Menopause and Mental Health

Abstract

Menopause is more than simply the end of menstrual cycles or having hot flushes—it marks a time of profound hormonal change which can cause a range of symptoms from poor sleep to anxiety, low mood, cognitive decline and difficulties with memory. These effects can be life-altering and can lead to social withdrawal, relationship strain and reduced capacity to work. With key neurotransmitter systems including serotonin, allopregnanolone and gamma-aminobutyric acid (GABA) being modulated by fluctuating levels of oestradiol, progesterone and testosterone, some women experience severe hormonally related depression and suicidality, as evidenced by the peak of women's suicide rates in midlife. Despite National Institute of Clinical Excellence (NICE) guidance recommending hormone replacement therapy (HRT) as a first-line treatment for perimenopausal mood disturbance, inconsistencies in clinical knowledge and lack of clinician awareness and confidence in prescribing HRT leave many women feeling unsupported and struggling to improve. By providing individualised menopause management through a biopsychosocial lens, supported by improved clinician training and further research, and offering treatment such as HRT alongside lifestyle and psychological support, there is potential not only to transform the lives of affected women but also to safeguard their long-term health. With nearly 40% of women’s lives spent post-menopause, combined with the extensive amount of time women sometimes spend in perimenopause (up to 12%), when mental health challenges are noted to be most acute, effective menopause management should be an urgent public health priority.

Key Summary Points

Menopause is more than simply the end of menstrual cycles or having hot flushes—it marks a time of profound hormonal change which can cause a range of symptoms from poor sleep to anxiety, low mood, cognitive decline and memory difficulties.

Individualised menopause management with a biopsychosocial perspective can transform women's lives and safeguard their long-term health.

Hormone replacement therapy (HRT) is the recommended first-line treatment for perimenopausal mood disturbance, and for most women the benefits of HRT will outweigh any risks.

Inconsistent clinical knowledge and awareness leave women feeling unsupported and struggling to feel better.

Research into women’s hormonal health must be prioritised to advance and improve patient management in this important domain and in dedication to the women already lost to menopause.

Introduction

An association between our hormones and mental health is becoming increasingly recognised [1], and with the increased risk of suicide in women aged 45–54 [2], it is important that the two are considered in combination. There is growing evidence that declining oestradiol, testosterone and progesterone levels can adversely impact mental health [3, 4]. Evidence shows that perimenopause can occur for up to 10 years before menopause, and it is accompanied by huge fluctuations in hormone levels (oestradiol, progesterone and testosterone) [1]. This information, combined with the NICE guidance on treating mood disorders during perimenopause [5] and the improvement in symptoms that women report upon commencing hormone replacement therapy (HRT) [1, 6, 7], shows the importance of improving menopause management by using a thorough biopsychosocial approach. We can no longer expect women to accept and tolerate these significant and often debilitating symptoms that affect not only their quality of life but also their cognition, sleep, relationships, ability to work and, sometimes, their ability to continue living, having a ripple effect that extends to those around them. In an ageing population, it is more important than ever for the quality of the latter years to be optimised, especially when women on average can expect to spend 38% of their lives in menopause and beyond [2].

Ethical approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Menopause

Menopause is defined as when the menstrual cycle stops in women, trans men and non-binary people registered female at birth and for whom there has been no menstrual period for at least 12 months [5]. It is a simple definition, but for those experiencing menopause it can be far from simple; much more than the cessation of menstruation should be considered. With cessation of menstruation comes a decline in production of the hormones oestradiol, progesterone and testosterone by the ovaries [3]. These hormones have vital roles in the function of the body and, as the levels decline, contribute to both menopausal symptoms experienced and future health risks [8–11].

The time before menopause when symptoms begin to arise is termed perimenopause. This can be protracted for some and precede menopause by many years. During this time, regular menstruation may continue, or there may be some changes in the pattern or flow of bleeding. Hormone levels can also become erratic, driving debilitating symptoms for some. As menstruation ceases, the erratic nature of hormone levels is less pronounced, but levels are lower so symptoms may become more consistent and will continue to have a detrimental impact on mental health and continue to impact future health [12]. For example, after menopause there is an increased likelihood of developing a multitude of conditions including osteoporosis, Alzheimer’s disease, diabetes [8] and cardiovascular disease [8, 10], thought to be in part a consequence of hormonal decline.

