Progesterone Imbalance: Signs & Treatments

Often referred to as the "pregnancy hormone," progesterone plays a vital role in female fertility and reproductive function. In fact, progesterone levels in a pregnant woman can reach ten times that of a non-pregnant woman!

Yet, progesterone has many other functions in the female and male bodies that aren't widely recognized. Therefore, understanding the impact of this hormone is essential for both sexes to enhance fertility and optimize their overall health.

This article will explore progesterone and the critical factors of how it's regulated and managed.

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What is Progesterone?

Progesterone is a natural steroid hormone (chemical messenger) with 21 carbon rings. It belongs to the progestogens group (hormones with a similar action to progesterone). You may also have heard of progestins. These are synthetic hormones that have comparable action to progesterone.

Progesterone is formed from cholesterol. It is produced mainly in the corpus luteum of the ovaries and in the testes but is also made in the placenta and adrenal glands. One of the main functions of progesterone is to regulate pregnancy and menstruation.

Progesterone's Role in Menstruation

Progesterone is secreted by the ovaries to prepare the inner lining of the uterus (endometrium) for pregnancy. It also inhibits muscular contractions that prevent the egg's adherence to the uterine wall.

If an egg is not fertilized, the ovaries will cease secreting progesterone.

After a few days, the drop in progesterone levels causes the endometrial lining to break down, ensuing with menstruation.

Progesterone's Role in Pregnancy

Following the implantation of a fertilized egg, the placenta (an organ produced by the developing embryo) supports additional progesterone production.

During pregnancy, progesterone influences the production of inflammatory mediators, such as white blood cells, to ward off infectious threats to the developing embryo and fetus.

After the baby is born, progesterone supports milk production for nourishment.

Progesterone's Role in Males

In males, progesterone facilitates sperm development and androgen synthesis (including testosterone). It facilitates the process of capacitation ( the interaction of the sperm with the egg).

Progesterone also decreases the risk of developing an enlarged prostate (benign prostate hyperplasia).

Progesterone's Role in Reproduction

Progesterone also plays a role in reproduction in other ways. It causes an increase in the mucous lining of the cervix and thickens it. This provides a barrier for sperm to penetrate through, preventing additional fertilizations. It also plays a role in immunity, protecting the cervix from infections.  

Progesterone's Role Systemically

Progesterone may also have a protective role in osteoporosis and in preventing nervous system disorders in both sexes. It has been touted to protect a woman from breast cancer and other female problems resulting from unopposed estrogen.

Allopregnanolone, a downstream progesterone metabolite, also has been found in some studies to support mood. This is through modulation of the GABAa (Gamma-aminobutyric acid) receptors in the brain. Therefore, when progesterone decreases, it can lead to lower levels of this calming neurotransmitter GABA. For this reason, progesterone has been said to have anti-anxiety and antidepressant effects.

At the systemic level, progesterone has other important functions, including:

1. Increasing urination (through interacting with the renin-angiotensin system)

2. Decreasing metabolic rate (catabolic)

3. Relaxing smooth muscle cells

5. Increasing the excretion of calcium and phosphorus

6. Raising basal body temperature

7. Sedative and pain-reducing (analgesic) effects

8. Improving visual memory

9. Supporting skeletal health (through the proliferation and differentiation of osteoblasts and bone cells)

10. An immunosuppressive effect (likely to prevent an immune response to egg implantation

How is Progesterone Controlled?

Hormones are regulated in two ways within the body. One way is direct. In this case, an endocrine gland releases its message straight to its target organ in response to its assigned cue.

The second way hormones are controlled is through a feedback loop between two or more endocrine glands. In this process, one gland releases a hormone that influences another gland's hormonal output. This then alters the feedback to the target tissue. This is the way progesterone is regulated. Specifically, your hypothalamus, pituitary gland, and gonads (ovaries and testes) interact in a three-way signaling process that influences the amount of progesterone secreted.

A women's ovaries are the primary source of estrogen and progesterone production. Once puberty is reached, the levels of these sex hormones impact the hypothalamus and its release of the gonadotrophin-releasing hormone (GnRH). When estrogen levels are high, GnRH stimulates a higher level of GnRH. This decreases follicle-stimulating hormone (FSH) and increases luteinizing hormone (LH) by the pituitary. These changes cause the release of the egg (ovulation). Ovulation then signals the release of more GnRH, and estradiol levels decline in response.

