CAN PROGESTERONE INFLUENCE THE DEVELOPMENT OF MENINGIOMAS?

Berni F. Can progesterone influence the development of meningiomas? International Journal of Infection. 2026;10(2):34-36.

F. Berni^*

Villa Ada World Medicine, Via Ceresio 20, Rome, Italy.

*Correspondence to:
Dr. Federico Berni,
Villa Ada World Medicine,
Via Ceresio 20,
Rome, Italy.
e-mail: dottorberni@yahoo.it

Received: 09 April, 2026 Accepted: 02 June, 2026

ISSN 3103-6678 [online] Copyright 2026 © by Biolife Publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

KEYWORDS: Meningioma, tumor, progesterone, receptor, immunology

INTRODUCTION

Meningioma is the most common primary intracranial tumor in adults and can develop in various locations around the brain or spinal cord (1). It is a tumor of the meninges, the membranes covering the brain and spinal cord, that originates from meningothelial arachnoid cells. Meningioma is usually a benign tumor in which tumor cells replicate slowly, but its growth can compress nervous tissue, causing clinical symptoms. It is classified as benign when grade I, atypical when grade II, or anaplastic/malignant when grade III (2).

In benign meningiomas, the abnormal and uncontrolled multiplication of cells occurs very slowly, while in atypical and anaplastic forms, the genetic alterations are more numerous and lead to more aggressive growth. A small portion of the tumor tissue may be malignant, with atypical cells. It originates from arachnoid cells that accumulate genetic alterations, impairing cell growth. The gene most prone to mutations is NF2, located on chromosome 22, which encodes the protein schwannomin. This protein, also known as merlin, functions as a tumor suppressor and regulates cell-cell adhesion, growth signal transduction, cytoskeletal organization, and inhibition of cell proliferation. Inactivation of the NF2 gene causes merlin to lose its function, proliferation pathways are activated, and cells begin to continuously divide abnormally (3).

CELLURLAR PROCESSES IN MENINGIOMA

In meningioma, biochemical pathways for cell activation are hyperactivated, as is the transmission of cellular signals. Among the altered activation pathways is the PI3K/AKT/mTOR pathway, which stimulates protein synthesis, increases cell growth, and reduces apoptosis. Another altered activation pathway is the MAPK/ERK pathway, which results in increased proliferation and promotion of the cell cycle (4).

Cell cycle control is lost in meningioma, and tumor cells bypass the G1/S and G2/M checkpoints; the activity of cyclins and kinases increases, and the effectiveness of oncogene suppressor genes is reduced. All these abnormal reactions lead to continued cell proliferation with reduced apoptosis as meningioma cells become more resistant to programmed cell death due to an increase in anti-apoptotic proteins, such as the Bcl-2 family, decreased caspase activation, and increased cell survival (5).

Tumor cell growth is fueled by angiogenesis, whose processes are activated in meningiomas, forming new blood vessels to ensure the supply of oxygen and nutrients. Angiogenesis is particularly important in second- and third-degree meningiomas, where it is associated with faster growth and peritumoral edema (6). During angiogenesis, initial hypoxia accompanies the growth of the meningioma, and the protein hypoxia-inducible factor 1-alpha (HIF-1α) (a transcription factor activated by hypoxia) is not degraded, whereas under normal conditions it is rapidly degraded. Failure to degrade HIF-1α causes it to accumulate in the cytoplasm and migrate to the nucleus, where it binds to HIF-1β, forming a complex that activates the transcription of pro-angiogenic genes, including the gene for the vascular endothelial growth factor (VEGF) protein (7). The main gene activated is VEGF-A, which is secreted by meningioma cells and spreads into the surrounding tissue. VEGF-A binds to the VEGFR-2 receptor on endothelial cells, causing receptor autophosphorylation and activation of various intracellular pathways.

MENINGIOMAS AND PROGESTERONE

Most benign first-grade meningiomas express progesterone receptors (PR) and respond to this hormone. PR-positive meningiomas are generally associated with a better prognosis, tend to be less aggressive, and grow more slowly. In contrast, grade II and III meningiomas often show a reduction or loss of PRs, a characteristic associated with increased growth and more aggressive biological behaviour, as occurs in meningiomas during pregnancy and during periods of elevated hormone concentrations (8). Prolonged use of high-dose progestin drugs is associated with the development of meningiomas. Discontinuing these drugs may slow the growth of the meningioma or make it less aggressive. However, the use of progesterone-blocking drugs has not demonstrated clinical benefit and is not used as a treatment for meningioma.

CONCLUSIONS

Meningioma is the most common primary intracranial tumor in adults and originates from the meningothelial arachnoid cells of the meninges. In most cases, it is benign (grade I) but can also present in atypical (grade II) or anaplastic/malignant (grade III) forms, characterized by more aggressive growth. Its onset is linked to the accumulation of genetic alterations, particularly in the NF2 gene on chromosome 22, which leads to the loss of function of the merlin protein, an important tumor suppressor, promoting uncontrolled cell proliferation. Furthermore, meningiomas exhibit hyperactivation of intracellular signalling pathways such as PI3K/AKT/mTOR and MAPK/ERK, which promote cell growth, protein synthesis, cell cycle progression, and reduced apoptosis. PR-positive genes indicate a less aggressive meningioma and a better prognosis, and prolonged exposure to some progestins may increase the risk of developing or promoting the growth of certain meningiomas.

Conflict of interest

The author declares that they have no conflict of interest.

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