Fluctuating and falling hormone levels can contribute to a plethora of possible symptoms (Table 1) and individual variation can be extensive, with some describing few or no symptoms and others experiencing symptoms to a life-altering extent. Symptoms can be divided into the physical and the psychological, and sometimes they overlap. An example of this is palpitations, which can be a symptom of anxiety but can also be a physical symptom not associated with anxiety.

Table 1.

Examples of menopause symptoms (this is not an exhaustive list)

Menopause symptoms
Physical	Psychological
Hot flushes and night sweats	Low mood
Dry hair and/or hair loss, dry eyes, dry and/or itchy skin	Mood swings
Dry mouth or burning mouth	Anxiety
Altered sense of taste or smell	Panic attacks
Joint and muscle pains and/or stiffness	Poor concentration
Palpitations	Poor memory
Headaches/migraine	Irritability and anger
Fatigue	Tearfulness
Weight gain	Hopelessness
Vaginal dryness	Anhedonia
Urinary symptoms/infections	Thoughts of self-harm and suicide
Constipation/diarrhoea, nausea, heartburn, bloating	Poor sleep
Pins and needles, formication, restless legs	Low motivation
Tinnitus	Low confidence
Dizziness	Low self-worth

Having to contend with these symptoms can take a huge toll on daily functioning, and mental and social wellbeing are both directly and indirectly impacted, with those affected describing a loss of their sense of self, low self-esteem and a lack of confidence. This can negatively influence home, social and work life, causing social isolation, difficulties in relationships, changing relationships, difficulties in lifestyle and/or ability to work and potentially financial struggles [13] at a time when women are juggling caring for their elderly parents, taking care of a young family and continuing to work.

Concerning menopause and its impact, we should not only think of those experiencing menopause in midlife. The average age of menopause in the UK is 51 years, but many experience early menopause because of medical treatment, surgery, a coexisting health condition or idiopathically. Early menopause is diagnosed when menopause occurs before the age of 45, and premature ovarian insufficiency (POI) is a loss of ovarian function (transient or permanent) before the age of 40. For many years, POI was thought to affect 1% of the population; however, more recent studies suggest this could be as high as 3.5% [14, 15]. For this group, it might be even harder to navigate this time in their lives because of social and societal pressures.

Brain function relies on oestradiol, progesterone and testosterone; therefore, mental health can be destabilised during perimenopause, during menopause and post menopause. Whether mental illness has been experienced previously and symptoms are exacerbated [16] or this is a first encounter with poor psychological wellbeing, it is imperative that the underlying biological changes are understood to help inform individualised menopause care.

It is well recognised that serotonergic pathways have a role in depression and anxiety, and oestradiol has a role in the modulation of serotonin [1]. It is therefore imperative to acknowledge that falling or fluctuating oestradiol levels seen in perimenopause and menopause can have a disruptive effect on both mood and anxiety, which can also be impacted by other neurotransmitter pathways that are seen to be affected by menopause such as dehydroepiandrosterone sulphate and gamma-aminobutyric acid (GABA) [1, 8].

Progesterone receptors are also plentiful in the brain although there is a less consistent demonstration of decline in mental health as a direct consequence of progesterone decline. However, we do know that progesterone is converted to allopregnanolone in the brain and that this has a key role at the GABA receptor​ [17] where modulation of mood and anxiety is an effect.

Similarly, testosterone receptors are abundantly present in the brain, and a decline in testosterone can be linked to hypoactive sexual desire disorder in addition to low mood, anxiety, fatigue, altered cognition and poor concentration [3, 4].

Mental Health Challenges of Menopause

Perimenopause, menopause, pre-menstrual and postpartum periods may coincide with distressing and debilitating mental health challenges, including cognitive difficulties, insomnia, pre-menstrual syndrome and premenstrual dysphoric disorder (PMS and PMDD), menopause-associated psychosis (MAP) anxiety, hormonally related depression (HRD) and, in the most vulnerable women, suicide[16]. ​

Cognitive Difficulties

Cognitive and memory difficulties during perimenopause and menopause present in up to two thirds of women [18]. ‘Brain fog’ can manifest as confusion, fatigue, forgetfulness and reduced concentration. This can range from a reduced verbal memory to difficulty learning new tasks or reduced executive functioning. In large part due to declining levels of oestrogen and testosterone, this loss of the previous level of functioning and new cognitive difficulties can be compounded by poor sleep and depression [19]. This has led to 27% of women feeling menopause has had a negative impact on career progression [20]. A further 28% of women working during menopause have reduced their hours and 13% of women have considered leaving work altogether because of the impact on their mood and cognitive function [21].

