Progress in progestin-based therapies for neurological disorders

Régine Sitruk-Ware, Population Council
Brooke Bonsack
Roberta Diaz Brinton
Michael Schumacher
Narender Kumar, Population Council
Jea-Young Lee
Vanessa Castelli
Sydney Corey
Alexandreya Coats
Nadia Sadanandan
Bella Gonzales-Portillo
Matt Heyck
Alex Shear
Cozene Blaise
Henry Zhang
Michael Sheyner
Julián García-Sánchez
Lisset Navarro
Martine El-Etr
Alejandro De Nicola
Cesario V. Borlongan


Hormone therapy, primarily progesterone and progestins, for central nervous system (CNS) disorders represents an emerging field of regenerative medicine. Following a failed clinical trial of progesterone for traumatic brain injury treatment, attention has shifted to the progestin Nestorone for its ability to potently and selectively transactivate progesterone receptors at relatively low doses, resulting in robust neurogenetic, remyelinating, and anti-inflammatory effects. That CNS disorders, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), and stroke, develop via demyelinating, cell death, and/or inflammatory pathological pathways advances Nestorone as an auspicious candidate for these disorders. Here, we assess the scientific and clinical progress over decades of research into progesterone, progestins, and Nestorone as neuroprotective agents in MS, ALS, SCI, and stroke. We also offer recommendations for optimizing timing, dosage, and route of the drug regimen, and identifying candidate patient populations, in advancing Nestorone to the clinic.