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OAT Axis Imbalance
By: Michael Lam, MD, MPH

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The endocrine system is made up of eight different glands located strategically throughout the body. Three of the most important ones for females are the ovaries, adrenals, and the thyroid gland.

Control over the adrenal and ovarian systems start at the hypothalamus. Specifically, the adrenal glands are regulated through the Hypothalamus-Pituitary-Adrenal (HPA) axis. Ovarian hormones are regulated through the Hypothalamus-Pituitary-Gonadal (HPG) axis. Each of the end organs (adrenals, thyroid, and ovaries) produces a variety of hormones that further exert their effects on the rest of the body. In addition, each of the end organs is tied into other organ systems hormonally via a series of network or axis.

One such intricate hormonal axis ties in the adrenals, thyroid and the ovaries. This axis is called the Ovarian Adrenal Thyroid (OAT) axis. What happens to one organ will affect the other organs physiologically, clinically or sub-clinically. These three organs are therefore intimately co-dependent hormonally on each other for optimal function. If the adrenal glands are weak, there is often concurrent thyroid malfunction and menstrual cycle irregularity. Similarly, an under-active thyroid often makes adrenal fatigue worse off. Lastly, those who suffer from ovarian hormonal imbalance such as estrogen dominance often exacerbate any pre-existing sub-clinical hypothyroidism.

All three organs of this axis must be in a state of optimum balance for a woman to feel good. Like a three-legged stool, all three legs must be in perfect balance for the stool to be safe to sit on. Imbalance of the OAT axis leads to a myriad of conditions that are annoying in their mildest form and incapacitating when severe.

OAT Axis

Common complaints of those suffering from OAT Axis Imbalance include a mixture of symptoms suggestive of concurrent decompensation of the adrenals, thyroid, and ovaries. Presenting symptoms are often, but not always, suggestive of Adrenal Fatigue, estrogen dominance, and hypothyroidism. Commonly, they can include insomnia, fatigue, chronic fatigue, joint pain, exercise intolerance, brain fog, sugar intolerance, diabetes, dry skin, feeling cold, slow metabolism, inability to lose weight, PMS, endometriosis, irregular menstrual cycle, fibrocystic breast disease, anxiety, depression, and accumulation of fat at the waist line.

Those with ovaries removed can still have OAT Axis Imbalance because estrogen imbalances are involved and the ovaries are not the only place where estrogen is produced. The adrenal glands as well as adipose tissue (fat cells) are also active production sites of estrogen.

OAT Axis Imbalance represents a state of hormonal axis irregularity yet to be recognized by conventional medicine. Its manifestation can be sub-clinical or clinical. Because its clinical presentation represents a convolution of multiple endocrine system imbalances, there is no definitive test that can isolate and precisely identify this imbalanced state with pinpoint accuracy. Formal and extensive research is sorely needed. Our current understanding of this state comes mainly from clinical experiences and case studies. As such, OAT Axis Imbalance should currently be viewed more appropriately as a clinical state and not as a disease state. This multi-organ clinical state that unifies common imbalances of the ovarian, adrenal, and thyroid systems into a triad should be considered only after conventional endocrine, diagnostic and therapeutic approaches have failed to bring relief and conventional investigative efforts have been exhausted.

Because the myriad of symptoms appears to be convoluted and diverse, physicians, even those who are naturally oriented, can easily be overwhelmed.

In males, this imbalanced state is also prevalent with low libido and testosterone being a surrogate of ovarian imbalance. Low androgen levels also affect the thyroid and adrenal functions.

To understand this imbalance better, we have to examine each of these three organ systems and how they tie into the OAT axis.

Ovarian System (females only)

The ovaries normally maintain hormonal control in the female by self-regulation of the key hormones: estrogen and its opposing hormone, progesterone. Estrogen is produced by the ovaries, egg follicles, the adrenal glands and in fat cells. Progesterone is produced almost entirely by the corpus luteum: a little mass of fat cells left over from the follicle after the egg leaves it at ovulation.



