Hormone replacement therapy alters your microbiome

the 💩💩 never lies

Photo by Michael Schiffer on Unsplash

As someone with OCD, I was very unsettled to learn about the microbiome. At first, I hated the idea that 2.5 pounds of my body weight is actually tiny microbes. I still have to remind myself that the microbiome is beneficial to health by aiding in digestion and establishing immunity. Reframing the microbiome as an example of human-bacteria symbiosis settles me. It’s truly a beautiful example of humans as truly living, biological beings no matter how much we pretend not to. You might even say we are all a little filthy.

Regardless, a pair of studies published in September tracked differences in gut and vaginal microbiome composition in trans folx on hormone replacement therapy (HRT). Both studies found that the microbiomes within the trans cohort were are congruous with the microbiomes of cis people of the same hormone composition.¹ With these findings, we can add the microbiome to the growing list of physiological changes that accompany gender affirming HRT, along with secondary sex characteristics, athletic ability, and immune function.

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Your microbiome is a thriving microbial community comprised of many types of of bacteria, viruses, and even fungi. However, the microbiome varies between individual people as these many microbes can be present in relative abundance. The cartoon below illustrates how between two individuals, the microbiome can vary based on the relative number of each microbe species (represented by the different shapes and colors) present.

A cartoon example of differences between microbiomes.

Scientists can assay the composition of the microbiome by taking a sample (such as a stool sample to assess the gut microbiome), growing the microbes in the sample on a plate (such as the one seen at the top of this post), and then use metagenomic sequencing to identify individual microbes. Yes, working with poop from patients is probably not the most ~glamorous~ research project.

Using this approach, scientists now appreciate that the microbiome varies across space and time even within a single individual. For example, while Lactobacillus bacteria are present throughout the microbiome, particular species are enriched in specific anatomical regions. Lactobacillus acidophilus and casei are typically found throughout the GI tract where they aid in digestion and fight off intestinal pathogens. Lactobacillus crispatus and jensenii are primarily found in the vagina where they promote healthy mucus membrane formation and vaginal integrity.

the gut microbiome

Recently, evidence has emerged that cis men and cis women have distinct gut microbiome compositions that emerge during puberty. Given that puberty is driven by surges in sex hormones (estrogens and androgens), a research team in Switzerland and Germany recently hypothesized that trans folx on affirming hormone replacement therapy (HRT) would see concomitant alterations in their microbiomes toward their affirmed hormonal sex.

This research team then analyzed stool samples from 17 transfemme and 19 transmasc volunteers on HRT. From these data, the authors concluded that the trans volunteers had microbiomes more consistent with their hormonal sex rather than their chromosomal sex (or sex assigned at birth). These results were published in BMC Medicine in September.

These microbiotic shifts were aligned with specific metabolic profiles along the female/male spectrum. For example, both cis and trans men demonstrated higher levels of fatty acid beta-oxidation which is critical for muscle building. In contrast, cis and trans women have elevated ornithine degradation. This pathway is a major producer of the calming neurotransmitter GABA. High levels of ornithine degradation is also protective against Clostridium difficile (commonly known as C. dif²) infections which cis women are less susceptible to than cis men.

In some wellness communities, the gut microbiome has become a topic du jour, especially for folx with intestinal discomfort. Indeed, you can receive a clinical diagnosis for an imbalanced microbiome (dysbiosis). Often, dysbiosis accompanies other health conditions like inflammatory bowel disease (IBS), Type 1 diabetes, autism, mood disorders, or colorectal cancer. From intestinal to neurological, this wide range of associated conditions hints at the critical role of the microbiome in maintaining health. If you think you may have dysbiosis, talk to your doctor about a probiotic or consider adding more fermented foods (like yogurt, kimchi, or kombucha) to your diet.

the vaginal microbiome

A similar study by an Austrian team in Scientific Reports (also published in September) on the vaginal microbiome compared the microbiotic diversity between premenopausal cis women, postmenopausal cis women, and transmasculine people who have been on HRT for at least one year.³ The vaginal microbiome of transmasc participants more closely resembled the microbiome of menopausal cis women. Both groups exhibited lower levels of estradiol (compared to premenopausal cis women) and less abundance of Lactobacillus species. Some menopausal cis women take exogenous testosterone as HRT, but this was not considered as a variable in this study.

Given the differences in vaginal microbiome composition, the study’s authors suggest this change may increase susceptibility to sexually transmitted infections (STIs). Indeed, there is also evidence that the gut microbiome may play a role in the transmission of STIs among those who participate in anal sex. Friendly reminder to practice safer sex and to not over-douche as douching (either the vagina or the anus) disrupts the local microbiome.

The Austrian study only considered the microbiomes of those assigned female at birth and did not assess the microbiome of the neovagina (e.g. a vagina constructed for a trans woman). Other studies, however, have asked this question. In short, the answer is complicated and appears to depend on the surgical method used. Nonetheless, the available evidence suggests that the neovaginal microbiome of tranfemmes resembles the vaginal microbiome of cis women with bacterial vaginosis (a common microbial imbalance of the vagina). Some researchers suggest a probiotic if you are experiencing symptoms like “malodorous discharge.”

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This relationship between sex hormones and the microbiome is not merely unidirectional. Your microbiome can influence your repertoire of sex hormones by breaking down estrogens and androgens. There is also evidence in mice that the microbiome can influence the onset of puberty - although it is unclear whether the same is true in humans.⁴

Regardless, the studies outlined here clearly indicate that an individual’s sex hormone composition contributes to their gut and vaginal microbiomes. For years, scientists assumed that chromosomal sex dictated these microbial communities. In reality, chromosomal sex is largely irrelevant— the real drivers are estrogens and androgens. HRT, therefore, actively alters the microbiome composition in an affirming fashion.

Perhaps scientists should spend more money studying medical transition ;;;

1. By hormonal sex, I am referring to the relative quantities of sex hormones (i.e. androgens and estrogens).

2. Or, as one of my grandmother’s former nurses used to call it, THE DIF.

3. The transmasc participants in this study had not undergone a hysterectomy and ranged in age from 18-32 years old.

4. Both mice and humans are able to transfer their microbiomes between individuals, but mice primarily do so through coprophagy (the eating of feces). Researchers use coprophagy to study the effects of the microbiome in mice (which is how they generated evidence about the microbiome’s influence on puberty). Most humans don’t practice coprophagy even when we are told to “eat shit.” Given these different methods of microbiome transmission between mice and humans, we should not assume the same dynamics are in play.