How Stress Can Contribute to Reproductive Hormone Imbalances

Below are diagrams of the Hypothalamic-Pituitary-Adrenal (HPA) and Hypothalamic-Pituitary-Gonadal (HPG) axes responsible for the production of cortisol and reproductive hormones. These hormone axes involve multiple organs and stimulating hormones.

In this post, we will discuss some of the ways that chronic stress (whether that be physical or emotional) & dysfunction in the HPA axis can affect the HPG axis and the normal monthly rhythm of our reproductive hormones.

Our brain (the hypothalamus & pituitary are glands in the brain) receives signals about stressors, which triggers the release of stimulating hormones – CRH and ACTH. These hormones tell the adrenal gland that it should release cortisol. The hypothalamus and pituitary are also responsible for sending out pulsed secretions of GnRH, LH, and FSH throughout the month to trigger production and release of estrogen and progesterone.

  1. Overlap Between HPA & HPG Axes
    Stress has an inhibitory effect on the HPG axis. Stress, and its associated hormones (CRH/ACTH/Cortisol), inhibit the release of GnRH from the hypothalamus, LH from the pituitary, and estrogen and progesterone from the ovary.
  2. Sympathetic Nervous System & The Ovary
    The sympathetic nervous system is stimulated by stress. It is responsible for our “Flight or Fight” response. The ovary is innervated by sympathetic nerves. These sympathetic nerve fibers have an effect on follicle development and ovarian hormone production.
  3. Stress Affects the Steroid Hormone Producing Enzymes
    Stress can also downregulate the activity of the enzymes responsible for making our reproductive hormones in the ovary.

High levels of perceived stress are associated with increased risks of menstrual irregularities including amenorrhea, premenstrual syndrome, and dysmenorrhea. High stress can also affect a woman’s ability to get pregnant. Research has shown that women with a history of depression are twice as likely to experience infertility. Salivary amylase, a marker of stress used in research, is also associated with longer time to pregnancy and increased risk of infertility.

Our hypothalamic-pituitary-adrenal axis responds both to physical stressors – intense exercise, caloric restriction, excess caffeine consumption, etc. – and emotional stressors. What are some signs you might be experiencing HPA axis dysfunction?

  • Blood sugar imbalances (feeling hangry between meals, feeling very tired after meals)
  • Sleep disturbances
  • Chronic fatigue
  • Anxiety/Depression
  • Cravings for sugar or salty foods
  • Weight gain around the middle
  • Temperature intolerance

Cortisol secretion has a circadian rhythm. Cortisol circadian rhythm typically shows a rise in cortisol during the night and a peak within the first hour after awakening. Cortisol levels drop quickly during morning hours, increase slightly after the mid-day meal, and decline slowly through the rest of the day to a low during the night. The multiple measurements of cortisol throughout the day are helpful because we can see if there is a disruption in this normal rhythm.

Here is an example of an optimal cortisol rhythm:

Certain times of day could have elevated cortisol.



Secretion could be high most of the day:

Secretion could also be low all day:

Assessing for hypothalamic-pituitary-adrenal dysfunction is an important part of treating reproductive hormone imbalances, irregular menstrual cycles, unexplained infertility, and providing preconception care. If you think you might be experiencing HPA axis dysfunction, ask your doctor about salivary 4-point cortisol testing and/or DUTCH hormone testing. These tests can provide you with a glimpse into your adrenal activity throughout the day, allowing your doctor to provide you with a personalized treatment plan.