Hormones are a Girl’s Best Friend: The Neuroprotective Role of Female Hormones

As women, we often view our hormones as things that hinder us, or that we need to learn to manage. With hormone-driven mood swings, premenstrual syndrome (PMS), menstrual pain, and an abundance of women’s health related conditions (that aren’t always taken seriously by medical professionals and society), it can be easy to feel frustrated by our hormones and the, often negative, role we perceive them to play in our life. Whilst this frustration is valid, it also means we may overlook the positive role that our hormones can play in our health and wellbeing. A key benefit of female hormones, particularly oestrogen and progesterone, is the neuroprotective role they play in the central nervous system.

What makes oestrogen and progesterone neuroprotective?

Oestrogen and progesterone play a key role in neuroprotection, from early embryonic development all the way through early adulthood. Oestrogen is thought to be neuroprotective because it enhances mitochondrial function, promotes DNA repair, has neurotrophic effects, and interacts with the gut microbiome to influence inflammation. Similarly, progesterone has been shown to exhibit neurotrophic, antioxidant, and anti-inflammatory effects, whilst also modulating glia, and promoting myelination and remyelination. Oestrogen has been found to degrade beta-amyloid plaques, reduce inflammation, and prevent both apoptotic neuronal cell death and tau protein phosphorylation (all key contributing factors to neurodegenerative disease such as Alzheimer’s disease). It is thought that their anti-inflammatory effects are largely what underpins their neuroprotective abilities. Research in recent years has found neuroinflammation to be a key mechanism in neurodegenerative disease (such as Alzheimer’s disease), as well as disorders of the central nervous system (for example, Multiple Sclerosis). This would suggest that oestrogen and progesterone may reduce the risk of such conditions for women.

Despite oestrogen and progesterone largely being considered female hormones, men do also produce oestrogen. However, they do not produce it in the same quantities as women, nor do they experience the same hormonal cycles that influence the production of such hormones (see Katherine Mortimer’s blog post “The brain, menstrual cycle and female sex hormones: acknowledging sex bias in neuroimaging research” for more on this). When women reach menopause, we begin to see significant decreases in levels of oestrogen and progesterone. Such reductions do ultimately lead to a reduction in the neuroprotective benefits they provide.

How does this post-menopausal decline in female hormones impact women?

Men do not experience the same age-related declines in oestrogen, so they do not lose the neuroprotective benefits. This is where we begin to see an increase in the risk of neurodegeneration in women compared to men. Post-menopausal deprivation of female sex hormones (largely oestrogen) is consistently associated with increased risk of Alzheimer’s disease in women relative to men. In addition, earlier onset of menopause and/or delayed onset of menstruation have also been linked to an increased risk of Alzheimer’s disease in women compared to men. It is theorised that this is due to a reduced exposure to oestrogen throughout a woman’s lifetime.

Similarly, when women have pre-existing disorders of the central nervous system, it is common that symptoms begin to worsen during, and post-, menopause. For example, women with Multiple Sclerosis (MS) typically have lower rates of neurodegeneration and disability compared to men. However, once they reach menopause, these symptoms tend to worsen and align more with the presentation seen in men. This is thought to be due to men and women possessing more similar levels of oestrogen and progesterone once women reach menopause and the neuroprotective benefits of such hormones are less evident.

Preventing and Treating Menopause-Related Declines in Neuroprotection

So, what can we do about this? Logically, it would be assumed that Hormone Replacement Therapies (HRT) for oestrogen and progesterone during menopause would prevent the loss of neuroprotection. However, it is not quite as straightforward as that. Whilst there is some evidence to suggest that HRT, specifically with oestrogen, may mitigate the onset and progression of Alzheimer’s disease in post-menopausal women, this evidence is mixed and is largely dependent on the timing of the treatment. It is proposed that there is a “critical period” in which this treatment should be delivered, which is during the transition into menopause. It has been found that delayed treatment outside of this critical period may result in worsened cognitive outcomes and increased risk of Alzheimer's in women.  Pinpointing this critical period for each individual woman would be extremely challenging and would require highly tailored treatment plans, with early intervention being key. Implementing such treatment in women’s healthcare would be no easy feat and is unlikely to be something that we will see anytime soon.

Research has also highlighted that women typically have better cognitive outcomes than men following severe traumatic brain injury (TBI) and this is thought to be due to the neuroprotective role of progesterone. When levels decrease with age, women may be more at risk of worse outcomes. Animal studies have investigated the benefits of progesterone specific HRT to tackle neurological deficits and brain oedema following experimental TBI. Progesterone treatment improved neurological deficits, suggesting that its administration could be used to regulate immune/inflammatory reactions to neurological injury and improve outcomes for patients that have suffered a TBI. Whilst these findings are promising, strong clinical evidence of benefits for progesterone treatment following TBI in humans is yet to be revealed and, there are currently no ongoing clinical trials aiming to fill this research gap. Therefore, understanding the true efficacy of progesterone treatment for neurological injury in humans remains limited. Moreover, women have been historically underrepresented in TBI studies, which further limits our understanding of TBI outcomes for women. Further research with human subjects, specifically women, is required to ultimately understand the benefits of progesterone treatment and its role in neuroprotection following traumatic brain injury.

