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A study published in the British Medical Journal (BMJ) in January 2019 found that hormone replacement therapy (HRT) hormones absorbed through the skin are safer than HRT hormones swallowed as a tablet or capsule. The large observational study, based on women in the UK aged 40 to 79 years, provided information on the risk of a blood clot in the legs or to the lungs (venous thromboembolism) in women taking different types of HRT. This study showed that transdermal HRT (absorbed through the skin) isn’t associated with any increased blood clot risk. With oral products, however, there is a risk of blood clots; this varies with type of oestrogen, type of progestogen and the doses used.

This article was included in issue 81 (summer 2019) of The Menopause Exchange newsletter.

So does this research mean that all women should be using non-oral HRT rather than oral HRT?

HRT choices
HRT is routinely available in various forms: patches, gels, oral tablets, oral capsules, vaginal preparations and the levonorgestrel-releasing intrauterine system. It can contain either oestrogen only or a combination of oestrogen and progestogen. Women who’ve had a hysterectomy can use oestrogen-only products. Other women need to use a combination of oestrogen and progestogen in either a cyclical fashion (giving a regular bleed) or as a continuous combined preparation (no regular bleed).

The decision over which preparation a woman chooses can be complex. Personal experience influences the decision to choose a particular HRT (e.g. my friend used HRT A and she said it was brilliant). There may be practical reasons to choose one preparation over another, such as an allergy to the glues used in the patches, or a runner where the patches keep peeling off due to sweating. Sometimes preparations are chosen because the ideal choice for a patient is no longer manufactured and they need to find the closest alternative. In the modern NHS, there are cost issues to consider as well, and patches and gels are often more expensive.

The National Institute for Health and Care Excellence (NICE) guidelines recommend that women with any risk factors for blood clots should use transdermal HRT. These factors include lifestyle factors, such as smoking and high body mass index, but also personal or family history of blood clots. However, the recent BMJ study shows a significantly reduced risk with non-oral preparations, so non-oral regimes may be more suitable in some women.

Transdermal: pros and cons
One advantage of using non-oral HRT preparations is that it means your hormone levels can be measured. Oral preparations get broken down rapidly into hormones that aren’t easily measured in the laboratory. Measuring your hormone levels may be particularly useful if you’re struggling with ongoing symptoms and need to be sure you’re on the correct dose. Women with migraines may also benefit from using non-oral preparations, as the patches provide a steady dose of hormone rather than fluctuating levels.

Transdermal preparations can also be linked to some problems. As already mentioned, some women are allergic to, or react to, the glue used in patches, and although gels cause fewer reactions they are often perceived as messy. Some women find patches don’t stick very well but this can often be resolved by changing to twice-weekly patches instead of the seven-day patches. Some women find the gel time-consuming to apply, which puts them off using it regularly.

The range of transdermal products on the market is also limited, and the combination products often only come in one dose. This means that sometimes bespoke combinations of oestradiol patches and progestogen tablets/capsules have to be used instead, and this can be difficult if a doctor isn’t familiar with prescribing these types of combinations.

When to use oral HRT
Sometimes a doctor may recommend an oral preparation. Women with no risk factors for blood clots or breast cancer who are struggling with low libido may prefer to use tibolone (a combination of oestrogenic, progestogenic and androgenic properties). This recent BMJ study showed that tibolone, like non-oral HRT, isn’t associated with an increased risk of blood clots.

There may be some women who want their HRT to be as breast-friendly as possible; there is some evidence that dydrogesterone-containing HRTs may be safer from a breast cancer point of view than combination products containing other progestogens. The only way to give a combination product containing dydrogesterone is to use the oral preparations that are currently on the market. Fortunately these products appear to be safer from a blood clot point of view, as the recent BMJ study suggested that neither cyclical nor continuous oestradiol with dydrogesterone were associated with a statistically significantly increased blood clot risk.

We have relatively little data on young women who have gone through the menopause early and need HRT for bone protection and/or symptom relief. It’s possible that younger women may not be at the same level of risk with HRT as older women so oral preparations may be just as safe.

If a woman chooses an oral preparation for convenience or just because she prefers to take this, then the BMJ study provides some useful data about oral HRT too. The results suggest that oral oestradiol preparations are safer than conjugated equine oestrogen, whether in oestrogen-only or combined preparations, and that oestradiol with dydrogesterone had the lowest risk of blood clots for oral preparations.

Making a choice
It’s very important that women are involved in the discussion about HRT preparations so that they can decide with the help of their doctor or nurse what might suit them best.


Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ January 15, 2019; 364 (162).

About the author
Dr Kathryn Clement is a consultant in sexual and reproductive healthcare in Newcastle upon Tyne where she specialises in medical gynaecology (including menopause care), contraception and colposcopy.

Created Summer 2019

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