Milano Project study No. 2 reveals ‘a dichotomy between immediate and delayed’ effects of the embattled drug
March 9, 2026
Dear Friends:
If you’ve ever likened PFS to being turned into a bundle of nerves and tossed into solitary confinement, science can now testify on your behalf.
Quitters don’t win
Last month, Roberto Cosimo Melcangi, PhD, and his team at the Neuroendocrinology Unit in the Department of Pharmacological and Biomolecular Sciences at the University of Milano (UniMi) unveiled a study comparing the behavior of rats newly on finasteride with their behavior after going cold turkey.
Published in the Journal of Neuroendocrinology, Finasteride Withdrawal Induces Anxiety-like Behavior and Novelty Avoidance in Adult Male Rats marks the first known effort to elucidate how and why certain adverse reactions to finasteride differ from post-finasteride syndrome.
“[A]lthough finasteride has limited behavioral effects after chronic treatment, the drug suspension leads to persistent behavioral alterations characterized by increased locomotion, increased anxiety-like behavior, and marked avoidance of novel stimuli,” write coauthors Lucia Cioffi, PhD(c) and Silvia Diviccaro, PhD.
The rodents more or less traveled
In all, 40 adult male rats were used in the study, half exposed to a vehicle solution alone for 20 days straight (the control group), and the other half exposed to the same solution plus 3 mg daily of finasteride for the same duration. The animals were then run through two testing protocols, first during finasteride treatment, then 30 days after discontinuation of the drug:
▪ Open field-based behavioral assays: Part 1 involved releasing the rats into an object-free, walled-in, 50-cm square arena to see how they behaved in a space they’d never seen before. Part 2 involved releasing them into the same arena, but with two objects, each differing in shape and color, placed in opposite corners. Movement patterns were analyzed to assess anxiety-like and novelty-seeking behaviors.
▪ Elevated plus maze behavioral assays: These involved placing the rats on a cross-shaped structure elevated 50 cm above the floor. One arm was 50 cm long by 10 cm wide, with no vertical barriers, making it diving-board-like. The other arm measured the same dimensions but with a 40 cm wall on each side, making it tunnel-like. Time spent on the open, potentially dangerous arm versus the safe-feeling closed arm was analyzed to assess levels of anxiety-like behavior.
While on finasteride, the rats didn’t display significant differences than the control group, suggesting that the drug causes limited behavioral changes during administration.
Cautionary tails
Yet post-use of the drug, a number of statistically significant behavioral alterations emerged. Specifically, the finasteride-treated rats:
▪ Exhibited increased locomotor activity, and markedly decreased freezing time (i.e., stopping dead in their tracks).
▪ Spent less time in the center of the open field.
▪ Reared up on their hind legs more frequently and for longer periods of time.
▪ Took longer to initially approach the two new arena objects, and spent less time exploring them.
▪ Spent increasingly less time in the zones where the new objects were located.
“Our results revealed a dichotomy between immediate and delayed finasteride effects… [S]howing a picture of increased vulnerability, [they] are in agreement with clinical reports of PFS, highlighting the relevance of our model for this condition,” Cioffi and Diviccaro conclude. “Moreover, the data here described strengthen the importance of monitoring patients not only during treatment but also following discontinuation of finasteride therapy.”
“The data we’ve obtained through these behavioral tests are now helping us identify which areas of the brain can be correlated to various PFS symptoms,” Prof. Melcangi tells us. “That in turn has helped us build a roadmap of tissues to target in our ongoing molecular analyses.”
As for other adverse reactions arising in the course of chronic treatment, the authors note at the outset of their study:
“The description of finasteride as a well-tolerated and relatively safe drug has recently been challenged by experimental findings that led to a more critical re-evaluation of [its approved indications]. Indeed, this drug induces a wide variety of side effects during treatment and upon withdrawal, such as sexual dysfunction and cognitive and psychological disorders, hallmarks of the so-called post-finasteride syndrome.”
The money plea
This latest research marks the completion of study No. 2 within the Milano Project. Launched April 2024 in partnership with the PFS Foundation and SIDEfxHUB, the project is comprised of seven preclinical studies designed to map the basic science of PFS and, in turn, identify potential therapies for this emerging epidemic.
To date, your donations have funded 37% 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. If you’ve yet to donate, we hope that the stellar progress Team Melcangi has made these past two years will motivate you to start giving in 2026.
“Hardly a day goes by when I’m not contacted by new PFS patients and their families from across the globe, virtually all of whom ask the same question: Is there any cure for this horrific condition?” says PFS Foundation President Philip Recchia.
“No matter how many of these calls I get, having to break the news that there are currently no proven therapies for PFS never gets easier. My only solace is being able to tell them about the Milano Project.”
Pipeline update
Here’s what to expect next from the project:
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: Team Melcangi’s Silvia Giatti, PhD, recently obtained interesting results on PIEZO 2 in the PFS experimental model, so the manuscript for this study will be submitted for publication as soon as possible.
Investigation 4: Can bad connections trigger anxiety and brain fog?
Synaptogenesis, the creation of new connections between brain cells, is a neurodevelopmental process that’s most intense pre-birth and during infancy but continues throughout adult life. It’s critical to learning, memory, and adapting to new experiences. Recent investigations into finasteride’s impact on brain function, via Team Melcangi’s animal model, have shed new light on the drug’s potential to alter synaptogenesis, a pathology that has been linked to cognitive dysfunction and behavioral changes. This study will roll the new data on altered synaptogenesis into existing morphological and molecular results for a further behavioral analysis.
Status: The manuscript will be completed in the coming weeks and submitted in the latter half of 2026.
“If all goes as planned,” Prof. Melcangi adds, “these two new studies will be published before year end.”
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.