Drug

Estradiol-Norgestimate

Common brand names:

Ortho-Prefest, Prefest

Summary of Interactions with Vitamins, Herbs, & Foods

  • Negative Interactions

    5

    • Estradiol

      Grapefruit

      Potential Negative Interaction

      In a small, controlled study of women with surgically removed ovaries, estradiol levels in the blood were significantly higher after estradiol was taken with grapefruit juice than when estradiol was taken alone. These results have been independently confirmed, suggesting that women taking oral estradiol should probably avoid grapefruit altogether.

      Grapefruit
      Estradiol
      ×
      1. Schubert W, Cullberg G, Edgar B, Hedner T. Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized women. Maturitas 1994;20:155-63.
      2. Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinylestradiol bioavailability? Contraception 1996;53:41-7.

    • Estradiol

      Pomegranate

      Potential Negative Interaction

      Pomegranate juice has been shown to inhibit the same enzyme that is inhibited by grapefruit juice. The degree of inhibition is about the same for each of these juices. Therefore, it would be reasonable to expect that pomegranate juice might interact with estradiol in the same way that grapefruit juice does.

      Pomegranate
      Estradiol
      ×
      1. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol 2006;98:705-6.
      2. Summers KM. Potential drug-food interactions with pomegranate juice. Ann Pharmacother 2006;40:1472-3.

    • Estradiol

      Quercetin

      Potential Negative Interaction

      Studies have shown that grapefruit juice significantly increases estradiol levels in the blood. One of the flavonoids found in grapefruit juice is quercetin. In a test tube study, quercetin was found to change estrogen metabolism in human liver cells in a way that increases estradiol levels and reduces other forms of estrogen. This effect is likely to increase estrogen activity in the body. However, the levels of quercetin used to alter estrogen metabolism in the test tube were much higher than levels found in the body after supplementing with quercetin.

      There is evidence from test tube studies that another flavonoid in grapefruit juice, naringenin, also has estrogenic activity. It has yet to be shown that dietary or supplemental levels of quercetin (or naringenin) could create a significant problem.

      Quercetin
      Estradiol
      ×
      1. Schubert W, Cullberg G, Edgar B, Hedner T. Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized women. Maturitas 1994;20:155-63.
      2. Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinylestradiol bioavailability? Contraception 1996;53:41-7.
      3. Schubert W, Eriksson U, Edgar B, et al. Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17 beta-estradiol. Eur J Drug Metab Pharmacokinet 1995;3:219-24.
      4. Kuiper GG, Lemmen JG, Carlsson B, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998;139:4252-63.

    • Ethinyl Estradiol and Norgestimate

      St. John’s Wort

      Potential Negative Interaction

      Eight cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

      St. John’s Wort
      Ethinyl Estradiol and Norgestimate
      ×
      1. Safety of St. John's wort (Hypericum perforatum) [letters to the editor from various authors]. Lancet 2000;355:575-7.
      2. Ernst E. Second thoughts about safety of St. John's wort. Lancet 1999;354:2014-6 [letter].

    • Estradiol

      Zinc

      Potential Negative Interaction

      This interaction is based on this drug belonging to a drug class. While this drug may differ from the text and references below, drugs within this class work in a similar way and this interaction is applicable to drugs within the same class.

      In a group of 37 postmenopausal women treated with conjugated estrogens and medroxyprogesterone for 12 months, urinary zinc and magnesium loss was reduced in those women who began the study with signs of osteoporosis and elevated zinc and magnesium excretion. The clinical significance of this interaction remains unclear.

      Zinc
      Estradiol
      ×
      1. Herzberg M, Lusky A, Blonder J, Frenkel. The effect of estrogen replacement therapy on zinc in serum and urine. Obstet Gynecol 1996;87:1035-40.

  • Supportive Interactions

    11

    • Ethinyl Estradiol and Norgestimate

      Folic Acid

      Replenish Depleted Nutrients

      Oral contraceptive (OC) use can cause folic acid depletion. In a double-blind trial of OC users with cervical dysplasia, supplementation with very large amounts (10 mg per day) of folic acid improved cervical health. Women with cervical dysplasia diagnosed while they are taking OCs should consult a doctor. Mega-folate supplementation should not be attempted without a doctor’s supervision, nor is there any reason to believe that folic acid supplementation would help people with cervical cancer.

