A practice-based survey of HRT prescribing – is endometrial protection in place?

Hormone replacement therapy (HRT) is widely used to treat symptoms of the menopause in women. In recent years there has been an upsurge of interest in, and use of HRT, with one primary care-based study noting a 13.64% year-on-year increase from 2010 to 2021.¹ One of the key tenets of safe prescribing is ensuring that women with an intact uterus receive progesterone to protect the endometrium from the risk of hyperplasia and carcinoma, which are recognised risks of unopposed oestrogen.

This study was conducted at Chorleywood Health Centre, a 4-doctor training practice with a list size of 7,200 located in an affluent commuter zone to the North-West of London, and with an above-average age distribution. It reviewed all women being prescribed oestrogen-only preparations to assess whether they were receiving appropriate concomitant progesterone. Women being prescribed combined HRT preparations (e.g. Evorel Conti) were excluded.

During this search, a small cohort of patients who had undergone subtotal hysterectomy was identified, and inconsistencies in the prescription of HRT in this cohort were noted. There is currently limited guidance regarding HRT prescription in women having undergone a subtotal hysterectomy, though reference is made to some of this literature.

Method

A search was conducted on the practice’s EMIS computer system to identify all women who had been prescribed oestrogen-only HRT during a one-year period from 18/02/2021 to 17/02/2022. For each of these women, the electronic record was analysed to ensure that one of the following three criteria was met:

1. Appropriate co-prescription of progesterone, whether this be in an oral or transdermal preparation.
2. A 52mg Levonorgestrel intrauterine system (LNG-IUS), Mirena, was in place and in-date.
3. The patient had undergone a total hysterectomy.

Results

The initial search yielded 137 patients prescribed oestrogen-only preparations of HRT during the one-year period. Analysing the records yielded three who did not fulfil any of the criteria:

1. Patient 1 was found to have a Mirena IUS that had expired.
2. Patients 2 and 3 were found to have both undergone subtotal hysterectomy without any evidence of having progesterone cover.

For patient 1 whose Mirena had expired, we ensured she was referred for a replacement, whilst also arranging a pelvic ultrasound to assess the thickness of the endometrium. For patients 2 and 3 who had undergone subtotal hysterectomy, we sought advice from our local gynaecology team. As neither of the patients had completed an initial three-month sequential regime, nor had they experienced any irregular bleeding, we decided to keep them on their current regime without the need for additional progesterone.

Discussion

It is well recognised that unopposed oestrogen replacement is associated with a significant increase in the risk of endometrial hyperplasia and endometrial cancer.^2-6. A large, randomised control trial carried out in the 1990s showed that unopposed oestrogen was associated with a substantially increased risk of endometrial hyperplasia compared with placebo.⁷ Therefore, it is imperative to ensure that women prescribed HRT are appropriately prescribed progesterone, where indicated.

A key focus was on the key difference between total and subtotal hysterectomies and the implications this would have on HRT prescribing, given the scant guidance regarding this. The cervix-sparing approach is thought to be technically simpler in comparison to a total abdominal hysterectomy (TAH) and avoids the communication of the abdominal cavity and potentially contaminated vagina.⁸ Conversely, with this method there is a chance that there may be some residual endometrial tissue in the cervical canal which, if exposed to unopposed oestrogen, could lead to hyperplasia and subsequently neoplasia. Other factors to consider with subtotal hysterectomy include the risk of persistent vaginal bleeding and the need for ongoing cervical screening.

There is a paucity of evidence in relation to the need of progesterone following subtotal hysterectomy. It is common practice to recommend a three-month sequential HRT trial, to look for monthly withdrawal bleeds, which suggests the presence of endometrial tissue in the remnant cervical stump responding to sequential progesterone. In women who experience cyclical bleeding with sequential HRT during these three months, it is advised to continue with an ongoing combined regime.⁹

Mirena is licensed for endometrial protection when prescribed with oestrogen for HRT.^10-11 Unopposed oestrogen can have a stimulatory effect on the endometrium and there is extensive date to support Mirena’s effectiveness in protecting the endometrium against this.^12-15 This option as the progesterone arm of HRT offers the additional benefit of also being able to be used as contraception. As it stands, in the UK the Mirena coil is only licensed for use for 4 years with HRT,¹¹ however, most clinicians support use for up to 5 years off-label. As many of these women may no longer require the Mirena for contraception, this may increase the risk of the replacement date being forgotten or overlooked.

Conclusion

This practice-based survey has highlighted the lack of guidance related to HRT prescribing in women who have undergone subtotal hysterectomy. Despite there being suggested regimes available, we propose that formal guidelines for such prescribing should be created.

Shalinee Patel, GP Registrar, West Hertfordshire GP Specialist Training Programme, Watford General Hospital, 60 Vicarage Road, Watford, Hertfordshire

Edin Lakasing, GP, trainer and tutor, Chorleywood Health Centre, 15 Lower Road, Chorleywood, Hertfordshire

Email: [email protected]

Competing interests: none.

References 

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