Written by Lindsay Christensen, MS, CNS, LDN

Hormones are profoundly important chemical communication messengers inside the body. Many of us understand hormones as being essential for reproduction, but in fact, they are fundamental to all biological systems. Put quite simply, without hormones our bodies wouldn’t know how to function. Produced inside the brain and endocrine organs like the hypothalamus, pituitary, thyroid, adrenals, ovaries, and testes, these messengers relay information to tissues throughout the body impacting diverse physiological functions. Unfortunately, many aspects of life can disrupt the body’s hormonal balance, with one of the biggest contributors being chronic stress. Luckily, we have many of nature’s tools at the ready to support us. Read on to learn about our body’s stress response system and how specific adaptogens – potent plant botanicals, can help the body adapt to stress and provide whole-body wellbeing.

Chronic Stress and the HPA Axis

Hormone production begins in a region of the brain called the hypothalamus. The hypothalamus is the epicenter of the hypothalamic-pituitary-adrenal (HPA) axis, a complex network of endocrine glands, hormones, neurons, and various signaling molecules that regulates the body’s stress response and hormone production. The HPA axis consists of three main endocrine glands – the hypothalamus, the pituitary gland, and the adrenal glands. These glands, in turn, regulate the production of a range of downstream hormones, including cortisol, DHEA, estrogen, progesterone, and testosterone.

Research indicates that the HPA axis is a truly ancient physiological system. It helped our hunter-gatherer ancestors respond adeptly to acute stressors, such as being chased by a lion on the African savannah. In the face of acute stressors, the HPA axis switches on, releasing glucocorticoids such as cortisol to help the body mobilize energy (primarily in the form of glucose) to fuel sympathetic “fight or flight” activity. However, once an acute stressor has passed, the HPA axis switches on a negative feedback system that resolves the stress response, allowing the body to shift back into the parasympathetic “rest and digest” state. Unfortunately, much of the stress we face today is chronic rather than acute, presenting a rather novel stimulus to our HPA axis. Repeated activation of the HPA axis, in the context of chronic stress, creates tissue dysfunction by depleting metabolic resources, such as micronutrients, and can ultimately trigger an adaptive downregulation of the stress response, in an attempt to protect the body. Unfortunately, this downregulation of the HPA axis renders the body susceptible to various threats, including foreign invaders and autoimmune processes.

What constitutes “chronic stress?” Examples of common chronic stressors include:

• Perceived stress: No two people respond to stress in the same way. Higher levels of perceived stress are associated with unhealthy shifts in HPA axis function and hormone levels.  (1, 2)
• Circadian rhythm disruption: Your circadian rhythm is an internal set of biological processes that cycles roughly every 24 hours, regulating your sleep-wake cycle and numerous other biological processes. Alterations in circadian rhythms adversely affect the expression of countless genes regulated by circadian proteins, including genes involved in hormone production. (3)
• Poor blood sugar regulation: Poor management of blood sugar causes inflammation and physiological stress in the body which, in turn, can impact levels of sex hormones, such as testosterone. (4)
• Oxidative stress: Oxidative stress occurs when there is an imbalance between free radicals (reactive chemical compounds that damage cells) and the body’s capacity to neutralize them with antioxidants. The relationship between oxidative stress and the HPA axis is bidirectional, with HPA axis dysfunction triggering oxidative stress and vice versa. (5)
• Poor quality sleep: Chronic sleep deprivation or interrupted sleep are major stressors on the body and have been shown to disrupt HPA axis function. Chronically sleeping for less than 7 hours per night and waking frequently induce maladaptive alterations in the HPA axis, increasing glucose and insulin levels. Over time, poor quality sleep can thereby lead to blood sugar imbalances which can lead to sugar cravings and weight gain. (6)

HPA Axis and Hormones

The HPA axis governs the synthesis and activity of a handful of critical hormones. The disruptive effects of chronic stress on the HPA axis can cause significant imbalances in hormone production that can impact everything from energy levels, sleep quality, to body composition and longevity. Let’s review the critical hormones that can be affected by ongoing stress.

