In this cross-sectional study among premenopausal women, we did not find significant associations between dietary fat, fiber, or carbohydrates and plasma levels of estrogens, progesterone, androgens, or SHBG. However, we observed modest but significant inverse associations between the percentage of energy from dietary fat and plasma levels of both IGF-I and IGFBP-3 and a positive association between the percentage of energy from carbohydrates and plasma IGF-I levels.
Results from the few prior studies of premenopausal women have been inconsistent, although differences in study design (e.g., the intervention used, hormones measured) complicate comparisons. In a meta-analysis of 10 intervention studies conducted among premenopausal women, subjects changed from a high-fat (29 - 46% of fat in calories) to a low-fat (12 - 25% of fat calories) diet typically for 2 or 3 months, and overall a statistically significant 7.4% reduction in serum estradiol level was observed [64
]. However, only one of the 10 studies had a simultaneous control group [65
]. In one 2-month intervention study with 62 women a significant reduction was observed in luteal estradiol and estrone levels among wheat-bran but not oat- or corn-bran supplements groups [66
]. However, two other dietary intervention studies (using a 12-month low-fat/high-fiber intervention among 213 women [67
] or a 2-month replacement of saturated fat with polyunsaturated fat among 14 women [68
]) found no influence of diet change on blood estrogen levels in the luteal [67
] or follicular [68
] phases. Several cross-sectional studies found significant positive associations between total and monounsaturated fat intakes and follicular estrone levels [69
] or inverse associations between the ratio of polyunsaturated to saturated fat (P/S) and estradiol and estrone during the luteal phase [70
], or higher follicular plasma estrogen levels among high-fat/low-fiber group [71
]. In other studies, no significant associations were observed between dietary fiber intakes and estrogen levels during the follicular [69
] or luteal [68
] phases. Cumulatively, no strong consistent associations have been observed, and weak to moderate effects remain uncertain; our study, which is substantially larger than previous cross-sectional studies, suggests there is little, if any, association between these macronutrients and premenopausal estrogens. The significantly higher levels of follicular estradiol among those with the lowest percent energy from fat suggested a threshold effect, but we need to be careful in interpreting these data as there were only 20 participants in this category of intake.
Fewer studies have been done to investigate the associations between diet and endogenous levels of SHBG, androgens, or progesterone. A 2-month intervention study reported a significant reduction in follicular androstenedione and an increase in luteal testosterone levels after a low-fat/high-fiber intervention [72
]. Previous intervention studies also found no significant change in blood SHBG after a 2-month high-fiber intervention [66
] or in luteal progesterone levels after either a low-fat/high-fiber [67
] or bran supplement [66
] intervention. Several cross-sectional studies found higher SHBG levels with increased monounsaturated fat intake [69
] or in the high-fat/low-fiber intake group [71
]. Other studies also reported significant positive associations between P/S intakes with DHEAS [70
], or an inverse association between dietary fiber with serum luteal levels of androstenedione among premenopausal women [73
]. However, in these studies, no differences were found in plasma testosterone levels between groups[71
], and no significant associations of fat and fiber intake with androgens or SHBG [70
] or fiber with androgen, SHBG, or progesterone [73
]. Similarly, we observed no association between fat/fiber and plasma androgens or progesterone.
We found modest but significant associations between plasma IGF-I levels and both total fat (inverse association) and carbohydrates (positive association). Since the percentage of energy from total fat and from carbohydrates is highly correlated (Spearman correlation coefficient is −0.86), it is hard to distinguish the effect of fat versus carbohydrates. The inverse association between total fat and IGF-I is consistent with a previous intervention study which found IGF-I that levels rose significantly after an intervention to reduce total fat intake [74
]. However, in other intervention studies, IGF-I levels did not change [75
] after a low-fat/high-fiber diet intervention. Previous cross-sectional studies reported positive [49
] or no [51
] associations between fat intake and IGF-I levels. The significant but modest inverse associations between intakes of total fat, animal fat, saturated fat, and monounsaturated fat and plasma IGFBP-3 observed in our study are supported by some previous cross-sectional studies in which IGFBP-3 levels were inversely related to fat intakes[48
] but not another large cross-sectional study including 2,109 women which found no significant associations with dietary fat intake [51
]. Our findings did not appear to be due to total energy or to protein intake, since neither of them was significant in our multivariate models. Residual confounding by known confounders also is unlikely since the results did not change substantially after multivariable adjustment. The modest positive association between carbohydrates and plasma IGF-I is inconsistent with the few prior cross-sectional studies which found no association among premenopausal women [78
] or an inverse association among healthy adults ages 30 to 84 years old [49
The strengths of our study include its relatively large sample size, generally low laboratory CVs, and evaluation of a large number of hormones with careful timing by menstrual cycle phase. Our study also had several potential limitations. The women in our study are well-nourished, and the average intake of fiber and percent energy from fat per day were 20.2 g/day and 29.1%, which were less extreme than those in a few prior studies [66
]. If there are associations between diet and endogenous hormone levels and the associations are non-linear (a possibility suggested by our findings on fat intake and follicular estradiol), our study might not have a sufficient number of subjects in the effect range. But we previously reported an inverse association between fat intakes and plasma sex steroid hormone levels among postmenopausal women [61
], and associations of both total fat [79
] and fiber [80
] with disease risk. Error in our diet assessment is also a concern, although our use of two FFQs collected 4 years apart should dampen this error. Finally, although the intraclass correlation coefficients (ICC) for IGFs and androgens were quite high (range from 0.59 to 0.89 over up to 3 years), the ICC for estrogens and progesterone were lower [57
]. Although we controlled for day of luteal blood draw, the possible associations could be attenuated due to that source of within-person variability. Finally, we made a large number of comparisons in this analysis, and we cannot rule out the possibility of observing several associations by chance.
In conclusion, our results suggest that a low-fat/high-fiber and carbohydrate diet within the range of intake generally observed in the USA is not importantly associated with endogenous levels of sex steroid hormones but may modestly increase IGF-I and IGFBP-3 levels among premenopausal women. Further large studies are needed to investigate the relationships between dietary intakes and endogenous hormone levels throughout the menstrual cycle.