Some of those taking progesterone as part of their HRT may experience symptoms due to progesterone intolerance. But what is it? How do you know if have it and what can you do?
We were joined by Dr Abbie Laing of My Menopause Centre, rated ‘outstanding’ by the Care Quality Commission, to find out more.
Henpicked: Can you tell us more about progesterone and what it does?
Dr Abbie Laing: Progesterone is a naturally occurring hormone produced by the ovaries. It plays an important role in the menstrual cycle and has an effect on the womb lining which is called the endometrium. It is used as part of HRT in women who still have their womb (uterus). This is because oestrogen makes the lining of the womb grow and progesterone reverses this, keeping the womb lining thin and healthy. If a woman with a uterus took oestrogen alone, without taking a progesterone, the womb lining would grow and over time this could turn into a womb cancer.
Henpicked: For those who don’t have a womb but are on HRT, would they be given progesterone?
Dr Abbie Laing:
Most individuals who have had a hysterectomy do not need to take a progestogen. This is because their womb lining has been removed. There can however be two exceptions to this rule:
- If a person has had a subtotal hysterectomy their womb will have been removed but their cervix will have been left in place. In this situation sometimes there can be womb lining left behind in the residual cervix and a progestogen would still be needed if this is the case.
- If a person has had a total hysterectomy meaning their womb and cervix has been removed but they still have endometriosis then these endometriosis deposits can grow in response to oestrogen treatment. A progestogen should be given to prevent this.
Henpicked: How is progesterone given in HRT?
There are lots of different types of progestogens and they differ by their molecular structure. The easiest way to remember this is that at one end of the scale there is body identical progesterone (Utrogestan) which is identical in structure to our natural progesterone and then at the other end of the scale there are progestogens that are more similar in structure to testosterone. These are termed more androgenic progestogens.
Body identical progesterone (Utrogestan) is a common progesterone that is given first line in many HRT regimes. It comes as a capsule that you swallow in the evening because it can be sedating. In general, it tends to be quite a well-tolerated progesterone, although not always.
The Mirena coil is another progestogen. This can be used as the progestogen arm of HRT for up to 5 years and contains a progestogen in it called levonorgestrel. It releases a small dose of levonorgestrel into the womb daily and most of it is absorbed into the endometrium with only small levels passing into the blood stream. Because the coil is associated with very low blood levels of a progestogen it usually has fewer side effects.
There are two combination patches available. These patches contain oestrogen and a progestogen built into it together. They care called Evorel Sequi or Conti and FemSeven Sequi or Conti patches. The progestogens in these are either norethisterone or levonorgestrel.
There are also other tablet progestogens that can be prescribed called norethisterone or provera and sometimes two minipills are used but this is an off-license regime.
You might sometimes hear about progesterone creams however there are concerns that these are not well absorbed and therefore their use is not recommended.
Henpicked: Are many people intolerant to progesterone?
Dr Abbie Laing: As a general rule of thumb, I find that about 10% of women feel better on progesterone, 10% of women feel worse on it and 80% of women feel the same.
In general body identical progesterone is usually quite well tolerated. Although, this is not always the case and it is possible for a person to not get on with their own natural progesterone. Signs that might suggestive this are if you have a history of PMS or PMDD because the week before your period is a time when natural progesterone levels are high.
Sometimes I do think a person can grow into progesterone intolerance or have worsening symptoms of progesterone intolerance in the menopause transition. This has not been well studied but one line of thought is that a progesterone is less well tolerated if oestrogen levels are reduced.
Henpicked: What are the symptoms associated with progesterone intolerance?
Dr Abbie Laing: The first thing is to find someone with a menopause interest as it’s quite a nuanced subject, so find the right person. They can confirm the diagnosis. If you remove your progesterone for a short period of time and you’re fine then you know that’s likely to be the problem. We can then retry the progesterone with an increased dose of oestrogen. Mild side effects often improve within a few months. But if you’re really struggling, then you could try a different type of progesterone.
When I first start someone on HRT I commonly start one hormone at a time. For example, by introducing a transdermal oestrogen first and then a progestogen 1-2 weeks later. This helps to identify cause and effect with any symptom improvement but also with side effects such as a progestogen intolerance.
Side effects can be split into those that affect mood or those that cause physical symptoms.
Side effects that affect mood include anxiety, irritability, restlessness, panic symptoms, depression, apathy, poor concentration, forgetfulness and lethargy. In some very severe cases people can develop suicidal thoughts. Usually there is a clear time scale between starting a progestogen and the onset of symptoms. Sometimes I have seen however it take a few weeks for these side effects to settle after stopping a progestogen.
Side effects that cause physical symptoms can be related to fluid retention and include bloating, weight gain, abdominal cramps, nausea and breast engorgement. Other side effects include headaches, dizziness, acne and greasy skin.
While all progestogens can cause mood changes, those more similar in molecular structure to testosterone are more likely to cause physical side effects.
Henpicked: How can people manage an intolerance?
My first piece of advice would be to find a clinician with an interest in the menopause who would be able to work with you through this.
