Interesting Gender Research Findings RE: Levodopa Absorption Rates

[BeedieBird]

I read this morning in my Women's Parkinson's Project Newsletter the following and found it very interesting. I'm glad to see some research that deals with gender differences in Parkinson's for better treatment options.

The following copied from the above newsletter written by Richelle Flanagan. womensparkinsonsproject.com...

A recent study by Contin et al (2022) looked at the absorption rates of levodopa into the body. They found that women absorbed levodopa 27% more than men.

As a result of this higher absorption rate, women also had higher levels of levodopa-induced dyskinesia. Of note younger people also tend to suffer more from dyskinesia.

Whilst this study did not find body weight as a causative factor for the higher absorption in women, another recent study by Conti et al (2022) found that the body mass index (BMI), was a factor. These authors also suggest other causative factors such as women having a slower rate of gastric emptying and approximately 25% less COMT enzyme (which breaks down levodopa) than men.

Another interesting finding by Contin et al (2022) found a 20% higher absorption of levodopa in patients treated with levodopa/benserazide versus levodopa/carbidopa formulation. These are all important findings for women with Parkinson's. Considering that women seem to suffer more from levodopa-induced dyskinesias which can be very debilitating especially when women are invariably juggling work and family commitments, it would seem unbelievable that there is not more research to develop more personalized, gender-based dosing guidelines. If you are suffering from levodopa-induced dyskinesia you should consider bringing these papers to your neurologist to discuss more individualized levodopa therapy.

pubmed.ncbi.nlm.nih.gov/363... - 1st paper

pubmed.ncbi.nlm.nih.gov/125... -2nd paper

[Smokeypurple]

Brilliant - thank you. We all read things as and when they become relevant otherwise we'd go pop. Your post and this one by Esperanto are fascinating.

healthunlocked.com/cure-par...

This page is also linked in the latest update (bottom of original post) to this post by park_bear which is how I found it.

healthunlocked.com/cure-par...

I started c/l in January and started getting involuntary movements in my ankle about 5 months later. I'm met with almost incredulity at the hospital as I'm early stage and on a very low dose. Now I have something to digest and take with me to my next appointment. It seems obvious to me that appropriate dosages must vary enormously. I'm young, small and female - from what I read they are all factors which might mean I need to be careful with what is generally used as a starting dose.

[Esperanto in reply to Smokeypurple]

Remarkable that you are startet rather late with C/L after your diagnosis (5 years ago?). It is interesting to know what the doctors considered a good (exhausted) starting dose for you and whether you are still at that same level. 🍀

[Smokeypurple in reply to Esperanto]

Hey Esperanto good to hear from you.

I was diagnosed 7 years ago - early diagnosis perhaps, slow progression, diet/exercise/mind changes implemented. I started Rasagiline 2 years ago with no negative effect and slight improvement. It was all ok - with effort in those areas - until it was too much like hard work. At my appointment in Jan they said 'it's time to start levadopa' and I replied, 'that's what I'm here for today, what do you recommend?' They nearly fell over - had me down as a 'refuser' I think.

Starting dose was 12.5/50 3x a day for a fortnight then to go up to 25/100 thereafter. I did go up to 25/100 but went down again as it felt like too much. I was very happy with 12.5/50, exercising and doing yoga like a pro again, playing my violin (the only time I'd take a dose of 25/100 was for the dose ahead of a concert to make sure finger wiggle was up to scratch), back to super sociable self, normal levels of engagement in the world without feeling like i was pushing myself (although I'll never know what was Covid social contraction and what was Parkinson's in that regard)

All good until May - twitchy big toe which after a few weeks turned into twitchy foot.

Generally about 30 mins after dose.

Now it lasts about 2 hours starting 30mins after the dose. I tried reducing the dose further, which did reduce dyskinesia (assuming that's what it is) but it didn't give me enough dopamine (the c/l makes a clear difference). I mentioned it in June at my appointment but it had only recently started and i don't think they could get their heads round it as I'm on such as small dose.

So I'm reading around hence finding your post.

[park_bear in reply to Smokeypurple]

Clearly dyskinesia. A timed to release version of C/L definitely worth a try.

If the MD is in denial I suppose you could take a dose a half hour before your next appointment. If they remain in denial best to find another MD.

[Juliegrace in reply to Smokeypurple]

I had dyskinesia at four months in on low dose c/l. I take c/l 10/100 because it has less absorption than 25/100. Many years in now and I’m not sure how much of a difference it has made though.

[Smokeypurple]

Thanks for sharing Julie. I'm not sure we can get prescribed 10/100 in the UK. I'll look into it.

[Juliegrace in reply to Smokeypurple]

Winnie the Poo takes it although he lives in France (I believe)so it should be available out of the US., hopefully in the UK.

[Esperanto in reply to Smokeypurple]

The EMC, electronic medicines compendium, indicates that Sinemet 10 mg/100 mg Tablets is available in the UK (as in most European countries); Company:  Organon Pharma (UK) Limited; ATC code: N04BA02

Thanks for the clarification. I myself also take 4 x half 10/100 Sinemet IR per day in France, being below the starting dose of 3 x 10/100 1.5 years ago. After six months, by the way, this had been increased to 5 x 20/200. So irresponsible… Given that, as a woman, you probably need half the C/L and, moreover, with your smaller height and weight, another half will suffice, It is actually irresponsible of C/L pharmas to produce only such large units.

There might even be an argument in your case for working with quarters (even of the 25/100) and taking them more frequently. A pill cutter would come in handy.

[Smokeypurple in reply to Esperanto]

That's a really interesting point - the more I read, the more I agree about smaller doses. Once you start chopping and chopping the dose accuracy must get lower though. You're right, female, small, young onset. I'll make a plan tomorrow!

Come to think about it the nurse did say that she wasn't going to recommend goimg up to 'full dose' as initially planned as women of low weight could be more likely to get dyskinesia and we needed to be careful.