Has anyone else experienced insulin resistance on norethisterone?

[AnnaS70]

I am 52 years old and periods stopped at 49. It was such a relief. Then, I started having terrible night sweats and hot flushes. After a year without periods, I was put on Lenzetto and Utrogestan (bio-identical progesterone), to be taken continously. They helped with symptoms, but the problem was my periods started again. They were regular but much heavier than before. All exams were normal. My doctor said bio-identical hormones, especially progesterone, can trigger periods in postmenopausal women and suggested I take Kliofem instead. Each pill contains 2 mg of estradiol and 1 mg of norethisterone. It has worked great, all symptoms are gone, and the periods have stopped, but my latest annual check-up showed my fasting insulin levels have increased from normal to very high (50; ref 2.6-24.9). I have also gained some weight lately and insulin resistance is known to cause weight gain. My doctor suspects Kliofem is responsible for this and wants me to switch back to transdermal estrogen + Utrogestan. I have found some articles stating that norethisterone can indeed affect insulin production among other things and also inhibit the benefits of estrogen therapy...! The only problem for me is that I absolutely do not want to have periods again! On the other hand, I cannot think of any other reason why insulin levels would increase this much. I wanted to know if anyone else has experienced this on Kliofem or other forms of HRT?

There is a lot in your post that is slightly odd (in terms of what your dr said.)

Are you in the UK? Is this your GP?

Body-identical (they call it that now, not bio) doesn't 'start periods again' in post menopausal women. It's sometimes poorly absorbed and women get some breakthrough bleeds. It sounds more like the regular bleeds were you own periods that hadn't really finished, perhaps? 49 is a bit early as the average is 51-52 now.

I have also gained some weight lately and insulin resistance is known to cause weight gain.

It's usually the other way round. Weight gain causes insulin resistence (ie diabetes.)

Do youusually have an annual insulin test? Is there a history of it ?

Have you been diagnosed as diabetic now? Are you making changes to your diet? Or are you on drugs?

Weight gain, lack of exercise and eating a lot of carbs can cause insulin resistence.

I've never seen anything really definitive about Norethisterone and insulin resistence, because a lot of women use combined patches and pills that have it in.

Thank you for your input.
Yes, I[´m in the UK. I was put on body-identical hormones by one doctor and Kliofem by a gynaecologist. The first doctor believes that body-identical hormones and transdermal estrogen are safer than oral estrogen and progestins since oral estrogen has to be metabolised by the liver and also increases the risk of blood clots. Also, progestins such as norethisterone are not identical to the progesterone produced by our bodies. But, on Lenzetto + Utrogestan, my estrogen levels were only half of what they are on Kliofem (my doctor wants them around 100 ng/L, they were only 50 even on three sprays of Lenzetto daily = 450 mg of estradiol). On Lenzetto + Utro, my FSH levels dropped to pre-menopause levels (from 32 (>30 = post-menopause) to 11), and the gynaecologist thinks that is what restarted periods.
Like you say, it would seem some do not absorb body-identical hormones properly. I feel much more stable on Kliofem. That does not mean I intend to stay on it forever, but at least until age 54-55 when most women have stopped having periods. If I go back on body-identical hormones before that, I am afraid periods will start again. I am aware of the increased risks related to oral estrogen, but also understand that in otherwise healthy postmenopausal women under 60 (no family history of heart disease or VTE), oral estrogen is considered safe when used for no more than five years. The side effects reported in the past seem more related to CEE (Premarin) than to body-identical estradiol which is used in Kliofem.
I stopped eating gluten years ago due to autoimmune thyroid disease, so practically all carbs I eat come from vegetables and unsweetened berries. I favour healthful fats like coconut oil, olive oil, and fatty fish, and eat a lof of lean protein. Thyroid disease can mess you up terribly, and affect blood glucose metabolism, so many thyroid patients have insulin resistance to some degree even if they eat a healthy diet and exercise regularly. I also had high LDL and triglyceride levels until I was optimised on thyroid hormone treatment so there is definitely a connection. It seems the body has more difficulty regulating hormone production when your thyroid hormone levels are off as all endocrine hormones interact.
Oral estrogen also decreases the main thyroid hormone, free T4, by increasing thyroid-binding globulin, so I need more thyroid hormone since starting Kliofem. However, having no hot flushes/night sweats and no periods are worth it for me for the time being.
There are many medical websites where insulin is described as a fat-storing hormone so I guess it[´s all about the chicken and the egg...does insulin resistance cause weight gain or weight gain insulin resistance?
I am just surprised my insulin levels went up so much, as insulin is normally secreted in response to increased blood sugar levels, but my blood sugar is in range.

