Want to Increase Your Oestrogen Dose When You're Already on High-Dose HRT?

The BMS recognises that some women may require higher doses of oestrogen, including women who do not absorb transdermal medication effectively. However, higher doses outside of the product licence should not be regarded as standard practice.

The BMS statement on HRT prescribing highlights several important considerations:

• Most women respond to licensed doses of oestrogen.
• Higher doses can increase the risk of abnormal bleeding requiring investigation and risking endometrial hyperplasia and endometrial cancer.
• Higher oestrogen doses require appropriate consideration of the progestogen dose for endometrial protection in women who have a uterus.
• There is actually no established target systemic oestradiol level that should be achieved for routine HRT symptom control.
• HRT should be individualised, with decisions based on the woman's symptoms and clinical circumstances.

The BMS also emphasises that there is no justification for routinely combining different oestrogen formulations or increasing doses outside the licence simply to manage ongoing symptoms.

Sources: British Menopause Society, HRT prescribing statement (updated March 2024) and BMS consensus resources.

One of the most frustrating experiences can be taking what seems like a substantial amount of HRT and still not feeling well.

It is natural to think:

"If I am still experiencing symptoms, perhaps I need more oestrogen."

But the BMS highlights a phenomenon called tachyphylaxis, which is important to understand.

1. Tachyphylaxis: When increasing the dose may not help

Tachyphylaxis describes a reduction in response to a medication that was previously effective.

In relation to oestrogen, the BMS explains that some women who are already using high doses may continue to experience symptoms, leading them to believe they need even more oestrogen.

However, increasing oestrogen further may not resolve the symptoms. The BMS notes that excessively high oestradiol levels can also be associated with adverse mood-related symptoms, including low mood and anxiety.

This means that more oestrogen is not necessarily the solution to persistent menopause symptoms.

A clinical review should consider whether the symptoms are related to menopause, whether the medication is being absorbed adequately and whether another cause or condition may be contributing.

Source: BMS, Tachyphylaxis with HRT, September 2023.

2. You may not be absorbing your HRT effectively

Some women do not absorb transdermal oestrogen as well as others.

This is one situation where the BMS acknowledges that a higher dose may sometimes be appropriate, supported by low systemic oestradiol levels.

However, a blood test needs to be interpreted carefully. Oestradiol measurements are affected by the timing of the dose, the type of preparation and the laboratory assay used.

A single blood test cannot necessarily demonstrate the full level of exposure throughout the day. Finger prick/ non venous sampling is not reliable.

3. Your symptoms may have another cause

Menopause symptoms can overlap with other health conditions and life circumstances.

For example, ongoing fatigue, poor sleep, anxiety or low mood may be influenced by:

• Sleep disorders or persistent sleep disruption.

• Stress and psychological factors.

• Thyroid conditions or other medical issues.

• Medication side effects.

• Other conditions that need assessment and management or treatment.

This doesn't mean that your symptoms aren't real or that menopause isn't contributing. It means that increasing HRT should not be the only option considered.

If you are already using a high dose, any further increase requires an individualised clinical assessment.

The BMS 2024 guidance on unscheduled bleeding explains that if high-dose oestrogen is considered necessary, preparation changes, holistic management and other causes of ongoing symptoms should first be explored.

Where an off-label dose is used, the prescribing clinician should discuss the uncertainties, risks and available evidence with the patient to support informed, documented decision-making.

This is particularly important when considering long-term treatment.

Before increasing your dose, a thorough consultation should explore:

• Are your symptoms being caused by low oestrogen?

Review the symptoms, their pattern, duration and response to current treatment.

• Are you absorbing your HRT effectively?

Consider the formulation, administration, adherence and whether further investigation is clinically justified.

• Is your progestogen providing adequate endometrial protection?

If you have a uterus, your progestogen regimen must be reviewed when oestrogen is increased.

• Could another treatment approach or dose help?

Consider changing the HRT preparation, addressing individual symptoms or investigating other causes.

• Have the benefits and risks been reviewed?

Consider your medical history, current dose, duration of treatment and individual circumstances.

If you have a womb, oestrogen stimulates the lining of the uterus (endometrium). A suitable progestogen is needed to protect against excessive thickening of the lining.

The higher the oestrogen dose, the more important it is to review whether your progestogen provides adequate protection.

The BMS advises that higher doses of oestrogen require a higher dose of progestogen to ensure adequate endometrial protection.

However, the evidence for specific progestogen doses at high, off-label oestrogen doses is limited. This means that prescribing decisions must be carefully individualised rather than relying on a simple assumption that any particular increase in progesterone will provide guaranteed protection.

Unscheduled bleeding, particularly when persistent or occurring outside an expected pattern, should be assessed appropriately.

Source: BMS updated dose tables and guidance on endometrial protection.

Many women ask whether they should have their oestradiol levels checked before increasing their HRT.

The BMS states that routine serum oestradiol testing is unnecessary for most women using HRT. Also, there is no recommended systemic oestrogen level that reliably determines symptom control for everyone.

Blood tests may be considered in specific clinical circumstances, such as suspected absorption problems, but results must be interpreted in context. (Remember to use the arm you don’t apply your HRT spray or gel to when having a blood test, or wait to apply your HRT after the blood test has been taken.

A blood test result should not be used in isolation to decide whether you need more oestrogen.

Your symptoms and clinical assessment remain central to treatment decisions.

If you are already using a high dose and still struggling, it can be helpful to arrange a structured menopause review.

Rather than focusing solely on increasing your oestrogen, the consultation should look at the whole clinical picture.

A personalised review may include:

1. Reviewing your current HRT. What you take, how you take it and how long you've been using it.

2. Assessing your symptoms. Which symptoms persist, how severe they are and how they affect your daily life.

3. Considering alternative preparations. A different formulation or delivery method may be worth discussing.

4. Reviewing progesterone protection. Particularly if you have a uterus and are using higher doses of oestrogen.

5. Exploring other causes. Where symptoms may not be explained by oestrogen deficiency alone.

6. Agreeing a safe treatment plan. Including follow-up and a review of benefits and acknowledging risks.

The aim should be to find an effective and safe treatment approach for you, rather than simply increasing the dose.

Speak to your prescribing clinician before making any changes to your HRT.

Seek appropriate medical assessment if you experience:

• New, persistent or unexpected vaginal bleeding.

• Symptoms that are worsening despite using treatment.

• Significant new mood changes or anxiety.

• Symptoms that concern you or affect your ability to function.

Unexpected bleeding while using HRT may require investigation, especially when risk factors or a high oestrogen dose are involved.