Lack of safety data prompts guidance on oestrogen therapy

Genitourinary symptoms are common in women with breast cancer, but many GPs may be unsure when to consider prescribing oestrogen treatments and when to discuss this with a cancer specialist.
 
A recently published article in the Australian Journal of General Practice (AJGP) aims to address this gap by examining the safety and efficacy of vaginal oestrogens for genitourinary symptoms in breast cancer survivors, providing guidance for GPs around prescribing and the available treatments.
 
The paper highlights that despite there currently being no large studies to assess safety, current evidence suggests reassurance can be provided to the majority of women with a history of breast cancer who are considering vaginal oestrogens.
 
Dr Karen Magraith is a GP and past President of the Australasian Menopause Society, as well as co-author of the paper, alongside an endocrinologist, oncologist and surgeon.
 
She told newsGP the research has generated ‘quite a lot’ of interest. 
 
‘Around 75% of women with breast cancer develop genitourinary symptoms and the question of vaginal oestrogen comes up quite frequently for GPs,’ Dr Magraith said.
 
‘For some of these women it is just because they are menopausal. However, breast cancer treatments themselves can make genitourinary symptoms worse than they may be for other women.
 
‘For example, aromatase inhibitors work by reducing the circulating oestrogen to very low levels which can cause severe genitourinary symptoms for some women.’
 
For postmenopausal women in general, genitourinary symptoms are also common, with Dr Magraith noting that estimates vary from 27–84% of women, but ‘a fair estimate’ is at least 50% of women experience symptoms such as vaginal dryness and irritation, urinary urge and frequency.
 
‘If genitourinary symptoms occur they do not resolve spontaneously, but instead they tend to worsen over time,’ she said.
 
‘This is due to low oestrogen levels, and longer exposure to low levels makes the problem worse.
 
‘Another consideration is women who have early menopause as a result of breast cancer treatments. These women may have significant symptoms plus they are experiencing them at a young age, which can be particularly distressing.’

The AJGP paper states that women with breast cancer experiencing genitourinary symptoms face ‘a difficult decision’ when considering vaginal oestrogen therapy.
 
Initial management of women with these symptoms and a history of breast cancer should be non-hormonal vaginal moisturisers and lubricants, the authors recommend.
 
If vaginal oestrogen is being considered, an individualised discussion is required, balancing the risk of cancer recurrence with the efficacy of non-hormonal therapies, severity of symptoms and associated quality of life.
 
According to Dr Magraith, women ‘generally appreciate’ being asked about genitourinary symptoms when discussing menopause or breast cancer treatment.
 
‘Acknowledging that genitourinary symptoms are a common issue is the first step,’ she said.
 
‘Where possible I discuss the proposed prescription of vaginal oestrogen with the patient’s cancer specialist. Ideally the discussion should involve the GP, patient, and cancer specialist – usually oncologist.
 
‘Some women have completed their cancer treatment and no longer regularly see a cancer specialist. For these women I may prescribe vaginal oestrogen using a shared decision-making process with the patient.’
 
Making an assessment including a thorough history and offering an examination, ensuring that non-hormonal measures are in place, will help to quantify the individual woman’s risk of breast cancer recurrence, the paper states.
 
It also enables a shared decision-making process that takes into account severity of symptoms, cancer type and risk of cancer recurrence, the type of endocrine therapy the patient is using, if any, and personal preferences and values.
 
The group of women Dr Magraith would ‘definitely discuss’ with the oncologist are those using aromatase inhibitors, as safety is uncertain in women with early breast cancer on aromatase inhibitors and further studies are needed.
 
‘This is the group we have the most concern with,’ she said.
 
‘The issue is that any oestrogen absorbed systemically bypasses aromatase conversion and therefore continues to act in women on aromatase inhibitors.’
 
For women on aromatase inhibitors, including pre-menopausal women on gonadotropin-releasing hormone agonists plus aromatase inhibitors, switching to tamoxifen, with or without stopping the agonist, can help.
 
The paper recommends that vaginal oestrogens can be offered to women with persistent symptoms, which Dr Magraith says includes vaginal lubricants and moisturisers as first-line treatments for vaginal dryness and pain with sexual activity.
 
Lubricants are not expected to help with urinary symptoms such as urgency or frequency.
 
‘I would ask the patient whether these have helped sufficiently at the next review,’ she said.
 
‘This might typically be a few weeks. If they are not enough, and the patient still has symptoms that bother her, we would then discuss the option of vaginal oestrogen.’
 
In Australia treatment options are oestriol cream or pessaries, and oestradiol pessaries, which are all PBS listed. Treatment is usually commenced with daily use for 14 days, then twice weekly use for long-term maintenance.
 
It’s also important to discuss the associated risks with vaginal oestrogen therapy with patients, Dr Magraith highlights, with the first step to distinguish clearly between vaginal oestrogen and systemic menopausal hormone therapy (MHT).
 
Systemic MHT, where oestrogen – and often progestogen – is delivered orally or transdermally is generally contraindicated in breast cancer survivors, regardless of the hormone receptor status of the tumour.
 
While vaginal oestrogen is a localised, topical treatment where the aim is to treat the local tissues only and to have minimal systemic absorption of the oestrogen.
 
‘I would let the patient know that a very small amount of oestrogen is absorbed systemically from vaginal oestrogen and we think that most of the time it is not enough to make us concerned about increasing the risk of breast cancer recurrence,’ Dr Magraith said.
 
‘For women using aromatase inhibitors, I would either ring their oncologist, or refer them to see the oncologist to discuss this question.’

Despite that, ‘unfortunately’ there are no large prospective trials to assess the safety of vaginal oestrogens and it’s ‘unlikely’ that such trials will ever be conducted, Dr Magraith says the existing evidence summarised in the AJGP paper is reassuring for women on tamoxifen or no adjuvant endocrine therapy who are considering using vaginal oestrogen.
 
‘Women with breast cancer may have a range of symptoms or concerns including genitourinary symptoms. Sometimes they might feel that they should just be grateful they have survived, and not complain,’ she said.
 
‘However, genitourinary symptoms can significantly impair health, sexual function, and quality of life for some women. Treatment of symptoms can improve quality of life and reduce distress.
 
‘Women with breast cancer will benefit if their GPs are comfortable raising the topic of genitourinary symptoms and discussing treatment options.’
 
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breast cancer genitourinary symptoms hormone receptor menopausal symptoms vaginal oestrogens women’s health