TABLE 2.
Association between specific fatty acids and reproductive hormone concentrations in healthy premenopausal women1
| Total energy substitution model2 |
Carbohydrate substitution model3 |
|||||
| Type of fat | Tertile 2 vs. tertile 14 | Tertile 3 vs. tertile 1 | P-trend4 | Tertile 2 vs. tertile 1 | Tertile 3 vs. tertile 1 | P-trend4 |
| Total fat, % of energy | ||||||
| Estradiol, pg/mL | −1.9 (−7.6, 4.2) | −3.5 (−9.4, 2.8) | 0.27 | −2.1 (−7.9, 4.0) | −3.8 (−9.8, 2.5) | 0.23 |
| Free estradiol, pg/mL | −2.8 (−8.4, 3.1) | −3.6 (−9.4, 2.5) | 0.26 | −3.0 (−8.5, 2.9) | −3.8 (−9.7, 2.3) | 0.23 |
| FSH, mIU/mL | 1.5 (−3.4, 6.7) | 2.7 (−2.6, 8.2) | 0.32 | 1.6 (−3.3, 6.9) | 2.9 (−2.4, 8.5) | 0.29 |
| LH, ng/mL | −2.4 (−8.5, 4.1) | 5.0 (−1.9, 12.4) | 0.12 | −2.4 (−8.5, 4.2) | 5.0 (−2.0, 12.4) | 0.12 |
| Progesterone,5 ng/mL | −11.0 (−24.6, 5.0) | −13.7 (−27.3, 2.5) | 0.10 | −11.5 (−25.0, 4.5) | −14.4 (−28.0, 1.8) | 0.09 |
| SHBG, nmol/L | −2.4 (−6.9, 2.3) | −0.3 (−5.3, 4.9) | 0.65 | −1.6 (−5.4, 2.3) | −0.2 (−4.3, 4.1) | 0.99 |
| Testosterone, ng/dL | 1.4 (−1.5, 4.4) | 4.0 (0.7, 7.3)* | 0.01* | 1.6 (−1.3, 4.6) | 4.2 (0.9, 7.6)* | 0.01* |
| Free testosterone, ng/dL | 0.7 (−2.6, 4.0) | 4.1 (0.5, 7.7)* | 0.02* | 0.8 (−2.4, 4.2) | 4.3 (0.7, 7.9)* | 0.02* |
| Free androgen index | 1.2 (−3.6, 6.3) | 4.3 (−1.1, 10.0) | 0.11 | 1.3 (−3.6, 6.5) | 4.4 (−1.0, 10.1) | 0.10 |
| Saturated fat, % of energy | ||||||
| Estradiol, pg/mL | −0.2 (−6.1, 6.1) | −3.2 (−9.5, 3.6) | 0.27 | −0.9 (−7.2, 5.8) | −4.4 (−11.6, 3.4) | 0.21 |
| Free estradiol, pg/mL | 0.3 (−5.5, 6.5) | −3.6 (−5.5, 6.5) | 0.17 | 0.3 (−6.0, 6.9) | −3.8 (−10.9, 3.8) | 0.18 |
| FSH, mIU/mL | −0.7 (−5.6, 4.4) | −0.8 (−6.2, 4.9) | 0.87 | −0.9 (−6.2, 4.6) | −0.9 (−7.0, 5.8) | 0.93 |
| LH, ng/mL | −2.4 (−8.6, 4.2) | 2.4 (−4.7, 10.1) | 0.24 | −1.5 (−8.2, 5.7) | 4.4 (−4.0, 13.4) | 0.11 |
| Progesterone, ng/mL | 0.1 (−15.4, 18.4) | −13.2 (−27.5, 4.1) | 0.07 | 9.6 (−8.3, 31.1) | 0.0 (−18.8, 23.1) | 0.48 |
| SHBG, nmol/L | −1.1 (−4.9, 2.9) | 0.8 (−3.5, 5.4) | 0.45 | −2.9 (−6.9, 1.3) | −2.0 (−6.8, 3.1) | 0.99 |
