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Adolescents in need of birth control can be difficult to manage, especially when they have epilepsy, diabetes, or cystic fibrosis. An expert outlines the risks and benefits of prescribing oral contraceptives in light of these and other disorders.
Physicians are often reluctant to frankly discuss sexuality with their adolescent patients. This is particularly true if the teenager has a significant medical illness. Many clinicians have a tendency to treat ill adolescents as infants, rather than face the fact that they are struggling with the complex process of psychosexual development.
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This tendency is especially common when dealing with patients who have had a medical problem since infancy or childhoodjuvenile diabetes, for example. In situations like this, physicians may be so preoccupied in managing the primary disorder at each office visit that they forget to discuss sexuality.
Similarly, reproductive health professionals may be reluctant to discuss contraception in the ill teenager because of fear that the contraceptive method could worsen her medical condition.
Such reluctance usually does more harm than good, however. Sociologists tell us, for instance, that poor self-esteem is a common risk factor for adolescent pregnancy. The seriously ill adolescent is probably more likely than her healthy peers to suffer from a poor self-image because she perceives herself as different from them. This only increases her odds of having unprotected sexual relations.
Many healthy teenagers never hear a physician's recommendation to abstain from sexual relations because they don't regularly see medical providers during the years that they are likely to become sexually active. Most ill adolescents, on the other hand, see medical providers frequently. While specialists and subspecialists may not always focus attention on sexual history or an adolescent's possible need for contraceptives, ob/gyns can certainly take the lead on this area.
Adolescents who are medically ill should be counseled that a pregnancy or sexually transmitted disease may be especially dangerous in their specific medical condition. At the same time, they need to understand that although abstinence is ideal, you will assist them in protecting themselves from pregnancy and STDs if they are, or plan to become, sexually active.
With these goals in mind, this review will focus on the interaction of combination OCs with a variety of medical diseases. Unless otherwise indicated, please assume that we are referring to low-dose formulas (35 µg or less of ethinyl estradiol), the OC of choice in adolescents with medical illness. Also keep in mind that, given the high prevalence of STDs and the common practice of "serial monogamy"maintaining a monogamous relationship with one's current boyfriend until one finds a new partneryou will want to encourage every female patient to insist that her partner use a condom. Combining a hormonal contraceptive and condom, the so-called "belt and suspenders" approach, is an adolescent's safest approach to birth control.
Unfortunately, even experienced ob/gyns feel challenged when presented with a seriously ill adolescent who is sexually active. That is largely the case because the scientific literature on the interaction of OCs with medical illnesses often consists of poorly controlled retrospective reports rather than randomized double-blind trials. In fact, randomized controlled trials in adolescent contraception are almost nonexistent, which means we are forced to make recommendations on the basis of less than ideal data.
To help cope with the paucity of data, the World Heath Organization has published Improving Access to Quality Care in Family Planning.1 After analyzing the strength of the evidence, WHO has made recommendations on specific contraceptives, including low-dose OCs, in a variety of medical conditions, and has classified the advisability of using contraceptives in specific diseases by placing them into four groups. Category 1) means there are no restriction on their use; 2) indicates that the advantages generally outweigh the theoretical or proven risks; 3) means there are theoretical or proven risks that usually outweigh the advantages of the contraceptive; and 4) refers to a condition in which the contraceptive would create unacceptable health risks.1
Although these recommendations are helpful, balancing risks and benefits can still be difficult at times because, while the published data may indicate that a combination OC is dangerous in a given medical condition, pregnancy itself usually poses an even greater risk. That may be especially true in teenagers with severe diabetes and systemic lupus erythematosus (SLE). Similarly it can be argued that if estrogens are contraindicated in a particular disease, then pregnancy is certainly contraindicated.
Finally, when making a risk/benefit analysis in sexually active ill adolescents who need contraception, the clinician should always take into consideration the effect of normal adolescent development and a patient's cognitive skills. A 15-year-old may be unable to consistently and regularly use a condom, for instance, but with the cognitive development that comes by age 19, she may become a reliable condom user. Likewise, a 14-year-old may be unwilling to take a "birth control shot," but at age 16, it may become her method of choice.
