Progesterone intolerance Factsheet

What is it?

Progesterone intolerance is when you are particularly sensitive to the hormone progesterone or ­most likely ­it’s synthetic form, progestogen. The body reacts to the progesterone or progestogen, causing symptoms that can be similar to premenstrual syndrome.

What are the symptoms?

Symptoms of progesterone intolerance can be grouped into 3 main areas – psychological, physical and metabolic. Some types of progestogens are known to cause more physical or metabolic side effects, while other types are associated with more psychological reactions.

Possible psychological effects are anxiety, irritability, aggression, restlessness, panic attacks, low mood, poor concentration, forgetfulness, and heightened emotions. Physical consequences of progesterone intolerance can be acne, greasy skin, abdominal cramping or bloating, fluid retention, fatigue, headaches, dizziness, and breast tenderness. Metabolic reactions are when progestogens have a negative effect on systems that produce or regulate cholesterol, blood pressure and blood sugar levels. Progesterone does not usually have these effects.

Symptoms of progestogen intolerance affect around 10-­20% of women and it’s often seen in women who use contraception such as the combined pill, the mini­pill, an IUS (coil), or in women who take some types of HRT.

Types of progesterone and associated risks

There are two main types of progesterone: progesterone and progestogen. Progesterone is body identical, meaning it’s identical in structure to the natural progesterone hormone produced by your ovaries. It is derived from the yam root vegetable.

Progestogen, however, is synthetic (created chemically and structurally different to progesterone) and is the type that is used in all forms of contraception. Symptoms of intolerance are much more common with synthetic progestogens.

There are also more risks associated with progestogens than progesterone. Synthetic progestogens have been found to have a small risk of blood clot, heart disease and breast cancer. It is worth noting that these risks are very small, and your actual risk of such diseases depends much more on your overall health, genetics, weight, and lifestyle habits.

Progesterone as part of HRT

Most women need to take a form of progesterone if they are taking replacement estrogen and still have their womb. This is to counteract the effect of the estrogen, keep the lining of the womb thin and healthy, and minimise the risk of the cells in the lining turning cancerous.

If you had a period within the last 6 to 12 months, you will usually be given a cyclical regime of progesterone (or a progestogen). This is where you take progesterone for two weeks and then have a two­week break from taking it, to allow your womb to bleed for a few days, as this keeps the lining healthy. If it has been more than 6 to 12 months since your last period, you will usually take progesterone (or a progestogen) continuously, with no breaks.

You may notice you feel worse for the two weeks you take progesterone or notice a change when you first start taking it continuously. Some women react to certain types of progesterone/progestogen but don’t react the same way to other types. Some women show signs of intolerance to all types of progesterone, including what is released naturally by their ovaries.

Unfortunately, progesterone (or a progestogen) intolerance symptoms are a very common reason why women decide to stop taking their HRT, as the progestogen (or progesterone) part can make them feel so dreadful.

What can be done?

Systemic progesterone – absorbed by the whole body
You are less likely to get a negative reaction if the progesterone you take is body identical. Micronised progesterone (known as Utrogestan in the UK) is a capsule that you swallow and is body identical. It is the preferable one to take – especially if you are intolerant to progesterone.

Some women may still have a reaction on this type and then it’s worth discussing changing the dose, the way you take it or the number of days you take it, with your doctor, to see if you can improve any symptoms of intolerance. Make sure you always discuss any changes to your progesterone regime with your doctor as you may feel like reducing the number of days you take it, but you need to make sure it will still do the job of keeping your womb lining thin and healthy. Irregular bleeding can also be common if the progesterone routine is changed.

Local progesterone – released into the vagina or womb
Another way to take progesterone is to insert the tablet vaginally, at nighttime. This then works locally near your womb, where it is needed, and is not digested or absorbed into your whole body, so there is less chance of side effects. The dose of using progesterone this way is half the oral dose (so, for example, you can use one 100mg Utrogestan capsule vaginally alternate evenings). While the drug is not licensed to take in this way, it is perfectly safe to do so and there is good evidence to support its use this way.

There are progesterone pessaries available, such as Cyclogest or Lutigest, (more commonly used as part of fertility treatments) that contain progesterone and are specifically designed as vaginal pessaries. Some women find these preferable to use, instead of the Utrogestan vaginally.

A good alternative to Utrogestan is to have the Mirena coil fitted. This is a small plastic device that is inserted into your uterus and it stays there for 5 years, releasing a low and steady dose of progestogen straight into your womb where you need it most. This does a good job of keeping the womb lining thin and healthy (if you’re taking estrogen) and is also an excellent contraceptive if you need that too.

Some women do react to the progestogen in the Mirena; when it’s first inserted it can feel like you have PMS for the first few months. Any reaction tends to settle down at around 3 to 6 months and most women do not continue to have symptoms of intolerance after this.

Surgical intervention for severe cases of progesterone intolerance
If changing the type, dose and the way you take progesterone or progestogen has not helped, and symptoms are still severe and causing a major impact on your life, the very last thing left to try is to remove the womb entirely and have a hysterectomy. This means you can continue with the estrogen part of your HRT and then you don’t need to take any progesterone (in most cases). If you have your ovaries removed as well as your womb, you will not produce any progesterone yourself naturally either. This is obviously a very serious decision – you need to be aware of all the pros and cons of having a hysterectomy and discuss it in full with a gynaecologist before deciding about this.

If you are struggling with symptoms of progesterone intolerance because of your contraception or your HRT
regime and want to see if anything can be done to help you feel better, see your doctor or healthcare professional about it.

If your usual doctor does not have an interest in menopause then you should ask to see someone who does or consider an appointment with a menopause specialist to discuss progesterone intolerance and treatment options in greater depth.