Sleep Difficulties

Perimenopausal women with a history of mental health issues are particularly susceptible to the adverse effects of sleep loss, which may lead to cognitive impairment, mood instability and MAP [22]. The impact we see on sleep can be a consequence of the decline or fluctuation of one or all of the discussed hormones: oestradiol, progesterone and testosterone. If not adequately addressed, sleep disturbance increases the risk of mental illness [23, 24].

A potential link between menopause and psychosis is cited in the oestrogen protective hypothesis (1980s), which suggests that a decline in oestrogen creates increased vulnerability to psychotic symptoms in midlife given that oestrogen protects against psychotic symptoms from puberty to perimenopause [25, 26]. As oestrogen declines for some susceptible women, an onset of MAP may develop.

Anxiety and Hormonally Related Depression (HRD)

The perimenopausal and menopausal years often coincide with midlife stress, significant life change and the onset of additional health conditions that can cause or worsen feelings of anxiety and/or depression. Recent qualitative research on women who experienced mental health challenges during perimenopause indicated many reported feelings of dread, paranoia and intrusive thoughts, which could be suicidal in nature [27]. The research also indicated that HRD manifests with particular symptoms that differentiate it from clinical depression, an example of this being that women with HRD frequently maintain awareness and insight whilst experiencing it, understanding that their change in mood has a hormonal driver. This rational insight is not usually present in episodes of clinical depression. This can lead to a feeling of being powerless because they are aware of the decline in their emotional state but feel that they have no control over it [27].

Suicide

The above indicates the need for further research into the link between hormone decline and suicide rates. Suicide is a complex issue, and multiple factors are probably associated with the high rates that occur in mid-life. However, it may not be coincidental that the average age of menopause in the UK is 51, the age when suicide rates peak in women.

Published female suicide data from 2014 to 2023 show that peak rates occur in the 45–49 and 50–54-year age cohorts [28]. While male suicide rates are also higher in middle age, the relative increase is much higher for women [28]. Female data in 2023 in the 50–54 age group were 48% higher than in the preceding group. The equivalent male peak in 2023 was only 1.4% higher than in the previous age group [28]. This suggests a much more pronounced decline in female mental health in midlife than for males.

Most Vulnerable Sub-groups

Women With Long-term HRD

Women with a history of depression have a 70% higher risk of experiencing HRD [29]. Irritability as a characteristic of HRD is associated with increased suicidality [30].

Women with Early Onset Menopause

Early onset of menopause, particularly POI, is associated with a significantly elevated risk of suicide. The increased suicide risk associated with early menopause may be partially attributable to hormonal changes [31]. In addition, women with early onset menopause are at an increased risk of mental ill health due to the stress that might be associated with a diagnosis of early menopause, which may include feeling isolated from peers or navigating fertility treatments[23]. They may also have other medical conditions as either a cause or consequence of early menopause. Within this group we also see trans men who have had an oophorectomy and are traversing a challenging gender affirmation journey.

Women with Surgical Menopause

Surgical menopause causes an abrupt reduction in hormone levels which can lead to severe symptoms without hormonal replacement, especially in those who have had mental illness before [32]. The rate of new onset depression and anxiety symptoms following surgical menopause was double that of control groups [23]. NICE guidance clearly states women with surgical menopause should be on HRT until at least the average age of menopause, 51, unless contraindicated [5].

Women Post Sudden Cessation of HRT

Undue and/or sudden cessation of HRT can lead to the return of a multitude of symptoms and may also cause new health problems. Furthermore, mental wellbeing may decline when this treatment is removed. A 2015 clinical trial assessed women with past perimenopausal depression (PMD) who ceased HRT. The study found a resurgence in mental ill health with oestradiol withdrawal [6].

Women with Exposure to Significant Stressors Across their Lifespan

Women who are exposed to stressful life events are at greater risk of mental ill health during perimenopause and post-menopause. Those described as having very stressful life events have a greater risk of depression at times of hormonal change[23].

