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Applications | Women’s Health

Women’s Health

Discover the transformative potential of metabolomics in enhancing women’s health research and healthcare outcomes.

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Featured Women’s Health Resources

Infectious Disease and Metabolomics

Metabolomics in Women’s Health Research

Women’s health research has a long history of challenges that include gender bias, underrepresentation and lack of diversity in studies, hormonal variations, gender-specific conditions, stigmatized or underdiagnosed issues, limited awareness, insufficient funding, ethical concerns, the need for long-term studies, and slow policy implementation. These challenges hinder the understanding and improvement of women’s health, emphasizing the necessity for more inclusive and targeted research efforts to address sex-specific health issues effectively.

Metabolomics, a powerful tool in women’s health research, offers several advantages. It enables personalized healthcare by identifying individualized metabolic profiles, tailoring treatments to specific needs. Metabolomics aids in the early detection of women’s health conditions, improving prognosis and treatment options by identifying disease-specific metabolic signatures. Moreover, it advances gender-specific medicine by shedding light on unique metabolic differences between men and women, paving the way for more relevant diagnostic tests, treatments, and preventive strategies. These benefits highlight the transformative potential of metabolomics in enhancing women’s health research and healthcare outcomes.

Infectious Disease

Uncover Functional, Actionable Insights with Metabolomics

​To more thoroughly understand human disease and how to treat it, more emphasis must be placed on including women in research studies and clinical trials and in understanding gender-specificity of a wide variety of diseases. Metabolomics can aid these efforts by highlighting gender differences in disease and uncovering novel approaches to understanding, diagnosing, and treating disease.

Personalized Healthcare
Early Disease Detection
Advancing Gender-Specific Medicine

Personalized Healthcare

Metabolomics allows for the identification of individualized metabolic profiles and patterns. This means that healthcare interventions and treatment plans can be tailored to each woman’s unique metabolic needs. By understanding the specific metabolic pathways and biomarkers associated with certain conditions, healthcare providers can offer more personalized and effective treatments, leading to improved health outcomes. For example, a study of diabetes in pregnancy, expanded on below, makes strides toward individualized treatment plans.

Meek CL, Stewart ZA, Feig DS, et al. Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes. Diabetologia. 2023;66(11):2101-2116. doi:10.1007/s00125-023-05989-2

Early Disease Detection

Metabolomics can aid in the early detection of women’s health conditions and diseases. By identifying specific metabolic signatures associated with various diseases (e.g., breast cancer, gynecological disorders, pregnancy-related complications), healthcare providers can screen for these conditions at an earlier stage when interventions are more likely to be successful. Early detection can lead to better prognosis and treatment options. A study of cervicovaginal lavages provides an opportunity for noninvasive testing that identifies metabolite signatures of adenomyosis with potential diagnostic value.

Lorentzen GM, Łaniewski P, Cui H, et al. Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis. iScience. 2022;25(12):105508. Published 2022 Nov 4. doi:10.1016/j.isci.2022.105508

Advancing Gender-Specific Medicine

Metabolomics research can help bridge the gender gap in healthcare by providing insights into the unique metabolic differences between men and women. This information can inform the development of gender-specific diagnostic tests, treatments, and preventive strategies. It promotes a more comprehensive understanding of women’s health, ensuring that healthcare is not based solely on data from male populations and is more relevant to the specific needs of women. COVID-19, for example, is sexually dimorphic. A study published in Cell Death & Disease showed that bile acid metabolism significantly differs between male and female COVID-19 patients.

Escarcega, R.D., Honarpisheh, P., Colpo, G.D. et al. Sex differences in global metabolomic profiles of COVID-19 patients. Cell Death Dis 13, 461 (2022).

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Metabolomics Applications for Women’s Health Research

  • EBiomarker discovery
  • EPersonalized medicine research
  • EDisease risk assessment
  • EMonitoring treatment response
  • EPrediction of disease progression
  • EDrug discovery and development
  • EUnderstanding tumor physiology 
  • EEarly detection of altered pathways
  • ECharacterize disease resistance mechanisms
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“Our global metabolomics profile showed a metabolic shift in COVID-19 patients and sex-associated pathways. Lipids, bile acids, and aromatic amino acid metabolites in severe COVID-19 patients depended on sex, and an interplay of host-regulated and microbiome-regulated metabolic pathways appears to be a major underlying mechanism of sex differences in short- and long-term responses to COVID-19.”

Escarcega RD, Honarpisheh P, Colpo GD, et al.
Sex differences in global metabolomic profiles of COVID-19 patients. Cell Death Dis. 2022;13(5):461. Published 2022 May 14. doi:10.1038/s41419-022-04861-2 Available under CC BY 4.0

Sexual Dimorphism in COVID-19

COVID-19, also known as SARS-CoV-2, presents with an extensive range of symptoms. Some individuals are asymptomatic, while others experience mild to severe symptoms, such as loss of taste, pneumonia, and even death. COVID-19 vaccines and boosters are providing some protection against infection, but sexual dimorphism is an under-studied area of research that could lead to new treatment methods.