| Testosterone, ng/dL | −0.2 (−3.1, 2.8) | 0.1 (−3.2, 3.6) | 0.90 | 0.1 (−3.0, 3.4) | 0.9 (−3.0, 4.8) | 0.62 |
| Free testosterone, ng/dL | −0.6 (−3.8, 2.7) | −0.5 (−4.2, 3.4) | 0.92 | 0.0 (−3.4, 3.6) | 0.8 (−3.3, 5.2) | 0.63 |
| Free androgen index | −0.3 (−5.2, 4.8) | −1.2 (−6.7, 4.6) | 0.68 | 1.4 (−3.8, 7.0) | 1.9 (−4.4, 8.8) | 0.71 |
| Monounsaturated fat, % of energy | ||||||
| Estradiol, pg/mL | −0.4 (−6.4, 5.9) | −2.4 (−8.4, 4.1) | 0.44 | 1.3 (−5.4, 8.4) | 0.8 (−7.7, 10.0) | 0.90 |
| Free estradiol, pg/mL | −1.2 (−6.9, 4.9) | −3.1 (−9.0, 3.0) | 0.31 | 0.3 (−6.1, 7.3) | −0.3 (−8.4, 8.7) | 0.94 |
| FSH, mIU/mL | 2.9 (−2.2, 8.3) | 3.5 (−1.9, 9.1) | 0.23 | 3.4 (−2.3, 9.4) | 3.3 (−3.9, 11.1) | 0.44 |
| LH, ng/mL | 0.4 (−6.1, 7.3) | 1.7 (−5.1, 8.9) | 0.61 | −0.9 (−8.0, 6.6) | −1.9 (−10.7, 7.8) | 0.69 |
| Progesterone, ng/mL | 4.3 (−11.8, 23.2) | −18.1 (−31.1, −2.6)* | 0.01* | 9.4 (−9.0, 31.7) | −10.9 (−29.6, 12.9) | 0.24 |
| SHBG, nmol/L | 0.3 (−3.6, 4.3) | 3.1 (−1.0, 7.6) | 0.11 | 0.7 (−3.7, 5.2) | 3.7 (−2.2, 9.7) | 0.19 |
| Testosterone, ng/dL | 1.6 (−1.4, 4.6) | 2.5 (−0.7, 5.8) | 0.13 | 1.4 (−2.0, 4.8) | 1.1 (−3.1, 5.5) | 0.68 |
| Free testosterone, ng/dL | 1.5 (−1.8, 4.9) | 2.0 (−1.5, 5.7) | 0.27 | 1.6 (−2.1, 5.4) | 1.2 (−3.5, 6.2) | 0.70 |
| Free androgen index | 1.3 (−3.6, 6.5) | 0.6 (−4.5, 6.1) | 0.86 | 1.9 (−3.6, 7.8) | 0.9 (−6.2, 8.5) | 0.87 |
| Polyunsaturated fat, % of energy | ||||||
| Estradiol, pg/mL | −0.9 (−6.6, 5.1) | −0.2 (−6.2, 6.2) | 0.98 | −1.6 (−7.3, 4.4) | −2.3 (−8.8, 4.6) | 0.52 |
| Free estradiol, pg/mL | −0.3 (−5.9, 5.7) | −0.7 (−6.6, 5.4) | 0.81 | −0.7 (−6.4, 5.4) | −1.7 (−8.1, 5.2) | 0.62 |
| FSH, mIU/mL | 3.5 (−1.5, 8.7) | 4.1 (−1.2, 9.5) | 0.15 | 3.5 (−1.6, 8.8) | 3.8 (−2.1, 9.9) | 0.24 |
| LH, ng/mL | 1.4 (−4.8, 8.1) | 6.4 (−0.4, 13.7) | 0.06 | 1.6 (−4.8, 8.4) | 7.3 (−0.4, 15.5) | 0.06 |
| Progesterone, ng/mL | 8.9 (−7.6, 28.3) | 8.8 (−8.2, 28.9) | 0.37 | 12.7 (−4.5, 33.1) | 18.8 (−1.5, 43.2) | 0.08 |
| SHBG, nmol/L | 0.8 (−2.9, 4.7) | 2.8 (−1.2, 7.0) | 0.16 | 0.2 (−3.5, 4.1) | 1.0 (−3.4, 5.5) | 0.65 |
| Testosterone, ng/dL | 1.3 (−1.5, 4.3) | 3.7 (0.6, 6.8)* | 0.02* | 1.4 (−1.5, 4.4) | 4.2 (0.8, 7.8)* | 0.01* |