That does not mean I intend to stay on it forever, but at least until age 54-55 when most women have stopped having periods. If I go back on body-identical hormones before that, I am afraid periods will start again

On Lenzetto + Utro, my FSH levels dropped to pre-menopause levels (from 32 (>30 = post-menopause) to 11), and the gynaecologist thinks that is what restarted periods.

Is it possible that your dr isn't explaining this properly to you? (Or are they confused?)

HRT can't restart periods (not natural periods.) Once our ovaries have packed up and there are no eggs left, we don't have periods.

If your FSH level showed pre -menopause, then the obvious answer is you are not yet post menopause, and the periods you had were in fact natural ones.

If HRT caused periods, (natural ones) and restored fertility, women would be fertile (in theory) forever.
It would also mean that all the women using that combination would be having 'periods' and they aren't!

On a cyclical, (monthly) HRT regime (progestogen for 12 days per month) there is a withdrawal bleed at the end of each month. It's definitely not a 'period' in the true sense.

Some women who have high levels of estrogen (either in peri meno or with their HRT dose) and who use Utrogestan do get breakthrough bleeding but it's not regular. This is because Utrogestan is poorly absorbed when taken orally and it doesn't control the build up of the lining enough. To correct this, the dose can be increased to 200mgs every day, or the 100mgs dose used vaginally which improves absorption. It can also be taken with food (contrary to the instructions) as this doubles the concentration in the blood stream (when taken orally.)

You and your dr are right in that oral estrogen ( metabalised by the liver) can raise low density lipid levels. This is why it's not recommended for some women.

does insulin resistance cause weight gain or weight gain insulin resistance?
I thought it was accepted that insulin resistence caused loss of weight, as one symptom of undiagnosed diabetes is weight loss. But, many people with diabetes are overweight, and being overweight/ bombading the body with refined carbs can cause insulin resistence in the long term.

There is also a genetic link to diabetes, where diet and weight are not the overriding factors.

Basically, I'd suggest you try body-identical estrogen again - you can try a patch, or gel, as Lenzetto seems notorious for being poorly absorbed. Try using Utrogestan either a) with food or b) vaginally.

There are loads of women here on the forum using transdermal estrogen and Utrogestan and we don't have periods with it (unless using it on a cycle, giving a false period.) I've used it for many years.

I hope you find a way through this!

Thank you, I think my doctor did not express herself very well. I guess my problem with Utrogestan was that it was not absorbed well enough which could explain why my progesterone levels remained very low (bottom of range) on it, which can of course lead to estrogen dominance. My doctor has also mentioned the possibility of adding Duphston (dydrogesterone) 10 mg daily to transdermal estrogen instead of Utrogestan. It would seem it is very close to body-identical progesterone and has far less side effects than progestins.
Of course, I always took Utrogestan on an empty stomach as I was told to do so...
It is not always easy to find a solution as there are so many possible combinations of drugs and they all have side effects and interactions...
Thank you again!

Oh, I had no idea Lenzetto is known to absorb poorly...I thought that, since it[´s a spray and dries very quickly, it would absorb better than for instance Oestrogel...maybe the latter is better after all unless I can get patches.

Is the dr you see, a mainstream dr? NHS? Private but not at a clinic offering unlicensed 'bio' identical HRT?

I can't help feeling that you have not been given sound advice and information.

For example, it's not usual to ever test progesterone levels in women who are post menopause (or on HRT.) It's pointless.

Are you having to pay for all these tests?

There is no such thing as estrogen dominance. It's a term that originated in the US by a dr selling a progesterone cream.

Women do not need progesterone, pst menopause, it's only used to help control the stimulation of estrogen on the womb lining. Women who are not on HRT have no progesterone post menopause (as it'sonly produced as a result of ovulation.) Women who use estrogen-only HRT (women who have had a hysterectomy) do not suffer with 'estrogen dominance.'

Sorry if this sounds like a bit of a lecture, but I'm just wondering if your dr has been using these terms.

Dydrogesterone is not available in the UK as a separate progestogen. It is only available in tablet form, in the tablet form of HRT Femoston. A lot of women would love to use it as a separate progestogen but can't.

Does your dr not know this?

(I think it's possibly available in Ireland but you say you are in the UK.)

TBH I'd consider changing your dr. At the very least they ought to know all of the above, and not be doing tests for progesterone.

Saying this kindly, but it looks as if you have got into a muddle because your dr isn't giving you sound advice. They really ought to know that taking Utrogestan with food 'increases the bioavailability' (this is online for anyone to see.)

