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If you've wondered why progesterone makes you feel awful, when your friends rave about it or experience no side effects, read on! Progesterone intolerance occurs when women are extra sensitive to progesterone, which can be either the natural versiof or synthetic versions of progesterone (progestogens).
For women who are progesterone intolerant, synthetic progestogens (and sometimes natural progesterone) can produce negative physical, psychological and metabolic symptoms.
In this article, we will delve into progesterone intolerance, the symptoms, potential causes, and strategies for navigating hormonal balance with sensitivity.
What is Progesterone Intolerance?
Progesterone intolerance refers to a condition where some people are quite sensitive to the effects of progesterone in their body. Progesterone is a natural hormone in the female body but you may be extra sensitive to it's effects as you get a progesterone surge in the luteal phase of your menstrual cycle (the 2nd half of your cycle after ovulation).
Women who are more sensitive to progesterone can experience significant symptoms during their luteal phase or the second hald of your menstrual cycle that occurs between premenstrual symptoms such as premenstrual syndrome (PMS), premenstrual exacerbation of existing symptoms (PME) or premenstrual depression or premenstrual dysphoric disorder (PMDD).
Many women who are sensitive to the effects of natural progesterone, either produced by the body or from natural progesterone HRT, are more sensitive to synthetic progestogens.
If you experience progesterone intolerance, you may experience PMS/PMDD type symptoms while using natural progesterone or a synthetic progestogen. You may have worse symptoms if your estrogen is low while using progesterone.
Physical Symptoms of Progesterone Intolerance
Progesterone intolerance can manifest through a range of symptoms. They can vary between individuals, in severity and duration. The physical symptoms of progesterone intolerance can include:
Mood Swings and Irritability: Some individuals may experience mood fluctuations, ranging from mild irritability to more pronounced mood swings.
Fatigue and Drowsiness: Because progesterone is converted to allopregnanolone in the brain (a calming neurosteroid), it helps induce sleep and should be used before going to bed. For women with increased sensitivity to this, it can induce an exaggerated sense of drowsiness or lethargy.
Breast Tenderness: Increased progesterone levels may lead to breast tenderness or sensitivity.
Headaches or Migraines: Some individuals may be more prone to headaches or migraines in response to elevated progesterone.
Digestive Discomfort: Progesterone has a relaxing effect in the body. In relaxing the gut it can slow digestion, potentially leading to symptoms like bloating, constipation, or diarrhoea.
Fluid Retention: Swelling or bloating, particularly in the extremities, can occur with progesterone intolerance.
Skin Rashes: Some women have another type of reaction with progesterone use: autoimmune progesterone dermatitis. These women experience a rash with exposure to progesterone/progestogens.
It results in a rash in the luteal phase of the menstrual cycle (1-2 weeks before the period starts) or when using progesterone in as a hormone treatment.
Read more about Autoimmune Progesterone Dermatitis.
Psychological Symptoms of Progesterone Intolerance
In addition to physical symptoms, progesterone intolerance can also cause psychological symptoms. These may include:
Anxiety: Elevated levels of progesterone can cause anxiety in some individuals who are sensitive to its effects.
Depression: Progesterone is known to affect neurotransmitters and mood regulation in the brain. For those with increased sensitivity.
Metabolic Symptoms of Progesterone Intolerance
Progesterone intolerance can also manifest through metabolic symptoms. These may include:
Weight Gain: Elevated progesterone levels can sometimes lead to increased water retention and bloating, resulting in temporary weight gain.
Insulin Resistance: Some individuals with progesterone intolerance may experience increased insulin resistance, which increase affect blood sugar levels and increased cholesterol levels.
How common is it to be progesterone intolerant?
Approximately 10-20% of women are progestogen intolerant. It is often experienced in women who use:
the combined contraceptive pill,
the mini pill (progestogen only)
a Mirena IUD (coil), or
some types of HRT.
Types of Progesterone
Micronised Progesterone
This is the type of progesterone that is identical in structure and function to the body’s produced progesterone. It is also known as natural progesterone. It can be derived from plant sources or synthesised in a lab. Utrogestan is the natural progesterone that is available in New Zealand, and the UK. Prometrium is used in Australia. Micronised progesterone is now funded in New Zealand and is generally better tolerated in women who are progesterone intolerant.
Synthetic Progestogens
These are synthetic versions of progesterone, designed to mimic its effects in the body. They are bio-similar but not identical and include:
medroxyprogesterone acetate (MPA)
levonorgestrel,
drospirenone
norethindrone.
