CONCLUSION: Among this study sample of reproductive-age women,
intending pregnancy in the next year. Women were surveyed about their there was a high rate of combined hormonal contraceptive use in women
medical conditions, contraceptive use, and characteristics of their con- with a medical contraindication to estrogen use. These women may be at
traceptive provider. Women were considered to have a contraindication to an increased risk for cardiovascular events. Processes need to be
combined hormonal contraceptives if they reported a category 3 or improved to ensure that women with medical contraindications to
category 4 contraindication: hypertension, smokers older than age 35 estrogen-containing contraception are being offered the safest and most
years, a history of venous thromboembolism, diabetes with complications, effective methods, including long-acting reversible contraceptives, such
coronary artery disease, systemic lupus erythematosus with anti- as intrauterine devices and the contraceptive implant.
phospholipid antibodies, breast cancer, or migraine headaches with aura.
c2 tests for general association were used to compare combined hormonal Key words: combined hormonal contraception, medical
contraceptives use, contraceptive health provider characteristics, and contraindications
We described the prevalence of com- The outcome measure is the current use no evidence of disease for 5 years or
bined hormonal contraception use of a combined hormonal contraception, category 4 for current breast cancer), and
among women with medical contraindi- which was defined as combined birth (8) migraine with aura (category 4).
cations to estrogen use in a sample of control pills (containing both estrogen Health conditions were determined
reproductive-age women. Our hypothe- and progestin), the contraceptive patch, by a series of questions asking, “Has a
sis was that women with category 3 or 4 and the vaginal ring. doctor, nurse, or other health profes-
contraindications to estrogen-containing For women using birth control pills, sional ever told you that you had or
contraception would be less likely to use the survey response choice was birth have any of the following?” Smoking
combined hormonal contraception control pills and did not specify com- was assessed by asking, “Do you now
than women without a medical contra- bined pills or progestin-only pills. To smoke cigarettes every day, some days,
indication. We also explored whether make this distinction, pharmacy claims or not at all?” In several cases, our
inappropriate combined hormonal con- data were obtained from Highmark survey tool was unable to distinguish
traception use is related to contraceptive Health and used to determine whether category 3 from category 4 contraindi-
provider characteristics. the most recent pharmacy claim prior to cations. For example, women over the
the woman’s baseline survey was for age of 35 years who smoked every day
Materials and Methods combined or progestin-only oral con- were considered to have a contraindi-
This analysis was performed using the traceptive. All other contraceptives were cation, but we were unable to specify
baseline survey data from the MyNew- considered nonestrogen contraception, whether it was category 3 or 4 because
Options study, an ongoing randomized which included male and female con- the number of cigarettes smoked per
controlled trial to test an online repro- doms, the medroxyprogesterone acetate day was not ascertained.
ductive lifeeplanning intervention for injectable, intrauterine devices, dia- Of note, not all 18 category 3 and 4
assisting privately insured adult women phragm, cervical cap, contraceptive health conditions were ascertained by the
with personalized contraceptive decision foam, jelly, cream or suppository, the survey, so if women in the sample had
making. The sample included 987 female sponge, contraceptive implant, rhythm other category 3 and 4 contraindications
Highmark Health members in Pennsyl- or natural family planning, withdrawal, (severe liver cirrhosis, gallbladder disease,
vania between the ages of 18 and 40 and no method of contraception. liver tumors, peripartum cardiomyopa-
years. Women were eligible for the study thy, organ transplant, thrombogenic
if they were sexually active, not intending Medical contraindications to mutations, and valvular heart disease),
pregnancy in the next 12 months, not combined hormonal contraception they may have been misclassified.
surgically sterilized or with a partner We identified study participants with the
who was surgically sterilized, had following category 3 (theoretical or Contraceptive provider
Internet access and a valid e-mail proven risk usually outweigh the ad- characteristics
address. vantages) and category 4 (unacceptable Contraceptive provider characteristics
Participants then completed a baseline health risk) contraindications to com- were determined by a series of questions
survey that ascertained baseline de- bined hormonal contraception, accord- in which the respondent was asked about
mographics, current method of contra- ing to the Centers for Disease Control “the most recent health care visit where
ception, and their medical comorbidities. and Prevention Summary Chart of US you received any contraceptive or
Randomization and online intervention Medical Eligibility Criteria for Contra- women’s health care services.” The clinic
occurred after the completion of the ceptive Use6: (1) hypertension (category type (private office vs other clinic), spe-
baseline survey. Additional details 3 if adequately controlled or category 4 if cialty (obstetrics and gynecology vs other
regarding the study protocol have been poorly controlled), (2) smokers over the specialties), and provider type (physician
published elsewhere.8 age of 35 years (category 3 if <15 ciga- vs nonphysician provider) in which the
This study was approved by the Penn rettes/day or category 4 if 15 cigarettes/ contraceptive or women’s health care
State Hershey Institutional Review day), (3) a history of venous thrombo- services occurred were recorded.