Pregnenolone

The body’s steroid hormones, including cortisol, estrogen, progesterone, testosterone, and DHEA, are biosynthesized from an endogenous steroid precursor hormone called pregnenolone. Pregnenolone is made in the brain, adrenal glands, skin, testicles, ovaries, and retina. It facilitates the balanced production of all other steroid hormones listed above. Pregnenolone is a neuroactive steroid that influences memory processes and supports healthy brain aging. (7)

DHEA

Dehydroepiandrosterone (DHEA) is an androgen (male-centric hormone) secreted by the adrenal glands, ovaries, testes, and brain. It counteracts the adverse effects of cortisol excess. DHEA is the parent androgen, while DHEA-S is its sulfated derivative and represents the majority of DHEA present in the human body. DHEA production peaks between the ages of 25 and 30 and declines after that. Blood sugar dysregulation and chronic stressors, like excessive exercise, may lower DHEA levels. (8, 9)

Conversely, optimal DHEA-S levels are associated with better blood sugar regulation, immune function, and inflammatory balance, bone health in women, and brain function and may support healthy aging. (10, 11, 12, 13) It also has been found to improve skin health and libido in older women. Restoration of robust DHEA levels may thus counteract several of the most significant health declines associated with aging.

Cortisol

Cortisol is synthesized from cholesterol and is a central player in the body’s stress response. While cortisol is the quintessential “stress hormone,” it also plays vital roles in the body; we do not want cortisol to be chronically elevated, yet we also don’t want it to be too low. The acute release of cortisol helps our bodies respond to stress; however, chronically high cortisol levels triggered by chronic mental, emotional, and physiological stress have many adverse health effects. For example, chronic elevations in cortisol are associated with declines in brain function with aging. (14)

Over time, as the body secretes more and more cortisol to contend with chronic stress, counterregulatory pathways are turned on that ultimately inhibit cortisol synthesis. This shift can eventually lead to depleted cortisol levels and symptoms such as weakness, fatigue, and low blood pressure.

Estrogen

Estrogen is one of two main sex hormones that females have (the other being progesterone). The estrogen “family,” including estriol, estradiol, and estrone and plays roles in the female reproductive system, energy expenditure, skeletal integrity, and brain health. (15)

Estradiol is the main form of estrogen present in women of reproductive age and is the “strongest” estrogen. In cycling women, estradiol is released in the ovaries by a developing follicle, a small fluid-filled sac containing an immature egg in the ovary. In perimenopausal women, estradiol levels fluctuate wildly and decline significantly and permanently in the postmenopausal period. (16) Estradiol supports healthy bone tissue, the cardiovascular system, the brain, and skin.

Estriol is the dominant form of estrogen present in the female body during pregnancy. Levels of estriol are usually low in women who are not pregnant. Estrone is the main form of estrogen present in menopause; it has much weaker effects on the body compared to estradiol.

Estrogen is broken down in the body into metabolites, including 2-hydroxyestrone, 4-hydroxyestrone, and 16-hydroxyestrone. Excessive amounts of 16-hydroxyestrone can promote aberrant proliferation of estrogen-sensitive tissues. (17) Excessive 4-hydroxyestrone can promote DNA damage. (18)

Progesterone

Like estrogen, progesterone plays a crucial role in female reproductive health. However, it also has many effects outside of the reproductive system, including effects on immune function. (19) For a deep dive into progesterone, read our upcoming blogs.

Testosterone

While testosterone is considered the quintessential “male” hormone, both men and women have testosterone in circulation; testosterone levels are significantly higher in men. Low levels of testosterone are associated with changes in libido, mood, and body composition in men. Too much testosterone can promote androgenic symptoms, such as facial hair growth, thinning head hair, aggression, and agitation. Excessive testosterone can also adversely affect metabolic health in women , as exemplified by androgen excess in polycystic ovarian syndrome (PCOS). On the other hand, too little testosterone lowers libido and triggers lethargy and muscle weakness.

