Sex Hormones and Their Connection to Gut Microbiome

The steroid hormones estrogen, androgens, and progesterone are vital throughout life. During puberty, these gonadal hormones stimulate the function of reproductive organs and also influence the development of bodily processes, however, their roles extend beyond reproduction. These hormones also regulate immune responses and are vital to health and well-being as we age, affecting tissues from bone to brain. Intriguingly, research shows that the gut microbiome influences steroid hormone activity. Gut bacteria possess enzymes that metabolize hormones, altering their structure and function. For example, bacterial enzymes can deconjugate the estrogen metabolites that are flagged for excretion. This liberates the metabolites to re-enter circulation in an active, unconjugated form through enterohepatic circulation. Thus, commensal gut microbes mediate hormone bioavailability and activity.

As research on the relationship between hormones and the gut continues, evidence is growing that there are sexual differences in the gut microbiota. This means that the gut microbiome has dimorphism between sexes, with sex hormones influencing the composition and function of the bacteria present. Studies show that there is an association between a person's serum sex hormone levels and the makeup of their gut microbiome. This emerging research adds further complexity to the links between gut health, hormones, and chronic disease. It also presents another factor for clinicians to consider when developing personalized treatments to balance gut bacteria and hormones. The connection between sex hormones and the gut microbiota represents an intriguing new direction in understanding how hormones and intestinal bacteria interact and affect health.

Chronic Disease Impact of Sex Hormone & Gut Microbiota Interactions

Sexual differences in gut microbiota composition and how this may relate to chronic disease is an evolving, yet progressive research area. As research continues investigating how steroid hormones impact the gut microbiome's makeup and function, specialists suggest a potential bidirectional interaction between sex hormones and gut bacteria that could influence sex-specific disease development. For instance, a 2022 review of evidence found sexual differences in obesity, implicating a complex interplay of sex hormones, gut microbes, and intestinal inflammation in disease pathogenesis.

A 2023 study notes that sex differences in the prevalence of metabolic diseases like type 2 diabetes and metabolic syndrome. These reviews also highlight observed sex dimorphism in the gut microbiota and propose the hormone-microbe interaction may affect metabolic disease progression. Overall, research increasingly points to sexual dimorphisms in gut bacteria, bidirectional hormone-microbe interactions, and the potential role of this axis in sex-specific chronic disease development. Further study is warranted on how gut microbiota composition and cross-talk with steroid hormones may underlie sexual dimorphisms in disease susceptibility and outcomes.

A 2022 study illustrated the development of research on testosterone, gut microbiota, and disease. The study included 46 men with type 2 diabetes, 18 with low testosterone and 28 with average levels. It investigated associations between testosterone and gut microbiota makeup. Overall, the study found significant differences in gut bacteria between the low and average testosterone groups. The testosterone insufficiency group showed more severe gut dysbiosis, with a link shown between increases in pathogens and gram-negative bacteria leading to worse biomarkers. This demonstrates connections between low testosterone, an unhealthy gut microbiome, and poorer metabolic health in men. The study exemplifies growing research elucidating interactions between sex hormones, gut bacteria, and disease susceptibility.

How Do Sex Hormones Influence the Gut-Brain Axis?

Studies in animals and humans suggest that interplay between sex-specific factors like hormones and gut bacteria may influence gut-brain signaling, with relevance for mental health and neurological conditions. Expanding research is exploring these connections. One 2022 retrospective study with 1,143 men and 3,467 women looked at the association between certain gut microbes and the severity of psychological symptoms in four areas: depression, cognition, anxiety and stress, and fatigue and sleep. The overall gut microbiome makeup was similar between the sexes. However, links between specific bacteria and symptom severity differed between males and females for each of the four symptom categories. Females reported greater symptom severity overall. This study highlights sex-dependent connections between the gut microbiota and psychological symptoms, underscoring the potential role of sex-specific factors like hormones in gut-brain interactions related to mental health. More research is warranted on how hormones, gut microbes, and their interplay may underlie sex differences in neurological and psychiatric conditions.

