Alterations of gut microbiota composition in post-finasteride patients: a pilot study
Borgo F, Macandog AD, Diviccaro S, Falvo E, Giatti S, Cavaletti G, Melcangi RC
Journal of Endocrinological Investigation2021
In plain terms
Researchers compared the bacteria in stool samples from 21 men with lasting symptoms after finasteride with stored results from 10 healthy men studied earlier. On some measures the men with symptoms had a less varied mix of gut bacteria, and several kinds of bacteria were more or less common than in the healthy men. The men with symptoms fell into two groups with different bacteria, and one of these groups stood further apart from the healthy men than the other.
What it doesn’t show: It can't show whether these differences cause symptoms, result from them or come from something else: the study was small, the healthy men came from an earlier study and were on average about 12 years older, and each man gave only one sample.
Summary (paraphrased)
Pilot study comparing fecal microbiota of 21 PFS patients (23 recruited, 2 excluded for low sequencing depth) with 10 healthy men whose sequences came from an earlier study, using 16S rRNA sequencing. Two richness measures (Chao1 and Faith's phylogenetic diversity) were lower in the PFS group, while Shannon diversity, observed OTUs and evenness did not differ. A patient subset showed lower levels of Faecalibacterium and Ruminococcaceae and higher Alloprevotella and Odoribacter. The authors proposed gut dysbiosis as a possible diagnostic marker and therapeutic target for the syndrome.
Evidence
Extracted from the full text; page numbers refer to the paper. The library’s own notes are labelled as such.
- Design
- Case–control studyPilot case-control comparison at a single time point of stool bacteria (16S rRNA gene sequencing) in men with PFS vs healthy men whose sequences came from an earlier study
- Setting
- Patients from the Italian finasteride side effects network; Milan, Italy; ethics approval 2018 (protocol 434/2018); dates not stated
- Population
- Men aged 25–51 with persistent sexual and mental-health symptoms after finasteride 1–1.25 mg/day for hair loss, stopped at least 3 months earlier, with no psychiatric disorder or sexual dysfunction before finasteride and no drugs known to interfere with microbiome analysis. All white (Caucasian), on a Mediterranean diet, with no comorbidities, no prebiotics, probiotics or antibiotics after finasteride, and no constipation or irritable bowel syndrome. Controls: 10 healthy men from an earlier study, described as matched for ethnicity, sex, diet and BMI.
- Size
- 31 · 21 patients analysed (2 of 23 excluded for too few sequencing reads) and 10 healthy men
- Exposure
- Finasteride 1–1.25 mg/day for hair loss; mean treatment 1,176 days; 433–7,111 days since stopping (median 2,465)
- Compared with
- 10 healthy men whose raw sequences came from an earlier study (Borgo et al. 2018); their finasteride history is not stated
- Outcome
- Within-sample diversity of gut bacteria (Chao1, Faith's phylogenetic diversity, observed OTUs, Shannon, evenness), between-sample diversity (UniFrac, Bray–Curtis), and the relative abundance of bacterial groups.
- Follow-up
- None; a single home-collected stool sample per person
Key results
- Within-sample diversity: lower richness in PFS by Chao1 (p = 0.047) and Faith's PD (p = 0.047); no difference by observed OTUs (p = 0.40), Shannon (p = 0.75) or Simpson/evenness (p = 0.89) · p. 1266; Fig. 1, p. 1267
- Between-sample diversity separated PFS from healthy (unweighted UniFrac p = 0.001, Bray–Curtis p = 0.001, weighted UniFrac p = 0.05). Patients formed two sub-clusters; sub-cluster B did not separate from healthy on weighted UniFrac (p = 0.37). Sub-cluster sizes are not stated · p. 1266; Fig. 2, p. 1268
- Phyla (mean relative abundance, healthy vs PFS): lower Proteobacteria (10.2% vs 4.5%, p = 0.009) and Actinobacteria (22.6% vs 4.5%, p = 0.0003); Firmicutes 45.4% vs 57.6% (p = 0.09). Genera lower in PFS include Subdoligranulum (3.8% vs 0.9%), Phascolarctobacterium, Ruminococcaceae UCG-002 (4.2% vs 0.12%) and Escherichia–Shigella · pp. 1266–1267; Fig. 3, p. 1268
- In sub-cluster A only, vs healthy: lower Faecalibacterium (p = 0.02) and Ruminococcaceae UCG-005 (p = 0.02), higher Alloprevotella (p = 0.03) and Odoribacter (p = 0.02) · p. 1267; Fig. 4
- No significant association between the bacteria and participant or clinical characteristics; time since stopping finasteride leaned towards sub-cluster A (p = 0.06). The sub-clusters did not differ in age, BMI, treatment period, time since stopping or reported symptoms · pp. 1266, 1269
Limitations the authors note
- A small cohort, for an emerging and rare syndrome
- The symptom questionnaire is not validated
- Patients and controls differed in age (p = 0.002); the authors consider adult gut bacteria stable with age
- Two samples had too few sequencing reads and were excluded
Also worth weighing (library’s note)
- Controls were 10 men from an earlier study whose stored sequences were reused; the paper does not say whether their samples were collected, extracted and sequenced in the same way or run as the patients', which can by itself produce differences
- Controls were older; from Table 1, mean age 48.7 vs 36.9 in the 21 patients analysed
- Shallow sequencing (rarefied to 1,336 reads per sample), many diversity measures and many bacterial groups tested, with no correction for multiple testing stated; the two diversity differences are at p = 0.047
- Some reported abundances do not add up: the healthy group's phylum means sum to 118.6% (45.4 + 40.4 + 10.2 + 22.6), and in PFS the Bifidobacteriaceae family (12.3%) exceeds its own phylum, Actinobacteria (4.5%)
- The Discussion calls the Firmicutes increase significant (p. 1268); the Results give p = 0.09 (p. 1266)
- Recalled before finasteride, 16 of 23 (69.6%) reported irritability and 15 of 23 (65.2%) anxiety sometimes or often
Funding: Università degli Studi di Milano (open access, CRUI-CARE agreement); MIUR "Progetto Eccellenza"; Post-Finasteride Foundation to R.C. Melcangi Interests: None declared
What it can support (library’s note): Differences in gut bacteria between a small group of men with PFS and a smaller, older group of healthy men from an earlier study. It cannot show that finasteride caused the differences or that they cause symptoms, and it does not establish a diagnostic marker.
Why it’s in the corpus
Pilot evidence of an association between PFS and altered gut bacteria (21 patients vs 10 older healthy controls from an earlier study), with no significant link found between the bacteria and clinical characteristics; it connects to the growing body of Melcangi-group work on finasteride, microbiota, and neuroinflammation (see also DISC-009, DISC-010).
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