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[Mary G]

Hi Mary G

Yes it is the 8% Crinone, I don't think the other 4% is available any more. Yes, they come in boxes of 15, which is a months supply for me as I use it every other day.

I am not too worried about it not being licensed for HRT, as it is licensed for fertility treatment and so is obviously (to me) safe and probably safer than some of the synthetic alternatives that g.ps are happy to prescribe as it is bioidentical.

As for the dose,  nobody knows what level of progesterone is required for protection against oestrogen (no studies). The crinone dose (90 milligrams every 2 days, or 45mg a day) is higher than a mirena coil (21 micrograms daily) so again I am not concerned that it is inadequate. It is less than utrogestan but via a different route, and perhaps that is why it is tolerable.

Thanks Katie and I agree, just because it's not on an NHS list or licensed for HRT doesn't mean it isn't any good.  Utrogestan is not licensed by the NHS for vaginal use which is completely ridiculous and nobody even knows why.

Crinone @ 45mg every day sounds good and it's roughly the same dose that I take - it seems to be a magic number that most women can tolerate.

I think it's very wrong that women are left to struggle alone with the progesterone side of HRT when there are far better products out there that are much easier to tolerate. 

I also think the reason most women don't use HRT is because they don't get any meaningful help with it and many end up ditching it after a short time because they are on the wrong type/dose.

[AKatieD]

Yes, despite it seeming a no brainer, the g.p. "menopause specialists" seem to be unhelpful and very hasty to pass the buck off onto anyone else they can find, including the patient, if their standard treatment does not suit. Not prepared to engage own brains for fear of being criticised/ sanctioned. Which is especially annoying when it should be free (medical exemption cert), but because they wont prescribe, i have to do all the research,  arranging and paying.

As you say, if things are licensed for other uses abroad, it should be possible for the uk to fast track approval here too. As usual, we don't trust Johnny Foreigner to know what they are doing, to our detriment

[Hurdity]

Hi Mary G

Yes it is the 8% Crinone, I don't think the other 4% is available any more. Yes, they come in boxes of 15, which is a months supply for me as I use it every other day.

I am not too worried about it not being licensed for HRT, as it is licensed for fertility treatment and so is obviously (to me) safe and probably safer than some of the synthetic alternatives that g.ps are happy to prescribe as it is bioidentical.

As for the dose,  nobody knows what level of progesterone is required for protection against oestrogen (no studies). The crinone dose (90 milligrams every 2 days, or 45mg a day) is higher than a mirena coil (21 micrograms daily) so again I am not concerned that it is inadequate. It is less than utrogestan but via a different route, and perhaps that is why it is tolerable.

Hi AKatieD

Re Crinone gel - it is not possible to compare the amount of progestogen in a Mirena coil (which is a synthetic progestogen called levonorgestrel) and bio-identical micronised progesterone that is found in Crinone gel. They are completely different compounds.  One cannot even compare the total amounts of progesterone in different formulations such as Utrogestan vs Cyclogest vs Crinone for example - because although they all contain micronised progesterone, the way they are designed to enter the body is slightly different so the biologically active dose will be somewhat different. The totals in the dose give only a very approximate ballpark comparison.

Synthetic progestogens are all given in far lower doses partly because of their stability in the blood stream - so they last longer, and also because of their specific effect on protecting the endometrium which is greater than progesterone itself - an advantage when used as part of hRT, because the reason it is taken is to protect the uterus.

The British Menopause Society  produced a paper a couple of years ago in their "Tools for Clinicians" series entitled "Progestogens and endometrial protection"  - the title being self-explanatory.
https://thebms.org.uk/wp-content/uploads/2023/04/14-BMS-TfC-Progestogens-and-endometrial-protection-APR2023-A.pdf

Here is their account of studies using Crinone:

"Stute et al. 2016 reported a systematic review on the impact of micronised progesterone on the
endometrium. The authors suggested that estrogens with sequential micronised progesterone (4%
corresponding to 45 mg/day for 10 days per month) or intermittent (100 mg every other day) for up to
3–5 years may be safe (off-label use). The authors acknowledged that there was lack of sufficient data
regarding optimal vaginal administration within HRT to guide practice.18

However, more recently, a publication from the Early versus Late Intervention Trial with Estradiol
(ELITE) showed that lower dose vaginal intake of progesterone resulted in a substantially higher
rate of endometrial hyperplasia. This randomised double-blinded placebo-controlled trial, reported
on the effect of oral estradiol plus vaginal progesterone against placebo on endometrial thickness,
endometrial biopsy pathology, cervical cytology and total cancer incidence among healthy
postmenopausal women.20