Patient Management

Regarding mental health and considering appropriate menopause management, it is fundamental that individualisation is prioritised. There are many avenues to explore from a holistic viewpoint in approaching menopause management including lifestyle, which is key. However, lifestyle changes can be extremely difficult to maintain if blighted by troublesome menopause symptoms, particularly if mental health, psychological and social wellbeing are impacted. Therefore, an individualised approach is necessary so that each element of a management strategy is carefully considered and included, or disregarded, depending on a variety of factors including patient choice, symptomatology, past medical history, current medications and current social circumstances, among others.

Psychological Interventions

Cognitive behavioural therapy (CBT) forms part of the NICE guidance and has a strong evidence base at all life stages [5]. It has proven benefits in the management of depression, anxiety, sleep disturbance and vasomotor symptoms[23].

Self-Care Strategies

It is well documented that for anyone, at any life stage, reducing and/or avoiding alcohol, not smoking and participating in regular exercise improve overall health and psychological wellbeing. The perimenopausal and menopausal years are no different, and there is evidence to support that these interventions help reduce symptoms in addition to improving future health outcomes, which is important at this time. For example, reducing alcohol intake can improve palpitations and anxiety. Nutrition, specifically a Mediterranean diet [33], can be beneficial for menopause symptom management, future health and thus mental wellbeing. Some will also find supplements beneficial. Magnesium can aid sleep and anxiety [34]. B vitamins help manage anxiety and support psychological wellbeing [35, 36].

Social support and connection, complementary therapies and self-care should all be emphasised, as well as regular exercise [37], in whatever form that brings the patient joy and fulfilment, whether walking, yoga or weight training, or a combination.

Alternatives to HRT That Can Be Prescribed

Alternatives to HRT can be explored, but there is limited evidence for some of these [38]. Prescribed medications such as gabapentin and pregabalin, selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRI) form part of guidance [5]. These have a role when mental health symptoms are present and can be important options for some patients experiencing menopause symptoms who are unable or do not wish to use HRT. However, if low or fluctuating hormone levels are the primary driver for symptoms, then this treatment should be given adequate attention.

Those with complex health needs can have a particularly difficult time navigating menopause, especially if they have experienced breast cancer, for example. Women undergoing menopause care after breast cancer report that they have unmet menopause-related needs after breast cancer and that they do not feel involved in their menopause-related management decisions [39, 40].

Herbal Remedy Alternatives to HRT

Caution should be exercised with many of the herbal remedies available for purchase. There can be risk of interaction with other medications. For example, St John’s wort can interact with SSRIs and cause serotonin syndrome [41]. Some individuals do see benefit from herbal remedies, but a more in depth discussion of the available options is beyond the scope of this review. 

HRT

The risks of HRT have often been misrepresented, primarily because of the Women’s Health Initiative (WHI) study [42]. However, what is understood now, and is clearly apparent in published guidelines, is that for most women, the benefits of HRT outweigh the risks​ [5, 43, 44]​, and women who use HRT have marked mood improvement [1, 16, 45]. Therefore, providing a clear overview of the HRT option and its benefits, along with any risks, is imperative in informed patient care. The current challenge is the huge variation in training and experience of the healthcare professionals that patients might contact as well as the divided opinion on HRT management approaches; this can leave women feeling isolated and uncertain [27].

When considering HRT, three hormones are involved: oestradiol, progesterone and testosterone. A regimen best suited to the individual patient must be developed. The above guidelines [5, 42–44] favour using body identical HRT, which comprises transdermal (or in some situations oral) oestradiol, used in conjunction with micronised progesterone for those with a womb, or for some a Mirena coil may be preferred. Each option has advantages and disadvantages depending on the individual. We can also consider transdermal testosterone and, finally, vaginal hormones for genitourinary syndrome of menopause.

Oestradiol is a potent neurosteroid [1] and studies dating back many years demonstrate its efficacy in treating depression when given transdermally in high doses. In fact, there is no evidence that antidepressants are beneficial in treatment of new-onset low mood in perimenopause, and HRT is the first-line treatment [5]. Oestradiol is shown to be of benefit in this group both alone and as an adjunct to antidepressant medications when symptoms have not responded to their use in isolation [1].

Progesterone use in an HRT regimen is primarily considered to protect the endometrium from exogenous oestradiol but also plays a vital role for some patients in managing their psychological symptoms as a consequence of the impact on allopregnanolone and GABA receptors [7]. Some find the introduction of progesterone more transformative than oestradiol for this reason, and genetic factors are thought to underpin this difference in response. Synthetic progestogens in particular can contribute to side effects in many patients, but choosing a micronised progesterone preparation (orally, vaginally or rectally) can often be a key management approach [46].