| Free testosterone, ng/dL | 1.6 (−1.5, 4.8) | 4.0 (0.5, 7.5)* | 0.02* | 1.8 (−1.4, 5.1) | 4.7 (0.9, 8.7)* | 0.01* |
| Free androgen index | 1.8 (−3.0, 6.8) | 2.6 (−2.5, 8.0) | 0.32 | 2.3 (−2.4, 7.5) | 4.4 (−1.3, 10.4) | 0.14 |
| ω-3s, % of energy | ||||||
| Estradiol, pg/mL | −0.7 (−6.2, 5.1) | 2.7 (−3.4, 9.3) | 0.38 | 0.1 (−5.9, 6.4) | 3.0 (−4.4, 11.1) | 0.40 |
| Free estradiol, pg/mL | −2.0 (−7.3, 3.7) | 2.9 (−3.1, 9.3) | 0.32 | −1.0 (−6.8, 5.2) | 4.3 (−3.1, 12.3) | 0.22 |
| FSH, mIU/mL | 1.5 (−3.2, 6.4) | 1.5 (−3.6, 6.9) | 0.58 | 0.6 (−4.5, 5.9) | −0.4 (−6.5, 6.1) | 0.88 |
| LH, ng/mL | 7.6 (1.2, 14.3)* | 7.5 (0.6, 14.9)* | 0.04* | 5.7 (−1.1, 12.9) | 4.3 (−3.8, 13.1) | 0.36 |
| Progesterone, ng/mL | 14.2 (−2.7, 34.0) | 18.9 (0.4, 40.6) | 0.05 | 15.0 (−2.9, 36.2) | 20.1 (−2.2, 47.3) | 0.09 |
| SHBG, nmol/L | 1.5 (−2.0, 5.2) | −1.6 (−5.5, 2.4) | 0.41 | 1.8 (−2.0, 5.8) | −2.1 (−6.7, 2.7) | 0.32 |
| Testosterone, ng/dL | 1.7 (−1.0, 4.5) | 3.6 (0.5, 6.8)* | 0.02* | 0.7 (−2.2, 3.7) | 2.1 (−1.5, 5.9) | 0.25 |
| Free testosterone, ng/dL | 1.5 (−1.5, 4.6) | 4.9 (1.4, 8.4)* | 0.01* | 0.4 (−2.8, 3.7) | 3.3 (−0.9, 7.5) | 0.11 |
| Free androgen index | 0.1 (−4.3, 4.8) | 5.9 (0.6, 11.4)* | 0.02* | −1.1 (−5.8, 3.9) | 4.5 (−1.7, 11.1) | 0.12 |
| ω-6s, % of energy | ||||||
| Estradiol, pg/mL | −0.6 (−6.2, 5.4) | 0.0 (−5.9, 6.4) | 0.96 | −1.2 (−7.1, 5.0) | −1.7 (−9.0, 6.3) | 0.69 |
| Free estradiol, pg/mL | −0.1 (−5.6, 5.9) | −0.7 (−6.5, 5.5) | 0.82 | −0.9 (−6.8, 5.2) | −2.7 (−9.8, 5.0) | 0.48 |
| FSH, mIU/mL | 3.0 (−1.8, 8.2) | 3.7 (−1.5, 9.1) | 0.19 | 2.3 (−2.9, 7.7) | 1.8 (−4.6, 8.7) | 0.65 |
| LH, ng/mL | 0.7 (−5.4, 7.1) | 6.2 (−0.5, 13.4) | 0.06 | −0.9 (−7.2, 6.0) | 2.7 (−5.5, 11.7) | 0.47 |
| Progesterone, ng/mL | 10.6 (−6.1, 30.2) | 7.9 (−8.9, 27.8) | 0.45 | 13.4 (−4.4, 34.4) | 13.3 (−8.2, 40.1) | 0.30 |
| SHBG, nmol/L | 1.6 (−2.0, 5.4) | 2.2 (−1.8, 6.4) | 0.30 | 2.0 (−1.9, 6.1) | 2.9 (−2.2, 8.2) | 0.29 |
| Testosterone, ng/dL | 1.4 (−1.4, 4.3) | 3.8 (0.7, 6.9)* | 0.01* | 1.0 (−2.0, 4.1) | 3.1 (−0.7, 7.1) | 0.10 |
| Free testosterone, ng/dL | 1.5 (−1.5, 4.7) | 4.0 (0.6, 7.6)* | 0.02* | 0.9 (−2.4, 4.3) | 2.8 (−1.5, 7.3) | 0.19 |
