ESTRADIOL

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Estradiol is a semisynthetic human estrogenic hormone used to treat menopausal symptoms, to prevent osteoporosis in postmenopausal women, and as replacement therapy in other conditions of inadequate estrogen production.

Estradiol is available as an oral drug, a transdermal (skin) patch, and as a vaginal cream.

Safetychecker Summary for Estradiol
(for details about the summarized interactions, read the full article)

Avoid: Adverse interaction—Avoid these supplements when taking this medication because taking them together may cause undesirable or dangerous results.	Grapefruit* Quercetin*
Check: Other—Before taking any of these supplements or eating any of these foods with your medication, read this article in full for details.	Vitamin D
Depletion or interference	None known
Side effect reduction/prevention	None known
Supportive interaction	None known
Reduced drug absorption/bioavailability	None known

Interactions with Dietary Supplements

Quercetin
Studies have shown that grapefruit juice significantly increases estradiol levels in the blood.^{1 2} 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.³ 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 stuudies that another flavonoid in grapefruit juice, naringenin, also has estrogenic activity.⁴ It has yet to be shown that dietary or supplemental levels of quercetin (or naringenin) could create a significant problem.

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.^{5 6} 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.⁷ More research is needed to determine conclusively when vitamin D is important to add to hormone replacement.

Interactions with Foods and Other Compounds

Grapefruit
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.⁸ These results have been independently confirmed,⁹ suggesting that women taking oral estradiol should probably avoid grapefruit altogether.

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.

5. 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.

6. 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.

7. 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.

8. 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.

9. Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinylestradiol bioavailability? Contraception 1996;53:41–7.

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Copyright © 2002 Healthnotes, Inc.  All rights reserved. www.healthnotes.com

Please read the disclaimer about the limitations of the information provided here. Do NOT rely solely on the information in this article.

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over-the-counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2003.

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