With Comments by Adriane Fugh Berman, MD
No Interaction Between Soy and Oral Contraceptives
February 2000; Volume 2: 16
Source: Martini MC, et al. Effects of soy intake on sex hormone metabolism in premenopausal women. Nutr Cancer 1999; 34:133-139.
Design and Setting: Randomized, controlled, crossover study for four menstrual cycles.
Subjects: Forty premenopausal, free living women aged 18 to 40 years recruited from the University of Minnesota community. Twenty subjects were using oral contraceptives (OC). Thirty-six women were included in the final analysis.
Treatment/Dose/Duration: Subjects were randomized to control (10 fluid oz of skim milk) or soy beverage (10 fluid oz of skim milk plus 34 g Take Care providing 20 g protein and 38 mg total isoflavones, including 13 mg daidzein and 23 mg genistein) along with their normal diet. Subjects were asked to avoid soy products and flaxseed and to maintain their usual exercise levels. Each phase lasted two menstrual cycles.
Outcome Measures: Menstrual cycle length, serum levels of estrone, estradiol, sex hormone-binding globulin (SHBG), DHEAS, prolactin, and progesterone; urinary estrogen metabolites.
Results: Soy consumption did not result in any significant differences in menstrual cycle length, serum estrone, estradiol, SHBG, DHEAS, prolactin, or progesterone concentrations in either OC users or non-users. No significant changes in the ratio of the urinary estrogen metabolites 2-hydroxyestrone to 16a-hydroxyestrone were seen in either group; levels of these urinary estrogen metabolites, however, were significantly lower among OC users compared to non-users. Mean lengths of the follicular phase, luteal phase, or overall cycle did not change in non-OC users, and no anovulatory cycles occurred during the study. Although cycle length was not affected in OC users, three OC users reported either breakthrough bleeding or slightly delayed menses while they were taking soy. Soy consumption contributed to greater intake of protein, but did not significantly affect dietary intake.
Funding: Sponsored by the Minnesota soybean research and promotion council and Minnesota agricultural experimental station project 18-64. Protein Technologies International donated the soy drink.
Comments: This is a very interesting study that is the first phytoestrogen supplementation study to include women using oral contraceptives. Phytoestrogens are less than 1% as potent as estradiol, but the question has been raised nonetheless of possible interactions with estrogen-containing drugs. Although studies have been mixed on whether phytoestrogen supplementation in premenopausal women affects menstrual cycle length or hormone levels, more recent studies have indicated little to no effect. It must be kept in mind that this study utilized soy protein, which has been consumed as a food for thousands of years. Phytoestrogens are not interchangeable; it is not clear whether red clover or other phytoestrogen-containing plants would have the same effect.