Epilepsy is sometimes listed in older textbooks as a relative contraindication to the use of OCs but there's inadequate scientific evidence to indicate that OCs either exacerbate or improve seizure disorders.2
Some studies suggest that progestins increase the seizure threshold; others have concluded that estrogens decrease it. Interestingly, these effects may negate each other in combination OCs, as no well-designed study has shown that combination OCs exacerbate seizure disorders.2
Anecdotally, some clinicians report that teens with so-called catamenial seizuresseizures with a propensity to occur during menstrual sheddingrespond well to continuous OCs, although this indication goes beyond current product labeling.
You will also have to take into consideration the possible interaction of OCs with antiepileptics in patients with seizure disorders. Some antiepileptics, including phenytoin and phenobarbital, may significantly affect the metabolism of estrogen and progestin through their effect on cytochrome p450 and sex hormone binding globulin (SHBG). Unfortunately these effects vary greatly from individual to individual and are not predictable. It also appears that patients on such enzyme-inducing antiepileptics may have increased breakthrough bleeding on OCs, but it has not been shown that this bleeding is a reliable barometer of contraceptive efficacy.3
Other antiepileptics, including valproate, have very little effect on steroid levels and should not alter contraceptive efficacy.
In any case, since a pregnancy would be a tragedy in patients on enzyme-inducing antiepileptics, some experts recommend a higher dose OC containing 50 µg ethinyl estradiol.2 Of course, you may also want to consider consulting the patient's neurologist to discuss the feasibility of switching the patient to a nonenzyme-inducing antiepileptic drug.
Another issue to bear in mind is the possibility that a teenager taking an antiepileptic who is not on some sort of birth control risks the drug's teratogenic effects. On a separate but related issue, adolescent girls with epilepsy should also take folate supplements and this should be reinforced at each reproductive health visit. Other expert clinicians recommend using low-dose pills and condoms in women who consistently use condoms, a designation that is often inappropriate for teens.
In their review of the data, the WHO panel has categorized use of OCs as category 3the risks usually outweigh the advantagesin patients on phenytoin, barbiturates, primadone, and carbamazepine. The WHO also recommends other contraceptive methods. Unfortunately many of those, including IUDs, condoms, foams, and sterilization, are inappropriate for most adolescent patients. Some of the newer antiepileptic drugs, including topiramate and oxcarbazepine, are also enzyme inducing.
Similarly, Norplant subdermal capsules are inappropriate in patients on antiepileptics like phenytoin and phenobarbital because these drugs increase production of SHBG, which in turn decreases the contraceptive efficacy of Norplant.4 It is also prudent to avoid progestin-only OCs in these patients. Depot medroxyprogesterone acetate (DMPA) on the other hand, is a reliable form of contraception in patients on antiepeleptics.
Pregnant patients with sickle cell anemia are at high risk for both serious fetal and maternal complications, making the prevention of unintended pregnancy of paramount importance. Some experts have expressed concern, however, about the theoretical possibility that OCs might increase sickling and have concluded that the disease is a "relative contraindication" for OCs.
Despite their concerns, there are no studies to indicate that OCs actually do increase the risk of sickling or the severity of sickle cell crises.1,5 With that in mind, WHO has classified the use of OCs in women with sickle cell disease as category 2: Advantages generally outweigh risks.
Another option for the sickle cell patient is DMPA. In a 2-year crossover trial, sickle cell patients using DMPA actually had a significant increase in red cell survival and a decrease in clinically painful sickle cell crises.6
There are several theoretical concerns regarding the use of OCs in young diabetic patients. These include their impact on insulin requirements and lipid levels, and the possibility that because thrombosis may be a more significant baseline risk in the diabetics, OCs may be contraindicated because they could significantly increase the thrombotic risk.