Progestin intolerance is more common with synthetic progestins. These synthetic progestogens come in tablet form or in the Mirena which contains levonorgestrel.
Progesterone cream
Currently, there is not sufficient data to support the use of progesterone cream for endometrial protection when using oestrogen for HRT.
Why Is Progesterone Used As HRT?
Progesterone is often used as part of hormone replacement therapy (HRT) for women who are experiencing menopause symptoms. As the body's natural production of progesterone decreases with age, it can help to supplement this hormone to balance out oestrogen levels and alleviate symptoms such as hot flashes and mood swings.
Most people use oestrogen gel, oestrogen patches or oestrogen cream to manage hot flashes and other symptoms of perimenopause and menopause.
Progesterone capsules or a progestogen tablet is essential to use alongside oestrogen as it reduces the risk of developing endometrial cancer.
Managing Progesterone Intolerance
Check in with your Healthcare Provider
If experience symptoms of progesterone intolerance, talk to your healthcare provider. They can review you treatment and recommend alternate options.
Alternative Progesterone Formulations
Women with progesterone intolerance from synthetic progestins/progestogens may tolerate natural progesterone better (such as micronised progesterone/ Utrogestan/ Prometrium).
Alternate Progesterone Delivery Methods
Some women who have difficulty progesterone intolerance orally do tolerate progesterone delivered via alternate methods:
A Mirena coil (IUD) delivers levonorgestrel in low dose locally into the uterus.
Utrogestan or Prometrium (body identical natural progesterone) can be used off licence as vaginal progesterone pessaries, delivering the progesterone directly where it's needed and having fewer system effects.
In some countries such as Australia, you can use a combined oestrogen and progestogen patch (Estalis) so this may also have reduced side effects.
As none of these methods are oral, they are often associated with lower risk of progesterone intolerance.
Alternative HRT products that protect the endoemtrium but do not contain progesterone
There are a number of alternate HRT products available such as Duavive and Tibolone that do not contain progesterone/progestogens.
Duavive is a combination of conjugated oestrogens and bazedoxifene (a selective estrogen receptor modulator - SERM). The estrogens treat the menopause symptoms but the bazedoxifene inhibits the effect of estrogen in the uterus, preventing over-stimulation of the endometrial lining. It is also beneficial for bone health.
Tibolone is a synthetic steroid that has estrogenic, progestogenic, and weak androgenic effects. It could be a great alternative for you.
Reduce Progesterone Dose or Increased Estrogen Dose
Using more estrogen and lower progesterone may give you the benefits of HRT with fewer side effects of progesterone intolerance.
Non-hormonal treatments for menopause
Some women prefer to stop progesterone use altogether. They may use different treatments such as antidepressants, clonidine, gabapentin. Also vaginal oestrogen can be used without the need for progesterone.
Surgical Alternatives
Where other options are not helpful, a hysterectomy would mean you can continue to use oestrogen without the need to use progesterone. However all surgeries including a hysterectomy come with their own risks so make sure you have all your questions answered about this with your gynaecologist.
Monitoring and Communication
Tracking your symptoms helps your health provider support you in making the best decisions regarding your symptoms and your hormone treatment. Let your health are provider know if you have concerns with your treatment.
The Takeaway: Solutions for Progesterone Intolerance
Progesterone intolerance, can be tricky, but there are a number of options available if you are sensitive to progesterone.
If your regular GP/health provider does not have an interest in menopause then you should ask to see someone in the practice who does or consider an appointment with a menopause specialist. They can discuss progesterone intolerance and explore treatment options with you.
As a menopause doctor, Dr Deb Brunt @ Ōtepoti Integrative Health would love to support you through the perimenopause and menopausal stages of life, supporting all aspects of your health and wellbeing.
Dr Deb Brunt is a GP with an interest in menopause and women's health in New Zealand. She has a passion for supporting women adapt to their changing female physiology for optimum health so they are able to live their best life
Dr Deb Brunt | Ōtepoti Integrative Health | Book Appointment
More about Perimenopause and Menopause
References
Panay N, Studd J. Progestogen intolerance and compliance with hormone replacement therapy in menopausal women. Hum Reprod Update. 1997 Mar-Apr;3(2):159-71.
Shantha S, Brooks-Gunn J, Locke RJ, Warren MP. Natural vaginal progesterone is associated with minimal psychological side effects: a preliminary study. J Womens Health Gend Based Med. 2001 Dec;10(10):991-7.
Li RC, Buchheit KM, Bernstein JA. Progestogen Hypersensitivity. Curr Allergy Asthma Rep. 2018 Jan 19;18(1):1.
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