      Folic Acid
      Ethinyl Estradiol and Norgestimate
      ×
      1. Lindenbaum J, Whitehead N, Reyner F. Oral contraceptive hormones, folate metabolism, and the cervical epithelium. Am J Clin Nutr 1975;28:346-53.
      2. Butterworth CE Jr, Hatch KD, Gore H, et al. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr 1982;35:73-82.

    • Ethinyl Estradiol and Norgestimate

      Magnesium

      Replenish Depleted Nutrients

      Women using OCs were found to have significantly lower serum magnesium levels in a controlled study. In a preliminary study, blood levels of magnesium decreased in women taking an OC containing ethinyl estradiol and levonorgestrel. Although the importance of this interaction remains somewhat unclear, supplementation with 250–350 mg of magnesium per day is a safe and reasonable supplemental level for most adults.

      Magnesium
      Ethinyl Estradiol and Norgestimate
      ×
      1. Olatunbosum DA, Adeniyi FA, Adadevoh BK. Effect of oral contraceptives on serum magnesium levels. Int J Fertil 1974;19:224-6.
      2. Blum M, Kitai E, Ariel Y, et al. Oral contraceptive lowers serum magnesium. Harefuah 1991;121:363-4 [in Hebrew].

    • Ethinyl Estradiol and Norgestimate

      Vitamin B1

      Replenish Depleted Nutrients

      A review of literature suggests that women who use OCs may experience decreased vitamin B1, B2, B3, B12, C, and zinc levels. OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A. OCs may interfere with manganese absorption. The clinical importance of these actions remains unclear.

      Vitamin B1
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197-8.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.

    • Ethinyl Estradiol and Norgestimate

      Vitamin B12

      Replenish Depleted Nutrients

      A review of literature suggests that women who use OCs may experience decreased vitamin B1, B2, B3, B12, C, and zinc levels. OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A.OCs may interfere with manganese absorption. The clinical importance of these actions remains unclear.

      Vitamin B12
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197-8.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.

    • Ethinyl Estradiol and Norgestimate

      Vitamin B2

      Replenish Depleted Nutrients

      A review of literature suggests that women who use OCs may experience decreased vitamin B1, B2, B3, B12, C, and zinc levels. OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A. OCs may interfere with manganese absorption. The clinical importance of these actions remains unclear.

      Vitamin B2
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197-8.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.

    • Ethinyl Estradiol and Norgestimate

      Vitamin B3 (Niacin)

      Replenish Depleted Nutrients

      A review of literature suggests that women who use OCs may experience decreased vitamin B1, B2, B3, B12, C, and zinc levels. OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A. OCs may interfere with manganese absorption. The clinical importance of these actions remains unclear.

      Vitamin B3 (Niacin)
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197-8.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.

    • Ethinyl Estradiol and Norgestimate

      Vitamin B6

      Replenish Depleted Nutrients
      Laboratory evidence of vitamin B6 deficiency is common in women taking oral contraceptives.
      Vitamin B6
      Ethinyl Estradiol and Norgestimate
      ×
      1. Adams PW, Folkard J, Wynn V, Seed M. Influence of oral contraceptives, pyridoxine (vitamin B6), and tryptophan on carbohydrate metabolism. Lancet 1976;1:759-64.

    • Ethinyl Estradiol and Norgestimate

      Vitamin C

      Replenish Depleted Nutrients

      A review of literature suggests that women who use OCs may experience decreased vitamin B1, B2, B3, B12, C, and zinc levels. OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A. OCs may interfere with manganese absorption. The clinical importance of these actions remains unclear.

      Vitamin C
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197-8.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.

    • Ethinyl Estradiol and Norgestimate

      Zinc

      Replenish Depleted Nutrients

      A review of literature suggests that women who use OCs may experience decreased vitamin B1, B2, B3, B12, C, and zinc levels. OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A. OCs may interfere with manganese absorption. The clinical importance of these actions remains unclear.

      Zinc
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197-8.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.