Around day 14 of a women's menstrual cycle, estrogen levels are lowered, and progesterone levels become higher. This is due to a surge in LH that triggers the corpus luteum of the ovary (which is the area in the ovary that produces most of the progesterone) to form. High progesterone levels also increase FSH. These actions create the surge in progesterone needed to prepare the body for pregnancy.

At this point, if the egg becomes fertilized by sperm and gives rise to an embryo, the placenta will begin to secrete human chorionic gonadotropin (hCG). hCG is similar in structure to LH and activates the same receptors. This ensures that the uterine lining will not shed and that the womb stays strong and capable of holding the developing baby. If the egg is not fertilized, and menses ensues, FSH levels drop in response to the rise in estrogen, and the cycle continues into the following months.

In the males, GnRH stimulates LH and FSH. LH affects testosterone and androgen production, and FSH influences sperm production in the testicles. As testosterone levels increase, GnRH production ceases to help maintain normal levels. Progesterone's role, as the precursor to testosterone, is to suppresses more LH and FSH secretion.

Progesterone Levels

Below are normal, high, and low ranges of progesterone and what imbalances in levels could signify.

The following are normal ranges of progesterone based on certain phases of the menstrual cycle and pregnancy: (7-8)

• Female (pre-ovulation): less than 1 ng/mL
• Female (mid-cycle): 5 to 20 ng/mL
• Male: less than 1 ng/mL
• Postmenopausal: less than 1 ng/mL
• Pregnancy 1st trimester: 11.2 to 90.0 ng/mL
• Pregnancy 2nd trimester: 25.6 to 89.4 ng/mL
• Pregnancy 3rd trimester: 48 to 150 to 300 or more ng/mL
  

High Progesterone Levels May Indicate: (7-8, 15)

• Pregnancy
• A cyst in the ovaries
• A disorder in the adrenal glands (rare)
• Ovarian cancer (rare)
• Excessive levels of stress
  

Lower Progesterone Levels May Indicate: (7-8)

• Ectopic pregnancy
• Miscarriage
• Irregular Cycle
• Absence of menstruation (amenorrhea)
  

High Progesterone Symptoms

The following symptoms have been associated with levels of higher progesterone. They may be warning signs of high progesterone levels if occurring frequently:

• Lower sexual interest – studies report that during times of high levels of progesterone, there is less interest in sexual activity in women.
• Emotional eating and cravings
  

Low Progesterone Symptoms

Due to progesterone's role in preparing the uterus for pregnancy and regulating menstruation, many symptoms of low progesterone women may experience are linked to fertility and reproduction. Low progesterone symptoms include: (2-6)

• Abnormal uterine bleeding
• Irregular or missed periods (anovulation)
• Spotting and abdominal pain during pregnancy
• Frequent miscarriages
• Early labor
• PCOS
• High estrogen symptoms (decreased sex drive, weight changes, gallbladder issues)
• Mood fluctuations and worsening of PMS (premenstrual syndrome) and PDD (Premenstrual Dysphoric Disorder) symptoms. One study found lower levels of salivary progesterone have been linked to more irritability, aggressiveness, and fatigue in women

Progesterone as a Medication and Treatment

According to a review article on progesterone in perimenopause and menopause, there are currently several well-known indications for progesterone administration. These include:

• primary or secondary amenorrhea
• infertility due to known corpus luteum insufficiency
• treatment of endometriosis
• treatment of fibrocystic mastopathy
• treatment of premenstrual syndrome
• supporting the luteal phase during IVF treatment (IVF: in vitro fertilization)
• prevention of pregnancy loss
• protection of the endometrium during HT (hormone replacement therapy) with estrogen
  

Recently, it was also recommended by the French National College of Gynecologists and Obstetricians (CNGOF) and the French Menopause and Hormonal Aging Study Group (GEMVI) that during perimenopause, progesterone-only treatment dydrogesterone (Duphaston) should be taken on ten days per month for women with cycle irregularities to reduce to the risk of endometrial cancer.

Bioidentical Hormone Replacement Therapy (BHRT) is another FDA-approved option for hormone therapy (HT). These options include estradiol, estrone, and MP (micronized progesterone). Several studies have recently shown that micronized progesterone is tolerated better than synthetics. Many view BHRT to be a more natural alternative to conventional HT. Still, controversies do exist between various experts.  

