A Prospective Study of Dietary Fat Consumption and Endometriosis Risk

Stacey A. Missmer; Jorge E. Chavarro; Susan Malspeis; Elizabeth R. Bertone-Johnson; Mark D. Hornstein; Donna Spiegelman; Robert L. Barbieri; Walter C. Willett; Susan E. Hankinson

Disclosures

Hum Reprod. 2010;25(6):1528-1535.

Abstract and Introduction

Abstract

Background: Endometriosis is a prevalent but enigmatic gynecologic disorder for which few modifiable risk factors have been identified. Fish oil consumption has been associated with symptom improvement in studies of women with primary dysmenorrhea and with decreased endometriosis risk in autotransplantation animal studies.
Methods: To investigate the relation between dietary fat intake and the risk of endometriosis, we analyzed 12 years of prospective data from the Nurses' Health Study II that began in 1989. Dietary fat was assessed via food frequency questionnaire in 1991, 1995 and 1999. We used Cox proportional hazards models adjusted for total energy intake, parity, race and body mass index at age 18, and assessed cumulatively averaged fat intake across the three diet questionnaires.
Results: During the 586 153 person-years of follow-up, 1199 cases of laparoscopically confirmed endometriosis were reported. Although total fat consumption was not associated with endometriosis risk, those women in the highest fifth of long-chain omega-3 fatty acid consumption were 22% less likely to be diagnosed with endometriosis compared with those with the lowest fifth of intake [95% confidence interval (CI) = 0.62–0.99; P-value, test for linear trend (Pt) = 0.03]. In addition, those in the highest quintile of trans-unsaturated fat intake were 48% more likely to be diagnosed with endometriosis (95% CI = 1.17–1.88; Pt = 0.001).
Conclusion: These data suggest that specific types of dietary fat are associated with the incidence of laparoscopically confirmed endometriosis, and that these relations may indicate modifiable risk. This evidence additionally provides another disease association that supports efforts to remove trans fat from hydrogenated oils from the food supply.

Introduction

Endometriosis is the third leading cause of gynecologic hospitalization in the USA (Eskenazi and Warner, 1997). Despite the high morbidity and health care cost associated with endometriosis, the etiology has not been fully delineated and few modifiable risk factors have been identified. The pathophysiology likely includes hormonal, anatomic, genetic, immune and inflammatory factors. Risk may be associated with factors that increase the volume, frequency and duration of retrograde menstruation and promote implantation and growth of endometrial plaques (Oral and Arici, 1997).

Dietary factors have been the focus of a growing number of endometriosis patient-directed books and web-sites. Unfortunately, there is little direct scientific evidence to support these suggestions. Only one animal study has directly investigated the relation between diet and the incidence of endometriosis (Covens et al., 1988), which suggested that fish oil could induce regression of surgically induced endometriosis. In the one human study focused upon dietary intake, laparoscopically confirmed endometriosis was positively related to red meat consumption [odds ratio (OR) = 2.0, 95% CI = 1.4–2.8] and inversely related to current green vegetable (OR = 0.3, 95% CI = 0.2–0.5) and fruit consumption (OR = 0.6, 95% CI = 0.4–0.8). However, this study did not observe a significant association with butter, margarine or oil intake (Parazzini et al., 2004) Additionally, a study of organochlorines and endometriosis risk observed no relation between specific foods about which intake data were collected based upon their hypothesized potential organochorine content (Heilier et al., 2007).

There is also a growing body of literature suggesting relations between dietary factors and the physiologic processes or symptoms believed to be associated with endomEtriosis. Smooth muscle contractility, estrogen levels, inflammation, prostaglandin metabolism and menstrual cyclicity are some of the factors that may contribute to endometriosis and can be influenced by diet. For example, specific dietary fatty acids are known to influence the circulating levels of IL-6 and other inflammatory markers found in higher levels among women with endometriosis (Baer et al., 2004). Also, an inverse relation between fish oil supplementation and circulating levels of series 2 prostaglandins and inflammatory symptoms have been observed (Bartram et al., 1993). In addition, a double-blind crossover study involving fish oil supplementation showed a significant reduction in dysmenorrhea (Harel et al., 1996), and another study observed that menstrual pain increased as intake of alpha-linolenic acid decreased (Deutch, 1995). To follow-up on these findings, we used data from the Nurses' Health Study II, an ongoing, prospective cohort study of premenopausal USA nurses that began in 1989, to evaluate the relation between dietary fat consumption and the incidence of laparoscopically confirmed endometriosis.

1 2 3 4

Next Section

Cite this: A Prospective Study of Dietary Fat Consumption and Endometriosis Risk - Medscape - Jun 01, 2010.

