Progesterone

Progesterone, a vital hormone in the female reproductive system, plays a crucial role in regulating menstrual cycles and supporting pregnancy. Produced primarily in the ovaries following ovulation, progesterone prepares the uterus for potential pregnancy and helps maintain a healthy gestation. 

Understanding progesterone levels is essential for assessing fertility, managing menstrual irregularities, and monitoring pregnancy health. Various testing methods are available, including blood, saliva, and urine tests, each with its benefits and drawbacks. 

What is Progesterone?

Definition of Progesterone: Where Does Progesterone Come From?

Progesterone is a steroid hormone derived from cholesterol. Within the steroid hormone production pathway, progesterone is a precursor to other hormones such as cortisol, aldosterone, and testosterone.

It is synthesized primarily in the ovaries during the luteal phase of the menstrual cycle and in smaller amounts in the adrenal glands. 

During pregnancy, progesterone synthesis shifts from the corpus luteum in the ovary to the placenta. Initially, the corpus luteum secretes progesterone to support the early stages of pregnancy, but around the tenth week, the placenta takes over this role, producing progesterone to maintain the uterine lining and support fetal development.

Sources of Exogenous Progesterone

Exogenous progesterone refers to progesterone that is obtained from external sources rather than being produced by the body. It is commonly available in various forms such as oral pills, topical creams, vaginal suppositories, and injections. 

These exogenous progesterone sources are often prescribed to supplement natural progesterone levels in cases of deficiency or to support various medical treatments such as hormone replacement therapy, fertility treatments, and managing menstrual irregularities. 

Additionally, some over-the-counter products and herbal supplements may also contain synthetic or plant-derived progesterone-like compounds, although their efficacy and safety may vary.

Functions of Progesterone: What Does Progesterone Do?

Progesterone has various functions relating to hormone balance, reproduction and pregnancy: 

Maintains the uterine lining during the menstrual cycle: Progesterone helps maintain the thickened uterine lining (endometrium) in preparation for potential embryo implantation. If implantation doesn't occur, progesterone levels drop, triggering menstruation and shedding of the uterine lining.

Supports implantation of the fertilized egg in the uterus: Progesterone prepares the uterine lining for implantation by increasing blood flow and nutrient supply, creating a hospitable environment for the fertilized egg to attach and grow.

Helps sustain pregnancy by preventing uterine contractions: During pregnancy, progesterone maintains the uterine lining and prevents contractions that could lead to premature labor. It helps maintain a supportive environment for fetal development.

Stimulates the development of milk-producing glands in the breasts: Progesterone works alongside other hormones like estrogen and prolactin to stimulate the growth and development of alveoli (milk-producing glands) in the breast tissue, preparing the breasts for lactation.

Regulates the menstrual cycle and ovulation: Progesterone is involved in regulating the menstrual cycle, particularly the second half (luteal phase). It helps coordinate ovulation and prepares the body for potential pregnancy.

Contributes to the development of secondary sexual characteristics: Alongside other hormones, progesterone influences the development of secondary sexual characteristics such as breast development and regulation of the menstrual cycle, contributing to overall reproductive health.

Importance of Progesterone in Hormonal Balance

Progesterone plays a crucial role in maintaining hormone balance within the body, particularly in relation to estrogen and cortisol. 

Progesterone works in tandem with estrogen to regulate the menstrual cycle and promote reproductive health. Importantly, progesterone helps counterbalance the effects of estrogen, acting as a natural antagonist to prevent estrogen dominance, which can lead to various health issues including PMS symptoms, excessive bleeding, pelvic pain, and certain cancers.  [10.]

Progesterone also has an intimate relationship with cortisol, a master stress hormone produced by the adrenal glands. Progesterone is the direct precursor to cortisol.  Because of this, we see that increases in acute stress cause transient increases in progesterone as well as in cortisol.  [8.]  

This relationship goes the other way too: increases in progesterone, whether naturally due to cycle changes or pregnancy, or due to supplementation with hormones, can also cause a greater increase in cortisol levels than one would otherwise expect to see.  

Optimal progesterone levels help modulate the stress response and prevent cortisol from exerting excessive effects on the body. Thus, progesterone serves as a vital component in maintaining overall hormone equilibrium, ensuring optimal health and well-being.

Mechanism of Action and Biological Effects

Progesterone exerts its effects by binding to progesterone receptors throughout the body, which triggers changes in DNA expression.  [1.]  Metabolites of progesterone have various effects on the body, although their effects are commonly attributed to progesterone.