HT and BHRT can come with side effects such as weight changes, fatigue, headaches, and breast tenderness. Several serious risks with use also must be considered. These include blood clots (venous thromboembolism, gallbladder disease, stroke, and breast cancer. Dosage and use must be personalized by a physician based on the individual. (24-27, 31)

How to Test for Progesterone Levels?

Obtaining a baseline measurement of sex hormones and adrenal function can help determine progesterone levels and their interactions with these and other hormones. These tests can be used to personalize nutritional and hormonal supplemental support.

Each type of hormonal test, blood, salvia, and urine, has been touted to have unique advantages and disadvantages. Salivary tests measure free hormones, whereas serum tests measure bound hormones. Urinary tests measure hormonal metabolites and assist with determining how one processes hormones.

Tests are often chosen based on practitioner preference and experience. Below are examples in each category.

• A urine test provides a comprehensive analysis of a patient's hormone levels and can help monitor hormone replacement therapy. It evaluates free cortisol patterns, organic acids, melatonin, and 8-OhdG, along with androgen, progesterone, estrogen, cortisol, and cortisone metabolites. This test.
• Serum blood tests can assess 13 sex hormones and related biomarkers important in women's and men's health.
• Saliva Profile can also provide a baseline assessment of four sex and adrenal hormones, plus cortisol, and be correlated to blood and urine markers.
  

How is Low Progesterone Treated?

Due to their system-wide impact and the many influences hormones have, our body has complex feedback mechanisms to regulate them. For these reasons, functional medicine practitioners will often focus on the lifestyle, behavioral, and foundational support mentioned below before assessing the need to incorporate HT or BHRT. The process starts with the least invasive and lowest risk interventions to see if the body can come into balance more naturally.

Reducing Stress

Excessive stress can increase levels of stress hormones, such as cortisol, which can negatively impact the ovaries and sex hormones. This is why high levels of stress are often linked to menstrual irregularities. Meditating, exercising, breathing techniques, journaling, and essential oils (aromatherapy) can help reduce stress levels. What works for a person will vary from individual to individual.

Sleep

Stress can impact sleep which also plays a role in regulating hormone levels and balance. Prioritizing sleep and practicing good sleep hygiene are essential for everyone, especially those with hormonal issues. Adults generally need 7–9 hours of sleep every night.

(The Right Amount of) Exercise

Whereas moderate and healthy levels of exercise can relieve stress and support progesterone levels by lowering cortisol, overexercising can have the opposite effect. Strenuous or excessive activity has been associated with changes in ovulation that can interfere with conceiving. If cortisol levels are high in a man or woman, or if a woman is looking to become pregnant, one should moderate intensity in activity and limit vigorous exercise.

Nutrition

Environmental exposures in food including hormones, antibiotics, and pesticides, can alter hormones. Eating a diet that is lower in chemicals, preferably organic, and rich in whole foods can help to remedy endogenous exposures that can alter hormonal levels.

Diet can also influence hormonal health and ovulation based on specific nutrients needed to synthesize and regulate these hormones. Two examples are vitamin B6 and zinc. A person may find that having a diet rich in these foods could help reduce symptoms of low progesterone and regulate the menstrual cycle.

Vitamin B6

Vitamin B6 plays a role in liver function, which regulates hormonal levels and excretion. It also impacts anterior pituitary hormones, which affect progesterone levels.

Foods that contain vitamin B6 include:

• chickpeas
• tuna
• spinach
• bananas
• potatoes
• lean red meat
  

Zinc

Zinc plays a role in hormone production. It is involved in fertility in men and women and the development of the body during pregnancy.

The following are examples of foods rich in zinc:

• cashews
• almonds
• chickpeas
• kidney beans
• shellfish
  

Herbs

Chaste berry: (Vitex Agnus-cactus)- Low doses of this herbal extract have been found to decrease estrogen levels and increase progesterone and prolactin levels. This is most likely caused by inhibiting the release of follicle-stimulating hormone (FSH) and stimulating luteinizing hormone (LH) levels. *Note: Higher doses seem to have the opposite effect.

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Summary

Progesterone is a vital hormone that plays a role in fertility and has systematic effects in women and men. Understanding its effects, regulation, and evaluating levels in the body can help one search for underlying hormonal and metabolic issues and address the root cause of symptoms.

Although HT and BHRT can be helpful when one's progesterone level is low, balancing lifestyle factors such as stress, exercise, sleep, diet, nutrients, and herbs are vital to addressing some of the underlying root causes of the imbalance. Once these are dialed in, if necessary, any additional supplementation with progesterone will be more beneficial.