How to Test for The Root Cause of Progesterone Imbalance

Progesterone is a hormone that plays a pivotal role in the menstrual cycle but can also impact other body systems. This article will discuss what progesterone is, the symptoms and causes of progesterone imbalances, functional medicine testing to evaluate progesterone, and functional medicine treatments to ensure progesterone is at appropriate levels.

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What is Progesterone?

Progesterone is a reproductive hormone made within the ovary in women. To fully appreciate progesterone's role in women's health, we must first understand how the female menstrual cycle works.  

The Female Menstrual Cycle

The menstrual cycle is divided into three parts, the follicular phase, ovulation, and the luteal phase, and lasts about 21 to 35 days. The follicular phase begins with menstruation, with little production of estrogen and progesterone. Follicle-stimulation hormone (FSH) is released in this phase from the pituitary gland, stimulating follicles (which hold eggs) in the ovary. Between days five and seven, one of those follicles becomes dominant and increasingly produces estradiol. Estradiol stimulates the release of another hormone from the pituitary gland, luteinizing hormone (LH). As estradiol rises, LH also rises and causes the follicle's growth until the follicle ruptures, releasing the egg (a process called ovulation). If not fertilized, the luteal phase begins. The remnants of the ruptured follicle turns into a structure called the corpus luteum (CL), which produces progesterone. Without a fertilized egg, the CL will degrade, causing progesterone to decline. Estradiol levels are also falling at this time, and the low levels of both hormones signal the lining of the uterus to shed, which we call menstruation. The cycle will then begin again.  

It is important to emphasize that progesterone is made from the remnants of the follicle, only after ovulation. This means that if ovulation does not occur, progesterone is not made. If progesterone is not made, a hormonal imbalance occurs, as estradiol is still present.

Progesterone aids in the function of the uterine lining. It can increase the creation of small blood vessels that bring blood with oxygen and nutrients to the lining, helping with growth. Progesterone also inhibits contractions in the muscle of the uterine lining, which is pivotal if a fertilized egg is present, as contractions may lead to miscarriages. Progesterone also functions to balance out estrogen. In the uterine lining, progesterone can reduce the amount of estrogen receptors, thereby limiting the exponential growth of the lining. This is important, as overgrowth of the lining can lead to a precancerous condition called endometrial hyperplasia.

Progesterone can also be made from Dehydroepiandrosterone (DHEA), a hormone made in the adrenal glands. The amount made here is much lower than the amount produced during the menstrual cycle.

Progesterone can break down into a hormone called allopregnanolone. Allopregnanolone can enhance levels of GABA, a calming, relaxing neurotransmitter. This effect is potent; the anti-anxiety effect of allopregnanolone is similar to anxiety medications called benzodiazepines. Low levels of allopregnanolone have also been linked to depression. Allopregnanolone can also inhibit glutamate, an excitatory neurotransmitter, again contributing to a calming effect.

Progesterone can also affect other systems in the body. Progesterone can protect against osteoarthritis by enhancing bone mineral density and neurologic disorders by increasing nerve functioning.  

High Progesterone Symptoms

High progesterone symptoms include breast tenderness, abdominal cramping, back pain, vaginal bleeding, dizziness due to low blood pressure, and quick clotting (hypercoagulative state).

Low Progesterone Symptoms

Low progesterone symptoms may include irregular periods, headaches, infertility, difficulty sleeping, weight gain, mood changes including anxiety or depression, and hot flashes.

What Causes Progesterone to Be High?

High levels of progesterone are seen in the following conditions:

• ovarian cysts
• ovarian cancer
• pregnancy
• adrenal disorders

What Causes Progesterone to Be Low?

Low progesterone can be caused by the following:

• Anovulation, or lack of ovulation
• Polycystic Ovarian Syndrome (PCOS): a condition of reproductive hormones often causing a lack of ovulation
• Hypothyroidism: The thyroid gland produces hormones that affect every body system, including the reproductive system. Hypothyroidism, or underactive thyroid, can affect progesterone production.
• Hyperprolactinemia: High levels of prolactin, a hormone produced by the pituitary gland in the brain, can affect the reproductive system, including lowering progesterone levels.
• Low cholesterol
• Perimenopause
• High stress
• Eating disorders
• Excessive exercise
• High estrogen