Board under institutional review board embolism (category 3 if lower risk for
protocol 44583EP with informed con- recurrent venous thromboembolism or Statistical analysis
sent obtained online. category 4 if higher risk for recurrent All variables were summarized with fre-
venous thromboembolism), (4) diabetes quencies and percentages for categorical
Contraceptive method with complications (category 3 if variables or with means, medians, and
The survey measured the current con- microvascular complications or category SDs for continuous variables prior to any
traceptive method by asking women to 4 if vascular disease or diabetes >20 analysis. c2 tests for general association,
indicate the method of contraception years), (5) coronary artery disease with Fisher exact tests substituted as
used within the last month. If more than (category 4), (6) systemic lupus erythe- needed, were used to compare combined
1 choice was selected, participants were matosus with antiphospholipid anti- hormonal contraception use, contra-
then asked, “Which method do you bodies (category 4), (7) breast cancer ceptive health provider characteristics,
consider to be your primary method?” (category 3 if previous breast cancer with and sociodemographics between women
estrogen use. Almost half of women with (long-acting reversible contraceptives). Studies suggest there is an increased
migraine with aura, an unacceptable Long-acting reversible contraceptives, risk among migraine patients who are
health risk, were using combined hor- which include intrauterine devices and using combined hormonal contracep-
monal contraception in our sample. the contraceptive implant, are the most tion,14,17,18,22,23 although the risk of
Previous literature has shown lower effective reversible contraceptive ischemic stroke may be lower with low-
rates of combined hormonal contracep- methods currently available. dose estrogen preparations.20,22
tion use among women with contrain- Reducing unintended pregnancy by One limitation of our study is we were
dications compared with those without, increasing access to contraception has not able to distinguish whether some
although the association was no longer led to interest in over-the-counter oral women had category 3 (theoretical or
significant when controlling for socio- contraception. Whereas opponents have proven risk usually outweigh the ad-
demographic characteristics.3 Among argued that requiring a prescription al- vantages) or category 4 (unacceptable
the combined hormonal contraception lows providers to assess women for health risk) contraindications to com-
users, 11.23% had a contraindication to contraindications to combined hor- bined hormonal contraception. For
estrogen, similar to previously published monal contraception, our study results example, we ascertained whether
data.4,7 There were no differences in suggest that the current process is not women had hypertension but did not
contraceptive provider or clinic charac- effectively helping women obtain the have information on how well it was
teristic between those using combined safest methods for their individual controlled: adequately controlled hy-
hormonal contraception and those who characteristics. Previous studies have pertension is category 3 and poorly
were not. shown women are able to accurately self- controlled hypertension is category 4.
The concerns about combined hor- screen for contraindications to estrogen Similarly, we included women over
monal contraception use when contra- with a medical checklist.11 In a recent age 35 years who reported smoking every
indications are present center on survey of US women at risk for preg- day but do not know whether they
cardiovascular risk. Although combined nancy, more than 60% of the re- smoked <15 cigarettes/day (category 3)
hormonal contraception has consistently spondents were in favor of over-the- or 15 cigarettes/day (category 4).
been associated with an increased rela- counter access to over-the-counter oral Additionally, patients who reported
tive risk of venous thromboembolism,9 contraception, and almost one third of smoking some days may influence pre-
the overall absolute risk remains low, women not currently using contracep- scribing patterns, which was not
especially compared with the risk asso- tion said they were likely to start using addressed in our study.
ciated with pregnancy. A recent over-the-counter oral contraception if The high use of combined hormonal
Cochrane Review suggested there is no available over the counter.12 contraception in women with contrain-
increased risk of arterial thrombosis The largest contraindication category dications could be a result of patient and
including myocardial infarction or in our study sample was migraine with provider acceptance of the increased
ischemic stroke, in average-risk oral aura, which is classified as a category 4, associated risk with combined hormonal
contraceptive users with estrogen for- or unacceptable health risk. In our study, contraception in favor of the contra-
mulations <50 mg.10 However, for almost half of the women with migraines ceptive and noncontraceptive benefits
women with certain medical comorbid- reported having migraines with aura, associated with combined hormonal
ities, estrogen-containing contraception, and almost half of the women with contraception in women with category 3
or combined hormonal contraception, migraine with aura were using combined contraindications. However, less than
increases their risk of these cardiovas- hormonal contraception. Research has 20% of patients could potentially have
cular complications2 and should be suggested that migraine headaches are had a category 3 contraindication;
avoided. associated with an increased risk of therefore, most women with contrain-
Our study was designed using the ischemic stroke,13-15 with an increased dications in our study were using com-
Centers for Disease Control and Pre- risk in women with migraine with aura bined hormonal contraception despite
vention medical eligibility criteria, but when compared with those with unacceptable health risk.
