Cortisol: The No. 1 Overlooked Infertility Factor?

Here’s a startling statistic: As little as 20% higher cortisol levels over time can halt ovulation directly affecting women's fertility. While exploring the science behind cortisol, we also investigated the hormones at play during the fertility process, and what we found was eye-opening.

Recently, Stanford OB-GYN professors introduced us to Professor Sarah Berga who has made scientific breakthroughs in this area. Her research focuses on reproductive endocrinology, specifically stress’s role in reproduction, and Dr. Berga sits on the Mayo Clinic Proceedings and previously on The Journal of Clinical Endocrinology & Metabolism editorial board.

Her findings suggest that cortisol is an overlooked factor in infertility, not only estrogen or progesterone imbalances as many scientists previously thought. According to Dr. Berga “The amount of cortisol elevation required to stop ovulation is trivial. A 20% increase in cortisol in the morning could be responsible for a profound reduction in LH pulse frequency which halts the release of the follicle, leading to infertility. However, it’s reversible with Cognitive Behavioral Therapy (CBT),” nutrition, exercise, mindset and sleep therapies.

Women often do not notice stress or admit to it. “Nonstop pressure and chronic stress are worse than you think for your reproductive system," said Dr. Sarah Berga. It has a significant effect on fertility and prevents millions of women from getting pregnant.

How Stress Shuts Down Your Body

Cortisol is not only the main stress hormone, it’s the master hormone. It regulates your sleep-wake cycle, blood sugar levels, energy metabolism, blood pressure, immune system and more. When at optimal levels, it’s quietly working behind the scenes along with a score of other hormones, ensuring you’re operating at top form. But beyond those everyday jobs, cortisol has another vital function: It’s key to your stress response.

When you’re stressed — be it physically or mentally — your internal alarm system goes off. Suddenly, your brain tells the Hypothalamic-Pituitary-Adrenal (HPA) axis to start pushing out more cortisol to help you handle the threat. This can shut down functions considered “non-essential” (such as reproduction) — all to help you conserve energy.

That’s what many people are facing today — without ever realizing it. Their alarm systems are essentially stuck in “on” mode, causing long-term cortisol imbalances. Well, when your system is thrown out of whack, a momentary suppression can become a chronic crackdown. That’s why it’s so important to measure and validate your cortisol levels.

How Cortisol Suppresses the Female Reproductive System

Naturally, as a woman ages, the number and quality of her eggs will decrease. She’s born with about one million eggs, yet by her teens, only about 300,000 remain. During the next few decades, about 300 eggs will ovulate while being affected by other factors, such as weight and hormone imbalances. Our reproduction is regulated through the Hypothalamic-Pituitary-Gonadal (HPG) axis. With that in mind, let’s talk about exactly what happens when certain hormonal imbalances affect your reproductive health:

GnRH

When our stress levels rise, resulting in high cortisol, our main releasing sex hormone, gonadotropin releasing hormone (GnRH), which is secreted by the hypothalamus, gets suppressed. As a result, sperm count, ovulation, sex hormones and sexual activity can decrease.

LH and FSH

Both are secreted by the anterior pituitary in response to the GnRH-releasing hormone (GnRH). In men, FSH stimulates sperm production. In women FSH controls the menstrual cycle and promotes egg growth. In both sexes, LH encourages the production of sex steroids, estrogen, and testosterone. High cortisol (or exposure to exogenous steroids like prednisone) directly affects the HPG axis by central actions on the hypothalamus and pituitary.

Progesterone

Cortisol also affects progesterone, which is known as the pregnancy hormone. In women, its key role is to prepare the uterus to accept a fertilized egg. This is part of why progesterone is also known as the “stress buffer” hormone. Progesterone is a precursor to cortisol and its levels decrease when cortisol levels rise.

Estrogen

Then we have estrogen – we’re referring mostly to estradiol (E2) – the main sex hormone that regulates the menstrual cycle. Since estrogen and progesterone work together to promote fertility, it makes sense that levels of one will affect the other. Specifically, when progesterone levels are low, estrogen levels and the E/P (estrogen/progesterone) ratio can proportionally seem elevated. This “estrogen dominance” can cause symptoms like irregular periods, mood swings, headaches, sleep problems, anxiety, even hair loss.

In a nutshell, this tells us that cortisol imbalances can create a domino effect that resonates throughout the human endocrine system, hitting the reproductive system along the way. In fact, with constant high levels of cortisol, periods can become irregular, less frequent or stop altogether. (To learn more, we wrote about menopause and cortisol here.)

Forced Ovulation to bypass cortisol effects

In his book from 2004 “Safe Uses of Cortisol” endocrinology professor William McK. Jefferies MD, talks about the use of low physiologic doses of cortisol administered for ovarian dysfunction in women with low adrenal reserve instead of prescribing clomifene. Either a low or high cortisol pattern will hinder fertility. Clomifene – also known as clomiphene, Clomid or Serophene – bypasses the HPG axis and forces ovulation in women who have a hard time getting pregnant. It works in some patients by increasing certain hormones (FSH and LH) but clomifene is not natural. If high cortisol is halting ovulation it would be much better to try to fix the cortisol balance first, as clomifene can lead to multiple births or miscarriages. For those choosing the IVF route, reassuringly, perceived stress, infertility-related stress, and cortisol levels were not associated with IVF cycle outcomes in this study.

Stress’ effects can also be seen all around us. For example, just look at the high-stress medical field. In a 2016 survey of female physicians, nearly one in four of those who’d tried to have a baby were diagnosed with infertility — almost double the rate of the general public.

In men, cortisol has an inverse correlation with sperm count and total motility, imprinting a particular type of sperm kinetics, characterized by high energy but low progressiveness. Additionally, adrenal insufficiency associated with low cortisol in men showed a reduction in Leydig cell testosterone production and sperm density, similar to over-exposure to glucocorticoids. Clinical cases of hypercortisolism ( like Cushing’s) and hypocortisolism (like Addison’s disease) demonstrate the requirement for a precise amount of cortisol for proper testicular function and fertility.

The steroid-forming tissues of the ovaries, testicles and adrenal glands have the same embryologic origin, share many enzymatic steps in producing hormones (estrogens, progesterone, androgens, cortisol and aldosterone), and function in a very close relationship.

The effect of stress on the function of these glands is well known. It is essential to know that under stress, the body would preferentially produce cortisol at the expense of all the other steroid sex hormones. This is just one of the many reasons it’s important to know and balance your cortisol levels. One way to do that is by measuring your cortisol pattern, which you can soon do easily from home.

And we’re here all along the way to support you on this journey.

Before you go, we have one more question for you: How can we get better? Here at Pardigm.com, our goal is to gather the best information to help you understand the science of stress. If you think we missed anything in our research, please let us know here.

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