Abstract and Introduction
Materials and Methods
Results
Discussion
References

Table I. Distribution of potential risk factors for endometriosis according to total fat intake among women in the Nurses' Health Study II ( n = 70 709).*
	Total fat intake quintile (%)
	1	2	3	4	5
No. of women	14 095	14 320	14 170	14 099	14 025
Total fat median % of energy	24.4	28.7	31.6	34.5	38.7
Age (years)	35.6	35.5	35.5	35.7	35.9
Caucasian	89.6	92.3	92.7	92.9	93.6
BMI (kg/m²)
25–29.9 (overweight)	14.8	17.2	18.9	19.6	20.5
≥30 (obese)	7.2	9.4	11.0	14.4	18.0
Cigarette smoking
Never	67.2	67.2	66.9	65.8	64.2
Past	23.1	22.4	22.1	21.9	20.1
Current	9.6	10.3	10.9	12.2	15.5
Age at menarche
<12 years	23.6	23.2	22.9	23.4	24.5
12 years	30.2	29.9	30.3	30.8	30.5
13 years	27.4	28.4	28.7	28.0	27.1
≥14 years	18.5	18.3	17.9	17.6	17.6
Menstrual cycle length
< 26 days	11.5	11.2	11.2	10.8	11.8
26–31 days	66.4	66.8	67.3	67.6	66.7
32–50 days	17.4	17.6	17.2	17.2	17.0
Oral contraceptive use
Ever	81.7	83.3	83.3	83.9	84.7
Nulliparous	34.9	26.4	23.4	22.7	24.4
Lactation (among parous women)
None	8.0	9.1	10.1	11.6	14.0
≥ 24 months	13.6	14.4	14.1	12.3	9.6
Recent gynecologic exam
No exam	12.6	12.9	14.0	15.0	17.2

*All data shown are standardized to the age distributions of the cohort in 1991.

