新的动物模型研究表明,非 那雄胺造成大脑处理长期记 忆和情绪反应的区域“多处 改变”

SOMERSET, N.J., Oct. 1, 2018 – “Finasteride treatment causes several alterations in the hippocampus,” the section of the brain responsible for processing long-term memory and emotional responses, according to a new study conducted at the University of Milano, and the Cajal Institute and Carlos III Health Institute, both in Madrid.

Titled Treatment of male rats with finasteride, an inhibitor of 5alpha-reductase enzyme, induces long-lasting effects on depressive-like behavior, hippocampal neurogenesis, neuroinflammation and gut microbiota composition, the animal-model study was led by Roberto Cosimo Melcangi, Ph.D. at UM’s Department of Pharmacological and Biomolecular Sciences, whose team totaled seven researchers from the three institutions.
Results obtained show:

(i) Long-term depressive-like behavior.

(ii) Alterations in neurogenesis, gliosis and increased levels of inflammatory cytokines in the hippocampus.

(iii) Alterations in the composition of gut microbiota that was present one month after withdrawal of subchronic treatment of young male rats with finasteride.

This research marks the completion of Phase II of Prof. Melcangi’s ongoing investigation into post-finasteride syndrome at the molecular level, aimed at determining the root causes of the condition, while possibly setting the stage for the development of effective therapies.

Phase I of the investigation, published last year in The Journal of Steroid Biochemistry and Molecular Biology and titled Neuroactive Steroid Levels and Psychiatric and Andrological Features in Post-Finasteride Patients, demonstrated that PFS patients suffer from altered levels of critical brain-function regulators, including neuroactive steroids.

That three-year study, in which 16 men with PFS and 25 control patients were evaluated, also uncovered evidence of neuropathy of the pudendal nerve among those with severe erectile dysfunction.

“This is yet another example of the excellent research being conducted by Professor Melcangi and his team. It brings us one critical step closer to better understanding the underlying biochemistry of PFS and—hopefully—to an effective treatment. We already know how to prevent the condition,” said John Santmann, MD, CEO of the Post-Finasteride Syndrome Foundation, which co-sponsored both studies.

Post-finasteride syndrome occurs in men who’ve taken finasteride to treat hair loss or enlarged prostates. Reported symptoms include: loss of libido, erectile dysfunction, depression, suicidal ideation, anxiety, panic attacks, Peyronie’s disease, penile shrinkage, gynecomastia, muscle atrophy, cognitive impairment, insomnia, severely dry skin and tinnitus. The condition often has a life-altering impact on patients and their families, such as job loss and the breakup of marriages and romantic relationships, while also being linked to suicide.

The PFS Foundation has also funded clinical research and statistical analysis at other leading institutions, including:

• Brigham and Women’s Hospital (Boston): Characteristics of Men Who Report Persistent Sexual Symptoms after Finasteride Use for Hair Loss, The Journal of Clinical Endocrinology & Metabolism, September 2016

• Northwestern University Feinberg School of Medicine (Chicago): Persistent erectile dysfunction in men exposed to the 5α-reductase inhibitors finasteride or dutasteride, PeerJ, March 2017

• Baylor College of Medicine (Houston): Genetic and Epigenetic Studies on Post-Finasteride Syndrome Patients

As of September 2108, the World Health Organization Programme for International Drug Monitoring’s database of adverse drug reactions contained 14,925 finasteride ADRs, including 3,003 reports of erectile dysfunction, and 3,565 psychiatric disorders including 33 suicide attempts, and 59 completed suicides.

In May 2017, the UK’s Medicines and Healthcare Products Regulatory Agency issued a drug-safety update titled Finasteride: rare reports of depression and suicidal thoughts. “Depression and suicidal thoughts,” it read, “have been reported in men with and without a previous history of depression.”

Three months later, the European Medicines Association (EMA) issued a Periodic Safety Update, in which it noted, “Cumulatively 51 cases of suicidal ideation have been received… Taking into account the serious reported cases…[we] recommended to include a warning…to inform that mood alterations, depression and suicidal ideation have been reported with finasteride.” A year after that, based again on reported cases, the EMA added “anxiety” to its warning list of finasteride ADRs.

In March 2015, the U.S. National Institutes of Health listed PFS on its Genetic and Rare Diseases Information Center, noting that “some patients who have taken finasteride have referred to side effects such as sexual dysfunction and depression (sometimes severe)… Studies sponsored by the NIH and other organizations are underway to better understand the effects of 5-alpha reductase inhibitor drugs.”

About Roberto Melcangi, Ph.D.

Prof. Melcangi received his Ph.D. degree in Chemistry and Pharmaceutical Technology from the University of Milano in 1982. He is currently Professor of Neuroendocrinology and Head of the Neuroendocrinology Unit in the Department of Pharmacological and Biomolecular Sciences in the University of Milano, Italy, and serves on the editorial board of Frontiers in Aging Neuroscience. With 186 peer-reviewed publications (H-index = 46), he is a leading authority in the field of neuroendocrinology and neuroactive steroids, and is organizer of the International Meeting on Steroids and the Nervous System, held biannually in Turin, Italy.

About the PFS Foundation

Headquartered in Somerset N.J., the Post-Finasteride Syndrome Foundation was established in July 2012 as a 501(c)(3) organization, with private grants from families in the U.S. and abroad. Tax-deductible financial donations to the nonprofit organization can be made via PFSFoundation.org, which also houses patient-recruitment information on active clinical studies, published research, research goals, and media reports about PFS. In July 2015, the PFS Foundation established The Southwest Brain Bank in the Department of Psychiatry at the University of Texas Health Science Center, whose mission is to collect and study post-mortem human brain and spinal cord tissue in patients with PFS in order to better understand the pathology and etiology of the condition.

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Contact

Philip Roberts
Post-Finasteride Syndrome Foundation
proberts@pfsfoundation.org
(856)425-6046