General Neuroscience

Neurological Manifestations of Menopause

Alisha Chunduri


With the onset of 12-45 years of age, a female goes through various menstrual phases from menarche to menopause. Release of the endometrial lining in a rhythmic manner when the egg does not get fertilized is essential for women's health. The hormone release is regulated on the basis of this menstrual rhythm. As the ovaries age, menstruation becomes irregular, causing women to suffer from various symptoms, including insomnia, depression, and weight gain. These symptoms occur because of hormonal imbalances in aging women. Often, these symptoms are more neurological due to fluctuating neuroendocrine regulations. This article is an exploration of the neurological symptoms of menopause with an emphasis on sleep, behavioral and neurodegenerative impact in comparison to the pre-menopausal period.


 After a span of 12 months without a menstrual period, women are considered to have entered menopause. Most menopausal cases are diagnosed in the 40s or 50s. It is usually natural and a result of aging. The end of reproductive years is marked by the stages of perimenopause, menopause, and postmenopause.

Perimenopause occurs eight to ten years before menopause. This is followed by menopause and postmenopause, which is the after level of menopause. This natural biological process is accompanied by physical and psychological symptoms like irregular periods, followed by night sweats, mood changes, sleep disruptions, changed metabolism, and vaginal dryness. These symptoms vary from woman to woman. Postmenopause occurs a year after the menopause, for the rest of the life. Due to significantly decreased hormone production, various body systems are affected leading to symptoms including hot flushes, mood swings, dry vagina, mental confusion, osteoporotic symptoms, depression, and insomnia. The hormonal aspect of the transition depends on the changes in the production of the ovarian hormones estrogen (the hormone that is responsible for a female’s sexual and reproductive functioning) and progesterone. These changes manifest in symptoms like the weakening of bones, energy loss, and weight gain [1].


Changes in Sleep and Circadian Rhythm

Melatonin secretion by the pineal gland is an underlying mechanism of the circadian rhythm. With aging, the level of melatonin gradually decreases. The underlying reasons for this decrease vary with gender and age. Studies show that menopause is associated with fluctuating levels of melatonin. This is a plausible cause of sleep disruption in the menopausal phase. The circadian rhythm of melatonin secretion is correlated with normal sleep patterns [2]. Sleep deprivation can lead to consequences that are detrimental to human health. In fact, various conditions including increased risk of diabetes, obesity, hypertension, heart attack, and stroke are associated with sleep loss and sleep disorders [3]. In addition, women tend to experience higher sleep problems post-menopause compared to pre-menopause. Hot flushes, a symptom of menopause, have shown a circadian rhythm in its occurrence. Other studies looked at the suppression of Luteinizing hormone by melatonin. A possible explanation is that the pulsatile release of Gonadotropin-releasing hormone and Luteinizing hormone is by the same hypothalamic pulse generator. This could lead to hot flushes. Hence, there is a chance of relief from the hot flushes in postmenopausal women with supplemental melatonin, as it can suppress the pulse generator [4].


Behavioral Effects 

Behavioral symptoms vary from woman to woman. The transition into old age, improper sleep, hot flushes, and other symptoms leading to discomfort can make a woman feel unstable in 

terms of mood. Sudden and extreme bursts of panic, anger, restlessness, anxiety, and depression are variably experienced. The underlying chemical changes include altered estrogen levels. In menopause, there is a reduction in the ovaries’ production of estrogen, which also controls the amount of serotonin produced in the brain. Their production is positively correlated; decreased estrogen production implies that there is decreased serotonin production. The biological function of serotonin is complex and is involved in regulating mood and cognition [5]. Thus, overall, serotonin impacts the happiness and wellbeing felt by a woman. The control of psychological symptoms develops gradually as one becomes habitual of the transition. Other ways to manage the emotional symptoms include meditation, consumption of a balanced diet, and regular exercise.


Neurodegenerative Effects

Research shows that symptoms of neurological disorders, such as Alzheimer’s disease and multiple sclerosis, are worsened in postmenopausal women [6]. Estrogen receptors are located in the prefrontal cortex, amygdala, cingulate cortex, retrosplenial cortex, and various subfields of the hippocampus that are associated with learning, memory, emotion. Decrease of the same estrogen hormone in menopause, can be the underpinning of the neurodegenerative impacts in this phase.

Findings show the protective role of estrogen in neurodegenerative diseases, including Alzheimer’s disease. Estrogen’s role as an antioxidant is essential because there is a high level of oxidative stress in AD neuropathology [7]. There is genetic evidence linking menopausal loss of estrogen and increased risk for AD in women. A genetic overlap was found between the genes upregulated by estrogen and genes downregulated in the human postmortem AD brain [8]. There is a disruption in multiple systems in the menopausal transition. Studies have shown that the removal of ovaries before menopause triggers neurological symptoms that are similar to perimenopause. Restoring the estrogen levels has reversed the symptoms. Estrogen signaling receptors are involved in supporting the neurons’ energy demands. Glucose metabolism regulates depression and anxiety brain regions in complicated networks. Postmenopausal women with depression have hypometabolism and hypermetabolism in the pons, and the middle and inferior frontal gyri respectively [9].



The complications caused by the transition of phases in a woman’s life can be bothersome. Adapting to this change should be given importance in order to make the symptoms more bearable. The magnitude of impact due to hormonal changes can be mitigated via medication prescribed by a doctor. Additionally, lifestyle changes such as yoga, meditation, and a healthy diet (with natural supplements like flax seeds, vitamin E, and melatonin) can significantly improve one's lifestyle.


  1. Greendale, Gail et al. (13/02/1999). The menopause. The Lancet. Retrieved: 13/03/2021.

  2. Pines, Amos. (02/09/2016). Circadian rhythm and menopause. Climacteric. Retrieved: 13/03/2021.

  3. Colten, Harvey and  Bruce Altevogt. (2006). Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem, Institute of Medicine (US) Committee on Sleep Medicine and Research. Retrieved: 27/03/2021.

  4. Landis, Carol et al. (01/03/2005). Sleep and menopause. Nursing Clinics of North America. Retrieved: 13/03/2021.

  5. Matthews et al. Influences of Natural Menopause on Psychological Characteristics and Symptoms of Middle-Aged Healthy Women. Article in Journal of Consulting and Clinical Psychology. Retrieved: 13/03/2021.

  6. Bove, Riley et al. (01/06/2017).  Exploration of changes in disability after menopause in a longitudinal multiple sclerosis cohort. Retrieved: 27/03/2021.

  7. Simpkins, James et al. (2009). The Potential for Estrogens in Preventing Alzheimer's Disease and Vascular Dementia.  Therapeutic Advances in Neurological Disorders, 2(1): 31–49. Retrieved: 19/04/2021.

  8. Ratnakumar, Abhirami et al. (2019). Estrogen activates Alzheimer's disease genes. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 5:906-917. Retrieved: 19/04/2021.

  9. Sohrabji, Farida. (2002).  Neurodegeneration in women. Alcohol Research & Health : The Journal of the National Institute on Alcohol Abuse and Alcoholism, 26(4), 316–318. Retrieved: 13/03/2021.

Alisha Chunduri

Alisha Chunduri

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