| Free androgen index | 1.1 (−3.5, 6.0) | 2.7 (−2.4, 8.0) | 0.29 | 0.2 (−4.7, 5.3) | 0.9 (−5.4, 7.6) | 0.77 |
| trans Fat, % of energy | ||||||
| Estradiol, pg/mL | 1.1 (−4.9, 7.5) | −0.5 (−6.6, 6.0) | 0.83 | 1.6 (−4.5, 8.2) | −0.1 (−6.9, 7.3) | 0.92 |
| Free estradiol, pg/mL | 0.2 (−5.6, 6.4) | −0.5 (−6.5, 5.8) | 0.85 | 1.0 (−5.0, 7.4) | 0.7 (−6.1, 7.9) | 0.87 |
| FSH, mIU/mL | 3.4 (−1.7, 8.8) | 0.8 (−4.3, 6.2) | 0.90 | 3.4 (−1.9, 8.9) | 0.2 (−5.5, 6.3) | 0.93 |
| LH, ng/mL | 3.9 (−2.7, 11.0) | 1.0 (−5.5, 8.0) | 0.88 | 4.2 (−2.6, 11.3) | 1.8 (−5.6, 9.9) | 0.71 |
| Progesterone, ng/mL | −7.3 (−21.6, 9.5) | −16.7 (−29.7, −1.2)* | 0.03* | −2.8 (−18.0, 15.4) | −6.9 (−23.2, 12.7) | 0.46 |
| SHBG, nmol/L | 1.1 (−2.8, 5.1) | 2.0 (−2.1, 6.3) | 0.35 | 0.4 (−3.5, 4.4) | −0.4 (−4.8, 4.2) | 0.83 |
| Testosterone, ng/dL | 1.5 (−1.5, 4.6) | 2.3 (−0.8, 5.5) | 0.15 | 1.7 (−1.2, 4.8) | 3.1 (−0.3, 6.7) | 0.08 |
| Free testosterone, ng/dL | 1.3 (−2.0, 4.7) | 1.5 (−1.9, 5.0) | 0.42 | 1.7 (−1.6, 5.1) | 2.7 (−1.1, 6.7) | 0.17 |
| Free androgen index | −0.2 (−5.1, 4.9) | −0.4 (−5.4, 4.9) | 0.88 | 0.6 (−4.3, 5.9) | 2.1 (−3.6, 8.1) | 0.47 |
| α-Linolenic acid, g/d | ||||||
| Estradiol, pg/mL | −0.4 (−6.3, 5.9) | 0.6 (−6.3, 7.9 ) | 0.84 | −0.6 (−6.5, 5.8) | 0.0 (−6.9, 7.5) | 0.96 |
| Free estradiol, pg/mL | 1.8 (−4.1, 8.1) | 1.8 (−5.0, 9.2) | 0.64 | 1.8 (−4.2, 8.1) | 1.8 (−5.2, 9.2) | 0.66 |
| FSH, mIU/mL | 2.3 (−2.7, 7.7) | 2.3 (−3.4, 8.5) | 0.50 | 2.4 (−2.7, 7.9) | 2.1 (−3.8, 8.4) | 0.57 |
| LH, ng/mL | 5.4 (−11.8, 12.6) | 7.6 (−0.2, 16.1) | 0.08 | 5.2 (−1.6, 12.4) | 7.4 (−0.6, 16.0) | 0.09 |
| Progesterone, ng/mL | 11.3 (−6.0, 31.8) | −0.8 (−18.3, 20.4) | 0.75 | 12.6 (−4.8, 33.1) | 2.3 (−15.8, 24.5) | 0.99 |
| SHBG, nmol/L | −4.0 (−7.7, −0.2)* | −3.2 (−7.6, 1.2) | 0.25 | −4.1 (−7.8, −0.3)* | −4.0 (−8.2, 0.5) | 0.14 |
| Testosterone, ng/dL | −0.1 (−3.1, 2.8) | 2.8 (−0.6, 6.5) | 0.07 | −0.1 (−3.1, 2.9) | 2.7 (−0.8, 6.4) | 0.08 |
| Free testosterone, ng/dL | 1.7 (−2.2, 4.4) | 5.2 (1.3, 9.3)* | 0.01* | 1.1 (−2.2, 4.5) | 5.3 (1.3, 9.4)* | 0.01* |