Estrogen Effect Progesterone Effect
Causes Endometrium to proliferate Maintains secretory endometrium
Causes breast simulation that can lead to breast cancer Protects against fibrocystic breast and prevents breast cancer
Increases body fat Helps use fat for energy
Increases endometrial cancer risk Prevents endometrial cancer
Restrains osteoclast function slightly Promotes osteoblast function, leading to bone growth.
Reduces vascular tone Restores vascular tone
Increases blood clot risk Normalizes blood clot

Estrogen and progesterone hormones work in synchronization with each other as checks and balances to achieve hormonal harmony in both sexes. It is not the absolute deficiency of estrogen or progesterone but rather the relative dominance of estrogen and relative deficiency of progesterone that is the main culprit behind its role in OAT Axis Imbalance.

Let us take a closer look. While sex hormones such as estrogen and progesterone decline with age gradually, there is a drastic change in the rate of decline for these two hormones during the perimenopausal and menopausal years for women. From age 35 to 50, there is a seventy-five percent reduction in production of progesterone in the body. Estrogen, during the same period, only declines about thirty-five percent. By menopause, the total amount of progesterone made in the body is extremely low, while estrogen is still present in the body at about half its pre-menopausal level. When ovulation ceases, progesterone is no longer produced except for a very small amount made by the adrenal glands.


The primary causes include excessive environmental estrogen, obesity, stress, poor diet, lack of exercise, and unopposed estrogen given as part of a hormone replacement therapy. In addition, adrenal dysfunction and under active thyroid can worsen estrogen dominance.

Typical complaints from patients having estrogen dominance include swollen breasts and ring fingers, impatience and irritability, stomach cramps before menstrual cycle, irregular periods, fluid retention, foggy thinking, depression, and fatigue. It is the underlying common denominator for a variety of illnesses and syndromes that were previously regarded as unrelated entities. They in fact represent different expressions of the same illness in different cell settings. The continuum is a state of excessive estrogen throughout one's lifetime, with different manifestation at different times, starting with endometriosis, PMS, fibrocystic breast disease, PCOS and progressing to fibroids and breast cancer.

Estrogen Dominance and OAT Axis

Estrogen dominance may increase thyroid-binding proteins in the bloodstream. Thyroid blood test results may therefore be normal although there may be insufficient thyroid hormone in the tissues, resulting in a state of sub-clinical or clinical hypothyroidism.

When estrogen levels are high, the adrenal cortex fails to respond to signals from the brain. In other words, even though the brain is requesting more cortisol to be made, there is a blunted response from the adrenals in the face of this request. As a result, the cortisol output is sub-optimal relative to the demand signal. In addition, estrogen impairs adrenal functions by interfering with the release of cortisol from the adrenal cortex. High levels of estrogen can lead to a corresponding increase in the level of cortisol-binding globulin. In turn, the cortisol-binding globulin interferes with hormone functions and circulates in the bloodstream, binding to cortisol, and rendering it inactive. Thus, a woman with estrogen dominance may have adequate levels of total cortisol in her bloodstream. Her total cortisol level blood tests may be well within normal range but her free, available cortisol level may be low. Since only free cortisol can pass through cell membranes and activate receptors inside the cells, the effectiveness of cortisol is blunted at the cellular level.

Just as estrogen dominance can contribute to adrenal insufficiency, adrenal insufficiency can contribute to estrogen dominance. Cortisol is made in the adrenal cortex from progesterone. When the adrenals are weak, there is a tendency towards a lowered progesterone output in favor of cortisol. A low progesterone level is often the result, leading to a state of relative estrogen dominance with its many undesirable consequences mentioned above. This forms an adverse feedback loop and vicious cycle. Excessive estrogen affects both thyroid and adrenal function. In turn, dysfunctional thyroid and Adrenal Fatigue make estrogen dominance worse off.

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