Hormones serve as the body’s chemical messengers, influencing almost every organ and function. Progesterone is well-known for its role in pregnancy; however, this hormone influences many other aspects of our health, including mood and well-being. Are you experiencing mood swings or disrupted sleep? Progesterone imbalances could be to blame. Conventional medicine often considers progesterone primarily in the context of hormone therapy for specific reproductive health conditions. In this article, we will discuss how functional medicine takes a broader perspective on progesterone, emphasizing its role in overall hormone balance and well-being.

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What is Progesterone?

Progesterone is a steroid hormone produced primarily in the gonads and adrenal glands. After ovulation, during the luteal phase of the menstrual cycle, the corpus luteum, which develops from the ruptured ovarian follicle, secretes progesterone. It primes the uterine lining for potential implantation and pregnancy. If no pregnancy occurs, progesterone will decrease, facilitating the shedding of the endometrial lining, resulting in menstruation. If pregnancy does occur, progesterone will continue to be secreted by the corpus luteum in early pregnancy, followed by the placenta later in pregnancy. Progesterone has a relaxing effect on the smooth muscle of the uterus to prevent uterine contractions that could expel the fetus prematurely. It also regulates the maternal immune system so the body does not reject the developing fetus. A luteal phase deficiency or luteal phase defect (LPD) occurs when there is insufficient progesterone to maintain an adequate endometrium for implantation and support early pregnancy. It often presents as a luteal phase 9 days or shorter, spotting days before the start of menstrual bleeding, recurrent pregnancy loss, and infertility.

Our hormones function as a network, interacting with one another rather than working in isolation. Their actions both influence and are influenced by other hormones within our bodies. Some hormones work synergistically to enhance the function or production of another. In the case of the thyroid, progesterone can affect the level of thyroid hormones. Certain hormones help to counterbalance the actions of other hormones and maintain equilibrium, and such is the case for estrogen and progesterone. Because of their balancing effects on one another, when estrogen levels become high relative to progesterone levels, an imbalance known as estrogen dominance can occur, leading to symptoms like heavy bleeding, breast tenderness, and painful periods. (26) In breast tissue, estrogen and progesterone work in tandem to ensure the proper development of the mammary gland. Research suggests that progesterone counteracts the effects of estrogen, which increases cellular proliferation in breast tissue, by inhibiting cellular multiplication. This is achieved by inhibiting the replenishment of estradiol receptors and promoting the conversion of estradiol to estrone, a less proliferative form of estrogen. Progesterone demonstrates a similar anti-proliferative effect on the endometrium as well. Estrogen exposure without adequate progesterone in the uterus can lead to endometrial hyperplasia and cancer. Endometrial hyperplasia, when the uterine lining grows too much, can occur from anovulatory cycles or unopposed estrogen therapy. 

Progesterone exerts its influence outside of the reproductive system as well. It can influence metabolism and body temperature (38, 51), bone density, cognition and memory, the immune system and inflammation, and mood.

What is Progesterone's Impact On Mood?

Hormones can cross the blood-brain barrier, interacting with specific regions in the brain and regulating neurotransmitters associated with mood. Progesterone and its metabolite allopregnanolone exert an inhibitory effect on glutamate, an excitatory neurotransmitter in the brain, and potentiate GABA, a calming neurotransmitter, transmission in the brain. They also interact with dopamine and serotonin transmission in the brain. Imbalances in all of these neurotransmitters have been associated with mood disorders (25). Progesterone and allopregnanolone can modulate activity in a region of the brain called the amygdala, reducing anxiety.

Women’s reproductive hormones, including progesterone, fluctuate during the monthly menstrual cycle as well as throughout the different stages of life. These fluctuations can increase the risk of women experiencing mood disorders such as premenstrual dysphoric disorder (PMDD), postpartum depression, and perimenopausal depression. 

