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Understanding Progesterone Intolerance: Could Genetics Be the Key?

Updated: 4 days ago

Hormones play a crucial role in regulating numerous bodily functions, and progesterone is one of the key players, especially in reproductive health. However, not everyone responds well to this hormone. Some individuals experience what is known as progesterone intolerance, manifesting as adverse reactions or heightened sensitivity to progesterone or progestin-based therapies. But why does this happen? Emerging research suggests that genetics might be a significant factor.

The Genetic Basis of Progesterone Intolerance

1. Hormone Receptor Variants:

- Variations in the genes encoding progesterone receptors (such as the PGR gene) can affect how an individual's body responds to progesterone. These genetic differences might alter receptor sensitivity or function, leading to varying degrees of tolerance or intolerance to the hormone.

2. Metabolism Pathways:

- The metabolism of progesterone is influenced by enzymes encoded by specific genes, such as the CYP450 family (e.g., CYP3A4). Variations in these genes can affect how progesterone is processed in the body, influencing the levels of active hormone in the bloodstream and tissues, and potentially leading to intolerance.

3. Neurosteroid Effects:

- Progesterone is a precursor to neurosteroids, which have significant effects on the brain and nervous system. Genetic differences in enzymes that convert progesterone to neurosteroids (e.g., 5α-reductase) might impact neurological responses to progesterone, contributing to symptoms of intolerance.

4. Immune System Interactions:

- Progesterone has immunomodulatory effects. Genetic variations in immune-related genes might influence how an individual's immune system responds to progesterone, possibly leading to adverse reactions.

5. Polymorphisms and Epigenetic Factors:

- Specific polymorphisms or epigenetic changes in genes regulating hormone synthesis, transport, and receptor function could contribute to variability in progesterone sensitivity.

Symptoms of Progesterone Intolerance

Individuals with progesterone intolerance may experience a range of symptoms, including:

- Mood Changes: Anxiety, depression, irritability, or other mood disturbances.

- Physical Symptoms: Bloating, breast tenderness, headaches, or migraines.

- Menstrual Irregularities: Changes in menstrual cycle patterns or severity of premenstrual symptoms.

Addressing Progesterone Intolerance

  1. Using progesterone capsule vaginally can help reduce or eliminate the side effects. This is an off label use of the oral progesterone capsule (Prometrium in Australia), (Utrogestan in UK). If you are menopausal, your doctor may advise you to use Prometrium vaginally every other day. If you are Peri menopausal, use one daily vaginally for 2 weeks, then 2 weeks off and you will have a period. You then go back to oral route after the 3rd month.

  2. Monitoring and Support:Regular monitoring of symptoms and supportive care, including lifestyle modifications and possibly the use of adjunctive therapies to manage side effects, can be beneficial. Usually the progesterone intolerance seems to significantly improve and resolve by 3 months of using progesterone.


Progesterone intolerance can significantly impact an individual's quality of life.

Individualised care, can improve outcomes and enhance the well-being of those affected by progesterone intolerance.

By Dr Purity Carr

GP & Menopause Doctor

Harvey, WA 6220

0481 333 224

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1 комментарий

Неизвестный пользователь
17 мая

This is me, I can not use progrestrone I get Migraines from hell !

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