Your stress response changes in midlife. Can adaptogens help reset it?

If stress in your 40s or 50s feels different than it did a decade ago — less manageable, more physical, harder to shake — there's a reason. And contrary to what you may hear, it's not about resilience or mindset. It's about the HPA (hypothalamic–pituitary–adrenal) axis.

The HPA axis is your body's central stress-response system. Think of it as a thermostat that regulates how much cortisol your body produces when you're under pressure and how quickly it returns to baseline once the stressor passes. In perimenopause, that thermostat becomes more sensitive.

🌿 Unsure of where this fits into your supplement routine? Here’s how to think about a smarter supplement plan.

Estrogen helps regulate cortisol output, while progesterone has a naturally calming, buffering effect on the brain. When both begin to fluctuate and decline, as they do in perimenopause, the body loses some of its built-in stress protection, says Dr. Lamees Hamdan, an integrative medical doctor and naturopathic practitioner.

The result: cortisol levels can spike more easily, take longer to come down, and have a broader impact across the body. For many women, this shows up as a more intense "fight-or-flight" response, more difficulty recovering after stressful events, greater emotional reactivity, and trouble sleeping.

Estrogen and progesterone also influence the amygdala and hippocampus—the brain regions involved in emotional regulation and stress memory. So when these hormones shift, the emotional experience of stress can shift with them.

"Adaptogen" has become one of the most overused words in the wellness industry. But a true adaptogen is an active ingredient found in certain plants and mushrooms that helps the body cope with stress, anxiety, or fatigue. The key feature is bidirectionality: for example, a genuine adaptogen should help normalize cortisol levels, whether they're too high or too low.

Currently, ashwagandha (Withania somnifera), Rhodiola rosea, and Eleutherococcus (Siberian ginseng) have the strongest evidence base in both animal and human studies. Most other botanicals marketed as adaptogens lack this research foundation.

A 2025 systematic review in Frontiers in Pharmacology on botanicals for menopausal psychological symptoms identifies ashwagandha and Rhodiola as the best-evidenced options for women navigating this transition. Here's what they found:

Several randomized controlled trials in women show reductions in perceived stress and cortisol, improved sleep, and improvement in both vasomotor and psychological symptoms. The standardized root extract matters, though, and many powders on the market are processed in ways that reduce the active compounds.

Consistently shown to reduce fatigue and improve stress tolerance in working adults under high load. It helps normalize cortisol and supports cognitive alertness without worsening anxiety or disrupting sleep.

Often marketed for immune support and stress resilience, Reishi does have anti-inflammatory properties and some nervous system benefits. But the evidence for direct HPA-axis modulation in human trials is weaker than for ashwagandha or Rhodiola. 

Ginseng is among the most potent adaptogens, but Dr. Hamdan cautions that it's better reserved for use under the guidance of an integrative practitioner, particularly for women whose bodies already feel "burned out."

Sponsored by: Kerafactor

Noticing thinning or shedding? KeraFactor supports fuller-looking, stronger hair with growth factor technology designed for aging scalps. Take control of your hair health today and enjoy 20% off with code LIVELONG20.

It’s worth noting that the clinical studies we have are mostly small, often 56 to 120 participants, and large-scale trials in diverse female populations are still limited. There are also contraindication considerations. Some adaptogens interact with medications, particularly those affecting blood pressure, mood, or hormone levels. If you're on HRT, antidepressants, or thyroid medication, Hamdan recommends you check with your provider first. And if you have an estrogen-sensitive condition, she says, a personalized approach matters more than a general supplement recommendation.

If you're navigating perimenopause and stress feels harder than it used to, it's a physiological shift worth understanding. Adaptogens, particularly ashwagandha and Rhodiola, may genuinely support your stress resilience during this transition. But they work best layered into the fundamentals: good sleep, adequate nutrition, movement, and clinical support where appropriate.

The Livelong Women’s Inner Circle™ gives you access to dozens of recordings from the Women’s Health Summit featuring experts like Dr. Vonda Wright and Dr. Mark Hyman, alongside monthly virtual chats with experts in women’s health, a community of women navigating aging well together, and discounts on future event tickets.

Not ready to join the Livelong Women’s Inner Circle™, but still want to connect?

Our free Livelong Women’s community is where women can join real conversations about sleep, stress, midlife changes, heart health, prevention, and what actually works as we age.

Last week, we asked which Summit topics you would like to see covered more in future newsletters, and an overwhelming majority chose longevity mindset. Stay tuned for more on this topic!

🤔 Plus: Ask LIV: Get personalized longevity insights with our updated AI feature.