Table II. RR and 95% CIs for laparoscopically confirmed endometriosis according to quintile of cumulative averaged fat intake among women in the Nurses' Health Study II.
Type of fat	Quintile of intake					P-value*
Type of fat	1	2	3	4	5	P-value*
Total fat
Median intake (% of energy)	24.2	28.3	31.1	33.9	38.0
Number of cases	257	236	231	240	235
Age-adjusted RR (95% CI)	1.0 (referent)	0.91 (0.76–1.08)	0.91 (0.76–1.08)	0.95 (0.79–1.13)	0.95 (0.80–1.14)	0.89
Multivariable RR (95% CI)^†	1.0 (referent)	0.98 (0.82–1.17)	1.00 (0.84–1.20)	1.07 (0.89–1.27)	1.05 (0.88–1.26)	0.38
Multivariable RR (95% CI)^‡	1.0 (referent)	0.98 (0.82–1.17)	1.01 (0.84–1.20)	1.07 (0.89–1.28)	1.06 (0.88–1.27)	0.36
Vegetable fat
Median intake (% of energy)	9.4	11.7	13.5	15.4	18.5
Number of cases	252	253	217	242	235
Age-adjusted RR (95% CI)	1.0 (referent)	1.01 (0.84–1.20)	0.86 (0.72–1.04)	0.99 (0.83–1.18)	0.99 (0.83–1.19)	0.95
Multivariable RR (95% CI)^†	1.0 (referent)	1.02 (0.86–1.21)	0.87 (0.73–1.04)	0.99 (0.83–1.18)	0.96 (0.80–1.15)	0.69
Multivariable RR (95% CI)^‡	1.0 (referent)	1.02 (0.85–1.21)	0.87 (0.72–1.05)	0.99 (0.82–1.18)	0.96 (0.79–1.15)	0.66
Animal fat
Median intake (% of energy)	11.8	15.0	17.2	19.4	23.0
Number of cases	242	241	233	241	242
Age-adjusted RR (95% CI)	1.0 (referent)	0.98 (0.82–1.18)	0.95 (0.79–1.13)	0.98 (0.82–1.17)	0.99 (0.83–1.19)	0.98
Multivariable RR (95% CI)^†	1.0 (referent)	1.09 (0.91–1.30)	1.08 (0.90–1.30)	1.15 (0.96–1.38)	1.17 (0.98–1.41)	0.08
Multivariable RR (95% CI)^‡	1.0 (referent)	1.10 (0.92–1.32)	1.10 (0.92–1.33)	1.18 (0.97–1.42)	1.20 (0.99–1.45)	0.06
Trans-unsaturated fat
Median intake (% of energy)	0.9	1.3	1.5	1.8	2.3
Number of cases	229	219	241	242	268
Age-adjusted RR (95% CI)	1.0 (referent)	0.94 (0.78–1.13)	1.03 (0.86–1.24)	1.04 (0.86–1.24)	1.17 (0.98–1.39)	0.03
Multivariable RR (95% CI)^†	1.0 (referent)	1.03 (0.86–1.24)	1.16 (0.97–1.39)	1.16 (0.97–1.40)	1.28 (1.07–1.54)	0.003
Multivariable RR (95% CI)^‡	1.0 (referent)	1.09 (0.89–1.33)	1.26 (1.03–1.55)	1.30 (1.04–1.62)	1.48 (1.17–1.88)	0.001
Monounsaturated fat
Median intake (% of energy)	8.9	10.6	11.9	13.1	14.8
Number of cases	250	251	223	238	237
Age-adjusted RR (95% CI)	1.0 (referent)	0.99 (0.83–1.18)	0.90 (0.75–1.08)	0.97 (0.81–1.16)	1.01 (0.84–1.20)	0.89
Multivariable RR (95% CI)^†	1.0 (referent)	1.06 (0.89–1.27)	1.00 (0.83–1.19)	1.09 (0.91–1.30)	1.10 (0.92–1.32)	0.29
Multivariable RR (95% CI)^‡	1.0 (referent)	1.08 (0.87–1.33)	0.97 (0.75–1.24)	0.98 (0.74–1.30)	0.91 (0.66–1.26)	0.38
Polyunsaturated fat
Median intake (% of energy)	4.1	4.8	5.3	6.0	7.0
Number of cases	271	238	235	226	229
Age-adjusted RR (95% CI)	1.0 (referent)	0.88 (0.74–1.05)	0.90 (0.75–1.07)	0.88 (0.74–1.05)	0.93 (0.78–1.11)	0.59
Multivariable RR (95% CI)^†	1.0 (referent)	0.90 (0.76–1.07)	0.93 (0.78–1.10)	0.91 (0.76–1.08)	0.94 (0.79–1.12)	0.63
Multivariable RR (95% CI)^‡	1.0 (referent)	0.86 (0.72–1.03)	0.87 (0.72–1.05)	0.84 (0.69–1.02)	0.87 (0.70–1.06)	0.31
Long-chain omega-3 fatty acids
Median intake (% of energy)	0.4	0.5	0.6	0.7	0.8
Number of cases	269	247	256	227	200
Age-adjusted RR (95% CI)	1.0 (referent)	0.93 (0.79–1.11)	0.99 (0.84–1.18)	0.88 (0.74–1.06)	0.82 (0.68–0.98)	0.03
Multivariable RR (95% CI)^†	1.0 (referent)	0.94 (0.79–1.12)	0.98 (0.83–1.17)	0.86 (0.72–1.03)	0.77 (0.64–0.93)	0.003
Multivariable RR (95% CI)^‡	1.0 (referent)	0.94 (0.79–1.13)	0.98 (0.81–1.18)	0.86 (0.70–1.05)	0.78 (0.62–0.99)	0.03
Long-chain omega-6 fatty acids
Median intake (% of energy)	3.5	4.2	4.7	5.3	6.4
Number of cases	263	240	236	256	204
Age-adjusted RR (95% CI)	1.0 (referent)	0.90 (0.75–1.07)	0.90 (0.75–1.07)	0.99 (0.84–1.18)	0.82 (0.68–0.98)	0.11
Multivariable RR (95% CI)^†	1.0 (referent)	0.94 (0.79–1.12)	0.94 (0.79–1.12)	1.06 (0.89–1.25)	0.86 (0.71–1.03)	0.26
Multivariable RR (95% CI)^‡	1.0 (referent)	0.93 (0.77–1.12)	0.95 (0.77–1.16)	1.08 (0.88–1.34)	0.93 (0.73–1.20)	0.91
Saturated fat
Median intake (% of energy)	8.1	9.8	10.9	12.1	13.9
Number of cases	257	226	215	243	258
Age-adjusted RR (95% CI)	1.0 (referent)	0.86 (0.72–1.03)	0.82 (0.68–0.98)	0.90 (0.76–1.08)	0.98 (0.82–1.16)	0.70
Multivariable RR (95% CI)^†	1.0 (referent)	0.93 (0.77–1.11)	0.92 (0.77–1.10)	1.03 (0.86–1.22)	1.10 (0.92–1.31)	0.10
Multivariable RR (95% CI)^‡	1.0 (referent)	0.87 (0.71–1.07)	0.85 (0.68–1.07)	0.94 (0.74–1.20)	1.01 (0.77–1.31)	0.42