Functional Medicine Labs to Test for Root Cause of Progesterone Imbalance

DUTCH Cycle Mapping + Complete

The DUTCH Cycle Mapping + Complete test by Precision Analytical comprises two tests. First, the Cycle Mapping portion tracks estrogen and progesterone metabolites throughout the cycle. The Complete part assesses hormone metabolites, or breakdown products, in the urine, showing how hormones are metabolized. Regarding progesterone, the Cycle Mapping portion will show how many days progesterone is made and in what quantity. This assessment is valuable, as progesterone production can vary even in the luteal phase. The Complete portion can show if progesterone is being metabolized in a way that would elicit anti-anxiety effects. This portion of the test should be done in the luteal phase as it is the only cycle phase producing progesterone. Estradiol, estrone, and testosterone metabolism are also shown, giving a comprehensive view of the reproductive hormones. Lastly, this test has an adrenal section, providing insight into the patient's stress response which can also play a role in low progesterone.

Salivary Hormone Panel

A saliva panel assesses the amount of free hormone at the tissue levels. Free hormones are active, as opposed to hormones that are bound to carrier molecules which are inactive. You can check for free and bound hormones in the blood, but the saliva will always give you the free levels. The salivary hormones also represent the hormones in the tissues, unlike blood testing, which shows the hormones in the bloodstream. Like the DUTCH Complete, this test should be done during the luteal phase for accurate progesterone measurements.

Blood Hormone Panel

Blood testing can assess free and bound levels of the hormones in the bloodstream. A blood hormone panel can also include FSH and LH, the two hormones released from the brain that orchestrate the cycle. Like the DUTCH Complete and saliva testing, blood testing for progesterone also needs to be done in the luteal phase.

Thyroid Panel

A thorough Thyroid Panel is essential since the thyroid gland makes hormones that can influence every body system, including the reproductive system. Underactive thyroid, or hypothyroidism, can inhibit ovulation, leading to low progesterone levels.

Prolactin

Prolactin is a hormone released from the pituitary gland in the brain. When it is elevated, it can cause progesterone to be low. This test can be an add-on to many lab's hormone panels.

Cholesterol Panel

Assessing cholesterol levels via a lipid panel is vital since progesterone is made from cholesterol. Ensuring cholesterol production is occurring and at appropriate levels can be helpful.

Integrative Medicine Treatment for Low Progesterone

Nutrition

In order to make any hormone, adequate calories must be consumed. In the presence of a chronic caloric deficit, hormone production will slow or shut down. Additionally, while it's important to exercise, it's also important to not over-exercise, as that can lead to a severe caloric deficit, again affecting hormone production.  

Seed cycling can also be utilized to aid in healthy progesterone levels. Seed cycling is food as medicine in its truest form, as the protocol calls for the consumption of different types of seeds during the phases of the menstrual cycle to support the synthesis of the phases' dominant hormones. For the luteal phase, and thus progesterone, consuming sesame and sunflower seeds may aid in healthy progesterone levels.

Lowering Stress

Stress causes the body to release hormones, including cortisol. Cortisol can negatively impact the female hormone cycle, affecting the amount of progesterone made. Mindfulness, breathwork, and meditation can all aid in lowering stress levels.

Inositol  

Inositol is a compound found in fruits, grains, and nuts. Our bodies also naturally make them. Inositol can help with restoring normal ovarian functioning and response to pituitary hormones. There are also studies supporting inositol in the treatment of PCOS, a common cause of low progesterone.

Thyroid Supporting Nutrients

Selenium, vitamins A and D, zinc, and omega-3 fatty acids are all necessary nutrients for optimal thyroid functioning, which can influence progesterone production.

Estrogen Detoxification Support

Indole-3-carbinol, b vitamins, and calcium-d-glucarate are all supplements that can aid in metabolism, thus lowering estradiol. High estradiol can inhibit progesterone production, so ensuring it is adequately excreted is crucial.  

Integrative Medicine Treatment for High Progesterone

Treatment of high progesterone is best done with conventional medicine, as therapies needed often include surgery, chemotherapy, and other pharmaceuticals.

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Summary

Progesterone is a hormone that can influence reproduction, bones, and the nervous system.  Progesterone imbalances can be due to several reasons, and functional medicine testing can help get to the root cause of the imbalance. Once the root cause is revealed, a comprehensive treatment plan, including diet, exercise, stress reduction, and supplementation, can provide an evidence-based way to restore proper progesterone levels.