As society and medicine begins to place more value on women's health and the sex-related differences in neurodegenerative disease, it is hoped that more funding will be allocated to such areas of research. In turn, we would hope to see progression in our understanding of hormonal replacement therapy for neuroprotection during menopause and the development of more treatment options for women.

References:

• Bassani, T. B., Bartolomeo, C. S., Oliveira, R. B., & Ureshino, R. P. (2023). Progestogen-mediated neuroprotection in central nervous system disorders. Neuroendocrinology, 113(1), 14-35.

• Espana-Irla, G., Tinney, E. M., Perko, M., Nwakamma, M., Noble, S., & Morris, T. P. (2026). Traumatic Brain Injury Associated with Altered Corpus Callosum Microstructure in Females: Exploring the Roles of Menopause Timing and Hormone Therapy in UK Biobank. bioRxiv, 2026-01.

• Groswasser, Z., Cohen, M., & Keren, O. (1998). Female TBI patients recover better than males. Brain Injury, 12(9), 805-808.

• Haghi-Aminjan, H., Kouhestani, M., & Hosseini, A. (2024). The neuroprotective effects of progesterone against peripheral neuropathy: a systematic review of non-clinical studies. Metabolic Brain Disease, 40(1), 9.

• Lu, J., Xian, T. J., Li, C. J., & Wang, Y. (2025). The estrogen–brain interface in neuroinflammation: a multidimensional mechanistic insight. Frontiers in Aging Neuroscience, 17, 1671552.

• McCullough, L. D., & Hurn, P. D. (2003). Estrogen and ischemic neuroprotection: an integrated view. Trends in Endocrinology & Metabolism, 14(5), 228-235. (women protected from stroke in early years compared to men)

• Mervosh, N., & Devi, G. (2025). Estrogen, menopause, and Alzheimer’s disease: understanding the link to cognitive decline in women. Frontiers in molecular biosciences, 12, 1634302.

• Merz, S. (2025). The Critical Window for Estrogen Replacement Therapy in Menopausal Women: Exploring the Neuroprotective Effects of Estrogen in Reducing Dementia Risk. Brain Matters, 8(2), 11-15.

• Mortimer, K. (2024, March 11). The brain, menstrual cycle and female sex hormones: acknowledging sex bias in neuroimaging research. https://www.womeninneuroscienceuk.org/post/the-brain-menstrual-cycle-and-female-sex-hormones-acknowledging-sex-bias-in-neuroimaging-research

• Murgia, F., Giagnoni, F., Lorefice, L., Caria, P., Dettori, T., D’Alterio, M. N., ... & Atzori, L. (2022). Sex hormones as key modulators of the immune response in multiple sclerosis: a review. Biomedicines, 10(12), 3107.

• National Institute for Health and Care Research. (n.d.) All Studies. https://bepartofresearch.nihr.ac.uk/results/search-results?query=traumatic%20brain%20injury&location=

• National Library of Medicine (n.d.). ClinicalTrials.gov. https://clinicaltrials.gov/search?cond=Traumatic%20Brain%20Injury%20%5C(TBI%5C)&intr=Progesterone

• Peterson, A., Miller, E. C., De Jager, P. L., Avila-Rieger, J., Arce Renteria, M., Reed, A., ... & Tom, S. E. (2025). The association between age of menopause and hysterectomy status and alzheimer’s disease risk in a cohort of older white and black women. Journal of Women's Health, 34(10), 1195-1203.

• Raghava, N., Das, B. C., & Ray, S. K. (2017). Neuroprotective effects of estrogen in CNS injuries: insights from animal models. Neuroscience and neuroeconomics, 15-29.

• Suganya, S., Ashok, B. S., & Ajith, T. A. (2024). A Recent Update on the Role of Estrogen and Progesterone in Alzheimer's Disease. Cell Biochemistry and Function, 42(8), e70025.

• Valera, E. M., Joseph, A. L. C., Snedaker, K., Breiding, M. J., Robertson, C. L., Colantonio, A., ... & Bellgowan, P. S. (2021). Understanding traumatic brain injury in females: a state-of-the-art summary and future directions. The Journal of head trauma rehabilitation, 36(1), E1-E17.

• Wang, X., Feng, S., Deng, Q., Wu, C., Duan, R., & Yang, L. (2025). The role of estrogen in Alzheimer’s disease pathogenesis and therapeutic potential in women. Molecular and Cellular Biochemistry, 480(4), 1983-1998.

• Zhou, Z., Li, Y., Peng, R., Shi, M., Gao, W., Lei, P., & Zhang, J. (2024). Progesterone induces neuroprotection associated with immune/inflammatory modulation in experimental traumatic brain injury. NeuroReport, 35(6), 352-360.

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This article was written by Zoe Mason and edited by Rebecca Pope, with graphics produced by Suzana Sultan. If you enjoyed this article, be the first to be notified about new posts by signing up to become a WiNUK member (top right of this page)! Interested in writing for WiNUK yourself? Contact us through the blog page and the editors will be in touch.