Previously published research showed that the severity and prevalence of COVID-19 infection symptoms vary significantly in males and females. Male patients are more likely to experience “long COVID,” be hospitalized and require ICU care.1 However, many COVID-19 studies have not taken biological sex into account, leading to an insufficient amount of data on the unique effects COVID-19 has on sex-dependent metabolic pathways and associated biochemicals.1

Using the Global Discovery Panel, which draws from a reference library of more than 5400 metabolites, hundreds of biochemicals were identified in serum samples collected from two different groups: COVID-19 patients and healthy “control” matched individuals. Principal Components Analysis (PCA) and Random Forest Analysis (RFA) were also performed comparing subject serum samples.1

Among the serum samples analyzed, more than 1500 biochemicals were identified, 182 of which were significantly different in COVID-19- infected males compared to females.1 ANOVA contrasts helped distinguish differences between COVID-19 and control samples, including sex-specific biochemical differences. Statistical significance was determined using a p-value ≤ 0.05. Sex-associated differences identified with COVID-19 infection include biochemicals from lipid, carbohydrate, energy, nucleotide, steroid, and amino acid metabolic pathways (Figure 1).1 Amino acid metabolism was significantly altered by the presence of COVID-19 infection.1 Several amino acids were increased in males compared to females, including some branched-chain amino acid metabolites, which can enter the TCA cycle for energy production. Additionally, numerous metabolites from aromatic amino acids (phenylalanine, tyrosine, and tryptophan) were significantly higher in the COVID-19 males in relation to females, which can be associated with changes in gut microbial metabolism.

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Figure 1. Sex differences in primary and secondary bile acids metabolism pathways and in valine, isoleucine, leucine (BCAA) metabolism in COVID-19 groups, not present in control groups. a Primary bile acid metabolism and b, c secondary bile acid metabolism pathways. d Branched-chain amino acids, valine, isoleucine, leucine metabolism, *p ≤ 0.05 (two-way ANOVA).

Glucose can be used to support energy production, fatty acid synthesis, protein glycosylation, and nucleotide biogenesis. Glucose is metabolized through the glycolytic pathway in a series of metabolic steps generating pyruvate and lactate. Pyruvate can enter the TCA cycle and alter the energy state. Glucose and numerous glycolytic metabolites (eg, pyruvate and lactate), in addition to TCA-energy-related metabolites (eg, alpha-ketoglutarate) were significantly higher in COVID-19 subjects.

Numerous pentose sugar metabolites (eg, ribitol, xylose, and arabinose) were significantly higher in the male COVID-19 patients, while pyruvate was trending higher (not significant). Pentoses obtained from the degradation of plant polysaccharides by bacterial enzymes can serve as a carbon and energy source for gut microbes. Differences in pentose metabolism further support altered gut microbial action in COVID-19 patients.

Variations in numerous co-factors and vitamins were also observed in this study. They were generally lower, including heme being significantly lower in male COVID-19 patients compared to females. Heme is required for oxygen transport and is catabolized through biliverdin to bilirubin. Bilirubin is further processed through a series of multi-organ metabolic steps into L-Urobilin, which can be excreted in urine. In contrast to heme levels, L-Urobilin levels were extremely elevated in males compared to females. These heme metabolic signatures are a potential indicator of whether a male patient will exhibit extreme COVID-19 symptoms.1

A variety of metabolic changes in COVID-19 patients were observed in this study, including lipid, carbohydrate, amino acid, heme, and microbiome related metabolic pathways. Male COVID-19 patients have been shown to present with higher levels of proinflammatory cytokines, while female patients have more robust T-cell activation than males.1 Additionally, the association between worsening COVID-19 disease outcome and insufficient T-cell response appears to only occur in male patients.1 Sex hormones are also thought to be potential contributors to COVID-19 severity since they assist in the immune response. Further studies with individuals who experience biological sex-related hormonal variations could assist in identifying the impact of hormones and COVID-19 disease outcome.1 The metabolomic signatures identified in this study showed crucial variation between males and females infected with COVID-19. Understanding COVID-19 as a biological sex-associated disease could help provide greater direction for future therapeutic targets.

Escarcega RD, Honarpisheh P, Colpo GD, et al. Sex differences in global metabolomic profiles of COVID-19 patients. Cell Death Dis. 2022;13(5):461. Published 2022 May 14. doi:10.1038/s41419-022-04861-2

Women’s Health Publications and Citations

Metabolon has contributed extensively to publications ranging from basic research to clinical trials.

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