there are women with increased cardio- migraine without aura.16-18 Another possible explanation for the
vascular risk because of multiple risk The association between ischemic similar rates of combined hormonal
factors such as obese women who smoke stroke and migraine also appears stron- contraception use could be a lack of
or have migraines, for which this ger in younger women, particularly knowledge of contraindications to
guideline is less clear. Although not those younger than 34 years to 45 combined hormonal contraception by
addressed in our study, this group would years.15,16 Use of hormonal contracep- both the prescriber and the patient.
be of interest in future research. tion, particularly containing estrogen, is Previous research has demonstrated
Processes need to be improved to independently associated with an more than 30% of surveyed obstetrician-
ensure that women with medical con- increased risk of ischemic stroke.19,20 gynecologists and family physicians dis-
traindications are being offered the This risk increases with age, smoking, agreed with a statement that “migraine
safest and most effective noneestrogen- and other medical comorbidities that with aura should not be prescribed”
containing methods, including LARCs increase the risk of ischemic stroke.21 combined hormonal contraception.24
The Centers for Disease Control and bias is minimized with anonymous seeking combined hormonal contraception. Am
Prevention and World Health Organi- electronic surveys, this could still influ- J Obstet Gynecol 2014;210:210.e1-5.
5. World Health Organization. Reproductive
zation rate this a category 4, and this was ence patient reporting. Health and Research. Medical eligibility criteria
the largest group in our study at greater Many factors contribute to the deci- for contraceptive use, 4th ed. Geneva: Depart-
than 80%. This highlights the need for sion on contraceptive method. The de- ment of Reproductive Health and Research,
adequate provider education on appro- cision may be based on safety, efficacy, World Health Organization; 2010.
priate patient selection for the varying perceived pregnancy risk, desire for 6. Centers for Disease Control and Preven-
tion. US medical eligibility criteria for con-
contraceptive methods. future pregnancy, and method.28-30 The traceptive use, 2010: adapted from the World
The choice to use combined hor- decision also depends on access, avail- Health Organization Medical Eligbibility
monal contraception when contra- ability, and cost of a particular method.31 Criteria for Contraceptive Use. 4th ed.
indicated could also be related to cost The majority of women in our study MMWR Morb Mortal Wkly Rep 2010;59
considerations. Although our study was were college graduates, more than one (RRO4):1-6.
7. Grossman D, White K, Hopkins K, Amastae J,
conducted in a sample of privately third reported an income $75,000, Shedlin M, Potter JE. Contraindications to
insured women after the Affordable Care more than half were normal weight or combined oral contraceptives among over-the-
Act’s contraceptive coverage mandate, underweight, and there were very few counter compared with prescription users.
we have previously reported that Hispanic women in the study. The de- Obstet Gynecol 2011;117:558-65.
awareness of contraceptive coverage in cision to use combined hormonal 8. Chuang CH, Velott DL, Weisman CS, et al.
Reducing unintended pregnancies through
this sample is low.25 contraception for these women may not web-based reproductive life planning and con-
Another possible explanation for our be generalizable to all populations. traceptive action planning among privately
negative finding is a result of type II er- However, expansion of contraceptive insured women: study protocol for the
ror. A post hoc power analysis results in benefits through the Affordable Care Act MyNewOptions randomized, controlled trial.
only 38% power for a 2-sided c2 test can provide the opportunity for women Womens Health Issues 2015;25:641-8.
9. Food and Drug Administration. Combined
using a significance level of P ¼ .05. with contraindications to estrogen to hormonal contraceptives (CHC) and the risk of
However, our study still highlights a choose a safer, more effective method cardiovascular disease endpoints. Silver Spring
large number of women with contrain- without cost concerns. (MD): Food and Drug Administration; 2011.
dications to estrogen using combined In our study, inappropriate combined 10. Roach RE, Helmerhorst FM, Lijfering WM,
hormonal contraception who could hormonal contraception use was not Stijnen T, Algra A, Dekkers OM. Combined oral
contraceptives: the risk of myocardial infarction
potentially benefit from safer, more related to contraceptive provider char- and ischemic stroke. Cochrane Database Syst
effective methods of contraception. acteristics, suggesting contraceptive Rev 2015;8:Cd011054.