Transdermal testosterone can have a similarly transformative effect on psychological wellbeing, with some describing resolution of anxiety and episodic low mood [4].

We are learning more about cognition and use of HRT, too, which is an important aspect of mental health. Benefits are seen, but more research is needed to determine the appropriate timing and preparations for the best outcomes [47].

Future Therapies

How can we take this knowledge forward to help optimise women’s health? First, adequate training of medical students as well as GPs, psychiatrists, obstetricians and gynaecologists, and other practitioners in all medical specialties is warranted. This should include maintenance of mid-life care in the core curriculum from medical school to consultancy, in all specialties, and in the curriculum of all allied healthcare professionals.

Following the 2002 WHI study, there was a move away from prescribing HRT. In line with this, there was a subsequent move away from teaching about menopause in institutional and training settings [12]. This movement is slowly being reversed, and we can now build upon opportunities to discuss perimenopause and menopause with women in different healthcare settings.

One such opportunity is the over 40s health check, which is available in the UK within the NHS for individuals between the ages of 40 and 74 who do not have certain pre-existing conditions. A focus on hormonal health at this check-up will help identify whether individuals may benefit from HRT as well as contraception and other interventions such as weight-bearing exercise and diet. Those individuals who have pre-existing medical conditions will have regular check-ups as part of their management, and these sessions may provide an opportunity to alert women to information and to further discussions of this topic.

There also needs to be a focus on hormone health for individuals with neurodiversity and/or learning disabilities at all ages and an awareness among practitioners that women with conditions such as Down syndrome may experience early menopause [48]. Many women receive a late diagnosis of attention deficit hyperactivity disorder (ADHD) during perimenopause or menopause after losing the calming effects that their previously higher levels of oestrogen had on their brains. For many neurodiverse women or women with learning disabilities who experience poor sleep, agitation and declining cognition, this diagnosis (and the opportunity to manage it appropriately) is often missed, and the symptoms and signs are sometimes erroneously assigned to other factors, which may present additional risks.

For individuals consulting mental health professionals, a focus on hormonal health alongside treatment for depression, psychosis and other diagnoses, such as late diagnosis ADHD, can facilitate recovery and optimise management. For all women who have post-natal check-ups, a focus on this area is imperative, as it may be a factor when diagnosing and managing post-natal depression. In the hospital setting, an understanding among staff, including surgeons, that body identical HRT with transdermal oestradiol does not increase clot risk is important [49]. This will help ensure that women do not need to be destabilised unnecessarily by being taken off their hormonal treatment when it is effective for their health and wellbeing.

Finally, and perhaps most importantly, research into women’s hormonal health needs to be prioritised to a greater extent to help enable appropriate and optimised care for all. Women have long been underrepresented in research, and women in mid-life perhaps more so. This must change for the narrative to be overhauled regarding the care of women in all medical specialties, not only women’s health.

Conclusion

Hormone flux in midlife and at other life stages warrants increased attention when managing women's health and wellbeing. The impacts of oestradiol, progesterone and testosterone on different organ systems is well documented, including the heart, bones and the brain. These hormones impact neurotransmitters such as serotonin and GABA. Fluctuations in these hormones and their decline can lead to widespread symptoms and problems with both physical and mental health. Conditions such as ADHD can worsen or be unmasked, and symptoms of premenstrual disorders such as PMS and PMDD can escalate while hormones are in flux. Recognising this is the first step that practitioners and patients need to take. The second step is action in this area with replacement and optimisation of hormones alongside other treatment options, with research into women’s hormonal health being prioritised to advance and improve patient management in this pivotal and important realm. As clinicians, we owe this to women now suffering from, and in dedication to the women already lost to, menopause.

Author Contributions

Clair Crockett—Concept and design, drafting manuscript. Georgie Lichtveld—Concept and design, drafting manuscript. Rebecca MacDonald—Concept and design, drafting manuscript. Louise Newson—Drafting manuscript. Kulsum Janmohamed Rampling—Concept and design, drafting manuscript.

Funding

No funding or sponsorship was received for this study or publication of this article.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Clair Crockett, Georgie Lichtveld, Rebecca Macdonald, Louise Newson, and Kalsum Janmohamed Rampling have nothing to disclose.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.