Estradiol-Norethindrone Acetate

Drug Information

Common brand names:

Activella, CombiPatch

Summary of Interactions with Vitamins, Herbs, & Foods

Types of interactions:BeneficialAdverseCheck

Replenish Depleted Nutrients

  • Folic Acid

    Oral contraceptive use can cause folic acid depletion.

  • Magnesium

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Vitamin B1

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Vitamin B12

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Vitamin B2

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Vitamin B3 (Niacin)

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Vitamin B6
    Laboratory evidence of vitamin B6 deficiency is common in women taking oral contraceptives.
    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Vitamin C

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Zinc

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Reduce Side Effects

  • Folic Acid

    In a double-blind trial of oral contraceptive 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 oral contraceptives 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.

  • Vitamin B6
    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.

Support Medicine

  • Vitamin D

    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.

Reduces Effectiveness

  • none

Potential Negative Interaction

  • Zinc

    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.

  • 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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • 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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Quercetin

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • St. John’s Wort

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Explanation Required

  • Calcium

    A review of literature suggests that women who use oral contraceptives may experience decreased vitamin B1, B2, B3, B12, C, and zinc levels. 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

    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.

  • Iron

    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.

  • Manganese

    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 A

    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.

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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