Progesterone and one of its metabolites, allopregnanolone, increase following ovulation in the luteal phase and decrease quickly prior to the start of menses. This exposure, followed by rapid withdrawal, may play a role in PMDD. It has also been hypothesized that insufficient production of these hormones in the luteal phase can impair GABA-signaling in the brain, contributing to the symptoms experienced in premenstrual syndrome (PMS), such as mood swings, depressed mood or anxiety symptoms, appetite changes, and disrupted sleep patterns. (29) 

Progesterone is the most abundant hormone during pregnancy. The dramatic decrease in progesterone that occurs following birth might contribute to postpartum depression. This abrupt decline in progesterone, combined with the fact the ovaries do not resume progesterone secretion until after the first postpartum menstrual cycle, creates a temporary hormonal imbalance. The duration of this imbalance will vary depending on when menstruation resumes, potentially extending the vulnerability to postpartum depression in some women. 

Women are at an increased risk for mood disturbances during the menopausal transition, with 45% to 68% developing depressive symptoms. The hormone changes occurring during perimenopause that can potentially contribute to mood disturbances include higher and more variable levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), variability in estradiol, and low progesterone levels.

Functional Medicine's Approach to Progesterone Imbalances

Functional medicine uses a comprehensive and holistic approach to address progesterone imbalances, aiming to identify and treat the root causes of progesterone imbalance. This often involves reviewing an individual’s medical history, lifestyle, and functional medicine labs to look at unique physiological factors. By understanding the underlying factors contributing to progesterone imbalances, such as stress, nutritional deficiencies, environmental exposures, and other hormonal imbalances, functional medicine practitioners can create customized treatment plans. Treatment recommendations often include diet and lifestyle recommendations, supplement recommendations, and even, in some cases, bio-identical hormones.

Lab Testing for Progesterone Levels in Functional Medicine

Using functional medicine labs to evaluate progesterone levels is critical in understanding its relationship with other hormones, such as cortisol, estrogen, and thyroid, as well as exploring the multiple potential underlying root causes of progesterone imbalance, such as nutritional deficiencies, stress, and toxin exposure.

Several testing methods are available to assess hormone levels. While blood testing is the traditional approach, saliva, and urine tests are non-invasive options that also provide the option to measure bioavailable levels, hormone metabolites, and multiple collections throughout the day or cycle. Progesterone is only produced after ovulation, so it is recommended to measure it in the luteal phase around day 21 of a 28-day menstrual cycle or about one week after ovulation.

Salivary Hormone Panel

A salivary hormone panel measures the free hormone levels available to act on tissues.

Another option for salivary tests is Genova’s Rhythm test. This test takes multiple measurements of hormones over the course of a month to highlight unique hormone fluctuations throughout the cycle. The multiple measurements are also beneficial to assess how much progesterone is produced and for how many days during the luteal phase. Progesterone production can vary and is released in a pulsatile manner, making single measurements potentially less reliable for assessing overall hormone status.

Urinary Hormone Panel

The DUTCH Complete test is a dried urine test that assesses sex and adrenal hormone metabolites as well as the daily cortisol pattern. The addition of the sex hormone metabolites can be especially useful in assessing progesterone imbalances since we know that progesterone’s metabolites can play such an important role in mood regulation. It also measures a marker called 8-hydroxy-2' -deoxyguanosine (8-OHdG), which is a marker of DNA damage or oxidative stress. Long-term oxidative stress is associated with decreased ovarian function and progesterone production.

DUTCH also offers a Cycle Mapping urinary testing option for those interested in evaluating the fluctuations of estrogen and progesterone throughout the month and in relation to one another.

Additional Lab Tests to Consider

Environmental exposures, particularly to xenoestrogens, can contribute to hormone imbalances, like estrogen dominance and reproductive health conditions. The Environmental Toxins panel tests 39 different toxicants to help identify exposure to endocrine disruptors that contribute to hormone imbalances

Nutrients from our diet are used as cofactors for synthesizing and metabolizing hormones. The Micronutrient Test measures 31 vitamins, minerals, and other nutrients that can identify nutrient insufficiencies playing a role in hormone imbalances. 

Irregularities in blood sugar and high insulin levels can impact hormone production in the ovary and prevent regular ovulation. The Diabetes Panel measures six biomarkers associated with blood sugar regulation, including fasting blood sugar and insulin. (34, 37)

Thyroid hormones are critical in supporting proper ovarian hormone production. A complete thyroid panel measures TSH, T4, T3, free T4, free T3 and thyroid antibodies. Measuring all of these markers allows you to assess the total thyroid hormone production, how well T4 is being converted into T3, whether there are enough free or bioavailable hormones, and if there is an autoimmune condition affecting thyroid function.