Role of Progesterone in the Menstrual Cycle

Progesterone plays a crucial role in regulating the menstrual cycle, particularly during the luteal phase, which occurs after ovulation. 

Towards the middle of the menstrual cycle, the surge in progesterone levels is triggered by the mid-cycle release of luteinizing hormone (LH) towards the end of the follicular phase. This increase in progesterone facilitates a rise in follicle-stimulating hormone (FSH) as well.

During this phase, progesterone levels rise to prepare the uterus for potential pregnancy by thickening the uterine lining and promoting its vascularization. If pregnancy does not occur, progesterone levels decline, triggering menstruation and the shedding of the uterine lining. 

If implantation does occur, progesterone levels continue to rise to support the new embryo in the endometrium.  Progesterone also helps to maintain the pregnancy by supporting the development of the placenta and inhibiting uterine contractions, thereby preventing premature labor.

Impact of Progesterone on Reproduction and Pregnancy

In terms of reproduction and pregnancy, progesterone plays a vital role in maintaining a healthy gestation. It supports implantation by promoting the growth and vascularization of the uterine lining, ensuring a conducive environment for embryonic development. 

Progesterone is produced by the corpus luteum during the early stages of pregnancy; after about week 10, progesterone production shifts to the placenta. Progesterone helps prevent uterine contractions, supports fetal growth, and prepares the breasts for lactation. Additionally, progesterone's role in pregnancy extends beyond the uterus, influencing various physiological processes to ensure maternal and fetal well-being.

Progesterone’s Effects on Mood and Well-being

Progesterone is not only a key regulator of reproduction but also plays vital roles in the nervous system. Its effects in the nervous system are primarily due to its metabolite, allopregnanolone.  [5.]

As a neuroactive steroid, it contributes to the development of neurons and glial cells, as well as the myelination process.  [3., 11., 12.]  Moreover, progesterone demonstrates significant protective effects in neurodegenerative and psychiatric disorders.  [10.]

It interacts with neurotransmitter systems in the brain, particularly the gamma-aminobutyric acid (GABA) receptors.  GABA receptors have inhibitory effects on neuronal activity, leading to feelings of relaxation and tranquility.  [5., 15.]

Fluctuations in progesterone levels throughout the menstrual cycle and during pregnancy can influence mood and emotional stability, and higher levels in pregnancy may support nervous system health in the pregnant woman along with brain development in the baby.  [5.]  

Higher levels generally associated with a sense of calmness and lower levels potentially contribute to mood swings, anxiety, depression, PTSD, and other conditions.  [5., 9.] 

Decreasing progesterone during perimenopause and menopause can contribute to mood changes and sleep problems. Progesterone supplementation during this time may help alleviate these symptoms and restore hormonal balance.  [2., 14.]

Progesterone Testing Methods and Considerations

Blood Testing for Progesterone

Blood testing for progesterone involves collecting a blood sample, typically via venipuncture, and then analyzing the sample to measure the concentration of progesterone in the bloodstream.

Benefits: blood testing for progesterone levels provides a quantitative measurement of progesterone, allowing for precise assessment. Additionally, blood tests are widely available, making them accessible to many patients and healthcare providers. 

Drawbacks: blood levels of progesterone may not always accurately reflect tissue levels, particularly in certain clinical scenarios. Moreover, the timing of the test is crucial due to the fluctuating nature of progesterone levels throughout the menstrual cycle or pregnancy.

Saliva Testing for Progesterone

Progesterone saliva testing involves collecting saliva samples usually through passive drool or using absorbent swabs at specific times of the day.  Often, an at-home testing kit is used to collect samples, which are then shipped to a lab for analysis.   

Benefits: saliva testing for progesterone is a non-invasive method, which can be more comfortable for patients compared to blood draws. Saliva samples may also offer a potentially more accurate reflection of tissue levels, as they capture the free, unbound fraction of the hormone. Saliva testing is also an accurate method of assessment of progesterone levels in people supplementing with progesterone, particularly topical progesterone.  [6.]

Drawbacks: saliva testing for progesterone is less widely accepted in clinical practice. Limited availability of saliva testing and/or cost may also be limitations.

Urine Testing for Progesterone Metabolites

Urine testing for progesterone metabolites involves collecting urine samples over a specified period, often 24 hours.  Progesterone is not typically found in human urine; instead, the metabolites of progesterone are analyzed to provide insights into overall progesterone metabolism and hormonal balance.

