Recently, I wrote an article about the connection between estrogen dominance, mast cells, histamine intolerance, and PMS. Today, I want to discuss how improving your progesterone levels may help to improve estrogen dominance, PMS, symptoms of menopause, fertility, and mast cell activation issues. 

Using bioidentical progesterone can be a helpful strategy in many cases. Let’s get into it and discuss the benefits of improved progesterone levels and how bioidentical progesterone may help.

What Is Progesterone

Progesterone is a hormone made in the corpus luteum in the ovaries. Progesterone is also produced by the placenta and adrenal glands.

Female bodies go through a lot of hormonal changes during the menstrual cycle. During ovulation, the body releases an egg from one of the ovaries. This is when the corpus luteum is formed to make progesterone. Progesterone helps to prepare your uterus for a healthy pregnancy by supporting glandular development, creating new blood vessels, and setting up the environment for potential implantation.

If pregnancy doesn’t occur, the body breaks down the corpus luteum. Progesterone levels drop, leading to a menstrual period. If the egg is fertilized and pregnancy occurs, the corpus luteum continues to stick around, producing more progesterone. During pregnancy, progesterone is responsible for stimulating your blood vessels to supply the endometrium (lining of the uterus), which can then support the embryo with nutrients. Progesterone will also prevent the production of eggs during pregnancy. It will trigger and support lactation for future breastfeeding.  See how smart your body is?!!

However, it’s not only females that have progesterone. Male bodies also produce some progesterone in the adrenal glands. In males, progesterone supports sperm development.

Normal, High, and Low Progesterone Levels 

Testing your progesterone levels may be helpful in spotting potential health issues and their causes. Testing progesterone levels may help to (1):

  • Check if you are ovulating
  • Identify underlying issues behind infertility
  • See if ectopic pregnancy or a miscarriage has occurred
  • Check for high-risk pregnancy
  • Look at causes of abnormal uterine bleeding
  • Diagnosing adrenal health issues

Normal Progesterone Levels

Doctors can use blood tests to check for normal progesterone levels. Remember, levels can fluctuate through the menstrual cycle and pregnancy. (In Canada, for SI units, multiply by 3.18.)

Normal progesterone levels:

  • Pre-ovulation: <0.89 ng/mL
  • Ovulation: <12 ng/mL
  • Post-ovulation: 1.8 – 24 ng/mL
  • First trimester: 11 – 44 ng/mL
  • Second trimester: 25 – 83 ng/mL
  • Third trimester: 58 – 214 ng/mL
  • In men: <0.20 ng/mL

The Problems with High Progesterone

High progesterone levels often don’t cause any negative health effects. During pregnancy, high levels are natural. Oral contraceptives tend to use synthetic progesterone to trick your body and stop ovulation. Later in this article, you will learn how increasing your progesterone levels may actually benefit your health (2).

Problems with Low Progesterone

Low progesterone can affect your hormonal health, menstruation, fertility, and pregnancy. It can increase the risk of estrogen dominance. Low progesterone levels are not ideal for an egg to get fertilized and for a fertilized egg to develop. Low progesterone levels can lead to missed periods, absence of menstruation, poor ovarian function, infertility, and miscarriage. It may play a role in mast cell activation syndrome, too, as you will learn later in this article.

Health Benefits of Progesterone

This is a good follow-up to the PMS article. Since bioidentical progesterone (not progestins) can counteract estrogen dominance, treat PMS, and be an alternative to standard hormone therapy in a functional medicine paradigm. 

Potential benefits of progesterone hormone therapy:

  • Estrogen dominance: According to a 2020 article published in Drug Discovery Today, a healthy estrogen-progesterone balance is critical for women’s health (3). Using progesterone may help to restore this balance.
  • PMS: A 2012 review published in Cochrane has found that progesterone may be beneficial for PMS (4). According to a 2013 study published in Gynecology and Obstetrics, progesterone may help to improve PMS symptoms in PCOS patients (5).
  • Fertility: According to a 2015 research published in the Journal of Ovarian Research, progesterone may help to improve fertility (6).
  • Menopause: A 2014 study published in Geburdshilfe und Frauenheilkunde has found that progesterone may help to improve symptoms of perimenopause and menopause (7).
  • Sleep: According to a 2008 study published in the International Journal of Gynecology and Obstetrics, progesterone hormone therapy may help to improve sleep in postmenopausal women (8).
  • Bone health: According to a 2010 study published in the Journal of Osteoporosis, progesterone may help to support bone health in women (9).
  • Certain cancers: A 2003 study published in Reproductive Biology and Endocrinology has found that progesterone may help to reduce ovarian cancer (10). A 2019 review published in the Journal of Women’s Health has found that progesterone may help to reduce endometrial cancer risks (11).

Progesterone and Mast Cell Activation Syndrome

I’ve already written about why women tend to be more sensitive to histamine, histamine-estrogen connection, and mast cell-estrogen in this article. I have also written about the connection between PMS, histamine, and mast cells here. So it may not be surprising to learn that progesterone may be beneficial for those with mast cell activation syndrome (MCAS).