Influencing Microbial Diversity: Testosterone & Estrogen Levels

One investigative approach to unraveling the molecular underpinnings of the bidirectional relationship between sex hormones and gut bacteria has involved quantifying the amounts of specific gut microbes present alongside measurements of sex hormone levels across different populations. A 2022 systematic review compiled data from 13 observational studies involving a total of 852 participants, of which 91% were female. The review examined connections between gonadal steroid hormones and diversity of gut microbiota in humans. The populations studied included healthy men and premenopausal and postmenopausal women, as well as individuals with obesity, polycystic ovary syndrome, breast cancer, osteopenia, or osteoporosis. The hormones assayed were testosterone and estrogen. A synthesis of the study findings determined:

The studies reviewed support that there is a sexually dimorphic relationship between testosterone, estrogen, and diversity of the gut microbiota. However, the researchers noted that there is still a limited understanding of the specific molecular mechanisms by which sex hormones affect microbial populations in the gut, and vice versa. This is especially true for understanding the effects of testosterone on gut bacteria. More research is needed to uncover the intricate mediators involved in the cross-talk between sex hormones like testosterone and estrogen and the gut microbiome.

Clinical Applications & Continuing Research

Ongoing research continues to explore whether fluctuations in sex hormones primarily drive changes in the gut microbiota, if the reverse is true, or if both directions of influence are equally impactful. As this field expands, more opportunities will emerge to further customize personalized interventions. Therapies could be tailored to balance hormones in a way that benefits gut health and integrity. They could also support an optimal gut microbial composition and diversity that promotes an individual's hormone health. The future of this research will enable therapies that harness the hormone-gut connection for personalized treatments supporting whole-body wellness.

Recent clinical trials have started evaluating the potential for probiotic interventions to improve sex hormone balance. One broad review in 2023 examined the results of 28 meta-analyses of randomized controlled trials testing nutritional interventions for women with polycystic ovary syndrome (PCOS). Some of the randomized controlled trials included in these meta-analyses tested probiotics or synbiotics. The combined results from three of the meta-analyses found with moderate certainty that among women with PCOS, supplementation with probiotics or synbiotics not only helped decrease fasting blood glucose, insulin, and insulin resistance but also significantly reduced total testosterone levels on average by 0.14 ng/mL. This demonstrates the potential for probiotics to benefit both metabolic and hormonal health in PCOS, supporting further research into treatments targeting the microbiome to improve hormone balance.

Emerging research on the hormone-gut connection should inform the functional medicine practice, as it highlights the importance of considering gut health and sex hormone balance together. Clinicians can focus on supporting gut microbial diversity as part of hormone-balancing treatments and also aim to optimize sex hormone levels as part of gut-directed care. Awareness of the bidirectional relationship between the gut microbiome and sex hormones will enable more holistic interventions that synergistically support both intestinal and hormonal wellness.

Partner with Internal Healing & Wellness MD for Professional Hormone Testing

At Internal Healing & Wellness MD, we take a functional medicine approach to understand the root causes of health issues like hormone imbalances. Emerging research shows important connections between sex hormones like estrogen and testosterone and the gut microbiome. We provide cutting-edge testing to assess gut health and hormone levels, including stool testing to analyze the diversity and makeup of your gut bacteria. We also offer Dutch hormone testing to get a comprehensive picture of your estrogen, testosterone, progesterone, cortisol, and DHEA levels.

Based on test findings, our practitioners create personalized wellness plans. We use evidence-based natural therapies to support optimal hormonal balance and a healthy gut microbiome. This may include adjustments to diet, specific nutritional supplements, botanicals, stress management, and more. If you struggle with symptoms like fatigue, low libido, hot flashes, or mood changes, we can help identify the root cause. Contact us today to learn more about our functional medicine testing and customized protocols to address hormone-gut interactions and restore well-being.