ID-LC–MS/MS Used to Determine Associations Between PUFA and Estradiol Levels

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A recent study investigating the association between dietary polyunsaturated fatty acid (PUFA) intake and estradiol levels in women in the United States utilized isotope dilution liquid chromatography–tandem mass spectrometry to measure serum estradiol levels.

A study conducted by Department of Urology of People’s Hospital of Xinjiang Uygur Autonomous Region (Ürümqi, China) and the Graduate School, of Zhejiang Chinese Medical University (Hangzhou, China) investigated the association between dietary polyunsaturated fatty acid (PUFA) intake and estradiol levels in women in the United States, with serum estradiol levels measured using isotope dilution liquid chromatography–tandem mass spectrometry (ID-LC–MS/MS). The findings suggested that higher intake of eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) in non-menopausal women is associated with increased estradiol levels, which supports the importance of dietary components in regulating female reproductive health and hormone levels. A paper based on this study was recently published in Frontiers in Nutrition (1).

Estradiol is a crucial sex hormone in women, estradiol, which is produced by the ovaries, plays a significant role in sexual health and reproduction (2). Lower estradiol levels negatively impact both sexual and non-sexual aspects of an individual’s quality of life, with possible symptoms including low libido and difficulties in achieving orgasm (3–5). Non-sexual symptoms of lower estradiol levels include fatigue, poor concentration, depression, reduced muscle mass, weakened bone strength, and impaired iron metabolism (6-8). Due to these many wide-ranging effects, it is essential to address estradiol deficiency for overall health (9).

PUFAs are fatty acids containing two or more double bonds, with omega-3 and omega-6 as the primary types. Omega-3 fatty acids include α-linolenic acid (ALA), stearidonic acid (SDA), and docosahexaenoic acid (DHA), as well as EPA and DPA. Omega-6 fatty acids comprise linoleic acid (LA) and arachidonic acid (AA), both essential fatty acids primarily derived from crop seeds, vegetable oils, and cereal products (10,11). Though EPA and DHA are long-chain omega-3 fatty acids, they can also be synthesized from ALA (12). PUFAs maintain homeostasis in the body, and thus are essential, as an imbalance in the omega-6 to omega-3 ratio is associated with the development of a variety of diseases, including cardiovascular disease, cancer, inflammation, cardiovascular disease, and autoimmune disorders (13,14).

A total of 3095 women aged 20 years or older with complete data were included in this study. Weighted multivariate linear regressions showed positive associations between EPA and DPA intake and estradiol levels. Even in the fully adjusted model, EPA intake remained positively associated with estradiol levels in the menopausal (β = 78.08, 95% CI: 33.58, 122.58; p = 0.0006), non-menopausal (β = 287.61, 95% CI: 177.29, 397.94; p < 0.0001), and total-participant groups (β = 208.38, 95% CI: 139.81, 276.95; p < 0.0001), and DPA intake remained positively associated with estradiol levels in the non-menopausal (β = 318.87, 95% CI: 28.93, 608.82; p = 0.0313) and total-participant groups (β = 208.03, 95% CI: 22.89, 393.18; p = 0.0277). In the two-part regression model, EPA intake greater than 0.09 (p < 0.0001) and DPA intake greater than 0.05 (p = 0.0033) were positively associated with estradiol levels in non-menopausal women (1).

While the authors state that this study shows that estradiol levels in non-menopausal women increases with higher dietary intake of EPA and DPA, suggesting that dietary composition significantly influences women’s reproductive health and hormone regulation, further research is needed to clarify the mechanisms underlying these associations (1).

Microscopic illustration of polyunsaturated fatty acid molecules. © archiraya - stock.adobe.com

Microscopic illustration of polyunsaturated fatty acid molecules. © archiraya - stock.adobe.com

References

1. Guo, L.; Nan, Y.; Liang, K.; Yao, L.; Li, J. Association Between Polyunsaturated Fatty Acid Intake and Estradiol Levels Among U.S. Women. Front. Nutr. 2024, 11, 1500705. DOI: 10.3389/fnut.2024.1500705

2. Nelson, L. R.; Bulun, S. E. Estrogen Production and Action. J. Am. Acad. Dermatol. 2001, 45, S116–124. DOI: 10.1067/mjd.2001.117432

3. Burger, H. The Menopausal Transition—Endocrinology. J. Sex Med. 2008, 5, 2266–2273. DOI: 10.1111/j.1743-6109.2008.00921.x

4. Lara, L. A.; Cartagena-Ramos, D.; Figueiredo, J. B.; Rosa-E-Silva, A. C. J.; Ferriani, R. A.; Martins, W. P. et al. Hormone Therapy for Sexual Function in Perimenopausal and Postmenopausal Women. Cochrane Database Syst. Rev. 2023, 8, CD009672. DOI: 10.1002/14651858.CD009672.pub3

5. Bhasin, S.; Enzlin, P.; Coviello, A.; Basson, R. Sexual Dysfunction in Men and Women with Endocrine Disorders. Lancet 2007, 369, 597–611. DOI: 10.1016/S0140-6736(07)60280-3

6. Al-Azzawi, F.; Palacios, S. Hormonal Changes During Menopause. Maturitas 2009, 63, 135–137. DOI: 10.1016/j.maturitas.2009.03.009

7. Sun, Q.; Li, G.; Zhao, F.; Dong, M.; Xie, W.; Liu, Q, et al. Role of Estrogen in Treatment of Female Depression. Aging 2024, 16, 3021–3042. DOI: 10.18632/aging.205507

8. Kruger, M. C.; Coetzee, M.; Haag, M.; Weiler, H. Long-Chain Polyunsaturated Fatty Acids: Selected Mechanisms of Action on Bone. Prog. Lipid Res. 2010, 49, 438–449. DOI: 10.1016/j.plipres.2010.06.002

9. Shifren, J.L.; Gass, M. L. S. The North American Menopause Society Recommendations for Clinical Care of Midlife Women. Menopause 2014, 21, 1038–1062. DOI: 10.1097/GME.0000000000000319

10. Russo, G. L. Dietary n-6 and n-3 Polyunsaturated Fatty Acids: From Biochemistry to Clinical Implications in Cardiovascular Prevention. Biochem. Pharmacol. 2009, 77, 937–946. DOI: 10.1016/j.bcp.2008.10.020

11. Liu, Y.; Li, C. Hormone Therapy and Biological Aging in Postmenopausal Women. JAMA Netw Open. 2024, 7, e2430839. DOI: 10.1001/jamanetworkopen.2024.30839

12. Tocher, D. R.; Betancor, M. B.; Sprague, M.; Olsen, R. E.; Napier, J. A. Omega-3 Long-Chain Polyunsaturated Fatty acids, EPA and DHA: Bridging the Gap Between Supply and Demand. Nutrients 2019, 11, 89. DOI: 10.3390/nu11010089

13. Kang, J. X.; Liu, A. The Role of the Tissue Omega-6/Omega-3 Fatty Acid Ratio in Regulating Tumor Angiogenesis. Cancer Metastasis Rev. 2013, 32, 201–210. DOI: 10.1007/s10555-012-9401-9

14. Dennis, E. A.; Norris, P. C. Eicosanoid Storm in Infection and Inflammation. Nat. Rev. Immunol. 2015, 15, 511–523. DOI: 10.1038/nri3859

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