Отказ от препарата также модулирует потенциальный биомаркер PFS PPAR-α, в то время как ALLO восстанавливает экспрессию этого гена.
21 июля 2025 г.
Дорогие друзья!
Расстройства желудочно-кишечного тракта? Мышечная слабость? Колебания артериального давления? Быстрый набор веса? Плохое состояние костей? Ухудшение зрения? Головные боли? Бессонница?
Если вы раньше принимали финастерид и страдаете от таких постоянных побочных эффектов, однажды облегчение может прийти с помощью аллопрегнанолона (АЛЛО).
One down, six to go
Last week in Biomolecules, Roberto Cosimo Melcangi, PhD, Head of the Neuroendocrinology Unit in the Department of Pharmacological and Biomolecular Sciences at the University of Milano (UniMi) published the first of his Milano Project studies.
Titled Exploration of the Possible Relationships Between Gut and Hypothalamic Inflammation and Allopregnanolone: Preclinical Findings in a Post-Finasteride Rat Model, the research, led by Team Melcangi’s Silvia Diviccaro, PhD, “aimed to investigate the effects of finasteride withdrawal (FW) in a rat model and evaluate the potential protective effects of ALLO on gut and hypothalamic inflammation.”
In all, Diviccaro and her team of nine fellow researchers treated 16 adult male rats with finasteride for 20 days, followed by one month of FW. During FW, half of those rats were administered ALLO, while the other half were not. Separately, a control group of eight rats was given neither finasteride nor ALLO, but rather an inactive substance (aka vehicle solution).
“This preclinical study shows that FW causes inflammation in both the gut and hypothalamus in rats,” concludes Diviccaro. “ALLO treatment helped reduce several of these effects. These results suggest ALLO could have a protective role and have potential as a treatment for PFS patients.”
Symptoms of gut inflammation, which can occur anywhere in the gastrointestinal system, often include: abdominal pain, diarrhea, bloody stool, and chronic fatigue.
Inflammation in the hypothalamus—an area of the brain that links the endocrine system to the nervous system, thus maintaining a stable internal environment despite changes in external conditions—can manifest itself in an even greater number of symptoms. Among them are: out-of-control appetite and thirst, rapid weight gain or weight loss, frequent urination, low body temperature, heart-rate irregularities, insomnia, muscle weakness, poor bone health, reduced vision, headaches, insomnia, and infertility.
The prequel
Three years ago, Team Melcangi published its first ALLO study, Gut Inflammation Induced by Finasteride Withdrawal: Therapeutic Effect of Allopregnanolone in Adult Male Rats, marking the first-ever demonstration that it’s possible to recover from a PFS symptom. In that paper, lead researcher Diviccaro wrote:
[P]revious observations in PFS patients and an experimental model showed alterations in gut microbiota populations, suggesting an inflammatory environment. To confirm this hypothesis, we…explored the effect of chronic treatment with finasteride…and its withdrawal…on the levels of steroids, neurotransmitters, pro-inflammatory cytokines and gut permeability markers in the colon of adult male rat. The obtained data demonstrate that the levels of [ALLO] decreased after finasteride treatment and after its withdrawal.
Following the drug suspension, the decrease in ALLO levels correlates with an increase in IL-1 and TNF-, serotonin and a decrease in dopamine. Importantly, ALLO treatment is able to counteract some of these alterations.
[B]ecause sexual dysfunction may be related to alterations in gut microbiota and the existence of the well-described gut-brain axis, observations here obtained may provide an important background to explore [the] protective effect of ALLO on psychiatric and andrological dysfunctions.
Another first
In their new ALLO study, Team Melcangi once again pioneers PFS research, reporting:
FW increased colonic NF-kB expression and decreased PPAR-α and PPAR-γ levels, mirroring inflammatory signaling observed in IBDs. Notably, ALLO treatment specifically restored PPAR-α expression. This is significant because PPAR-α has been implicated in stimulating neuroactive steroid biosynthesis in the brain, and its upregulation may represent a key mechanistic pathway through which ALLO exerts anti-inflammatory effects. In line with a previous hypothesis, PPAR-α activation may potentially counteract NF-κB signaling, suggesting that ALLO’s restorative action on PPAR-α could underlie its ability to suppress colonic inflammation.
