In the first of a three-part mini-series, Dr Toni Hazell discusses some key decisions that need to be made when a woman is started on HRT for the first time
Who should start HRT, and when?
HRT should be started when a woman presents with symptoms of the menopause (defined as >12 months since the last period) or perimenopause, the latter being a time of hormonal fluctuation when periods are becoming less regular, and symptoms can be severe. Many women will present with vasomotor symptoms (VMS) such as hot flushes and night sweats, but around 25% will not have VMS so we should look out for other symptoms which she might not associate with menopause. These could include tiredness, cognitive dysfunction (‘brain fog’), anxiety, low mood, insomnia, genitourinary symptoms and joint pain; other differential diagnoses for these symptoms should also be considered. Whilst HRT carries some health benefits, particularly in reducing the risk of osteoporosis, it is generally not started for health promotion alone, in the absence of symptoms, with the exception to this being women who have an early menopause. In that situation, the default is generally to give HRT until the normal age of menopause, and it is sensible to refer to a specialist in menopause if there are contraindications to this.
How do I decide whether to give combined or oestrogen-only HRT?
The oestrogen in HRT treats menopausal symptoms, but giving unopposed oestrogen to a woman who still has her uterus is likely to cause endometrial hyperplasia and possibly malignancy. The general rule of thumb is therefore that women with a uterus get combined HRT (oestrogen and a progestogen), and those without a uterus get oestrogen-only HRT. Women who have had endometrial ablation should still have combined HRT, as it is unlikely that every bit of the endometrium will have been removed during the procedure.
There are two key exceptions to this rule. For those who have had a hysterectomy for endometriosis, particularly where it is widespread, the British Menopause Society (BMS) and European Society of Human Reproduction and Embryology (ESHRE) advise choosing combined HRT for at least the first few years after surgery and until the age of natural menopause. This is because there are likely to be some remaining patches of endometriosis in the pelvis or elsewhere, which could develop hyperplasia or malignancy under the influence of unopposed oestrogen. Consideration of a switch to oestrogen-only HRT after the age of natural menopause would need to balance the risk of malignancy against the possibly better safety profile of oestrogen-only HRT in terms of breast cancer risk; it would be sensible to discuss this with a menopause specialist and/or the gynaecologist who performed the hysterectomy.
For women who have had a sub-total hysterectomy (less commonly done now than in the past), there may be a small cuff of endometrium left behind with the cervix, which should not be exposed to unopposed oestrogen. There is little data to guide management here, but common practice is to give three months of sequential combined HRT and watch to see if the woman gets a withdrawal bleed. If there is no bleeding at all, it can be assumed that there is no residual endometrium and the woman can move to oestrogen-only HRT, but if withdrawal bleeds occur then she should stay on combined HRT.
For combined HRT, should it be sequential or continuous?
Long-term sequential HRT (sHRT), with two weeks each of oestrogen only/oestrogen and a progestogen, carries an increased risk of endometrial cancer, but a woman who starts continuous combined HRT (ccHRT) too soon is likely to have unscheduled bleeding, which may prompt unnecessary investigations. An easy way around this is to use a 52mg levonorgestrel intrauterine device (LNG-IUD) as the progestogen part of HRT, as this gives good endometrial protection and often minimal bleeding after the first few months, but it is not acceptable for all women.
If a LNG-IUD is not used, women in the perimenopause, with less than one year since the last period, should use sHRT. Those who have not had a period for at least a year can start straight onto ccHRT. This is the case whatever the reason for the amenorrhoea, be it due to the menopause, or due to the effects of a contraceptive method such as the implant causing amenorrhoea.
Women who start on sHRT should change to ccHRT after 1–5 years of HRT. The decision as to exactly when to make this change is individual and will often be guided by the pattern of the bleeding – unscheduled bleeding after the change is anecdotally less likely if there has been a long period of amenorrhoea before starting HRT and if withdrawal bleeds are light and start some days after the end of the two weeks of combined HRT. If there is unscheduled bleeding after changing to ccHRT, with no concerns about pathology, the woman can move back to sHRT and wait at least one year before another attempt to switch to ccHRT.