The study only included original ELITE participants with an intact uterus, who were randomised to
either daily oral estradiol 1 mg/day with 4% vaginal micronised gel 45 mg/day for 10 days each month
or placebo. Participants were assessed at baseline and annually during a median follow-up of 4.8 years.
Over up to 80 months of follow-up, participants randomised to oral estradiol plus vaginal
progesterone had progressive and statistically significant increases in endometrial thickness (p<0.001),
underwent more endometrial biopsies (RR 2.11; 95% CI 1.65-2.69) and had a substantially higher rate
of endometrial hyperplasia on endometrial biopsy (RR 15.9; 95% CI 0.97-260.7) compared with the
placebo group. The authors concluded that 10 days of vaginal progesterone 45 mg/day is insufficient
to completely oppose the effect of oral estradiol 1 mg/day on the endometrium.20

More evidence in adequately powered studies is required to assess the optimal dose and duration of
vaginal progesterone intake to provide optimal endometrial protection within HRT regimens.
Based on current evidence if progesterone was considered for vaginal administration (out of license
use) in women who experience side effects with oral intake, this should ordinarily be given in similar
doses and durations as suggested for oral progesterone intake with HRT."

So you're right in that we don't actually know what dose is required. I would always agree that any of the micronised progesterones - most of which are bizarrely only licensed for fertility - would be suitable also for endometrial protection - but we just need the studies.

Anyone using a sub-optimal dose of any of them and especially eg a dose that has been shown to be inadequate for endometrial protection, should only be using these low doses under medical supervision and regular scans. The reason it is well tolerated at low doses is because it is a low dose!! And because it is a low dose, may well not be effective for endometrial protection especially for higher oestrogen doses.

Those on low oestrogen doses such as a 25 mcg patch - then lower progesterone doses or longer cycles at standard doses if post-menopausal, may well be sufficient - but again, because we respond so individually to these hormones and different modes of delivery. medical supervision is needed.

Hurdity x

[AKatieD]

Hi Hurdity

No new info I know of, and as usual there are contradictory studies.

Yes, it seems sensible that a lower dose makes it tolerable, but it is not always that straightforward. Plus it would not make sense to me to conclude that only doses that for some have intolerable effects give adequate protection yo them, given we are talking about body identical hormones.

Oral progesterones are known to require higher doses to be effective as they are rapidly metabolized and it is the higher doses and the products of the metabolism that cause the side effects in some people.

There are studies that compare the effect of Crinone with other progesterones.  For example, https://pubmed.ncbi.nlm.nih.gov/10689005/

 Crinone is compared with 100mg Promterium (utrogestan) orally. The conclusion was Crinone results in greater bioavailability with less variability than oral progesterone, providing more reliable delivery of progesterone, compared with oral progesterone. The blood concentration was 5x higher for Crinone and it lasted longer. I have also read something that said tissue (rather than blood) levels were 10x higher using crinone than oral progesterone.

Therefore, compared to an oral progesterone, the effect of vaginal can be far higher than you might expect. 45mg daily equivalent should easily compare to 100mg or 200mg daily utrogestan.

I also compared it to a mirena coil as at least they have a similar site of action. As you say Mirena is synthetic but is similar in that it will also interact with the same receptors as natural progesterone that it is designed to mimic. I can't find any studies comparing Mirena with crinone or utrogestan.

FDA data sheets show however that steady state plasma levels for crinone as 5-15ng/ mL. That of mirena as 150-200 pg/mL(0.15 -2 ng/mL), albeit for progesterone vs progestogen.

As they always say, more studies required...

[AKatieD]

Hi Merrygoround



With regards to HRT I get it from Hormone Health in London, via telephone consultations so no need to attend in person. That is the practice headed up by Nick Pannay who had held several senior positions in medical establishment regarding menopause. I speak to one of the other consultants on his list as cheaper and appointments don't have 6 month wait as his do.

Ironically, I was advised to seek out this practice by g.p. who recommended him and said I would never get an NHS appointment so should go private. Even though she knew the reason for the appointment her was to try Crinone, she still objected to the treatment and refused to accept their instructions as she is the g.p. practice "menopause specialist" and knows better!

Best of luck

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Edit by Admin: reply to political statement removed.

[Mary G]

merrygoround, that is really terrible and you are definitely not getting the help you need.  You are right, I'm in Spain and have access to medication over the counter and it has been a real life saver for me.

I haven't used the NHS for years but from what I read on here and judging by my sister's experiences, it is really struggling and god knows how it will be resolved.  Frankly, I wouldn't know where to start although allowing pharmacists to sell more medication over the counter would be a massive step forward and take a lot of the strain off GPs.  My niece is a junior GP in the UK and she says she is forced to prescribe the cheapest stuff which means they have limited flexibility.  I've noticed there is more product variety in Spain than the UK which could be down to the new red tape (import controls?) you mentioned.

You are a prime example of someone who needs a personalised approach to HRT and to be able to take a lower dose of progesterone with regular scans.  The NHS will never agree to that and your only option is to go privately or do your own thing and pay for regular scans yourself.

Is it worth consulting a menopause specialist in GB as a one off?  They will all agree to telephone consultations.  It will cost a few hundred quid but if it points you in the right direction it would help.

[CLKD]

While we are on the subject you might want to check some of CLKD's input about the upcoming election. That is definitely not factual at all.

meno-brain here, mayB U would like to remind me of what I wrote, tnx.