What Are Mast Cells

Your mast cells are a type of white blood cells in your connective tissues, including your digestive tract, skin, respiratory tract, urinary tract, reproductive organs, surrounding your nerves, and near your blood vessels and lymph vessels. They play an essential role in your immune system by storing various inflammatory mast cell mediators, such as histamine. 

If you encounter a substance that triggers an allergic reaction, your mast cells will get activated and release histamine and other chemicals as part of your body’s natural immune response to protect you from harm. Your mast cells are programmed to react to other kinds of threats as well, including chemical exposures, such as toxic metals,  and physical stimuli, such as heat or cold. Your mast cells are essential for health. However, overactive mast cells lead to mast cell disorders, such as MCAS, which may result in a variety of symptoms and health issues.

Estrogen Dominance, Mast Cells, and Histamine Intolerance

To recap, estrogen plays many roles in your body, including by stimulating your mast cells to release more histamine. More estrogen leads to increased mast cell stimulation, histamine response, and histamine intolerance.

According to a 2012 study published in Frontiers in Immunology, too much estrogen can lead to an asthmatic response by triggering the mast cells (12). A 2013 study published in Current Opinions in Allergy and Clinical Immunology has also found that high estrogen may contribute to mast cell and histamine-related allergies and asthma (13).

If you have estrogen dominance, it can lead to mast cell activation, increased histamine levels, and symptoms of histamine intolerance. Increased histamine levels can lead to higher estrogen levels. You can see that this can turn into a vicious cycle of estrogen dominance, mast cell activation, histamine intolerance, and chronic symptoms.

Progesterone and Mast Cell Activation

Improving progesterone levels can reduce estrogen dominance, mast cell activation, histamine intolerance, and related symptoms. A 2006 study published in the International Journal of Immunopathology and Pharmacology has explained that mast cells are involved with allergic reactions, inflammation, and inflammatory issues, including inflammatory bowel syndrome (IBS), painful bladder syndrome (PBS), interstitial cystitis (IC), and migraines (14). They found that using progesterone may help to reduce mast cell activity and histamine secretion, reducing related inflammation, symptoms, and inflammatory conditions. A 2007 study published in the American Journal of Physiology, Endocrinology, and Metabolism has also found that progesterone may help to reduce mast cell activity (15).

Bioidentical Progesterone in Functional Medicine

Bioidentical hormones are processed hormones that are made to mimic your natural hormones to improve hormonal balance in your body. They are commonly used during perimenopause and menopause. 

Functional medicine practitioners, like myself, don’t routinely recommend synthetic hormone therapy, including synthetic progesterone, such as Progestin.  (Bear in mind that this concept is controversial and synthetic hormones remain standard practice in medicine for the most part.)  It is the same synthetic progesterone that’s used in hormonal contraceptives. It may cause unwanted side effects and health risks. For example, some evidence has linked synthetic progesterone to an increased risk of breast cancer (16, 17). 

However, you may benefit from using bioidentical progesterone, depending on your situation. It may be beneficial if you have symptoms of estrogen dominance, PMS, perimenopause, menopause, or mast cell activation issues. Bioidentical progesterone is generally well-tolerated, has fewer side effects, and has a lower risk of cancer and other health issues than its synthetic counterparts (18, 19, 20). I don’t recommend any changes to your treatment without discussing them with your Gynecologist or other specialist.

How I Use Bioidentical Progesterone in My Practice

After proper testing and assessment, using bioidentical progesterone may be beneficial for addressing estrogen dominance and/or mast cell activation syndrome. As always, it depends on your specific case. (One important caveat is the rare medical condition known as “catamenial anaphylaxis” also known as progesterone-induced anaphylaxis, would require special consideration.  And a different treatment strategy altogether, clearly one not involving progesterone therapy.)

Bioidentical hormones can come in different forms, including creams, gels, lotions, injections, and tablets, depending on the need and your doctor’s recommendation. Transdermal progesterone is the most commonly used form of bioidentical progesterone in functional medicine (21). This is what I’ve used for the past 25 years with high success rates. At a recent conference I attended, a presenter emphasized sublingual (dissolved under the tongue) progesterone as the preferred method for better absorption. It is certainly an interesting idea to explore, but I have less experience with it in my practice.  What I have seen is that oral and sublingual forms do help more effectively the brain symptoms, including sleep disturbance,  associated with relative progesterone deficiency.  And agree that the oral form is broken down in the gut so may won’t be absorbed as well as sublingual forms.  In other words, thoughtful assessment is best when it comes to hormone related treatment decisions. 

Next Steps

If you are dealing with symptoms of estrogen dominance, PMS, hormonal issues, or MCAS, you may benefit from taking bioidentical progesterone. However, working with a functional medicine practitioner (hint: me!) and proper testing is important before you decide on taking progesterone, and for determining which form, if any, is best for you. 

For mast cell issues, working with a healthcare practitioner knowledgeable about histamine intolerance and MCAS is the best way to get to the root cause of your symptoms and create an individualized treatment plan. I welcome you to start a functional medicine consultation with me for further personalized guidance to improve your health. You may book your consultation here. 

Check out my Histamine Intolerance Course here. Learn on your own time, from anywhere. Get an inside look at the most helpful functional medicine tests for pinpointing imbalances, ways to identify and manage the most common (and sometimes surprising) mast cell triggers, and learn what to eat, what to avoid, and why.

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