The evidence indicates that the currently used low-dose OC formulations do increase blood glucose levels somewhat, but their effect on insulin requirements appears very small and clinically insignificant.5 The progestin component of the Pill is the most critical in terms of carbohydrate metabolism.
Unfortunately the data on lipids and OCs in diabetic patients must usually be derived from nondiabetic groups of women on OCs. The impact of OCs on lipids in diabetic patients, of course, could be more clinically relevant or different than in patients without the disease. One conservative approach is to choose a formula that minimizes or has favorable effects on lipids in nondiabetic populations. It is still unknown if lipid changes are clinically relevant in either nondiabetic or diabetic populations. The effect of OCs on thrombosis is yet another area of controversy. Retrospective noncontrolled studies have reported an increase in thrombotic events.7
The WHO panel that evaluated the research on OCs and diabetes divided its recommendations into several categories, concluding that (1) no restrictions are necessary in women with gestational diabetes; (2) the advantages of OCs generally outweigh the risks among both insulin and noninsulin dependent patients with nonvascular disease; and (3) although patients with nephropathy, retinopathy, or neuropathy should be assessed individually, the risks usually outweigh advantages; otherwise OCs are unacceptable.1
With these guidelines in mind, you must constantly weigh the complications seen in diabetic pregnancies against some of the theoretical risks. In general, most experts have concluded that the benefits of OCs far outweigh risks in most diabetics, with the exception of those with severe disease and accompanying retinopathy, neuropathy, or nephropathy. Others have recommended that OCs only be used in diabetics without other significant risk factors (such as hyperlipidemia), that patients be strongly discouraged from smoking, or that adolescents and young women use OCs only until they can be switched to another reliable method such as an IUD.5
Given that progestins can thicken mucus, some authors have theorized that the progestin in OCs could worsen pulmonary function in cystic fibrosis (CF) patients. However, one study that evaluated 10 adolescents and young women with moderate-to-severe pulmonary disease at 0, 2, 4, and 6 months on OCs found no subjective indications of deterioration or objective decline in pulmonary function tests.8
Despite these findings, CF patients on OCs should be monitored for cholelithiasis because they are at an increased risk of this complication. Approximately three fourths of CF patients will also develop a polypoid cervicitis.8 While this self-limited problem is not dangerous, patients may present with breakthrough bleeding, or it may be difficult to perform a colposcopy if an abnormal Pap smear is coincidentally found.
It is well established that sex steroids are involved in SLE, and the disease is nine times more common in women than men. Interestingly, the rare male with SLE has an increased estradiol/testosterone ratio.10 In the animal model, estrogens clearly exacerbate and/or trigger a lupus-like autoimmune disease.
There are also several theoretical concerns surrounding the use of OCs in SLE patients. There is the possibility that estrogens exacerbate thrombosis among patients in a hypercoagulable state. Another possibility is that estrogens increase lupus flare-ups, a phenomenon sometimes seen in pregnancy. Retrospective studies have reported an increase in flare-ups in patients with severe lupus on combination OCs, compared to those on a progestin-only pill.12 With these data in mind, Speroff and Darney have concluded that OCs are contraindicated in SLE.5
Despite these concerns, among SLE patients who are unable or unwilling to use another birth control method, the medical risks of a pregnancy may outweigh the risk of using OCs. So clinicians must individualize each SLE patient's regimen and take into account the severity of the lupus, including life-threatening flare-ups, the presence of nephritis, and the patient's ability to use other contraceptive methods. A patient with mild disease who is just barely meeting the diagnostic criteria is significantly different from a patient with a recent life-threatening flare-up or with lupus nephritis. Medicolegal issues may also enter into the clinician's decision, especially if the adolescent is younger than 18 years.
If a clinician is thinking about prescribing OCs to a teenager with migraine headaches, two key questions have to be considered: Will the OCs exacerbate the migraines, and do migraine sufferers on OCs have an increased risk of cerebral vascular incidents?
