The Latest Research on Perimenopause Symptoms Will Surprise You

For me, perimenopause symptoms started at 40. The intense pain in my feet was like I was walking on nails. Then my knees started cracking every time I climbed a flight of stairs. Last, came the deep ache in my hips. Yet every time I went to a doctor, they would look at my labs and imaging and the answer would come back the same: "Everything looks normal."

For those of us in the perimenopause years, normal is a complicated word. Normal means the pain is real but nothing is showing up on the x-ray or MRI. It means you leave the appointment with no solutions, just a referral to yet another specialist. Or even worse, a narrative that the pain is all in your head.

As a clinical educator and an avid researcher, I can assure you that pain and the many other symptoms that can come with perimenopause are very real. But even with all my education and experience as a clinician, it took me years, numerous labs, and countless research hours to gain the language I needed to discuss my experience with doctors.

I wrote this article so you don't have to wait as long as I did — or work as hard — to get the care you need.

1. Perimenopause, not menopause, is the big transition

Perimenopause typically begins in the early to mid-40s, sometimes even the late 30s, and lasts on average 4 to 8 years.1 Clinically, perimenopause starts with the onset of irregular periods. It finally ends after 12 consecutive months without a menstrual cycle, which is the point that officially marks menopause.2

So menopause is actually a single point in time that is identified only after it's happened. Perimenopause is the actual struggle—when many of us face an unpredictable onslaught of whole-body symptoms.

2. Fluctuating estrogen — not low estrogen — drives perimenopause symptoms

Despite what you may have read or heard, the defining feature of perimenopause is not low estrogen, it's fluctuating estrogen. Estrogen levels during perimenopause do not steadily decline. They rise and fall like a rollercoaster, sometimes spiking higher than normal before crashing.345

And because estrogen receptors are spread out throughout the entire body, not just in the reproductive system, fluctuating levels can cause symptoms across every organ system, affecting the brain, heart, joints, muscles, bladder, skin, and hair.26

3. Perimenopause “brain fog” is more serious than you might think

Estrogen receptors are distributed throughout the brain, and many of the complaints that prompt women to seek mental health treatment during perimenopause can be traced back to fluctuating hormones.7

Researchers who have studied women in perimenopause have reported measurable changes in brain structure, connectivity, and energy metabolism throughout the transition.8 It's no wonder we can't think straight!

4. Perimenopause joint pain is real — and finally has a name

Estrogen receptors are present throughout joints, tendons, cartilage, skeletal muscle, and bone. As estrogen declines during the perimenopausal transition, it can lead to all of the following:

• Widespread joint pain
• Accelerated muscle and strength loss
• Increased tendon vulnerability
• Cartilage degradation
• Progression of osteoarthritis

Up to 71% of perimenopausal women experience these symptoms, and up to 25% will be disabled by them at some point during the perimenopause transition.9

In October 2024, researchers published a clinical review that officially gave a name to these collective effects: the Musculoskeletal Syndrome of Menopause (MSM).9

5. Perimenopause mood changes and pain make each other worse

Mood problems and pain can not only co-exist, they both amplify and fuel each other.

Research shows that:10

• Chronic pain increases anxiety and depression
• Anxiety lowers pain thresholds and heightens sensitivity
• Depression increases how intensely people perceive pain

Given that, it makes sense that the prevalence of depression and anxiety among adults with chronic pain is approximately 40% — significantly higher than in comparison groups.11

Perimenopause mood issues and pain can also be due to something called allostatic load. Basically, your body has a measurable tolerance for how much stress it can take before systems start to break down. When you're in your late 30s or 40s, things like long work days, active parenting, chronic pain, and financial strain can push you over the edge.

Research shows that chronic stress and high allostatic load are among the strongest risk factors for mood disorders during perimenopause, independent of hormonal levels alone.12

Clinicians often overlook allostatic load when diagnosing generalized anxiety disorder, major depressive episode, fibromyalgia, or somatization in perimenopausal women.

6. Antidepressants are overprescribed during perimenopause

Research has found that women ages 45 to 54 going through perimenopause experienced higher rates of common mental health diagnoses than men in the same age group. Women in this group were also prescribed more SSRIs and SNRIs than similar-aged men with the same diagnoses.13

At the same time, use of Menopausal Hormone Therapy (MHT) among US postmenopausal women dropped from 26.9% in 1999 to just 4.7% by 2020 due to a misrepresentation of findings in the Women's Health Initiative (WHI)'s 2002 study.14

The result is that women have been heavily medicated for mood and chronically undertreated hormonally.