| Free androgen index | 4.0 (−1.0, 9.3) | 8.2 (2.1, 14.6)* | 0.01* | 4.1 (−1.0, 9.4) | 8.8 (2.6, 15.3)* | 0.01* |
| EPA, g/d | ||||||
| Estradiol, pg/mL | −1.9 (−7.5, 4.1) | 5.9 (−0.5, 12.6) | 0.02* | −2.0 (−7.8, 4.3) | 5.5 (−1.3, 12.9) | 0.03* |
| Free estradiol, pg/mL | −1.5 (−7.0, 4.4) | 6.1 (−0.1, 12.6) | 0.02* | −1.3 (−7.0, 4.9) | 6.4 (−0.4, 13.7) | 0.02* |
| FSH, mIU/mL | −1.2 (−5.9, 3.9) | −1.6 (−6.6, 3.6) | 0.60 | −1.2 (−6.2, 4.1) | −1.9 (−7.2, 3.9) | 0.59 |
| LH, ng/mL | −0.9 (−7.0, 5.7) | 0.8 (−5.6, 7.8) | 0.70 | −1.0 (−7.4, 5.9) | 1.2 (−5.9, 8.9) | 0.60 |
| Progesterone, ng/mL | −15.2 (−27.9, −0.2)* | 19.4 (1.2, 40.9)* | 0.002* | −12.8 (−26.2, 3.1) | 22.1 (1.9, 46.4)* | 0.001* |
| SHBG, nmol/L | 2.0 (−1.8, 5.9) | −0.1 (−4.1, 4.1) | 0.62 | 1.9 (−2.0, 6.0) | −0.3 (−4.6, 4.2) | 0.53 |
| Testosterone, ng/dL | 1.6 (−1.3, 4.6) | 1.1 (−2.0, 4.3) | 0.72 | 2.0 (−1.0, 5.1) | 1.9 (−1.5, 5.3) | 0.50 |
| Free testosterone, ng/dL | 1.4 (−1.8, 4.7) | 1.4 (−2.0, 4.9) | 0.56 | 1.8 (−1.5, 5.3) | 2.2 (−1.5, 6.2) | 0.38 |
| Free androgen index | 0.3 (−4.4, 5.3) | 1.3 (−3.8, 6.6) | 0.62 | 0.8 (−4.1, 6.1) | 2.1 (−3.5, 8.0) | 0.48 |
| Docosapentaenoic acid, g/d | ||||||
| Estradiol, pg/mL | −2.5 (−8.2, 3.6) | 2.2 (−4.1, 9.1) | 0.33 | −3.1 (−8.9, 3.1) | 1.1 (−6.1, 8.9) | 0.55 |
| Free estradiol, pg/mL | −1.4 (−7.0, 4.6) | 0.9 (−5.4, 7.5) | 0.68 | −1.7 (−7.5, 4.5) | 0.1 (−6.9, 7.7) | 0.86 |
| FSH, mIU/mL | −0.7 (−5.5, 4.4) | 3.3 (−2.2, 9.0) | 0.16 | −0.1 (−5.2, 5.1) | 4.4 (−1.8, 11.1) | 0.11 |
| LH, ng/mL | −0.5 (−6.8, 6.2) | 0.5 (−6.2, 7.8) | 0.83 | −0.4 ( −6.9, 6.5) | 1.1 (−6.8, 9.5) | 0.74 |
| Progesterone, ng/mL | 10.3 (−6.5, 30.1) | 20.0 (0.5, 43.2)* | 0.05* | 13.7 (−4.2, 34.9) | 27.3 (3.8, 55.9)* | 0.03* |
| SHBG, nmol/L | −0.5 (−4.3, 3.5) | 1.0 (−3.2, 5.4) | 0.56 | −0.8 (−4.6, 3.3) | 0.6 (−4.2, 5.5) | 0.72 |
| Testosterone, ng/dL | −2.7 (−5.4, 0.2) | −1.0 (−4.1, 2.2) | 0.86 | −2.5 (−5.4, 0.5) | −0.4 (−4.0, 3.4) | 0.84 |
| Free testosterone, ng/dL | −2.7 (−5.8, 0.5) | −1.3 (−4.8, 2.2) | 0.72 | −2.5 (−5.7, 0.8) | −0.8 (−4.8, 3.4) | 0.98 |
| Free androgen index | −2.5 (−7.1, 2.4) | −2.3 (−7.4, 3.1) | 0.51 | −2.3 (−7.1, 2.8) | −1.8 (−7.7, 4.4) | 0.67 |
