Women’s Health and Hormonal Axes

What to Know about the Pregnenolone Steal and other Hormonal Interactions

Author: Courtney K. Pickworth

One of the cornerstones of women’s health is the pursuit of a balanced, optimally-functioning hormonal system. This goal is emphasized by practitioners of any type because of how absolutely critical it is for wellness and vitality, but the topic of hormone balance is particularly focused upon in the naturopathic community. Yet, there is always more to say about this topic, as there are many hormones in multiple systems, called hormonal axes, which work together in synchrony (or not, which can cause a lot of problems). This post will focus on these axes, how they can influence each other (dubiously called “the pregnenolone steal” among other interactions) and some lifestyle suggestions that help to optimize these axes.

Let’s start with the basics: what are hormones? Simply put, hormones are the chemical messengers of the body – they are responsible for communicating long distances, from the brain to many organs, and they regulate almost every key function of the body, including all of our vital signs but also physiological functions like the menstrual cycle and responses to stress.

Hormonal Systems and the HP Axes

Many hormones are released from the adrenal glands, which are small, triangle-shaped glands located on the top of the kidneys. More specifically, the adrenal glands are responsible for producing a lot of the steroid hormones, which are such an important component of the hormonal system that when they’re out of whack, a lot of processes (e.g., blood sugar regulation) can be affected.

The steroid hormones are divided into three types: mineralocorticoids, glucocorticoids and androgens. Mineralocorticoids (like aldosterone) influence salt and water balance. Glucocorticoids regulate the immune system by reducing its activity (it’s important to turn the immune system off and on at the right times, as you can imagine). The most important human glucocorticoid is cortisol, which we will discuss in more detail below. Androgens are the sex hormones, which influence both primary and secondary sex characteristics, including sexual behavior and the amount of fat we have on our bodies, especially women. And all of them have one common precursor: cholesterol.

Cholesterol is an infamous molecule that it is actually an incredibly important hormone precursor, meaning that it is the first molecule in a chain of reactions that produce the many steroid hormones. When we don’t eat cholesterol, it must be synthesized by the liver, which can influence our hormonal balance as well. Before all of the steroid hormones can be made, cholesterol is converted to pregnenolone. Pregnenolone is then shuttled to one of the three above pathways according to the body’s most urgent need. This step in the system is where a lot can go awry, because pregnenolone is often in demand from multiple systems!

Long story short, all of these hormones are major components of two axes that ultimately communicate with the brain and result in big changes in our health and behavior: the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis.

The HPG Axis is probably the hormonal axis that you’re most familiar with; its primary role is to control reproduction. It is also important for development (puberty and aging) and the immune system. The hypothalamus releases gonadotropin-releasing hormone (GnRH), which signals to the pituitary gland to secrete two hormones:  luteinizing hormone (LH) and follicle-stimulating hormone (FSH).  LH and FSH signal within the sex organs to produce estrogen and progesterone in women and testosterone in men (and, in smaller amounts, in women). There are many ways that the production of these hormones can be influenced, from lifestyle factors like not getting enough sleep to taking synthetic hormones.

The HPA Axis is responsible for the stress response. The hypothalamus (which receives signals from the hippocampus, the region of the brain that integrates information from all the senses) releases a hormone called Corticotrophin Releasing Hormone (CRH), which signals to the pituitary gland to release a hormone called Adrenocorticotropic Hormone (ACTH), which signals to the adrenal glands to secrete cortisol as well as catecholamines (like adrenaline). As I mentioned above, cortisol is the most significant, commonly-released glucocorticoid in the body. This hormone has an amazing range of effects in the body, including controlling metabolism, affecting insulin sensitivity, affecting the immune system and even controlling blood flow.

How the HPA & HPG Axes Interact

What makes understanding hormones even more complicated? These two axes are not isolated – they are linked up! For instance, progesterone, which is produced in the ovaries and adrenal glands, interacts with the HPA axis. In women, the purpose of progesterone is to prepare the body for pregnancy (for menstruating women, it is higher in the second half of our cycle; when a woman isn’t pregnant, it is the drop in progesterone that triggers menses). The relationship between progesterone and the HPA axis is likely responsible for metabolic shifts, immune system changes and differences in resource priorities during pregnancy. And considering that progesterone: ever wonder why we crave certain foods right before our periods? We can blame the lack of progesterone. Progesterone isn’t the only link between the HPA and HPG axes: the big one that many women experience is called the pregnenolone steal.

The Pregnenolone Steal occurs when the “mother hormone,” pregnenolone, is taken away from the HPG axis and is used by the HPA axis instead. Pregnenolone steal is most common in people who are experiencing chronic stress (this can also manifest as adrenal fatigue, which is a common concern among naturopathic patients), because the hypothalamus in the brain perceives so much stress over time that the adrenal glands begin to shuttle pregnenolone away from the HPG axis, which is what controls all the female sex hormones, and into the HPA axis to keep our cortisol high. Since pregnenolone is a precursor to both estrogen and progesterone, the side effects of dysfunctional axes can include amenorrhea (loss of menses) or other signs of hormonal imbalance such as acne or abnormal hair growth. Testosterone, a hormone that is present in smaller amounts in women, is also affected by the pregnenolone steal. In fact, this pathway is one of the reasons why chronic stress can lead to low testosterone in men.

There is one more way that these axes are linked. When DHEA (another steroid hormone produced by the adrenal glands) is low, the body tends to convert testosterone and what little DHEA is being produced into estrogen. Plus, environmental estrogens (molecules in food, cosmetics, and plastics that are shaped like estrogen and can act like it in the body) further increase estrogen. This can lead to a phenomenon called estrogen dominance, which is when there is too much estrogen in the system. Since there are a lot of factors at play that contribute to estrogen production, it can be very tricky to conquer. Plus, nutrient deficiencies and lifestyle factors like type and frequency of activity can further influence exactly what hormones are getting produced and what hormones aren’t. This is yet another reason why working with a naturopath who focuses on endocrinology (hormones) is a great idea for many women.

Lifestyle Support to Promote Healthy Hormones

Clearly, the hormonal axes are complex, and working with a practitioner like a naturopathic physician is the right choice if you are concerned that your hormones are out of whack. However, there are some lifestyle factors that can help to regulate your hormones and prevent the HPA and HPG axes from interacting in a detrimental way. Here are some helpful tips for hormonal health:

  • Focus on stress management. Some effective strategies include: mindfulness meditation, relaxing self-care routines like taking baths, and making sure that you have a strong support system in your everyday life.
  • Exercise regularly. A mixed routine of cardiovascular activity (like fast walking, jogging, or swimming) and strength training has been shown to improve hormonal balance.
  • Get enough sleep and pay attention to sleep quality. Sleep plays a critical role in our hormone production and function, so getting at least 8 hours of high quality sleep is essential to avoid dysregulation of the HPA or HP axes.
  • Avoid processed foods and body products with synthetic ingredients. These may all contain environmental estrogens that could interfere with your hormonal health.

While there are no guarantees in the world of hormones, dedication to the above list is going to benefit almost anyone who is worried about hormonal balance.


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