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Understanding Progesterone Intolerance


Progesterone is a hormone that plays a crucial role in the female reproductive system and pregnancy. It is produced primarily by the ovaries, although small amounts are also produced by the adrenal glands and the placenta during pregnancy.

Progesterone helps regulate the menstrual cycle and prepares the uterus for pregnancy by thickening the lining of the uterus to support implantation of a fertilised egg. If fertilisation occurs, progesterone continues to be produced to maintain the uterine lining and support the developing embryo. In pregnancy, progesterone also helps prevent contractions of the uterus that could lead to premature labour.

In addition to its role in the female reproductive system, progesterone also has other functions in the body. It helps regulate various metabolic processes, supports the development of breast tissue during puberty and pregnancy, and can have effects on mood and emotions.

Progesterone levels fluctuate throughout the menstrual cycle, peaking during the second half of the cycle after ovulation. If pregnancy does not occur, progesterone levels drop, triggering menstruation and the start of a new menstrual cycle.

Progesterone and hormone replacement therapy (HRT)

In hormone replacement therapy (HRT), progesterone is often used in combination with oestrogen to protect the uterus.  When oestrogen is used alone in HRT, it can increase the risk of endometrial (uterine) cancer. Progesterone is added to oestrogen therapy to counteract this effect and protect the lining of the uterus. Progesterone helps to regulate the growth of the uterine lining and reduces the risk of abnormal cell growth that can lead to cancer.

Progesterone's effect on mood

Progesterone can have various effects on mood due to its influence on the nervous system and neurotransmitter activity. Here are several ways progesterone can impact mood:

  1. Calming effect: Progesterone has been shown to have a calming effect on the brain. It acts on gamma-aminobutyric acid (GABA) receptors, which are inhibitory neurotransmitter receptors in the brain. By enhancing GABA activity, progesterone can help reduce anxiety and promote relaxation.

  2. Anti-depressant properties: Progesterone may have anti-depressant effects by modulating the activity of serotonin, a neurotransmitter involved in mood regulation. Studies have suggested that fluctuations in progesterone levels during the menstrual cycle and menopause may contribute to mood changes, including symptoms of depression.

  3. Stress response: Progesterone can influence the body's response to stress. It interacts with the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in regulating stress responses. By modulating the HPA axis, progesterone may help dampen the stress response and promote resilience to stressors.

  4. Oestrogen balance: Progesterone works in tandem with oestrogen to maintain hormonal balance in the body. Fluctuations in progesterone levels relative to oestrogen levels can impact mood. Oestrogen dominance or deficiency, in combination with progesterone levels, can contribute to mood swings, irritability, and other emotional symptoms.

  5. PMS: Progesterone levels fluctuate throughout the menstrual cycle, peaking during the luteal phase (the second half of the cycle). Changes in progesterone levels during this time can influence mood and emotions, leading to premenstrual symptoms such as irritability, anxiety, and mood swings.

  6. Pregnancy and postpartum: Progesterone levels rise significantly during pregnancy and play a role in regulating mood and preparing the body for childbirth. After childbirth, fluctuations in progesterone levels can contribute to postpartum mood disorders such as postpartum depression and anxiety.

It's important to note that individual responses to progesterone can vary, and factors such as genetics, hormonal balance, stress levels, and overall health can influence how progesterone affects mood. If you experience significant mood changes or symptoms of depression or anxiety, it's essential to discuss them with a healthcare professional for evaluation and appropriate management.

Progesterone Intolerance

Progesterone intolerance refers to a condition where the body has difficulty tolerating or processing progesterone. This intolerance can manifest in various symptoms, which can vary in severity among individuals. Some common symptoms of progesterone intolerance may include:


  • Irregular menstrual cycles: Women may experience irregular periods or changes in menstrual flow.

  • Mood swings: Fluctuations in progesterone levels can lead to mood changes, including anxiety, irritability, or depression.

  • Headaches: Some individuals may experience headaches or migraines as a result of progesterone intolerance.

  • Fatigue: Feeling tired or fatigued, even after getting enough rest, can be a symptom of progesterone intolerance.

  • Breast tenderness: Progesterone can cause breast tissue to become swollen or tender in some individuals.

  • Bloating: Progesterone can cause water retention and bloating in some people.

  • Acne: Fluctuations in hormone levels, including progesterone, can contribute to acne breakouts.

  • Digestive issues: Some individuals may experience digestive symptoms such as nausea, constipation, or diarrhoea.


It's essential to note that these symptoms can also be caused by other factors or medical conditions, so it's essential to consult with a healthcare professional for an accurate diagnosis and appropriate treatment if you suspect progesterone intolerance.

If you suspect that you have progesterone intolerance while using hormone replacement therapy (HRT), it's crucial to discuss your symptoms with your healthcare provider as adjustments to your HRT will help resolve this adverse effect.

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