IMO and it's only that, you were probably not post meno after a year (it's not black and white- some younger women like you go for a year then their periods resume.) If you had regular monthly bleeds (and not just breakthrough spotting) that is 99.9% a normal period and nothing to do with the type of HRT.

You would probably be better off using a cyclical regime (Utrogestan for 12 days a month) for a year which will give you a predictable monthly withdrawal bleed.

And change to gel rather than spray.

HTH!

Thank you for this message and words of encouragement!
Yes, I am seeing a private doctor and I am paying for these tests myself.
My doctor did not mention dydrogesterone not being available separately; she only mentioned trying it instead of Utrogestan. She did mention Femoston as one option if I prefer to stay on oral estrogen, as it is convenient to take all hormones in one pill.
I think what you say about not taking enough progesterone to stop breakthrough bleeding is interesting as no doctor has ever mentioned this to me. I was told you either take 100 mg of Utrogestan daily or 200 mg for two weeks every month, but never that you could take 200 mg continously. And yet, I told my doctor I was sick and tired of starting bleeding again.
Right now, I need a high dose of estrogen - on 2 mg of oral estradiol daily, I managed to get estradiol levels up to a point where the hot flushes and night sweats disappeared. Lenzetto never did that for me, possibly because I did not absorb it properly.
I am paying for a lot of tests and I am honestly not sure if they are all needed!
Especially my progesterone levels seem to be all over the place and never stable the way estradiol levels seem to be on HRT. So not sure how much these tests really tell us.
I have read about some women not taking progesterone with estrogen even if they still have a womb, as the risk of endometrial cancer is still very low. Some doctors (in the US) recommend that women with irregular periods take progesterone for two weeks every three months. That will produce a bleed every three months, possibly a more heavy and prolonged one, but at least that would be more predictable than breakthrough bleeding and irratic spotting. It would seem that, in 10.000 women, only one will develop endometrial cancer as a result of not being on daily prog or prog for 12 days a month (from what I read). So, some doctors do not agree you always have to take progesterone every month if you still have a womb. It would seem some women feel so bad on progesterone that they try taking estrogen only, and they feel much better once they are off prog. I was just so relieved when periods stopped, life became so much easier...and when they restarted I said to myself: "oh, no, please, this cannot be happening"...! All I cared about was making them go away and, so far, Kliofem is the only drug that achieved that (but then, of course, I never tried an estradiol gel/patch and/or 200 mg of Utrogestan daily).
Interesting what you say about estrogen dominance being a myth; there are several US doctors writing about this condition in their blogs and, as you say, they all promote progesterone cream and sometimes their own supplements, like DIM.
Thanks again, your advice is much appreciated and has given me a lot to think about!

Sorry you have had confusing info.

Can you find another dr? I'm sorry but this one doesn't sound great.

I have read about some women not taking progesterone with estrogen even if they still have a womb, as the risk of endometrial cancer is still very low.

Drs in the UK cannot prescribe estrogen-only if the woman has a womb. It's against licensing laws.

What they can do is vary the amount and the length of the cycle, as you have described, but that is all off-licence. It's done alongside regular scans to check all is ok and this is private treatment usually.

The risk of hyperplasia on estrogen-only is 20% in 1 year. Of that number, there will be a small percentage of cancer or pre-cancerous changes.

I think you need to find a dr who is more informed and not charging you for non-essential tests.

@AnnaS70 Picking up on a couple of points.
Yes, it's quite possible to be on a longer cycle of 2 -3 months when in peri (I was put on a 3-month cycle first by my gynae.) I am now still on a cycle longer than 4 weeks, years post meno, but I pay for scans every now and then to check things are ok. (This is privately.)

But no dr could ethically prescribe estrogen-only.

There is actually a 3-month tablet form of HRT called Tridestra, aimed at women in peri.

My feeling is that when you started HRT it was quite likely you were not actually post menopause. If you started having a regular bleed every month, that is not breakthrough bleeding from HRT or HRT causing your periods to start again (it simply doesn't do that.)

Most women do not have more periods after a 12-month gap but some do, especially if their periods stopped in their 40s.

It's quite possible that its not Kliofem that has 'stopped' the bleeding but that your own periods have now stopped for good.

From what you have said, I have no confidence in whoever is treating you. They are testing you when it's not necessary, and worse! The British Menopause Society issued new guidance on progesterone in January. In women who carry on bleeding on HRT, the daily dose of Utrogestan can be increased to 200mgs daily.

I don't think this applies to you for the reasons I've already said- like you were not really post meno when you started a continuous regime.

Maybe you ought to switch drs, even go to your GP, and try the usual regime of gel and Utrogestan ( 100mgs daily) and see how that goes.