Why is there so much norethisterone in Evorel Conti patches?

[NormaSnorks]

I have been happy on a low dose tablet form sequential HRT (Novofem) for many years, but my GP is pushing for me to change to transdermal continuous HRT citing:

• my age (58)
• risk of blood clots (I'd argue this is low, as I am otherwise healthy weight/ BP etc)
• unknown risk of long term sequential HRT use

I'm not keen, as I tried before and it was a disaster. I'm pretty sure I have a progesterone intolerance. I just about make it through my 12 days of norethisterone but can feel anxious and angry by the end.

I've just been looking at Evorel Conti again and saw that it is 50mcg Estradiol and 170mcg Norethisterone.

I understood a 1mg tablet to be approx equivalent to 25-50mcg through a patch, so why is the ratio of norethisterone more than 3 times that of the estrogen?

@JinglingSpringbells Do you know?

As you've tagged me...!

This is the online patient leaflet and this is the professional info.

Qualitative and quantitative composition
Each transdermal patch contains:
3.2 mg of estradiol hemihydrate equivalent to 3.1 mg estradiol
11.2 mg of norethisterone acetate equivalent to 9.82 mg norethisterone
Each patch releases a nominal 50 µ g estradiol and 170 µ g norethisterone acetate over 24 hours.

I am assuming that it's higher as this is a conti patch and that's what is needed to control the effects of estrogen on the womb lining.

You don't have to change to conti.
The risks of conti are higher for breast cancer. This is well established. The risk of sequi is endometrial hyperplasia but as this usually always shows with some spotting, it's far easier to diagnose and treat. And hyperplasia isn't always cancer- there are stages ranging from benign to cancer.

Haha! Thank you Jingling - such a speedy response! :-)

I guess I'm confused by the ratio, which is approx 1:3 estradiol to norethisterone whereas in continuous regimes in tablet form it's 2:1 the other way and I've seen that the equivalent of 1mg daily of norethisterone is considered enough to protect the womb lining.

Perhaps norethisterone is less well-absorbed transdermally?

The risks of conti are higher for breast cancer. This is well established.
Where would I find the clinical evidence to support this?

Thanks for your help!

@NormaSnorks Info as you asked for.

https://gpnotebook.com/en-GB/pages/gynaecology/review-of-the-evidence-for-breast-cancer-risk-and-hrt

https://www.imsociety.org/wp-content/uploads/2020/08/position-statement-hrt-breast-cancer-2020-08.pdf [page 3]

It's worth bearing in mind that the risks of endo cancer are tiny on HRT if it's used as it should be (ie not off-licence doses.)

The newest guidance for GPs for women with bleeding on HRT is a scan within 6 weeks, not 2 weeks which is for women with post menopausal bleeding, not on HRT.

It's puzzling how GPs seem to be so concerned about hyperplasia and endo cancer with HRT when the risk is so small.

Your GP is keen to get you off tablets, but why aren't they offering Utrogestan instead of Norethisterone? With BC risk there is a higher risk with synthetic progestogen- highest is MPA, then Norethisterone.

The figures in the links for BC do not include micronised progesterone use so they are slightly skewed as they are based on older forms of HRT.

There are other statements on this which show no added risk for 5 years' use at least.(You can find this by searching.)

Thank you, again!

I had such an extreme reaction to Utrogestan last time that I'm not keen to go back there, although I didn't try it vaginally, as that hadn't been widely adopted at that point.

I'm really keen to go for as little progesterone as I can get away, but I'm unlikely to get the 12 week option which is being prescribed off-licence in some private clinics I know.

@NormaSnorks It is true that there can be variations on the cycle length, off licence and that usually means privately. This option has been around for a long time (I did the 12 week cycle years ago). However, this often comes with the guidance that there should be a scan, usually once a year. The NHS doesn't, as a rule, provide this. Your GP may agree to it if you can convince them you are progesterone intolerant.

Going back to your first post, the change from tablets to transdermal is more important after 60, so you're not there yet.

Ideally, your GP should work with your preferences and have a discussion on all of this. If you want any more advice I'm fine about sharing my own experience (off licence) but by PM not on the forum.