Adaptogenic Herbs and Hormone Balance

Adaptogens are a powerful tool for supporting the HPA axis in the face of modern-day stressors and, in turn, can positively influence hormonal balance throughout the body.

To be defined as an adaptogen, a botanical must reduce or counteract the adverse effects of stress, such as fatigue and heightened susceptibility to infectious agents, optimize work capacity and mental performance without the downsides of conventional stimulants (like caffeine), and normalize, rather than perturb, physiological function. (20) In other words, adaptogens help the body to adapt to stress and increase resilience and vitality.

How do adaptogens work? Our understanding of adaptogens is still evolving, but research indicates several potential mechanisms by which adaptogens support hormone balance:

• Modulates heat shock protein expression: Heat shock proteins assist in protein folding, helping proteins in our bodies involved in numerous cellular functions form correctly. Properly-formed proteins are essential for healthy cellular function and hormone production. (21)
• Increase neuropeptide Y expression: Neuropeptide Y is a signaling molecule involved in physiological responses in the central (CNS) and peripheral (PNS) nervous systems. It acts as a physiological “brake” on the nervous system, toning down CNS activity by regulating the release of corticotropin-releasing hormone (CRH) and cortisol. (22, 23) Essentially, it acts as a “buffer” for the body’s stress response.
• Support AMPK activity: Adaptogens influence the AMPK pathway, an evolutionarily conserved pathway present in all complex life forms, from mice to humans. AMPK is a central regulator of metabolism and energy production and an elegant nutrient sensor that helps our bodies maintain optimal cellular energy levels in the form of ATP. (24)

The following adaptogens have been used for millennia in traditional herbal medicine to support stress resistance and resilience; a growing body of modern-day scientific research demonstrates their ability to maintain hormonal balance and a resilient HPA axis.

• Ashwagandha: Ashwagandha is an ancient plant originating from the Indian subcontinent with a long history of use in Ayurvedic medicine. Research indicates that Ashwagandha balances cortisol levels, promoting a resilient stress response system. (25) It also supports robust DHEA and testosterone levels in aging males, soothes agitation, and supports restful sleep, a crucial lifestyle factor that promotes hormonal balance. (26, 27)
• Rhodiola: Rhodiola root comes from the Rhodiola rosea plant that grows in the harsh, forbidding climates of the Arctic and northern Europe, and Asia. Rhodiola was reportedly used by the Vikings and indigenous Arctic peoples to support libido and fertility. (28) Research indicates that Rhodiola helps the body cope with stressors, such as a lack of sleep. In animal studies, it regulates gene expression involved in the stress response, balancing cortisol activity. (29)
• Panax Ginseng: Panax ginseng is a revered botanical in Traditional Chinese Medicine (TCM). It contains ginsenosides, phytochemicals that mitigate stress-induced gene expression and bolster DHEA levels, fortifying the HPA axis against chronic stress. (30) Ginsenosides also influence estrogen receptor alpha (ER-ɑ) and estrogen receptor beta (ER-Β) activity and may regulate menopausal health changes triggered by steep declines in ovarian estrogen production, such as vaginal dryness and weight gain.

• Astragalus: Astragalus is one of the fundamental, time-honored herbs used in traditional Chinese medicine (TCM). It helps maintain healthy brain function in the presence of environmental stressors and supports the immune system. (31)
  • • Chaste tree berry: Chaste tree berry helps maintain healthy female hormone levels, particularly levels of progesterone. (32) Healthy progesterone levels may mitigate the adverse effects of stress on the female body. (33)
• Licorice root: Like Astragalus, licorice root is a central herb in the TCM botanical compendium. It helps maintain healthy cortisol levels, keeping just enough of this hormone in circulation to support a healthy HPA axis without overwhelming the body. (34)

Stress is an inevitable part of life, but it doesn’t have to wreak havoc on your hormones! With the help of adaptogens, you can regulate your body’s stress response system and maintain healthy levels of crucial hormones, supporting whole-body wellbeing.