Understanding the HPO and HPA Axes in Women's Health

The HPO and HPA axes are two distinct feedback loops that regulate a series of functions in the body. These two feedback systems affect each other considerably, but they are separate.

Each axis is activated at specific times for specific reasons, with the HPA axis activated in times of stress, but also for other reasons. For example in the third trimester of pregnancy, the HPA axis is activated, then suppressed after birth.

The HPO axis continually runs in the background, unless it is deactivated, such as during periods of stress.

The hypothalamic-pituitary-ovarian (HPO) axis is a critical interplay of hormonal events that control the menstrual cycle
The hypothalamic-pituitary-adrenal (HPA) axis is a hormonal interplay responsible for our stress response (amongst other functions)

The hypothalamic-pituitary-ovarian (HPO) axis also known as the hypothalamic-pituitary-gonadal (HPG) axis

Hypothalamus – part of the brain that secretes gonadotropin-releasing hormone (GnRH), which stimulates the pituitary gland
Pituitary gland – part of the brain, just underneath the hypothalamus, that secretes follicle-stimulating hormone (FSH) and luteinising hormone (LH) in response to GnRH
Ovaries (or gonads) – found in the pelvis, secrete oestrogen and progesterone, levels of which tell the hypothalamus when to secrete more GnRH to repeat the cycle

How the HPO feedback loop works

At the beginning of the menstrual cycle when oestrogen levels are low, GnRH is secreted and stimulates FSH to start the process of ovulation
Follicles develop and an egg will eventually be released from the follicle, triggered by a surge of LH
Rising oestrogen levels inhibit FSH (so stop follicles from developing any further) and stimulate LH secretion to trigger ovulation
Once ovulation has occurred, progesterone levels rise and both progesterone and oestrogen inhibit FSH, meaning follicles are not stimulated again until next cycle when oestrogen and progesterone are not inhibiting FSH

When the HPO axis gets disrupted

The hypothalamic-pituitary-adrenal HPA axis

This interconnected system becomes activated during stress and involves your adrenal glands and your nervous system. Adrenaline is released into the system by the HPA axis when it is ‘told’ to. The HPA axis switches ‘on’, and releases the needed hormones to get us through a stressful situation.

The HPA axis consists of:

Hypothalamus – part of the brain
Pituitary gland – part of the brain
Adrenal gland – found sitting just on top of the kidneys, secretes adrenalin, cortisol, and other steroids to modulate our response to stress (keep us safe when we need it)

Adrenal hormones include androgens, which can be converted into more potent androgens such as testosterone, or into oestrogens in the body as per need.

How the HPA axis affects the HPO axis

When the HPA axis is activated, your stress response has kicked in. This activation affects your whole body. The HPA axis activation effectively halts the HPO – reproductive – axis (and many other body systems) to conserve energy.

Stress can thus effectively stop you from ovulating and as a result, menstrual periods may stop or become irregular. When your periods stop because the HPA axis is turned on, it’s called hypothalamic amenorrhoea.

That is, the hypothalamus has stopped producing GnRH, and therefore no FSH or LH is being produced, and the menstrual cycle is stopped in its tracks. The HPA axis has been turned on for too long, so the HPO axis has been turned off as a result. This is why chronic stress may impair ovulation and fertility.

Some states/conditions are related to HPA axis regulation, such as polycystic ovarian syndrome (PCOS), anorexia (the eating disorder), and the third trimester of pregnancy are all conditions whereby the HPA axis is activated. The hormone secreted is important for foetal development later in the pregnancy.

Conversely, the HPA axis is suppressed for a period of time immediately after giving birth (postpartum) and is a possible reason for post-natal depression. The hormones that keep the HPA axis in check are also essential to foetal development.