Page 46 - JCTR-11-5

Journal of Clinical and
Translational Research Vaginal microbiota in menopause pathologies

elements such as race, ethnicity, and economic status Prevotella, Porphyromonas, Firmicutes, Spirochaetes,
may elevate the risk. In the United States, both Black Atopobium, and Bacteroides, in combination with
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and non-Hispanic White women exhibit high incidence elevated vaginal pH, have been linked to the development
rates of this disease; however, African American women of endometrial cancer. 56,77,83,84 These microorganisms
face nearly double the mortality rate compared to other trigger the production of proinflammatory cytokines like
racial groups. 56,75 Key contributing factors include obesity, IL-1α, IL-1β, IL-17α, and TNFα, which are commonly
chronic inflammation, disruptions in estrogen pathways, overexpressed in various malignancies, including those of
and the use of ET after menopause. These elements are the endometrium. IL-17α in particular has been shown
associated with alterations in both the gut and VM, to stimulate endometrial cell growth and facilitate the
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indicating that microbial changes may play a role in the progression of endometriosis through its role in promoting
pathogenesis of endometrial cancer. Obesity contributes inflammation and angiogenesis. 26,85 Recent studies
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to endometrial cancer development through multiple indicate that the gut-brain axis plays a role in controlling
biological pathways, including elevated insulin levels and circulating estrogen levels, involving the “estrobolome,”
increased bioavailability of insulin-like growth factor a collection of bacteria capable of modifying estrogen
1, both of which stimulate cellular growth and reduce enterohepatic circulation. These bacteria produce
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programmed cell death in the endometrium. 26,78 This β-glucuronidase, an enzyme that reactivates estrogens,
condition is a major contributor to the rising incidence enabling their interaction with receptors and influencing
of endometrial cancer, partly due to enhanced estrogen estrogen-dependent biological functions. 24,26 Disruptions
synthesis by adipose tissue, which drives endometrial in the estrobolome, or dysbiosis, can cause imbalances
cell division and tumor progression. Estrogens also play that contribute to diseases, including cancer. Research
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a critical role, reinforcing how external influences such has identified a distinct microbial profile in endometrial
as high-fat diets are associated with a heightened risk cancer tissues compared to adjacent non-cancerous
of the disease. While ET may help relieve menopausal tissue, with higher amounts of genera like Prevotella,
symptoms, it has also been linked to a greater likelihood Atopobium, and Porphyromonas in tumor tissues, while
of developing endometrial cancer. 26,78 Recent studies Lactobacillus predominates in surrounding tissues. In
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have suggested that both the intestinal and VM could be addition, elevated Prevotella levels and increased D-dimer
indirect risk factors, highlighting their importance in the in cancer tissue have been linked to more advanced disease
etiology of the disease. In summary, endometrial cancer and poorer outcomes. Various explanations for bacterial
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is a multifactorial disease in which genetic, hormonal, overgrowth in endometrial cancer include changes in the
environmental, and microbiological components interact, tissue environment that promote bacterial proliferation,
underscoring the need for preventive and therapeutic weakened immune defenses, or altered bacterial adherence
approaches that consider this complex interaction of and colonization. These observations suggest that the
factors. microbiota may influence the development, etiology, and

The long-held belief that the uterine cavity was sterile progression of endometrial cancer, a field that requires
has been questioned by several studies using 16S rRNA further investigation.
sequencing, which confirmed the existence of a resident
microbiota. Microorganisms may reach the uterus through 10.3. Microbiota and ovarian cancer
hematogenous spread, ascend from the lower genital tract Ovarian cancer is the second most common cancer
during different menstrual phases, or be introduced during in women, with more than 313,000 new cases and
gynecological interventions such as assisted reproductive 152,000 deaths in 2020. The incidence varies across
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technologies. Compared to the vagina; the microbiota of different demographic groups, being highest among
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the upper genital tract is less abundant but more diverse, non-Hispanic White women (11.6/100,000), followed
whereas the vaginal flora is primarily dominated by by Native American, Hispanic, non-Hispanic Black, and
Lactobacillus species. 81 Asian and Pacific Islander women. The lack of specific
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Chen et al. reported that the composition of the symptoms often delays diagnosis, leading to 70% of cases
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microbiota differs along the female reproductive tract and being detected at advanced stages. Incidence increases in
undergoes fluctuations depending on the menstrual cycle postmenopausal women, with various factors contributing
phase. During the secretory phase, there is a notable increase to the risk. 26
in microbial presence, especially Propionibacterium acnes, 10.3.1. Risk factors
along with heightened metabolic activity involving purines,
pyrimidines, amino acids, and peptidoglycan synthesis. Recent investigations suggest that microbial communities
Furthermore, certain vaginal bacterial species such as may play a role in the onset and development of ovarian

Volume 11 Issue 5 (2025) 40 doi: 10.36922/JCTR025150016