Benefits: urine testing for progesterone metabolites provides insights into the overall metabolism of progesterone in the body. This non-invasive method involves analyzing metabolites of progesterone excreted in urine samples. It can be particularly useful in research settings or when assessing overall hormone metabolism patterns. 

Drawbacks: urine testing for progesterone metabolites may not directly measure progesterone levels, making interpretation more challenging. Additionally, its clinical utility may be limited in certain cases where direct measurement of progesterone levels is necessary for diagnostic or monitoring purposes.  

Clinical Considerations and Timing of Progesterone Supplementation

Clinical Applications and Indications for Progesterone Therapy

Progesterone therapy may be prescribed for various clinical indications, including the management of irregular menstrual cycles, amenorrhea, infertility, premenstrual syndrome (PMS), and menopausal symptoms. 

Additionally, progesterone is often used in hormone replacement therapy (HRT) for postmenopausal women to protect the uterine lining and mitigate the risk of endometrial hyperplasia associated with estrogen-alone therapy. 

Furthermore, progesterone supplementation may be recommended during assisted reproductive technology (ART) procedures to support embryo implantation and early pregnancy maintenance.

Time Frame for Onset of Action with Progesterone Pills:

Progesterone supplementation via oral pills is commonly prescribed, although progesterone is also supplemented via transdermal or vaginal cream, gel, or in pellets.  

Oral progesterone may require several days to exert its full effects due to the time needed for absorption and metabolism in the body. The onset of action can vary depending on factors such as the specific formulation of the pill, individual metabolism, and the intended therapeutic outcome. 

While some individuals may experience symptom relief within a few days of starting progesterone therapy, particularly with sleep problems, others may require a longer duration for noticeable improvements.

What Causes Low Progesterone Levels?

Anovulation: irregular or absent ovulation can lead to low progesterone levels.

Stress: Chronic stress can disrupt the balance of hormones, including progesterone through various mechanisms that impair ovulatory function.  [17.]

‍Poor Diet: nutrient deficiencies, especially of zinc, vitamin C, vitamin B6, and magnesium, can affect progesterone production.

‍Hormonal Imbalance: conditions such as polycystic ovary syndrome (PCOS) or thyroid disorders can disrupt progesterone levels.

Aging: progesterone levels naturally decline with age, particularly during perimenopause and menopause.

High blood sugar: elevated blood sugar levels affect many hormones and often plays a role in hormone imbalance.  [18.]

Excessive Exercise: intense or excessive physical activity can affect hormone balance and lower progesterone levels.

Hypothyroidism: the thyroid hormone T3 stimulates progesterone release from the ovary.  [4.]  Hypothyroidism may lower progesterone levels.

Medications: certain medications, including hormonal contraceptives and corticosteroids, may suppress progesterone production.

Environmental Factors: exposure to endocrine-disrupting chemicals in plastics, pesticides, and personal care products can interfere with hormone function, causing increased hormonal symptoms, earlier menopausal transition, and increase the risk of certain cancers.  [NEFF

Natural Strategies to Support Progesterone Levels

Nutritional Support

• Include sources of healthy fats like avocados, nuts, and olive oil in your diet, as these fats support hormone production.
• Incorporate foods high in vitamin B6 such as bananas, potatoes, and poultry, as vitamin B6 plays a role in progesterone metabolism.
• Phytoprogestins are plant-based compounds that may modulate symptoms of hormone imbalance.  Specific foods containing phytoprogestins include vegetables (parsley, celery, onions), fruit (oranges, lemons, and grapefruit), herbs (chamomile, thyme, oregano, basil), and tea.  Additionally, luteolin has emerged as a phyotoprogestin, and is widely available in many plant-based foods.  [7.]

Lifestyle Modifications to Enhance Progesterone Production

• Practice stress-reduction techniques such as mindfulness meditation, yoga, or deep breathing exercises to lower cortisol levels, which can inhibit progesterone production.
• Get regular exercise, aiming for a balance of cardiovascular workouts and strength training, as physical activity can help regulate hormone levels.
• Prioritize sufficient sleep each night to support overall hormone balance and production, aiming for 7-9 hours of quality sleep.

Herbal Remedies and Supplements for Progesterone Support

• Consider supplementing with vitex (chasteberry), an herb known for its ability to support hormonal balance and regulate menstrual cycles.  [16.]
• Evening primrose oil supplements contain gamma-linolenic acid (GLA), which may help support progesterone production.
• Adaptogenic herbs like ashwagandha and rhodiola rosea can help balance hormones and reduce stress, potentially supporting progesterone levels.