To date, no studies have explored whether ALLO modulates PPAR expression in the colon, making these findings particularly novel.
In a review article published eight months ago in the Journal of Neuroendocrinology (The gut-microbiota-brain axis: Focus on gut steroids), Diviccaro noted the significance of PPAR-α—a gene that regulates energy combustion, inflammation and lipid metabolism—within the search for effective PFS therapies:
Considering the important evidence suggesting the interaction of PPAR-α and ALLO in the [gut-microbiome-brain axis] (GMBA), it will be crucial to investigate whether this interaction is altered in the PFS animal model… PPAR-α was proposed as a potential biomarker in [inflammatory bowel disease] (IBD). Therefore, the potential significance of ALLO-based intervention in shaping future treatment options could be definitely a new approach for PFS.
Pipeline update
Launched April 2024 in partnership with the PFS Foundation, the Milano Project is a three-year effort comprised of seven preclinical studies designed to map the basic science of PFS and, in turn, identify potential therapies for this emerging epidemic.
In addition to Exploration of the Possible Relationships Between Gut and Hypothalamic Inflammation and Allopregnanolone, two separate studies are currently in the works.
Investigation 2: Does loss of libido originate in the brain?
Many behavioral parameters have been analyzed in a PFS animal model, confirming alterations in motivational behavior and anxiety-like behaviors. The resultant data helped identify areas of the brain involved in various PFS symptoms, thus providing a roadmap of which tissues to focus on in subsequent analyses.
Status: This paper is complete, and will soon be submitted for publication.
Investigation 3: How don’t you feel?
Possible mechanisms involved in genital numbness and paresthesia (aka “pins and needles”), symptoms common among PFS patients, have been identified in an animal model. Among those mechanisms is the expression of PIEZO 2, which can play a role in sexual dysfunction and genital insensitivity. These observations, which represent the first-ever explanation of the latter PSF symptom at the genetic level, may represent a possible target for future therapeutic strategies.
Status: Interesting results obtained thus far by Team Melcangi’s Prof. Silvia Giatti, PhD, on PIEZO 2 in the PFS experimental model will be submitted for publication before the end of the year.
To date, your donations have funded 26% of the Milano Project’s $300,000 budget, for which we thank you. But we still have a way to go before hitting our target, so if you’ve given in the past, please consider doing so again, while asking family members and friends to do the same. If you’ve yet to donate, we hope that the stellar progress Team Melcangi has made these past 15 months will motivate you to give before the end of 2025—and again in 2026.
Finasteride was originally developed by Merck & Co., Inc., and first approved by the US Food and Drug Administration in 1993 as Proscar (5 mg, for enlarged prostate), and again in 1997, as Propecia (1 mg, for hair loss).
In June 2021, Merck spun off its Organon subsidiary as an independent public company (NYSE: OGN). Founded in the Netherlands in 1923, Organon bills itself as a “global health care company dedicated to making a world of difference for women, their families and the communities they care for.”
Among the Merck products Organon acquired in the deal were Proscar and Propecia. To report adverse events for either finasteride product, call the Organon Service Center at (844)674-3200, or email Service_Center@Organon.com.
Anyone living in the US who suffers from PFS should also report his or her symptoms to the US FDA. Anyone living outside the US who suffers from PFS should report his or her symptoms to the US FDA as well as to his or her local DRA, as directed on our Report Your Side Effects page.
If you or a loved one are suffering from PFS, and feeling depressed or unstable, please don’t hesitate to contact the PFS Foundation as soon as possible via our Patient Support hotline: social@pfsfoundation.org
Thank you.