On the bright side, new guidelines make it clear that clinicians must identify women's menopausal stage and assess co-occurring hormonal symptoms before diagnosis and treatment.15 When hormonal symptoms are overlooked, treatments may provide partial relief, enough to feel helpful, but not enough to address the root cause of symptoms.16

7. Thyroid problems are harder to diagnose in perimenopause

Subclinical hypothyroidism, a condition where TSH (Thyroid Stimulating Hormone) is mildly elevated but thyroid hormone levels appear normal, affects an estimated 6 to 10% of women during their reproductive years.17

The symptoms, which include fatigue, cognitive impairment, mood lability, and sleep disturbance, overlap so significantly with perimenopausal depression that the two are difficult to distinguish without more complete testing.18

A TSH value is a starting point, but including free T3, free T4, and TPO antibodies in lab testing tells a more complete story. If you are experiencing the symptoms listed above and have not found relief with standard treatment, ask if you can get a full thyroid panel.

8. Sedatives won’t work for perimenopause sleep disruption

If you're in the age range for perimenopause, it's critical to consider hormones when evaluating sleep disturbance (aka you wake up after you've fallen asleep). Fluctuations in estrogen and progesterone directly affect sleep quality, while vasomotor symptoms (hot flashes and night sweats) are documented contributors to nocturnal awakenings.1819

What's happening in a nutshell: Your hormones are erratic, your body temperature is dysregulating in the middle of the night, and that is likely what's waking you up.

Research findings also show that abnormal sleep in perimenopausal women — specifically lower sleep efficiency (how long you're in bed vs. how long you're asleep), increased wakefulness after sleep onset, and reduced REM sleep — are significantly associated with higher cortisol levels, which isn't the case for self-reported insomnia and sleepiness outside of perimenopause.20

This cortisol link is a vicious cycle: It's caused by poor sleep AND it actively prevents deeper, restorative REM sleep from happening. Taking sedatives will not break this cycle.

For women also experiencing MSM, sleep disruption is also frequently pain-driven, and co-existing musculoskeletal disorders are documented contributors to sleep disturbance alongside vasomotor and mood symptoms.19

9. Vitamin deficiencies in perimenopause can mimic mood disorders

Although doctors seldom mention it in routine appointments, women in perimenopause are at significantly increased risk of deficiencies in specific vitamins and nutrients. And those deficiencies can produce symptoms that look nearly identical to a mood disorder.

• Low vitamin B6 is linked to cognitive decline, and mood disruption.
• Low vitamin B12 is associated with depression, cognitive impairment, and increased dementia risk.
• Vitamin D deficiency presents as fatigue, mood instability, immune dysregulation, and bone loss.
• Iron deficiency, which can accelerate during perimenopause when cycles become irregular and heavier before stopping, contributes directly to fatigue, brain fog, and low mood.
• Omega-3 fatty acids, which most of us are not consuming at adequate levels through diet alone, are linked to vasomotor symptom management, mood regulation, and sleep quality.21

10. Wearable devices can help track perimenopause symptoms

Consumer wearable devices like an Apple Watch, Oura Ring, WHOOP, or Garmin provide long-term continuous monitoring across sleep, rest, and activity. This data can provide a clinician with a helpful, longer-term picture of what's happening with your body.22

One thing to look for is heart rate variability (HRV), which is measurably decreased during perimenopause. Lower HRV correlates with more perimenopause symptoms.23

11. HRT can significantly improve mood in perimenopause

Research shows that for women whose depression and anxiety started during perimenopause (particularly those without a significant psychiatric history), antidepressant treatment alone is incomplete.1624

Adding HRT can help. A study assessing the impact of transdermal estradiol (aka an estrogen patch) — with or without progesterone and testosterone — on mood symptoms in 920 peri- and postmenopausal women, found significant improvements across mood-related symptoms, with additional benefit in women who received both estradiol and testosterone.24

12. The right medical team makes all the difference

Women in perimenopause are routinely undertreated for a host of reasons:

• Symptoms are distributed across the entire body
• Imaging is often normal
• The clinical picture does not fit neatly into any single specialty's lane
• Most providers have not been trained to assess hormonal patterns

So if you're experiencing symptoms that non-hormonal treatments aren't fully addressing, it's worth finding both mental health and medical providers with a passion for perimenopause.

Medical providers can include a primary care provider, an endocrinologist, and a gynecologist.

Counseling is also essential.18 A good mental health provider who understands this landscape can help you build language for medical conversations, process the grief of a body that is changing without warning, and hold the emotional weight while the medical picture gets sorted.

One last fact: perimenopause care isn’t equally available to everyone

Access to hormonal evaluation, specialist care, and emerging options (like medical cannabis for pain) is not equally distributed across income, geography, or race. For example, it's well documented that Black women's concerns are dismissed more frequently compared to White women.25

If you have encountered barriers, delays, or dismissals, that experience reflects a systemic issue, not the validity of your symptoms. Keep advocating!

Bring this article, bring your data, and find a provider who speaks this language, because you deserve a complete assessment and informed treatment. The pain that I started feeling at 40 was not stress, it was not anxiety, and it was not just getting older; it was hormonal, and it had a name all along.