Perimenopause exhaustion: what a new global study of 7,975 women found

Perimenopause exhaustion: what a new global study of 7,975 women found

On July 28, 2026, researchers from Mayo Clinic and Flo Health published a study in Menopause, the journal of The Menopause Society, comparing psychological symptoms in 2,353 women in perimenopause against 5,622 women who were not. The perimenopause group scored 52% higher on the psychological domain of the Menopause Rating Scale. The single symptom with the widest gap was not depression and not anxiety. It was exhaustion, at 56% higher.

That distinction matters because exhaustion, as the scale defines it, is not simply feeling tired. The Menopause Rating Scale groups physical and mental exhaustion together with a general decrease in performance, impaired memory, reduced concentration, and forgetfulness. It describes a state of being used up rather than a state of being sleepy. Women who report it are often the ones telling their doctors that they are functioning, but at a fraction of their old capacity.

This article explains what the study measured, why the hormonal shifts of perimenopause produce exhaustion and irritability ahead of low mood, and what the research supports for managing the psychological symptom load during the transition.

The measure What the 2026 study found
Overall psychological score 7.3 in perimenopause versus 4.8 in premenopause on a 0 to 16 scale, roughly 52% higher
Exhaustion 2.04 versus 1.31 on a 0 to 4 scale, a 56% difference and the largest of the four symptoms
Irritability 1.82 versus 1.18, a 54% difference and the second largest
Depressive mood and anxiety Both about 50% higher, real but smaller gaps than exhaustion and irritability
After statistical adjustment Every gap held after accounting for existing anxiety or depression diagnoses, age, income, education, ethnicity, BMI, smoking and alcohol
Who was excluded Women taking hormone therapy or hormonal contraception, so the scores reflect an untreated hormonal state

What the study measured and what it found

The researchers surveyed Flo app users aged 35 and over across 20 countries and six continents, in English, French, Portuguese and Spanish, between December 2024 and May 2025. Participants completed the Menopause Rating Scale, a validated questionnaire used widely in menopause research. The psychological domain of that scale contains four items: depressive mood, irritability, anxiety, and physical and mental exhaustion. Each is scored from 0 to 4, giving a domain total between 0 and 16.

Women in the perimenopause group averaged 45 years old. The premenopause comparison group averaged 39. Anyone using hormone therapy or hormonal contraception was excluded from the study, which means the scores describe what these symptoms look like without hormonal treatment in the picture.

The headline result was a psychological domain score of 7.3 in perimenopause against 4.8 in premenopause. Broken into individual symptoms, exhaustion led at 2.04 versus 1.31, followed by irritability at 1.82 versus 1.18. Depressive mood and anxiety both sat around a 50% difference. In the adjusted regression model, exhaustion again carried the largest coefficient at 0.63, with irritability at 0.58, anxiety at 0.48 and depressive mood at 0.46.

The adjustment step is the part worth pausing on. The authors controlled for whether a woman already carried a diagnosis of anxiety or depression, along with age, language, education, income, ethnicity, BMI, smoking and alcohol. The gap survived all of it. As the paper puts it, this suggests an additional component is driving these symptoms during perimenopause beyond pre-existing mental health conditions and demographics.

One further finding is worth reading with care. The international analysis showed wide country variation, from a mean score of 3.50 in Nigeria to 7.82 in Brazil, with the United Kingdom at 7.80 and the United States at 7.32. The authors label this exploratory and note it was not adjusted for social determinants of health. Cultural willingness to report mental health symptoms is a plausible driver of some of the spread, and the paper says so directly.

Why perimenopause hormones hit energy and temper first

Perimenopause is defined as the years leading up to the final menstrual period plus the twelve months after it, and Mayo Clinic notes that estrogen rises and falls rather than simply declining during this window. That instability, not a low average, is the mechanism most closely tied to mood change in the research literature.

Estradiol variability rather than estradiol level. A 2020 study in the Journal of Clinical Endocrinology and Metabolism led by Hadine Joffe followed 50 unmedicated perimenopausal women weekly for eight weeks. Greater week to week variability in estradiol was associated with higher depressive symptom scores. Notably, the frequency of hot flashes was not. The discussion section of the new 2026 paper points to this same body of work, attributing psychological symptom risk during perimenopause to variability in estradiol combined with low progesterone.

Missed ovulation and the progesterone gap. In that same Joffe study, only about half of participants had progesterone levels consistent with ovulation, and the absence of ovulatory progesterone was independently associated with worse mood. Progesterone converts to allopregnanolone, a neurosteroid that acts on the same receptor system as calming medications. Cycles where ovulation is skipped produce less of it. In perimenopause, skipped ovulation becomes routine, which is why the calm that used to arrive in the second half of the cycle stops arriving reliably.

