{"entity": "publication", "iuid": "1f04975682124ba7b6794e148f9cf893", "timestamp": "2026-09-23T17:47:34.663Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1f04975682124ba7b6794e148f9cf893.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1f04975682124ba7b6794e148f9cf893"}}, "title": "The circulating dihydrotestosterone/testosterone ratio is increased by gut microbial 5\u03b1-reductase activity in females.", "authors": [{"family": "Ohlsson", "given": "Claes", "initials": "C"}, {"family": "Li", "given": "Lei", "initials": "L"}, {"family": "Horkeby", "given": "Karin", "initials": "K"}, {"family": "Lawenius", "given": "Lina", "initials": "L"}, {"family": "Colld\u00e9n", "given": "Hannah", "initials": "H"}, {"family": "Sj\u00f6gren", "given": "Klara", "initials": "K"}, {"family": "Baldanzi", "given": "Gabriel", "initials": "G"}, {"family": "Engstr\u00f6m", "given": "Gunnar", "initials": "G"}, {"family": "\u00c4rnl\u00f6v", "given": "Johan", "initials": "J"}, {"family": "Orho-Melander", "given": "Marju", "initials": "M"}, {"family": "Fall", "given": "Tove", "initials": "T"}, {"family": "Grahnemo", "given": "Louise", "initials": "L"}], "type": "journal article", "published": "2025-11-00", "journal": {"title": "EBioMedicine", "issn": "2352-3964", "volume": "121", "pages": "105978", "issn-l": "2352-3964"}, "abstract": "Dihydrotestosterone (DHT), the most potent ligand to the androgen receptor, is synthesised from testosterone (T) by 5\u03b1-reductase type 1 and 2. While type 1 is expressed in several non-reproductive tissues in both sexes, men also express high levels of the high-affinity type 2 isoform in reproductive tissues; yet women have a higher circulating DHT to T (DHT/T) ratio than men. We hypothesised that the high DHT/T ratio in women is caused by high gut microbiota (GM) 5\u03b1-reductase activity or altered \u03b2-glucuronidase-induced androgen reabsorption from the gut.\n\nWe used a large cross-sectional subsample of the Swedish CArdioPulmonary bioImage Study (2897 women and 4338 men, 50-65 years of age) with GM composition and functionality determined by metagenome sequencing and circulating androgens determined by liquid chromatography-tandem mass spectrometry.\n\nWe confirmed that women had higher (+194%) circulating DHT/T ratio than men. The relative abundance of microbial genes for 5\u03b1-reductase type 1 (P = 3 \u00d7 10-4), but not \u03b2-glucuronidase, was positively associated with the DHT/T ratio in women. In women, the GM relative abundances of Odoribacter splanchnicus and Parabacteroides distasonis were positively associated with the relative abundance of microbial genes for 5\u03b1-reductase type 1 (P < 2 \u00d7 10-149) and the circulating DHT/T ratio (O. splanchnicus P = 3 \u00d7 10-6; P. distasonis P = 5 \u00d7 10-5). In mechanistic studies, we observed very high DHT/T ratio in intestinal content of female conventionally-raised but not germ-free mice. In female mice, the DHT/T ratio was 86.9% higher in serum from the portal vein than in inferior vena cava (P = 0.007).\n\nThese findings demonstrate that the circulating DHT/T ratio is increased by GM 5\u03b1-reductase activity in females. We propose that the GM acts as an endocrine organ influencing the androgenic status in females.\n\nSee Acknowledgements.", "doi": "10.1016/j.ebiom.2025.105978", "pmid": "41124778", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12589954"}, {"db": "pii", "key": "S2352-3964(25)00422-0"}], "notes": [], "created": "2026-09-23T11:37:27.015Z", "modified": "2026-09-23T11:37:27.054Z"}