Fruit and Vegetable Consumption and Risk of Endometriosis

H. R. Harris; A. C. Eke; J. E. Chavarro; S. A. Missmer

Disclosures

Hum Reprod. 2018;33(4):715-727. 

In This Article

Results

During 840 012 person-years of follow-up contributed by 70 835 women, 2609 incident cases of laparoscopically confirmed endometriosis were reported. Of these, 2114 never reported infertility and 313 cases reported an infertility evaluation during the same follow-up period as their laparoscopic confirmation of endometriosis. Women with the greatest intake of fruits were slightly younger, less likely to be Caucasian, less likely to be current smokers, nulliparous and obese than those with lower total fruit intake. Those who had the greatest intake of vegetables were more likely to be physically active and had an earlier age at menarche than those with lower total vegetable intake (Table I).

Higher consumption of total fruits and vegetables was associated with reduced endometriosis risk. Women consuming 3, 4, 5 and ≥6 servings/day of fruits and vegetables had 9% (95% CI = 0.77–1.07), 10% (95% CI = 0.76–1.06), 18% (95% CI = 0.69–0.97) and 12% (95% CI = 0.75–1.03) reduced risks for endometriosis compared to women consuming ≤2 servings/day, respectively (P trend = 0.32) (Table II). In a model using restricted cubic splines, the relation between total fruit and vegetable intake and endometriosis appeared non-linear (P non-linearity = 0.01) and was statistically significant (P significance of the curve = 0.02) (Figure 1).

Figure 1.

Hazard ratios of endometriosis by total fruit and vegetable intake. Test for non-linearity = 0.007, P significance of the curve = 0.02.

When fruits and vegetables were examined separately, total fruit consumption was associated with a lower endometriosis risk. Women consuming 3 servings of fruits/day had a 14% lower risk of endometriosis compared to women consuming <1 serving/day (95% CI = 0.76–0.98); however, the association was not significant for those consuming ≥4 servings/day (RR = 0.93; 95% CI = 0.80–1.07) and there was no significant linear trend (P trend = 0.16) (Table II). In a model using restricted cubic splines, the relation between fruit intake and endometriosis appeared non-linear (P non-linearity = 0.002) and was statistically significant (P significance of the curve = 0.005) (Figure 2).

Figure 2.

Hazard ratios of endometriosis by total fruit intake. Test for non-linearity = 0.002, P significance of the curve = 0.005.

No association was observed between total vegetable intake and endometriosis risk: the RR for women consuming ≥6 servings/day of vegetables was 1.04 (95% CI = 0.91–1.19; P trend = 0.57) compared to women consuming ≤2 servings/day. No departure from linearity was observed for total vegetable intake (results not shown).

When the association between specific fruit groups and endometriosis risk was examined, citrus fruits (oranges, grapefruit, orange juice, grapefruit juice) were associated with a lower risk of endometriosis. Women consuming ≥1 servings of citrus fruits/day had a 22% lower endometriosis risk (95% CI = 0.69–0.89; P trend = 0.004) compared to those consuming <1 serving/week (Table II). When this relationship was evaluated by case subtype, this inverse association was only observed among women who had never reported infertility (RR = 0.75; 95% CI = 0.65–0.87; P trend = 0.006); however, the test for heterogeneity between the two case types was not significant (P heterogeneity = 0.76). When individual citrus fruits were examined, oranges demonstrated the strongest association with endometriosis risk (Table III).

When types of vegetables were examined, women consuming ≥1 servings/day cruciferous vegetables (broccoli, cauliflower, cabbage and Brussel sprouts) had a 13% higher risk of endometriosis (95% CI = 0.95–1.34; P trend = 0.03) (Table II). This positive association was apparent only among women who had never reported infertility (RR = 1.12; 95% CI = 0.93–1.36; P trend = 0.05) while no higher risk was observed among women reporting concurrent infertility (RR = 0.90; 95% CI = 0.54–1.51; P trend = 0.94) (P heterogeneity = 0.045). When individual cruciferous vegetables were examined Brussel sprouts, raw cabbage/coleslaw, and cauliflower were all related to higher endometriosis risk (Table III). Among other types of vegetables, intake of corn and peas/lima beans was also associated with a higher risk while romaine/leaf lettuce was associated with a lower risk (Table III).

Beta-cryptoxanthin intake had an inverse association with endometriosis risk (RRfifth quintile = 0.88; 95% CI = 0.78–1.00; P trend = 0.02) (Table IV). As expected, the association between beta-cryptoxanthin and endometriosis was no longer significant after adjustment for citrus fruits, the main source of beta-cryptoxanthin in this population. No statistically significant associations were observed for any of the other nutrients examined (RAE, beta-carotene, alpha-carotene, lycopene and lutein/zeaxanthin) and endometriosis risk (Table IV).

The associations between fruit and vegetable intake and endometriosis risk were consistent across different time intervals between dietary intake and endometriosis diagnosis (Table V). The strongest inverse associations were observed for fruit intake 4–6 years before endometriosis diagnosis; those consuming ≥4 servings/day had RR = 0.82 (95% CI = 0.68–0.99; P trend = 0.03) compared to those consuming <1 serving/day. This differential association was not observed for the citrus fruits. No associations were observed with total vegetable intake for any time interval. In addition, adjustment for intake of trans fat and omega-3 fatty acids, which have previously been associated with endometriosis in this cohort, did not influence the results.

Finally, we assessed whether the associations between fruit and vegetable intake or related nutrients were modified by cigarette smoking. The protective effect of fruit consumption, total and specific groups, was stronger among ever smokers compared to never smokers (Table VI). This was particularly apparent for total fruits (Figure 3) and rosaceae fruits, while for citrus fruits a protective effect was observed for both ever and never smokers. No effect modification by smoking was observed for vegetable intake, total or specific groups, or by nutrient intake (RAE, beta-carotene, alpha-carotene, beta-cryptoxanthin lycopene and lutein/zeaxanthin) (results not shown).

Figure 3.

Hazard ratios of endometriosis by total fruit intake stratified by smoking status. Test for non-linearity among never smokers = 0.005, P significance of the curve = 0.02. Test for non-linearity among ever smokers > 0.05, P linear relation = 0.009.

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