Why exhaustion and irritability outrank low mood. Estrogen receptors sit densely in the prefrontal cortex and hippocampus, the regions handling working memory, sustained attention and emotional regulation. When estrogen output becomes erratic, those systems lose their steady input. The result reads as depleted capacity and a shorter fuse rather than sadness. That maps neatly onto how the Menopause Rating Scale defines its two top-scoring items: exhaustion as reduced performance, memory and concentration, and irritability as nervousness, inner tension and feeling aggressive.

The 2026 authors point out that this territory is under-researched compared with perimenopausal depression. They cite the Women Living Better survey, where 57% of women in the late reproductive stage reported irritability and around half reported fatigue, and a separate study across 12 Latin American countries that also found higher exhaustion and irritability scores in perimenopause. Their conclusion is that additional contributors remain to be identified.

Ingredients with clinical backing for exhaustion and irritability

No supplement replaces a conversation with a clinician about hormone therapy, and none of the following treats a diagnosed mood disorder. What the research supports is nervous system and stress axis support, which is the layer that exhaustion and irritability sit on. The evidence is stronger for some of these ingredients than others, and it is worth saying which is which.

Ashwagandha, the strongest evidence of the group. Withania somnifera has been studied in more randomized placebo-controlled trials than any other adaptogen on this list, with research pointing to reduced perceived stress, lower cortisol and improved sleep. Two clinical trials published in 2025 looked at menopausal populations specifically. The safety picture matters too. Ashwagandha is well tolerated over short periods, long-term safety has not been established, and there are case reports linking it to liver injury and to changes in thyroid function. Anyone with thyroid or liver disease should clear it with a clinician before starting.

Rhodiola rosea, promising but not settled. Rhodiola is widely marketed for mental fatigue, and the honest position is that the trial evidence is contradictory. Some studies report improvements in mental performance under load, others find no effect, and reviewers have repeatedly flagged that the trials carry a high risk of bias. It is a reasonable ingredient for this symptom picture. It is not a proven one.

Magnesium glycinate. Magnesium is a cofactor in hundreds of enzyme systems, including those governing nerve and muscle function, and a large share of adults consume less than the recommended amount. The glycinate form is chelated to glycine, which is better tolerated in the gut than magnesium oxide.

L-theanine and GABA. L-theanine is an amino acid found in tea leaves, studied for its effect on subjective stress without sedation. The trial base is smaller than for ashwagandha. It pairs logically with the irritability item on the scale, which the researchers define as nervousness and inner tension rather than low mood.

B vitamins, particularly B1. Thiamine and the wider B group are required for converting glucose into usable energy in neurons. Deficiency presents with fatigue and irritability, and requirements rise under sustained stress.

Pro Tip: Adaptogens need consistent daily dosing to show an effect, and the ashwagandha trial data generally runs six to twelve weeks before differences appear. Taking it only on difficult days is the most common reason women conclude it does nothing.

Natural support alongside hormone therapy and other options

The new study deliberately excluded women on hormone therapy, so it says nothing about whether treatment closes the gap. The authors flag that as a question for future research. What follows is how the main options compare on the specific symptoms of exhaustion and irritability.

Approach Pros Considerations Best for
Menopausal hormone therapy Addresses estradiol instability at the source. Trial evidence for mood improvement in perimenopause specifically Requires prescription and individual risk assessment. Access and supply have been uneven Women with vasomotor symptoms alongside psychological ones, and no contraindications
Antidepressants Established for diagnosed depression and anxiety. Some also reduce hot flashes Targets the two symptoms that showed the smallest gap in this study. Side effect profile to weigh Clinically diagnosed depression or anxiety, with or without perimenopause
Cognitive behavioral therapy Trial support for perimenopausal depressive symptoms and for insomnia, with effects that persist Requires time commitment and access to a practitioner. Does not alter hormone dynamics Women whose exhaustion is compounded by broken sleep or high life stress
Targeted supplementation Addresses stress axis and nervous system load. No prescription needed. Combines with other approaches Takes eight to twelve weeks. Quality and dosing vary widely between products Exhaustion and irritability as the leading symptoms, or as support alongside hormone therapy
Strength training and sleep repair Regular moderate activity is associated with lower odds of depressive symptoms across midlife cohort studies, and it protects the muscle mass that falls with estrogen Hardest to start when exhaustion is already the main symptom Everyone, as the base layer under any other approach

 

These approaches are not mutually exclusive, and in practice most women who get relief use more than one. A woman with disruptive night sweats, poor sleep and daytime depletion has a different starting point from a woman sleeping through the night who still cannot hold her concentration through a meeting. The first case points toward addressing vasomotor symptoms. The second points toward the stress axis and cognitive load.