| DHA, g/d | ||||||
| Estradiol, pg/mL | −1.5 (−7.1, 4.6) | 5.4 (−1.1, 12.4) | 0.04* | −1.5 (−7.4, 4.8) | 4.9 (−2.1, 12.4) | 0.07 |
| Free estradiol, pg/mL | −0.8 (−6.5, 5.2) | 5.3 (−1.1, 12.1) | 0.05* | −0.4 (−6.3, 5.8) | 5.4 (−1.5, 12.9) | 0.07 |
| FSH, mIU/mL | 1.3 (−3.6, 6.5) | 0.3 (−4.9, 5.8) | 0.96 | 1.3 (−3.8, 6.7) | 0.5 (−5.2, 6.5) | 0.99 |
| LH, ng/mL | −1.5 (−7.6, 5.0) | 1.3 (−5.4, 8.5) | 0.55 | −1.6 (−8.0, 5.2) | 1.7 (−5.6, 9.6) | 0.48 |
| Progesterone, ng/mL | −8.6 (−22.4, 7.6) | 18.2 (−0.5, 40.4) | 0.01* | −5.0 (−19.7, 12.5) | 21.7 (0.7, 46.8)* | 0.01* |
| SHBG, nmol/L | 0.0 (−3.8, 3.9) | −1.0 (−5.1, 3.3) | 0.59 | −0.5 (−4.4, 3.5) | −1.3 (−5.6, 3.3) | 0.57 |
| Testosterone, ng/dL | 1.7 (−1.3, 4.7) | 2.3 (−0.9, 5.7) | 0.21 | 1.9 (−1.1, 5.0) | 3.3 (−0.2, 6.8) | 0.10 |
| Free testosterone, ng/dL | 1.5 (−1.7, 4.9) | 2.4 (−1.2, 6.1) | 0.24 | 1.9 (−1.4, 5.4) | 3.3 (−0.6, 7.3) | 0.13 |
| Free androgen index | 1.4 (−3.4, 6.5) | 2.4 (−2.9, 8.1) | 0.41 | 2.1 (−3.0, 7.4) | 3.4 (−2.5, 9.4) | 0.32 |
1
Values are percentage changes with 95% CIs in parentheses. Linear mixed models with random intercepts were used to evaluate associations between average dietary fat intake (as percentage of energy for each type of fat) across the cycle (averages calculated on the basis of up to 4 recalls/cycle) and log serum concentrations of reproductive hormones at each cycle visit. The models took repeated measures into account and included up to 16 hormone concentrations/participant (up to 8/cycle) for a total of 3899 study visits with dietary intake and hormone concentrations. *P < 0.05. FSH, follicle stimulating hormone; LH, luteinizing hormone; ref, reference; SHBG, sex hormone–binding globulin.
2
Adjusted for age, race, BMI, and total energy intake.
3
Adjusted for age, race, BMI, and total energy intake, plus intake for the remaining types of fat (saturated, monounsaturated, polyunsaturated, and trans fat) and protein intake.
4
Calculated with the median intake of fat in each tertile as a continuous variable.
5
Includes only measurements of progesterone during the luteal phase.