Skip to content

Initiating Oral Contraception Does Not Change Gut Microbiome in Healthy Women

Key findings

  • This longitudinal study of ten healthy women systematically examined whether initiation of oral contraception (OC) influences the diversity, composition, or function of the gut microbiome
  • No changes were noted in the diversity or composition of the gut microbiome within six months after OC initiation, but the relative abundance of the biosynthesis pathways of peptidoglycan and certain amino acids increased
  • Although initiation of OC was not associated with major changes in gut microbiome composition, serum levels of endogenous estradiol and sex hormone–binding globulin (SHBG) were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium
  • Similarly, microbes involving biosynthesis of L-lysine, L-threonine, and L-methionine were significantly associated with lower estradiol and SHBG and higher total testosterone
  • Here we did not observe a significant shift in the gut microbiome composition with initiation of OC use. Interestingly, several associations between endogenous sex hormone and microbial features were observed. Future larger studies are needed to characterize the associations between OC, endogenous sex hormones, and the gut microbiome

Human and animal evidence suggests both exogenous and endogenous sex hormones can affect the microbiome.

Researchers at Massachusetts General Hospital recently completed the first systematic study of how the initiation of oral contraception (OC) affects the structure and function of the gut microbiome. Xinwei Hua, PhD, MPH, a research fellow in the Division of GastroenterologyHamed Khalili, MD, MPH, a gastroenterologist and internist in the Clinical and Translational Epidemiology Unit, and colleagues found no significant change in microbiome diversity or composition after OC initiation. However, the relative abundance of some metabolic pathways changed, as reported in the Journal of Medical Microbiology.

Methods

The longitudinal study involved 10 healthy women ages 16 to 40 who started OC use between January 2015 and August 2018. They provided blood and stool samples before initiation of OC, one month later, and six months later.

The Microbiome and Oral Contraception Use

Initiation of OC use was not linked to any significant change in microbial diversity or composition (159 species analyzed). However, OC use influenced the function of the microbiome; specifically, it was associated with significant enrichments in certain metabolic pathways (272 analyzed):

  • Microbial functions involved in the synthesis of amino acids, including L-lysine, L-threonine, L-methionine, and L-tryptophan
  • Synthesis of peptidoglycan, the main component of bacteria cell walls
  • Metabolism of coenzymes during oxidation reactions

The Microbiome and Endogenous Sex Hormones

The team observed several significant associations between serum levels of endogenous sex hormones and the composition of the microbiome:

  • Estradiol and sex hormone–binding globulin (SHBG) were positively associated with the relative abundance of Eubacterium ramulus, a flavonoid-degrading anaerobe commonly involved in fermentation in the gastrointestinal tract
  • Progesterone was positively associated with the abundance of E. ventriosum
  • Lower levels of estradiol and higher levels of total testosterone were associated with more abundant Megasphaera unclassified
  • SHBG was negatively associated with Bifidobacterium animalis, a lactic acid–producing anaerobe

Significant associations were also noted between endogenous sex hormones and microbiome function. Specifically, several amino acid biosynthesis pathways (L-lysine, L-threonine, and L-methionine) were enriched in women who had modest decreases in endogenous levels of estradiol or SHBG or higher levels of total testosterone.

Continued Scrutiny Needed

OC use has been linked to several immune-mediated diseases, including Crohn's disease, rheumatoid arthritis, and systemic lupus erythematosus.

Here we did not observe a significant shift in the gut microbiome composition with the initiation of OC use. Interestingly, several associations between endogenous sex hormone and microbial features were observed. Future larger studies are needed to characterize the associations between OC, endogenous sex hormones, and the gut microbiome is needed.

Visit the Division of Gastroenterology

Refer a patient to the Division of Gastroenterology

Related topics

Related

Bharati Kochar, MD, MS, and colleagues have demonstrated that among older adults with new-onset inflammatory bowel disease, a higher risk of frailty is associated with a three-fold higher risk of all-cause mortality and two-fold higher risk of all-cause hospitalization, even after accounting for comorbidities.

Related

Kate L. Jeffrey, PhD, Fatemeh Adiliaghdam, MD, MPH, and colleagues found the intestinal virome autonomously contributes to human health, but when perturbed, can trigger inflammation and provoke inflammatory bowel disease (IBD). The results have implications for novel virus-based IBD therapies.