One caution about self-interpretation. Exhaustion with impaired memory and concentration overlaps with thyroid disease, iron deficiency, sleep apnea and B12 deficiency, all of which become more common in the same decade. A study of self-reported symptoms cannot separate those, and neither should you.

Know when to seek professional evaluation:

  • Exhaustion that has not improved after three months of better sleep and consistent nutrition
  • Memory or concentration changes that interfere with work tasks you previously handled easily
  • Any thoughts of self-harm, or low mood that persists most days for two weeks or longer
  • Irritability severe enough to damage relationships or employment
  • Fatigue with additional signs such as hair loss, cold intolerance, unexplained weight change or heavy bleeding, which warrant thyroid and iron testing
  • Loud snoring or witnessed pauses in breathing during sleep

Where Botavive Tranquility fits when exhaustion and irritability lead

Most menopause products are built around hot flashes. The 2026 data points somewhere else. Exhaustion and irritability produced the widest gaps between perimenopause and premenopause, and both persisted after adjusting for existing anxiety and depression diagnoses. That is a symptom pattern with fewer targeted options than it deserves.

Botavive Tranquility was formulated around the stress response rather than around temperature regulation. It combines Ashwagandha, the adaptogen with the strongest trial record for perceived stress and cortisol, with Rhodiola, L-theanine, GABA, magnesium glycinate and vitamin B1. The Rhodiola and B1 components speak to the depletion and reduced performance side of the exhaustion item, though as noted above the Rhodiola evidence is mixed rather than settled. The L-theanine, GABA and magnesium components speak to the inner tension the scale describes as irritability.

Supplementation is one layer of a broader approach, not a substitute for hormone therapy, therapy, or a diagnostic workup for the conditions that mimic this symptom picture. It supports the nervous system while the rest of the plan does its work.

Frequently asked questions

Is perimenopause exhaustion different from ordinary tiredness?

The Menopause Rating Scale treats them differently. Its exhaustion item covers physical and mental exhaustion together with a general decrease in performance, impaired memory, reduced concentration and forgetfulness. Ordinary tiredness improves with sleep. The pattern this scale measures often does not, because the limiting factor is cognitive capacity rather than sleep debt.

Why did exhaustion score higher than depression and anxiety in this study?

The authors do not offer a definitive answer and describe it as an area needing further research. What the data shows is that the gap held after adjusting for whether a woman already had a diagnosis of anxiety or depression, which suggests exhaustion is not simply an expression of those conditions. Estrogen receptors are dense in the brain regions handling attention and working memory, so erratic estrogen output plausibly registers as depleted capacity before it registers as low mood.

Does the study prove hormones are the cause?

No. This was a cross-sectional survey with self-reported reproductive stage and no hormone measurements. It establishes a strong and consistent association across 20 countries after controlling for many confounders. Causation comes from the separate body of longitudinal work on estradiol variability, which the authors reference in their discussion.

Why do scores differ so much between countries?

Nigeria recorded the lowest mean psychological score at 3.50 and Brazil the highest at 7.82. The authors label this analysis exploratory and note it was not adjusted for social determinants of health. They suggest cultural willingness to recognize and report menopause and mental health symptoms is one likely driver, alongside differences in healthcare access and menopause awareness.

Does exhaustion resolve on its own after menopause?

This study only compared perimenopause with premenopause, so it cannot answer that. Broader research indicates that hormone levels stabilize after the transition and that mood risk drops from its perimenopausal peak without returning fully to premenopausal levels. The practical point is that the transition averages about six years, which is a long time to wait rather than manage.

Sources

  1. Cunningham AC, Hedges MS, Hewings-Martin Y, et al., 2026. Global study of 7,975 women finding perimenopause psychological symptom scores 52% higher than premenopause, with exhaustion showing the largest difference. Menopause, published ahead of print July 28, 2026. Psychological symptoms during perimenopause: a global perspective
  2. Mayo Clinic, 2025. Perimenopause overview, including the pattern of estrogen rising and falling rather than declining steadily, and the range of onset ages. Perimenopause: symptoms and causes
  3. Joffe H, de Wit A, Coborn J, et al., 2020. Study of 50 unmedicated perimenopausal women finding that estradiol variability and the absence of ovulatory progesterone, but not hot flash frequency, were associated with depressive symptom burden. The Journal of Clinical Endocrinology and Metabolism 105(3):e642 to e650. Impact of estradiol variability and progesterone on mood in perimenopausal women with depressive symptoms

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