A limitation of our study is that we providers of all types and specialties can 11. Grossman D, Fernandez L, Hopkins K,
relied on self-report of medical comor- play a greater role in identifying contra- Amastae J, Garcia SG, Potter JE. Accuracy of
bidities and did not verify through ceptive contraindications and offering self-screening for contraindications to combined
oral contraceptive use. Obstet Gynecol
medical records. Previous studies, how- safer alternatives. n 2008;112:572-8.
ever, have shown strong concordance 12. Grossman D, Grindlay K, Li R, Potter JE,
between physician screening and patient Acknowledgments Trussell J, Blanchard K. Interest in over-the-
reporting of medical comorbidities for Study data were collected and managed using counter access to oral contraceptives among
contraindications to combined hor- REDCap electronic data capture tools hosted at women in the United States. Contraception
the Penn State Milton S. Hershey Medical Center 2013;88:544-52.
monal contraception, 90% or higher for 13. Nightingale AL, Farmer RD. Ischemic stroke
and College of Medicine. This study had the
many of the conditions we studied.26 study Identifier of NCT02100124 (ClinicalTrials. in young women: a nested case-control study
In our study, there were higher gov). We thank Highmark Health for their assis- using the UK General Practice Research Data-
numbers of migraine with aura than in tance with participant recruitment. base. Stroke 2004;35:1574-8.
previous studies. This could also be a 14. Lidegaard O. Oral contraceptives, preg-
nancy and the risk of cerebral thromboembo-
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21. Bushnell C, McCullough L. Stroke preven- 29. Egarter C, Frey Tirri B, Bitzer J, et al. presented are solely those of the authors and do not
tion in women: synopsis of the 2014 American Women’s perceptions and reasons for choosing represent the views of Highmark Health.
Heart Association/American Stroke Association the pill, patch, or ring in the CHOICE study: a All statements in this report, including its findings
guideline. Ann Intern Med 2014;160:853-7. cross-sectional survey of contraceptive method and conclusions, are solely those of the authors and
22. Schwartz SM, Petitti DB, Siscovick DS, et al. selection after counseling. BMC Womens Health do not necessarily represent the views of Highmark
Stroke and use of low-dose oral contraceptives 2013;13:9. Health.
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23. Chang CL, Donaghy M, Poulter N. Migraine method use, United States, 2004. Perpect Sec the writing of the report; and in the decision to submit the
and stroke in young women: case-control study. Reprod Health 2008;40:94-104. article for publication.
The World Health Organisation Collaborative 31. Weisman CS, Lehman EB, Legro RS, REDCap is supported by the Penn State Clinical and
Study of Cardiovascular Disease and Steroid Velott DL, Chuang CH. How do pregnancy in- Translational Science Institute, Pennsylvania State Uni-
Hormone Contraception. BMJ 1999;318:13-8. tentions affect contraceptive choices when cost versity Clinical and Translational Science Institute, Na-
24. Dehlendorf C, Levy K, Ruskin R, Steinauer J. is not a factor? A study of privately insured tional Institutes of Health/National Center for Advancing
Health care providers’ knowledge about con- women. Contraception 2015;92:501-7. Translational Sciences grant UL1 TR000127.
traceptive evidence: a barrier to quality family This study was supported through a Patient-Centered
planning care? Contraception 2010;81:292-8. Outcomes Research Institute program award (CD-1304-
25. Chuang CH, Mitchell JL, Velott DL, et al. Author and article information 6117).
Women’s awareness of their contraceptive From the Division of Maternal Fetal Medicine, Department R.S.L. is a consultant for Bayer, Takeda Pharmaceu-
benefits under the Patient Protection and of Obstetrics and Gynecology (Dr Lauring), Department tical Company, and Lupin Pharmaceuticals and has other
Affordable Care Act. Am J Public Health of Public Health Sciences (Mr Lehman), Division of research funded by Astra-Zeneca, Ferring Pharmaceuti-
2015;105:S713-5. Minimally Invasive Gynecologic Surgery, Department cals. The other authors report no conflict of interest.
26. Shotorbani S, Miller L, Blough DK, of Obstetrics and Gynecology (Dr Deimling), Division of Corresponding author: Julianne R. Lauring MD.
Gardner J. Agreement between women’s and Reproductive Endocrinology, Department of Obstetrics and jlauring@hmc.psu.edu