*P-value, test for linear trend calculated with median intake of fat in each quintile as a continuous variable.
^†Multivariable model was stratified by age in months at start of follow-up and calendar year of the current questionnaire cycle and was simultaneously adjusted for age at menarche (<10, 10, 11, 12, 13, 14, 15, 16, >16 years), length of menstrual cycle (<26, 26–31, 32–50, 51+ days), parity (nulliparous, 1, 2, 3, 4+ pregnancies lasting >6 months), BMI (<19, 19–20.4, 20.5–21.9, 22–24.9, 25–29.9, 30+ kg/m²) and energy (continuous).
^‡Total fat multivariable model additionally adjusted for protein. Animal fat multivariable model additionally adjusted protein and vegetable fat. Vegetable fat multivariable model additionally adjusted for protein and animal fat. Trans-unsaturated fat multivariable model additionally adjusted for protein, monounsaturated fat, saturated fat, polyunsaturated fat. Monounsaturated fat multivariable model additionally adjusted for protein, saturated fat, polyunsaturated fat, trans-unsaturated fat. Polyunsaturated fat multivariable model additionally adjusted for protein, monounsaturated fat, saturated fat, trans-unsaturated fat. Omega-3 fat multivariable model additionally adjusted for protein, monounsaturated fat, saturated fat, trans-unsaturated fat, long-chain omega-6 fatty acids. Omega-6 fat multivariable model additionally adjusted for protein, monounsaturated fat, saturated fat, trans-unsaturated fat, long-chain omega-3 fatty acids. Saturated fat multivariable model additionally adjusted for protein, monounsaturated fat, polyunsaturated fat, trans-unsaturated fat.

Table III. RR and 95% CIs for laparoscopically confirmed endometriosis according to quintile of *trans*-unsaturated fat intake and long-chain omega-3 fatty acid intake by infertility status in premenopausal women enrolled in the Nurses' Health Study II (carbohydrate substitution ^‡).
Quintile	Case definition
	All women (n = 1199)		Never infertile* (n = 970)		Concurrent infertility* (n = 228)		P-value^¥
	Cases	MV RR (95% CI)	Cases	MV RR (95% CI)	Cases	MV RR (95% CI)	P-value^¥
Trans-unsaturated fat
1	229	1.00 (referent)	177	1.00 (referent)	51	1.00 (referent)	0.22
2	219	1.09 (0.89–1.33)	164	1.00 (0.79–1.25)	54	1.56 (1.03–2.36)
3	241	1.26 (1.03–1.55)	195	1.21 (0.96–1.53)	46	1.56 (0.99–2.45)
4	242	1.30 (1.04–1.62)	207	1.31 (1.02–1.67)	33	1.24 (0.74–2.08)
5	268	1.48 (1.17–1.88)	227	1.48 (1.14–1.93)	44	1.72 (1.00–2.96)
Test for linear trend		P-value = 0.0008		P-value = 0.0007		P-value = 0.16
Long-chain omega-3 fatty acid
1	269	1.00 (referent)	217	1.00 (referent)	52	1.00 (referent)	0.97
2	247	0.94 (0.79–1.13)	201	0.92 (0.75–1.12)	44	0.95 (0.62–1.44)
3	256	0.98 (0.81–1.18)	210	0.96 (0.78–1.18)	48	1.09 (0.71–1.69)
4	227	0.86 (0.70–1.05)	181	0.82 (0.65–1.03)	45	0.94 (0.59–1.48)
5	200	0.78 (0.62–0.99)	161	0.76 (0.59–0.99)	39	0.80 (0.47–1.35)
Test for linear trend		P-value = 0.03		P-value = 0.03		P-value = 0.36

*Infertility is defined as attempting to become pregnant for >1 year without success. Cases with 'no past or concurrent infertility' are women who never reported infertility. Cases with 'concurrent infertility' are women who reported an infertility evaluation in the same follow-up cycle as laparoscopic-confirmation of endometriosis.
^†Total energy substitution multivariable models were stratified by age in months at start of follow-up and calendar year of the current questionnaire cycle and was simultaneously adjusted for age at menarche (<10, 10, 11, 12, 13, 14, 15, 16, >16 years), length of menstrual cycle (<26, 26–31, 32–50, 51+ days), parity (nulliparous, 1, 2, 3, 4+ pregnancies lasting >6 months), BMI (<19, 19–20.4, 20.5–21.9, 22–24.9, 25–29.9, 30+ kg/m²) and energy (continuous).
^‡ Trans-unsaturated fat carbohydrate substitution multivariable model additionally adjusted for protein, monounsaturated fat, saturated fat, polyunsaturated fat; omega-3 fat carbohydrate substitution multivariable model additionally adjusted for protein, monounsaturated fat, saturated fat, trans-unsaturated fat, long-chain omega-6 fatty acids.
^¥ P-value, test for heterogeneity comparing the effect of fat consumption among women with no past or current infertility to those with concurrent infertility.

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.