The association between OCs and worsening of migraine headaches is not supported by scientific evidence. Almost all the studies linking OCs and migraines have been uncontrolled, anecdotal, or retrospective. The Walnut Creek study did not show an association between OC use and migraines.13
Experts have made various recommendations, based not on evidence-based medicine but on clinical opinion and the best available information. Some recommendations include routine provision of OCs to most migraine sufferers. Among patients with focal neurological findings like blindness or unilateral paresthesias, however, OCs might best be withheld, a position that's consistent with the WHO recommendations.1,13
Regarding the issue of cerebrovascular risk, the Collaborative Group Study of Stroke in Young Women is often quoted as evidence that OCs may be associated with an increased risk of thrombotic events in patients with migraines. This study reported an increased risk in thrombotic stroke and a decreased risk in hemorrhagic strokes in migraine sufferers on OCs, compared with control patients with migraines. The authors noted that it was difficult to make solid conclusions, however, because of the small numbers and differences between the hospital and community controls.9
Whether or not migraine patients with focal neurological signs are at increased risk for thrombosis, compared with women with common migraines who do not suffer neurological signs, is unknown. However, neurologic findings may be the result of thrombotic episodes, and at least from a medicolegal vantage, it is probably wise to withhold estrogens in these women. Many experts also feel it is best to use monophasic preparations to avoid waxing and waning of estrogen levels, a phenomenon that appears to be related to migraines in some women.13
Although it is impossible to make broad generalizations about the use of OCs in ill adolescents, applying the WHO criteria and individualizing your care when appropriate will provide teens the protection they need during their complex transition into adulthood.
1. Improving Access to Quality Care in Family Planning. Medical Eligibility Criteria for Contraceptive Use. Family and Reproductive Health World Health Organization, 1996.
2. Mattson RH, Cramer JA, Darney PD, et al. Use of oral contraceptives by women with epilepsy. JAMA. 1986;256:238-240.
3. Diamond MP, Greene JW, Thompson JM, et al. Interaction of anticonvulsants and oral contraceptives in epileptic adolescents. Contraception. 1985;31:623-632.
4. Haukkamaa M. Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment. Contraception. 1986;33:559-565.
5. Speroff L, Darney P. Summary: OC use and medical problems. In: Speroff L, Darney P, eds. A Clinical Guide for Contraception. Baltimore, Md: WIlliam and WIlkins; 1992;81.
6. DeCeulaer K, Gruber C, Hayes R, et al. Medroxyprogesterone acetate and homozygous sickle cell disease. Lancet. 1982;2:229-231.
7. Steel JM, Duncan LJ. Contraception for the insulin-dependent diabetic woman: the view from one clinic. Diabetes Care. 1980;3:557-560.
8. Fitzpatrick SB, Stokes DC, Rosenstein BJ, et al. Use of oral contraceptives in women with cystic fibrosis. Chest. 1984;86:863-867.
9. Oral contraceptives and stroke in young women. Associated risk factors. JAMA. 1975;75:718-722.
10. Inman RD, Jovanovic L, Dawood MY, et al. Systemic lupus erthyematosis in the male: a genetic and endocrine study. Arthritis Rheum. 1979;6:624.
11. Steinberg AD, Melez KA, Raveche ES, et al. Approach to the study of the role of sex hormones in autoimmunity. Arthritis Rheum. 1979;22:1170-1176.
12. Jungers P, Dougados M, Pelissier C, et al. Influence or oral contraceptive therapy on activity of systemic lupus erthyematosis. Arthritis Rheum. 1982;25:618-623.
13. Mattson RH, Rebar RW. Contraceptive methods for women with neurologic disorders. Am J Obstet Gynecol. 1993;168:2027-2032.
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Ann J. Davis, MD, has received honoraria and done research for several pharmaceutical companies, including Ortho-McNeil, Pharmacia & Upjohn, Wyeth-Ayerst, and Organon.
Ann Davis. CME: Should you prescribe OCs to ill teenagers?. Contemporary Ob/Gyn 2000;10:102-110.