There are so many preparations on the market – how do I choose between a tablet, patch, gel, spray or vaginal HRT?
Personal preference is important here, but a key fact is that oral HRT doubles the background risk of venous thromboembolism (VTE), whereas transdermal (TD) HRT doesn’t affect it. Anyone with an increased background risk of VTE should therefore have TD HRT; this would include those with obesity or a family history of VTE. As micronised progesterone is likely to carry a lower risk of VTE than the progestogens contained in available TD sHRT or ccHRT preparations, another option that is often used in those with high background VTE risk is oral micronised progesterone with TD oestrogen. (Note dydrogesterone is also likely associated with a lower risk of VTE but is currently only available in the UK as a combined oral HRT preparation.) Those with a higher risk of arterial disease, for example due to hypertension or older age when starting HRT (or with known arterial disease) should also use a TD preparation.
The choice between patch, gel or spray is individual, and in recent years in the UK has also been affected by HRT shortages and the question of exactly which preparations a pharmacy can get hold of. Patches will usually stay on in the shower or swimming pool, though those who do activities which cause excessive sweating (such as hot yoga) will find the adhesive inadequate. Some prefer a spray or gel as it is ‘over and done with’ once applied, rather than having to keep a patch on all day, whereas others conversely find a spray/gel to be sticky and time-consuming to apply and would prefer a patch. Some may need to try more than one brand before being happy with their choice.
Vaginal HRT can be used alone or in combination with systemic HRT and/or non-hormonal lubricants and is an effective treatment for genitourinary syndrome of the menopause (GSM, also known as urogenital atrophy). There is no need for a progestogen if it is used without systemic HRT and there are a variety of preparations available. It probably does not increase the risk of breast cancer recurrence for women with a history of an oestrogen-negative breast cancer, but discussion with her specialist is always sensible, and vaginal oestrogen should be avoided in women taking aromatase inhibitors for previous breast cancer.
Do women taking HRT still need contraception?
Loss of fertility can be assumed one year after the last period (if it occurs over the age of 50), or two years if younger than 50. Many women on HRT will therefore also need contraception, and those who are amenorrhoeic due to their method of contraception will not be able to tell when they have reached the menopause. This cohort can either continue to use contraception until the age of 55, at which point they can assume loss of fertility, or they can do a one-off follicle stimulating hormone
blood test at the age of 50. If it is in the menopausal range, contraception can be stopped one year later. A LNG-IUD nicely combines the progestogenic part of HRT with effective contraception, and other methods such as the progestogen only pill and implant can also be used alongside HRT. The depot injection and combined hormonal contraception are generally not recommended over the age of 50. More information on this can be found in the relevant Faculty of Sexual and Reproductive Healthcare (FSRH) guideline.
Dr Toni Hazell is a portfolio GP in north London
Sources
- BMS. Induced menopause in women with endometriosis. 2022
- BMS. Consensus Statement: BMS & WHC’s 2020 recommendations on hormone replacement therapy in menopausal women. 2020
- BMS. Surgical menopause: a toolkit for healthcare professionals. 2024
- BMS. Progestogens and endometrial protection. 2023
- BMS. Consensus statement: Urogenital atrophy. 2024
- ESHRE. Guideline Endometriosis. 2022
- FSRH Guideline. Contraception for women over aged over 40 years. Last update 2023
- NICE. Menopause identification and management. [NG23] 2024
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Personally, I try very hard never to have my name on the prescription, so that when Ms “GPs know nothing, I know I need hrt” comes back with breast cancer it’s not me having to deal with “I never would have taken it if the doctor had told me” complaint.
ps The BNF has a very helpful table of the numerical value for the risks associated with the different drugs, which can be shown to patients.