Practice observed

Putting guidance into practice

Dear Sarah

What can I tell one of my patients who is now 54? She had a brachial artery thrombosis in her 30s. She had been taking ‘the pill’ and was told never to touch estrogen again. Her husband had a vasectomy and her periods finally stopped about five years ago. She now has awful vaginal dryness which is completely preventing sex, and she has had three bouts of cystitis so far this year. One of my colleagues gave her some Vagifem® last year but she read the leaflet and is too afraid to use it. We agreed that I would ask you … .

There is absolutely no doubt that this lady is postmenopausal as it is at least five years since her last period. No investigations are needed. My conversation with her GP should ensure that she has been examined to exclude vulval dystrophy or significant anatomical anomaly. I think that she should confirm the diagnosis of atrophy and assess its degree if we are entering this conversation. However, even if things do not look too bad, she should not refuse to consider further, as the symptoms experienced by the patient do have significant impact and therefore justify discussion.

It is often about five years on that that urogenital atrophy becomes so intrusive that intervention is needed. We know from clinical practice and NICE NG23 reinforces that vaginal estrogens are highly effective in treating these symptoms. In the real world, is it often difficult to persuade women that we are not trying to poison them when the patient information leaflet is read. It is absolutely crucial to explain that these are standard warnings for systemic HRT and are not specific to the very low doses of the vaginal products.

NICE NG23 states that clinicians can

1.4.10 Consider vaginal oestrogen for women with urogenital atrophy in whom systemic HRT is contraindicated, after seeking advice from a healthcare professional with expertise in menopause.

These are the points I would suggest are included in the discussion.

Estrogen is not inherently bad. This lady did experience a very serious problem but it was perhaps 20 years ago and had periods for over 10 years following it. During those years and particularly towards the end, the hormone levels of a natural ovulatory cycle will have varied widely and at times been very high.

In relation to venous thromboembolism (which is most affected by clotting), NICE NG23 asks clinicians to

1.5.1 Explain to women that:

• the risk of venous thromboembolism (VTE) is increased by oral HRT compared with baseline population risk

• the risk of VTE associated with HRT is greater for oral than transdermal preparations

• the risk associated with transdermal HRT given at standard therapeutic doses is no greater than baseline population risk.

Arterial disease is more complex as there also vessel wall factors. NICE NG23 does not specifically address peripheral arterial disease but advises clinician to:

1.5.4 Ensure that menopausal women and healthcare professionals involved in their care understand that HRT:

• does not increase cardiovascular disease risk when started in women aged under 60 years

• does not affect the risk of dying from cardiovascular disease.

1.5.5 Be aware that the presence of cardiovascular risk factors is not a contraindication to HRT as long as they are optimally managed.

So … this lady has a problem that is significantly affecting her physical health (UTIs), her relationship and her quality of life. There is a potential solution that should offer relief. She has already been given a prescription for estradiol 10 µg vaginal tablets.

These deliver a very low dose. It is worth explaining that a whole year’s worth is the same amount of estradiol as in one of the smallest available licensed tablets. There is published data showing that if used as licensed (daily for two weeks and then twice a week) serum levels are never elevated above the postmenopausal range. There may be a small increase in the first two weeks due to very limited systemic absorption but that by two weeks this will have returned to baseline. This is because once the atrophy begins to reverse absorption is minimal. This is far less than the levels of her own estradiol to which she has previously been exposed. The two factors of minimal systemic absorption and not being absorbed from the gut mean that we can anticipate no significant effect on her clotting tendency.

I would advise that while the decision is ultimately that of the patient I think it is reasonable to use the product as potential benefit exceeds risk. I would advise her to allow two to three months of use as prescribed and then review. There is comparable data from the previously available 25 µg estradiol product showing systemic absorption at steady state to be very close to baseline. I would be prepared to increase frequency of use of the 10 µg product if not improving significantly. Up to 5 of the 10 µg tablets could be used a week without requiring endometrial protection by extrapolating the data from the 25 µg product which had an indefinite license if used twice a week, as referred to by NICE NG23:

1.4.11 If vaginal oestrogen does not relieve symptoms of urogenital atrophy, consider increasing the dose after seeking advice from a healthcare professional with expertise in menopause.

I would offer to see the patient but if my colleague felt confident to convey these points and explain fully to the patient then an appointment with myself would not be required.

I would have given exactly the same advice before publication of NICE NG23 in November 2015. It is, however, very helpful to have endorsement from NICE. I think that this will allow more women to make the right decisions for them and be supported by their GPs as their advice can be referenced. My sincere hope is that we can move further away from the misinformation and media scare stories of the last decade or so.