Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug 12;12(8):760.
doi: 10.3390/pharmaceutics12080760.

Progestogens Are Metabolized by the Gut Microbiota: Implications for Colonic Drug Delivery

Zoe Coombes  1 , Vipul Yadav  2 , Laura E McCoubrey  2 , Cristina Freire  2   3 , Abdul W Basit  2 , R Steven Conlan  1 , Deyarina Gonzalez  1
Affiliations

Progestogens Are Metabolized by the Gut Microbiota: Implications for Colonic Drug Delivery

Zoe Coombes et al. Pharmaceutics. .

Abstract

Following oral administration, the bioavailability of progestogens is very low and highly variable, in part due to metabolism by cytochrome P450 enzymes found in the mucosa of the small intestine. Conversely, the mucosa in the colon contains much lower levels of cytochrome P450 enzymes, thus, colonic delivery of progestogens may be beneficial. Microbiota in the colon are known to metabolize a great number of drugs, therefore, it is important to understand the stability of these hormones in the presence of colonic flora before developing formulations. The aim of this study was to investigate the stability of three progestogens: progesterone, and its two synthetic analogues, medroxyprogesterone acetate (MPA) and levonorgestrel (LNG), in the presence of human colonic microbiota. Progesterone, MPA, and LNG were incubated in mixed fecal inoculum (simulated human colonic fluid) under anerobic conditions. Progesterone was completely degraded after 2 h, whereas levels of MPA and LNG were still detectable after 24 h. The half-lives of progesterone, MPA, and LNG in fecal inoculum were 28, 644, and 240 min, respectively. This study describes the kinetics of colonic microbial metabolism of these hormones for the first time. MPA and LNG show promise for delivery to the colon, potentially improving pharmacokinetics over current oral delivery methods.

Keywords: colonic stability; gastrointestinal bacteria; large intestine metabolism; levonorgestrel; medroxyprogesterone; microbiome; progesterone; steroids.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Chemical structures of (a) progesterone, (b) levonorgestrel, and (c) medroxyprogesterone acetate.
Figure 2
Figure 2
Stability profile of progesterone in human fecal slurry (mean ± S.D.) and control medium.
Figure 3
Figure 3
Stability profile of levonorgestrel in human fecal slurry (mean ± S.D.) and control medium.
Figure 4
Figure 4
Stability profile of medroxyprogesterone acetate in human fecal slurry (mean ± S.D.) and control medium.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Sato T., Miyagawa S., Iguchi T. Subchapter 94A—Progesterone. In: Takei Y., Ando H., Tsutsui K., editors. Handbook of Hormones. Academic Press; San Diego, NY, USA: 2016. pp. 507–508.
    1. Schumacher M., Zhu X., Guennoun R. 3.11—Progesterone: Synthesis, Metabolism, Mechanism of Action, and Effects in the Nervous System. In: Pfaff D.W., Joëls M., editors. Hormones, Brain and Behavior. 3rd ed. Academic Press; Oxford, UK: 2017. pp. 215–244. - DOI
    1. National Institute for Health and Care Excellence (NICE) British National Formulary (BNF) NICE; London, UK: 2020. Progesterone.
    1. BesinsHealthcare . Electronic Medicines Compendium. EMC; London, UK: 2019. Utrogestan 100mg Capsules Summary of Product Characteristics.
    1. Bayer . Electronic Medicines Compendium. EMC; Leverkusen, Germany: 2019. Levonelle 1500 Microgram Tablet Summary of Product Characteristics.

LinkOut - more resources