Oral contraceptives (drug interactions)
Oral contraceptives (OCs) are medications used primarily to prevent pregnancy, but their effectiveness can be influenced by various drug interactions. Certain herbal supplements and foods, such as St. John's wort, grapefruit, and indole-3-carbinol, may alter how OCs work, potentially leading to decreased effectiveness or increased side effects. For example, St. John's wort may speed up the metabolism of OCs, resulting in breakthrough bleeding or unintended pregnancies. Other substances, like grapefruit, can cause estrogen levels to rise excessively, leading to adverse effects such as irregular periods.
Additionally, supplements like milk thistle and licorice could hinder the absorption or action of OCs, while some interactions may enhance the risk of harmful effects, such as increased sensitivity to sunlight. While some interactions are well-documented, others are still being studied, highlighting the importance of consulting healthcare providers when combining OCs with other medications or supplements. Women using OCs should stay informed about potential interactions to ensure their contraceptive method remains effective and safe.
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Subject Terms
Oral contraceptives (drug interactions)
DEFINITION: Drugs used to prevent pregnancy.
INTERACTIONS: Androstenedione, aloe vera, black cumin, chamomile, chasteberry, dong quai, folate, Echinacea, ginseng, grapefruit, green tea, indole-3-carbinol, licorice, marijuana, milk thistle, red bush, resveratrol, rosemary, saffron, St. John’s wort, saw palmetto, soy
TRADE NAMES: Alesse, Brevicon, Demulen, Desogen, Estrostep, Genora, Jenest, Levora, Cryselle, Micronor, Mircette, Modicon, Nelova, Nordette, Norethin, Norinyl, Errin, Triphasil, Zovia, Sprintec, Tri-Lo-Sprintec, Quartette, Aviane, Mili, Altavera, Amethia, Camrese, Daysee, Dolishale, Xulane, Balziva, Briellyn, Gildagia, Modicon, Philith, Wera, Zenchent, Yaz, Ocella, Beyaz
Folate
Effect: Supplementation Possibly Helpful
Although the evidence is not consistent, women who are taking oral contraceptives (OCs) may need extra folate. Because folate deficiency is fairly common, even among women who are not taking OCs, and because the body should not lack an essential nutrient, taking a folate supplement may be useful.
St. John’s Wort
Effect: Decreased Effectiveness of Drug
Reliable case reports, as well as controlled clinical trials, indicate that St. John’s wort interferes with the effectiveness of oral contraceptives by speeding up their breakdown. It may lead to breakthrough bleeding and even unwanted pregnancies.
A literature review in 2012 confirmed that St. John's wort decreased the plasma concentration of several common OC compounds. Negative interactions were less likely among those taking extracts containing under 1 percent hyperforin, the active compound in St. John's wort; however, supplements tend to vary in their contents and lack labeling regarding hyperforin content.
Indole-3-Carbinol
Effect: Possible Reduced Effectiveness of Drug
Indole-3-carbinol (I3C) is a substance found in broccoli that may have cancer-preventive effects. One of its mechanisms of action is thought to involve facilitating the inactivation of estrogen, as well as blocking its effects on cells. The net result could be decreased OC effectiveness.
Dong Quai, St. John’s Wort
Effect: Possible Harmful Interaction
OCs have been reported to cause increased sensitivity to the sun, amplifying the risk of sunburn or skin rash. Because dong quai and St. John’s wort may also cause this problem, taking these herbal supplements while taking OCs might add to this risk. Wearing sunscreen or protective clothing during sun exposure is advisable if one takes one of these herbs while using OCs.
Rosemary
Effect: Possible Harmful Interaction
Weak evidence hints that the herb rosemary may enhance the liver’s ability to deactivate estrogen in the body. This could potentially interfere with the activity of medications that contain estrogen.
Grapefruit and Other Citrus Fruits
Effect: Possible Harmful Interaction
Grapefruit juice slows the body’s normal breakdown of several drugs, including estrogen, allowing it to build up to potentially excessive levels in the blood. This can lead to side effects like irregular periods and breast tenderness. However, experts believe it will not decrease the effectiveness of birth control pills. If one takes estrogen, the safest approach is to avoid grapefruit juice altogether. Similar effects have also been observed from consuming Seville oranges, pomelos, tangelos, and limes.
Resveratrol
Effect: Possible Harmful Interaction
The supplement resveratrol has a chemical structure similar to that of the synthetic estrogen diethylstilbestrol and produces estrogenic effects. For this reason, it should not be combined with prescription estrogen products.
Milk Thistle
Effect: Possible Decreased Action of Drug
One report has noted that an ingredient of milk thistle, silibinin, can inhibit a bacterial enzyme called beta-glucuronidase. This enzyme helps OCs work. Taking milk thistle could, therefore, reduce the effectiveness of OCs.