If you suspect that you have a progestogen intolerance you could remove your progestogen just for 1-2 weeks to confirm the diagnosis. If you feel better this would support this. Long term however a progestogen is needed to protect your womb lining and so this can only be done on a short-term basis.
It can be helpful sometimes to optimise your oestrogen levels for a few weeks before reintroducing a progestogen back in. Sometimes a progestogen is better tolerated if oestrogen levels have been optimised first.
If you are getting side effects that are mild then often these will improve within a few months and therefore in this situation I would usually advice to persist with it and let time help. However, if you are really struggling with side effects then I would recommend you stop that type of progestogen a try a different one.
It can sometimes be helpful to look back at your contraceptive history and see if there has ever been a progestogen that you have got on with before. For example, if you felt well using microgynon or rigevidon in the past, this might suggest that you will tolerate levonorgestrel.
Sometimes body identical progesterone (Utrogestan) is given by the vaginal route. This is off license but has been supported by the British Menopause Society. When using it by this route the same dose as the oral route should be tried first. Using progesterone by the vaginal route can be associated with fewer side effects because the enzymes in the gut metabolise progesterone into an intermediate molecule that can cause side effects in some people. These enzymes are not present in the vaginal skin.
If you have tried most or all the different progestogens and you continue to have symptoms of progestogen intolerance then there can be consideration to reduce the progetogen dose. For example, by using a half dose or taking progesterone for two weeks every 3 months (quarterly regimes). This is unlicensed and there is not enough evidence to confirm that taking reduced doses will protect the lining of the womb. Therefore, I would advise undertaking low dose regimes under specialist supervision with an annual ultrasound scan arranged to monitor the endometrial thickness. If using a low dose progestogen regime there should also be a low threshold to monitor for any bleeding.
If someone is unable to tolerate taking a progestogen every 3 months then a hysterectomy can be considered. This would usually be a last resort.
Henpicked: Is there an alternative to HRT?
Dr Abbie Laing: Alternatives to HRT include lifestyle changes, herbal remedies and non-hormonal prescribable alternatives.
Lifestyle changes can have an enormous positive impact on quality of life and the effect of investing time into this cannot be underestimated. It includes embracing self-care measures and relaxation techniques, exercising, eating well, avoiding refined sugars and caffeine, minimising alcohol, encouraging a good sleep hygiene and embracing positive mental health strategies such as using CBT and mindfulness.
Herbal remedies can be helpful for symptoms however they have not always been subject to robust safety tests. You should look for the symbol THR if using these which stands for the traditional herbal registration and indicates some form of safety testing. Femal is an example, this is a bee pollen extract that has been shown to help with hot flushes and sleep. Some women get benefit from using magnesium supplements which can help with sleep.
There are lots of prescribable alternatives to HRT which can help with some menopausal symptoms. Oxybutynin is an example which can reduce hot flushes and improve urinary urgency. Amitriptyliine can sometimes help with sleep and body pains. Hyalofemme is a vaginal gel that can improve dryness and contains hyaluronic acid.
Henpicked: There have been some shortages of progesterone lately. What would you recommend?
Dr Abbie Laing: There are some shortages of the body identical progesterone (Utrogestan) at the moment. If you want to continue using this type of progestogen you could switch to a vaginal pessary version such as Cyclogest or Lutigest. These are not licensed but have been supported by the British Menopause Society.
If you have been considering having a mirena coil inserted then this might be a good time to have this done. The mirena coil can be used for 5 years as the progestogen arm of HRT, provides contraception and in most women stops bleeding episodes.
If you are using a patch then you could switch to a combination patch. Combination patches can be cut in half to adjust the dose accordingly. For example, you can wear 1.5 Evorel Conti patches this will give you 75mcg of oestrogen or 2 Evorel Conti patches will give you 100mcg of oestrogen.
There are other progestogens that can be used such as Provera or Norethisterone. Norethisterone is not recommended however if your BMI is greater than 30.
Another option is to use two minipill tablets such as two cerelle or cerazette daily. This is not licensed but has been demonstrated in other pills to protect the endometrium.
Henpicked’s Michelle Gascoine was joined by Dr Abbie Laing of My Menopause Centre, rated ‘outstanding’ by the Care Quality Commission.
Dr Abbie graduated from the University of Bristol in 2011 in medicine and also holds a Bachelor of Science in Neuroscience. She has always been drawn to women’s health and initially worked in Obstetrics and Gynaecology both overseas in Perth Western Australia and within the UK. She then chose to undertake training in General Practice and completed the Diploma in Sexual and Reproductive Health and the Advanced Menopause Specialist certificate from the Faculty of Sexual and Reproductive Health. She also achieved the Southampton Richard Percival MRCGP excellence award for her GP training.
As well as her work with My Menopause Centre, she also works within an NHS menopause centre. She looks forward to each of her consultations, talking with each person about their individual journey and making decisions together. Her hope is for women to achieve a positive experience during their menopause transition and feel empowered with their choices.
Check out the rest of Henpicked’s Lunch & Learn video series!
Available from Bloomsbury, Waterstones, Amazon and good bookshops.
