Epilepsy Rx may impact young women's bones
Recent research findings indicate that young women who use the commonly used epilepsy drug phenytoin for one year showed significant bone loss compared to women taking other epilepsy drugs.1 What implications, if any, does such research hold for family planning clinicians who prescribe contraception for patients with epilepsy?
To perform the study, researchers examined the bone health of 93 women with epilepsy who were between ages 18 and 40 and were taking the antiepileptic drugs (AEDs) phenytoin, carbamazepine, lamotrigine, or valproate. Bone mineral density was measured at the spine and two areas of the hip (the femoral neck and total hip) at the beginning of the study and one year later. Researchers also analyzed the women's nutrition and physical activity levels, along with other factors that affect bone health.
Findings indicate that women taking phenytoin for one year lost 2.6% of their bone density in the femoral neck of the hip. Women who were taking the other epilepsy drugs did not lose any bone density in the femoral neck. There was no bone loss at the spine or the total hip in any of the groups, researchers report.
The study represents one of a few longitudinal studies to evaluate the individual effects of several commonly used AEDs on bone mineral density (BMD) and markers of bone and mineral metabolism, the researchers note. Other longitudinal studies have evaluated a single drug or have studied patients taking multiple AEDs. In addition, researchers controlled for other factors known to affect bone health, they explain.
An important limitation of the study lies in the fact that researchers did not include a group of women without epilepsy to serve as normal controls and might have missed subtle differences in bone and mineral metabolism. Women who participated in the study were not randomly assigned to the studied drug but were receiving the AED best able to control their seizure activity, researchers note.
Bone health is important
How do such findings come into play for family planning clinicians who prescribe contraception for women with epilepsy?
"I think it's important when considering an AED or, in this case, a contraceptive choice that you consider other comorbidities such as bone," says Alison Pack, MD, assistant professor of clinical neurology at the Neurological Institute at Columbia University in New York City and the lead author of the current bone health article. "I think the significance of this work is that you're not just prescribing for the main effect of the medication; you're also subjecting that individual to potential long-term consequences, which may be bone."
Bone health is an important consideration in providing care for all women. Osteoporosis, a condition characterized by low bone mass and structural deterioration of bone tissue, is a key concern for women, particularly as they age. Some 10 million Americans — 80% of them women — have osteoporosis, according to the National Institutes of Health's Osteoporosis and Related Bone Diseases National Resource Center.2 The center estimates that an additional 34 million Americans have low bone mass (osteopenia), placing them at increased risk for osteoporosis and related fractures.2
Adolescence is an important time when it comes to bone health: Half of a woman's bone mass is gained during puberty and the first several years after menarche; peak bone mass is achieved in the early to mid-20s.3
Family planners must take several things into consideration when reviewing contraceptive options for women with epilepsy. Epilepsy and AED-related changes in hypothalamic, pituitary, and gonadal hormones have been associated with increased rates of infertility, anovulatory cycles, menstrual irregularity, and polycystic ovaries. Children who are born to women with epilepsy have a higher risk of birth defects, probably related to in-utero exposure to antiepileptic drugs.4
Cytochrome P450-inducing antiepileptic drugs enhance hepatic metabolism of contraceptive steroids and increase binding of steroids to serum proteins, which results in a reduction of the concentration of biologically active steroid hormone.4 Women receiving a liver enzyme-inducing antiepileptic medication have at least a 6% failure rate per year for OCs.5
Reports have associated the contraceptive injection depot medroxyprogesterone (DMPA, Depo-Provera, Pfizer; New York City) with a decrease in the frequency of seizures.6 However, clinicians have been taking a hard look at DMPA use following the Food and Drug Administration's 2004 addition of a "black box" warning to the drug's labeling to highlight that prolonged use may result in the loss of bone mineral density. According to the revised labeling, the injectable contraceptive should be used as a long-term birth control method (longer than two years) only if other birth control methods are inadequate. Women who continue to use Depo-Provera past the two-year mark should have their BMD evaluated, according to the labeling.
Research released in 2005 indicates that lower bone density appears to recover in adolescent females once they stop using DMPA.7 Findings from another study indicate that while BMD may decline in adult users of DMPA, it is followed by substantial recovery after discontinuation.8
Another option for women in epilepsy is to use the copper T-280A intrauterine device (ParaGard IUD, Duramed, a subsidiary of Barr Pharmaceuticals; Pomona, NY) or the levonorgestrel intrauterine system (Mirena IUS, Bayer HealthCare Pharmaceuticals; Wayne, NJ).
Advise women to check for breakthrough bleeding while on hormonal contraception. Such bleeding midcycle may be a sign of ovulation.9 Provide women with condoms or spermicide as backup contraception.9
References
- Pack AM, Morrell MJ, Randall A, et al. Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy. Neurology 2008; 70:1,586-1,593.
- National Institutes of Health. Osteoporosis and Related Bone Diseases National Resource Center. What Is Osteoporosis? Fact sheet. March 2006. Accessed at www.niams.nih.gov.
- DMPA and bone density loss: An update. Contraception Report 1999; accessed at www.contraceptiononline.org.
- Morrell MJ. Epilepsy in women. Am Fam Physician 2002; 66:1,489-1,494.
- Mattson RH, Cramer JA, Darney PD, et al. Use of oral contraceptives by women with epilepsy. JAMA 1986; 256: 238-240.
- Frederiksen MC. Depot medroxyprogesterone acetate contraception in women with medical problems. J Reprod Med 1996; 41(5 Suppl):414-418.
- Scholes D, LaCroix AZ, Ichikawa LE, et al. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Arch Pediatr Adolesc Med 2005; 159:139-144.
- Kaunitz AM, Miller PD, Rice VM, et al. Bone mineral density in women aged 25-35 years receiving depot medroxyprogesterone acetate: Recovery following discontinuation. Contraception 2006; 74:90-99.
- Epilepsy Foundation. Birth Control for Women with Epilepsy. Accessed at www.epilepsyfoundation.org.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content