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Strategies to Boost and Balance Progesterone Naturally

It is possible to boost progesterone naturally by following nutrition and lifestyle recommendations. 

Nutrition

In general, adopting a whole-foods diet emphasizing low-glycemic carbohydrates, antioxidants, and healthy fatty acids can support regular ovulation and progesterone production. On the contrary, dietary components like high-glycemic carbohydrates, excess saturated fat, and trans fatty acids have adverse effects. Moreover, there are specific nutrients vital for progesterone production and function.

Vitamin B6, or pyridoxine, is important for hormone metabolism in the liver and anterior pituitary function, which impacts progesterone levels and overall hormone balance. B6 is rich in foods like beef liver, tuna, salmon, chickpeas, poultry, dark leafy greens, bananas, papayas, oranges, and cantaloupe. In one study, women who received B6 supplements had lower estrogen, higher progesterone, and less premenstrual syndrome (PMS) symptoms. 

Magnesium plays a role in regulating the hypothalamic-pituitary-adrenal (HPA) axis and the stress response. It can also impact LH levels, which are responsible for proper ovulation and, therefore, progesterone production. (2, 33) Magnesium-rich foods include greens, nuts, seeds, beans, and whole grains.

Zinc is a mineral that serves as a cofactor for 300 enzymes in the body and plays a crucial role in the reproductive system. Low zinc can affect FSH and LH levels, which impact estrogen and progesterone production throughout the cycle. Zinc is also critical for sex hormone receptor function (39). Zinc-rich foods include shellfish, beef, poultry, pork, legumes, nuts, seeds, and whole grains.

Lifestyle

High stress can lower progesterone levels through its modulation of the HPA axis and cortisol. Meditation, regular movement or exercise, and breathing exercises can all help to manage stress (17, 18, 30).

Over-exercise, similar to mental-emotional stress, can negatively impact the HPA axis and progesterone levels. Regular, moderate-intensity exercise can help manage stress and regulate hormone levels and menstrual cycle regularity.

Herbs & Supplements

Vitex agnus-castus, also known as chaste berry, can help to support progesterone levels by regulating pituitary hormones such as LH, FSH, and prolactin. It has been used as a treatment for PMS, PMDD, and hyperprolactinemia (36, 46).

Future Research in Progesterone and Mood

Progesterone's influence on mood and well-being is complex, and the specifics are still being researched. Progesterone’s metabolite allopregnanolone appears to influence affective symptoms, but further research is necessary to understand if this is due to its total levels, fluctuation in levels, effect on receptor function, and/or its interaction with other systems like the HPA axis, for example. Furthermore, additional research can be conducted to explore the role of other progesterone metabolites on mood. 

Research is also ongoing to explore how progesterone can be utilized as a therapy. Since progesterone can help to prevent muscular contractions in the uterus, it is being explored as a treatment option for preventing preterm birth and recurrent miscarriage. A rapid decrease in progesterone and allopregnanolone at the end of pregnancy might contribute to postpartum depression. In 2019, the FDA approved a drug called Brexanolone, which is allopregnanolone created in the lab, as a treatment for postpartum depression. It is also a possibility that progesterone therapy could be used to increase allopregnanolone levels to alleviate postpartum depressive symptoms.

Phytoprogestins are plant-based compounds that can interact with progesterone receptors. Some examples include kaempferol, apigenin, luteolin, and naringenin. Extensive research has been done on phytoestrogens in treating hormone imbalances and reproductive diseases, but less has been done on phytoprogestins thus far. Future research can delve into phytoprogestins’ potential for modulating progesterone function and women’s health complaints.

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Summary

The significance of progesterone in women's physical and emotional well-being cannot be overstated. A functional medicine approach provides a comprehensive understanding of how multiple hormones interact within the body. It focuses on identifying and addressing the root causes of hormonal imbalances rather than merely treating symptoms. This approach utilizes nutrition, lifestyle changes, and targeted therapies to support progesterone and overall hormone balance. By recognizing the vital role of progesterone and considering the broader context of hormonal health, women can enhance their physical and emotional well-being, ensuring a higher quality of life throughout all stages of their reproductive journey.