Printed on: December 21st, 2024

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Approaching and managing problematic bleeding on HRT

Approaching and managing problematic bleeding on HRT

This article was updated in April 2024.

In 2024, the British Menopause Society, in partnership with the RCOG, the British Gynaecological Cancer Society and other associated bodies, published a guideline on the management of unscheduled bleeding on HRT. The guideline focused on:

• Prevention: optimising HRT prescribing to prevent problematic bleeding occurring.
• Assessment: guiding investigation and referral of bleeding issues based on endometrial cancer risk stratification.
• Management: giving evidence-based strategies to manage persistent bleeding.  

This article summarises the assessment and management part of the BMS guideline, focusing on the information relevant to primary care. There is a separate article on HRT regimens and endometrial cancer risk, which looks at optimal HRT prescribing.

For more detail or specific information, we suggest looking at the original guidance (BMS – management of unscheduled bleeding on hormone replacement therapy). Other sources used are referenced. 

• The rise in HRT use in recent years means that more women are experiencing relief from distressing and disturbing menopausal symptoms.
• However, unscheduled uterine bleeding is a common side-effect of HRT use, so this increase has also led to increased numbers of menopausal women experiencing troublesome bleeding.
• This, in turn, has led to an increase in gynaecological referrals for abnormal bleeding.
• Urgent referrals through the suspected cancer pathways increased by 43% between 2021 and 2024, but this rise was not accompanied by increased endometrial cancer diagnoses.  

• The mechanisms that lead to unscheduled bleeding on HRT are poorly understood.
• Perimenopausal and menopausal women are prone to bleeding issues due to their endogenous hormonal fluctuations, which may cause, or exacerbate, bleeding.  
• Older women are more likely to have gynaecological pathology, including endometrial cancer, which may also present as abnormal bleeding.

• Endometrial cancer is the 4^th commonest cancer in women.
• Incidence increases with age.
• However, the age-related risk in newly-menopausal women is low (0.7% in those age 50–54y and 1.2% in those age 55–59y).
• Sequential HRT regimens may be associated with increased risk of endometrial cancer when used beyond 5y, whereas continuous combined regimens are associated with a reduced risk of endometrial cancer compared with baseline.  

(BMS – management of unscheduled bleeding on hormone replacement therapy)

There is no normal! Perimenopausal bleeding patterns may become progressively lighter or heavier, infrequent or more frequent, according to fluctuating hormonal levels.

We should arrange further investigation along the appropriate pathway if a woman reports:

• Persistent intermenstrual bleeding (usually >3m).
• Persistent irregular bleeding.
• Infrequent heavy bleeding in the presence of obesity or a history of PCOS.
• Postcoital bleeding.
• Postmenopausal bleeding (occurring >1y after last period).
• Heavy bleeding associated with other symptoms such as pain or pressure.

(NG12, 2015 (updated 2023); NG88, 2018 (updated 2021); Obstetrics and Gynaecology International, 2014: Article ID:19208).

The oestrogen component of HRT causes endometrial proliferation, and the progestogen suppresses growth and induces endometrial atrophy (and therefore stops bleeding). Erratic bleeding is common in the first 6 months of HRT use or within 3 months of a change in dose, affecting around 40% of users.

Mechanisms that lead to abnormal bleeding on HRT are poorly understood, and may relate to:

• Hormonal stimulation of existing pathology (e.g. endometrial polyps, hyperplasia, cancer, ovarian cysts).
• Poor compliance with treatment.
• Malabsorption of treatment.
• Drug interactions (e.g. with enzyme-inducers).
• Combined effect of HRT and endogenous oestrogen production stimulating the endometrium (e.g. in obese women).
• Vascular and endothelial factors in the endometrium.

(The Obstetrician & Gynaecologist, 2019;21(2):95).

Prior to starting HRT, we should ensure that:

• Any pre-existing bleeding issues are investigated and fully managed.
• We choose the correct type of HRT (sequential or continuous regimen).
• An adequate progestogen regimen is given to match the dose of oestrogen.

(See article on HRT regimens and endometrial cancer risk for guidance on progestogen regimens.)

The flowcharts below summarise the BMS guidance on the investigation of unscheduled bleeding on HRT. There is limited data looking at the rates of endometrial cancer in women who experience unscheduled bleeding on HRT; the BMS has therefore adopted a pragmatic approach based on risk stratification for endometrial cancer (although this is also based on limited evidence). 

The BMS divides endometrial risk factors into major and minor, to guide appropriate investigation of abnormal bleeding in different HRT users:  

(Note: MPA = medroxyprogesterone acetate)

Mirena is the only intrauterine system currently licensed for endometrial protection with HRT, and this is for 4y. However, evidence shows that all brands of 52mg IUS provide endometrial protection for up to 5y. The BMS recommends that:

• Any brand of 52mg IUS may be used for endometrial protection for up to 5y.
• If new-onset bleeding occurs with an IUS after 4y of use, change IUS for new device AFTER pathology has been excluded (which, in practice, means an examination and TVS – or referral for further investigation if other symptoms or risk factors are present).

• A malpositioned IUS is one that is located >2cm from the uterine fundus, or is partially/fully displaced into the cervical canal.
• If a woman experiences bleeding on HRT and has an ultrasound scan which shows the IUS to be malpositioned, the BMS suggests that the IUS should be replaced.
• Although there is no data showing that a non-fundally-placed IUS is less effective, it may provide more irregular endometrial suppression and could be more likely to cause breakthrough bleeding.  

You review an ultrasound report for your patient, Mariam, which states that the endometrium is 8mm thick and recommends clinical assessment. A glance at her notes tells you the scan was not requested due to any bleeding issues. What should you do next?

The BMS guidelines recommend the following action:

Approaching and managing problematic bleeding on HRT Unscheduled bleeding on HRT is common, especially in the first 6m of use. We should manage any pre-existing bleeding problems prior to starting HRT, and ensure that the regimen is appropriate for the stage of menopause, and that adequate progestogen is given. Initial assessment of bleeding involves history, examination and assessment of endometrial risk factors. Further investigation and referral pathway will depend on endometrial cancer risk, nature of bleeding and duration of HRT use. First-line investigation is transvaginal ultrasound scan to look for pathology and at endometrial thickness. Endometrial thickness on sequential HRT should be ≤7mm, and on continuous combined HRT should be ≤4mm. Most unscheduled bleeding caused by HRT can be managed by altering the dose, type or regimen of hormones.