Androstenedione
Effect: Theoretical Harmful Interaction
Androstenedione has become popular as a sports supplement, on the theory that it increases testosterone levels, as well as sports performance. However, there is no evidence that it is effective. In addition, androstenedione appears more likely to elevate estrogen than testosterone levels. This could increase the risk of developing estrogen-related diseases, including breast and uterine cancers. Women taking estrogen should not take androstenedione.
Soy
Effect: Probably No Interaction
Fears have been expressed by some experts that soy or soy isoflavones (phytoestrogens) might interfere with OC action. However, one study of thirty-six women suggests that such concerns are groundless.
Chasteberry
Effect: Possible Reduced Effectiveness of Drug
Chasteberry, or chaste tree berry (Vitex agnus-castus), is often taken for menstrual problems or acne. However, it may change the balance of estrogen and progesterone, thus interfering with OC effectiveness.
Saw Palmetto
Effect: Possible Reduced Effectiveness of Drug
Saw palmetto may reduce estrogenic effects, thereby inhibiting OC effectiveness.
Licorice
Effect: Possible Harmful Interaction
Limited study evidence suggests prolonged consumption of licorice may raise blood pressure and lower potassium levels when taken with OCs.
Black Cumin
Effect: Probably No Interaction
The phytoestrogen in black cumin (Nigella sativa) does not appear to bind well to estrogen receptors and, therefore, may have little effect on OCs. A 2013 study found that it could induce menstruation.
Ginseng
Effect: Possible Reduced Effectiveness of Drug
Ginseng (Panax spp.) may both reduce the metabolism of the estrogen compound in OCs and promote certain estrogen receptors.
Other Interactions
Several studies suggest that OCs may interfere with the absorption or metabolism of magnesium, vitamins B2, B6, B12, B9, C, and zinc. Except for the trials involving magnesium, these studies used older, high-dose OCs. Modern, low-dose OCs may not affect nutrients to the same extent. Women taking OCs should make sure to get enough of these nutrients. Other supplements believed to interfere with some hormonal birth control methods include flaxseed and garlic. Some OCs raise the levels of iron in the blood. Women using oral birth control methods should avoid iron supplementation unless instructed by their physician.
A 2020 literature review suggested supplementation with aloe vera (Aloe barbadensis), green tea (Camelia sinenesis), chamomile (Matricaria chamomilla), marijuana (Cannabis sativa), or red bush (Lessertia frutescens) may inhibit the function of enzymes needed to metabolize estrogen-based OCs, reducing their effectiveness. Saffron (Crocus sativus) and purple coneflower (Echinacea purpurea) were also linked to lower OC concentrations in the blood.
Bibliography
Bradlow, H. L., et al. “Multifunctional Aspects of the Action of Indole-3-Carbinol as an Antitumor Agent.” Annals of the New York Academy of Sciences, vol. 889, 1999, pp. 204–13.
"Grapefruit and Birth Control Pills: Your Questions Answered." Drugs.com, 26 Jan. 2024, www.drugs.com/article/grapefruit-and-birth-control.html. Accessed 20 Sept. 2024.
Gurley, Bill, et al. “Pharmacokinetic Herb-Drug Interactions (Part 2): Drug Interactions Involving Popular Botanical Dietary Supplements and Their Clinical Relevance.” Planta Medica, vol. 78, no. 13, 2012, pp. 1490–1514, doi:10.1055/s-0031-1298331.
Hall, Stephen D., et al. “The Interaction between St. John's Wort and an Oral Contraceptive.” Clinical Pharmacology and Therapeutics, vol. 74, no. 6, 2003, pp. 525-35, doi:10.1016/j.clpt.2003.08.009.
Hlengwa, Nokulunga, et al. “Herbal Supplements Interactions with Oral Oestrogen‐Based Contraceptive Metabolism and Transport.” Phytotherapy Research, 3 Feb. 2020, doi:10.1002/ptr.6623.
Martini, M. C., et al. “Effects of Soy Intake on Sex Hormone Metabolism in Premenopausal Women.” Nutrition and Cancer, vol. 34, 1999, pp. 133–39.
"Medicines That Interfere with Birth Control Pills." WebMD, 27 May 2024, www.webmd.com/sex/birth-control/medicines-interfere-birth-control-pills. Accessed 20 Sept. 2024.
Meng, Q., et al. “Indole-3-Carbinol Is a Negative Regulator of Estrogen Receptor-Alpha Signaling in Human Tumor Cells.” Journal of Nutrition, vol. 130, 2000, pp. 2927–31.
Michnovicz, J. J. “Increased Estrogen 2-Hydroxylation in Obese Women Using Oral Indole-3-Carbinol.” International Journal of Obesity and Related Metabolic Disorders, vol. 22, 1998, pp. 227–29.
Preston, Claire L. Stockley’s Drug Interactions. 12th ed., Pharmaceutical Press, 2021.
Takanaga, H., et al. “Relationship between Time after Intake of Grapefruit Juice and the Effect on Pharmacokinetics and Pharmacodynamics of Nisoldipine in Healthy Subjects.” Clinical Pharmacology and Therapeutics, vol. 67, 2000, pp. 201–14.