    • Estradiol

      Vitamin D

      Support Medicine

      In controlled studies, the addition of 300 IU per day of vitamin D3 (cholecalciferol) did not improve the bone-preserving or fracture-preventing effects of hormone replacement with estradiol plus a progestin (a synthetic form of progesterone) in postmenopausal women without osteoporosis. However, in a controlled study of osteoporotic women, only those receiving both hormone replacement and vitamin D had increases in bone density of the hip; no improvement occurred in the hip with hormones alone. More research is needed to determine conclusively when vitamin D is important to add to hormone replacement.

      Vitamin D
      Estradiol
      ×
      1. Komulainen M, Kroger H, Tuppurainen MT, et al. Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized trial. J Clin Endocrinol Metab 1999;84:546-52.
      2. Komulainen MH, Kroger H, Tuppurainen MT, et al. HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial. Maturitas 1998;31:45-54.
      3. Tuppurainen MT, Komulainen M, Kroger H, et al. Does vitamin D strengthen the increase in femoral neck BMD in osteoporotic women treated with estrogen? Osteoporos Int 1998;8:32-8.

    • Ethinyl Estradiol and Norgestimate

      Vitamin B6

      Reduce Side Effects
      In a double-blind trial, supplementation with 20 mg of vitamin B6 twice a day for 2 months improved depression in women taking oral contraceptives who had laboratory evidence of vitamin B6 deficiency. However, vitamin B6 did not relieve depression in women who did not have vitamin B6 deficiency.
      Vitamin B6
      Ethinyl Estradiol and Norgestimate
      ×
      1. Adams PW, Wynn V, Rose DP, et al. Effect of pyridoxine hydrochloride (vitamin B6) upon depression associated with oral contraception. Lancet 1973;I:897-904.
      2. Adams PW, Wynn V, Seed M, Folkard J. Vitamin B6, depression, and oral contraception. Lancet 1974;2:516-7.

  • Explanation Required

    5

    • Ethinyl Estradiol and Norgestimate

      Calcium

      Needs Explanation
      Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A. Oral contraceptives may interfere with manganese absorption. The clinical importance of these actions remains unclear.

       

      Calcium
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Berg G, Kohlmeier L, Brenner H. Effect of oral contraceptive progestins on serum copper concentration. Eur J Clin Nutr 1998;52:711-5.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.

    • Ethinyl Estradiol and Norgestimate

      Copper

      Needs Explanation
      Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A. Oral contraceptives may interfere with manganese absorption. The clinical importance of these actions remains unclear.

       

      Copper
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Berg G, Kohlmeier L, Brenner H. Effect of oral contraceptive progestins on serum copper concentration. Eur J Clin Nutr 1998;52:711-5.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.

    • Ethinyl Estradiol and Norgestimate

      Iron

      Needs Explanation

      Menstrual blood loss is typically reduced with use of OCs. This can lead to increased iron stores and, presumably, a decreased need for iron in premenopausal women. Premenopausal women taking OCs should have their iron levels monitored and talk with their prescribing doctor before using iron-containing supplements.

      Iron
      Ethinyl Estradiol and Norgestimate
      ×
      1. Frassinelli-Gunderson EP, Margen S, Brown JR. Iron stores in users of oral contraceptive agents. Am J Clin Nutr 1985;41(4):703.

    • Ethinyl Estradiol and Norgestimate

      Manganese

      Needs Explanation
      Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A. Oral contraceptives may interfere with manganese absorption. The clinical importance of these actions remains unclear.

       

      Manganese
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Berg G, Kohlmeier L, Brenner H. Effect of oral contraceptive progestins on serum copper concentration. Eur J Clin Nutr 1998;52:711-5.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.

    • Ethinyl Estradiol and Norgestimate

      Vitamin A

      Needs Explanation
      Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A. Oral contraceptives may interfere with manganese absorption. The clinical importance of these actions remains unclear.

       

      Vitamin A
      Ethinyl Estradiol and Norgestimate
      ×
      1. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 210-1 [review].
      2. Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-4.
      3. Berg G, Kohlmeier L, Brenner H. Effect of oral contraceptive progestins on serum copper concentration. Eur J Clin Nutr 1998;52:711-5.
      4. Holt GA. Food & Drug Interaction. Chicago: Precept Press, 1998, 197.
The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist.

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