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Exemestane and IGF-1 Levels

sdstealth

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Can anyone comment on whether there are connections between IGF-1 levels and use of exemestane/Aromasin? I've seen conflicting reports on the way that different AIs affect IGF-1, and I'm especially curious if anyone can share both anecdotal and research-based info on how Aromasin may affect IGF-1. The conflicting reports are that many forum posts say that exemestane raises IGF-1, while others have said that it lowers it. To confound things, on another forum I've seen comments that Arimidex lowers IGF-1 while Aromasin raises it. I'd be grateful for any feedback, guidance, etc.

Many thanks!
 

sdstealth

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I'd have to do more in depth research on AROMASIN but I've seen solid research showing LETROZOLE increased IGF1 levels some where around 20%


Thanks, I'd be grateful for anything you can share that's legit!
 

sdstealth

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Granted this is in women with breast cancer, but exemestane does appear to have caused a 35% increase in IGF-1 levels.

Screen_Shot_2018-08-13_at_9.43.55_AM.jpg
 

MyNameIsJeff

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Suppression of estrogen, via estrogen receptor or aromatase blockade, is being investigated in the treatment of different conditions. Exemestane (Aromasin) is a potent and selective irreversible aromatase inhibitor. To characterize its suppression of estrogen and its pharmacokinetic (PK) properties in males, healthy eugonadal subjects (14–26 yr of age) were recruited. In a cross-over study, 12 were randomly assigned to 25 and 50 mg exemestane daily, orally, for 10 d with a 14-d washout period. Blood was withdrawn before and 24 h after the last dose of each treatment period. A PK study was performed (n = 10) using a 25-mg dose. Exemestane suppressed plasma estradiol comparably with either dose [25 mg, 38% (P ≤ 0.002); 50 mg, 32% (P ≤ 0.008)], with a reciprocal increase in testosterone concentrations (60% and 56%; P ≤ 0.003 for both). Plasma lipids and IGF-I concentrations were unaffected by treatment. The PK properties of the 25-mg dose showed the highest exemestane concentrations 1 h after administration, indicating rapid absorption. The terminal half-life was 8.9 h. Maximal estradiol suppression of 62 ± 14% was observed at 12 h. The drug was well tolerated. In conclusion, exemestane is a potent aromatase inhibitor in men and an alternative to the choice of available inhibitors. Long-term efficacy and safety will need further study.
https://academic.oup.com/jcem/article/88/12/5951/2661508
It's hard to crash your Estrogen levels with Exemestane, so the risk of lowering IGF-1 levels with it is also low. Especially if you use the drug to only bring your estrogen levels back into the normal range, there should be no negative effect on IGF-1.
 

MyNameIsJeff

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Here another study that compared Letrozole to Anastrozole:

Results:
Thirty-nine boys have completed 1 year of treatment. Baseline means were age 14.1 years, PAH 166 cm, and testosterone 198 ng/dL. At 1 year, letrozole resulted in higher LH (L 6.1 ± 2.5 vs A 3.2 ± 1.7 IU/L) and testosterone (1038 ± 348 vs 536 ± 216 ng/dL) with lower estradiol (2.8 ± 2.8 vs 5.6 ± 2.9 pg/mL) and IGF-1 (237 ± 51 vs 331 ± 79 ng/mL). First year growth velocities were identical (7.2 cm/year), but an increase in PAH was greater in the anastrozole group (4.2 ± 3.5 vs 1.4 ± 4.4 cm, p = 0.03) after 1 year.
https://academic.oup.com/jcem/article/99/11/4086/2836489

If you look at table 2 in the linked article, you can see that Letro decreased both Estradiol and IGF-1 levels compared to baseline, while Anastrozole left Estradiol and IGF-1 levels unchanged. Given that The letro group had much higher test levels, it is reasonable to conclude that the excessive lowering of Estradiol levels caused the lower IGF-1 levels.
 

sdstealth

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https://academic.oup.com/jcem/article/88/12/5951/2661508
Especially if you use the drug to only bring your estrogen levels back into the normal range, there should be no negative effect on IGF-1.

Thanks. I'm actually concerned in the other direction about whether exemestane could have raised it. I got some labs back with high IGF-1 (79% over the range on one and 65% over the range on another) and elevated IGF-BP3 (31.3% above the upper limit of normal). I'm concerned about acromegaly/pituitary tumor and trying to assess whether anything in my TRT protocol may have interfered with the results or skewed my IGF-1 higher.
 

MyNameIsJeff

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Thanks. I'm actually concerned in the other direction about whether exemestane could have raised it. I got some labs back with high IGF-1 (79% over the range on one and 65% over the range on another) and elevated IGF-BP3 (31.3% above the upper limit of normal). I'm concerned about acromegaly/pituitary tumor and trying to assess whether anything in my TRT protocol may have interfered with the results or skewed my IGF-1 higher.
I have not seen any studies to suggest that AIs can significantly increase IGF-1 in males.

TRT can increase IGF-1 levels a bit, but 79% above range is way too high for that. Would definitely follow up with a doctor. He/she will likely want to do a glucose suppression test, which is pretty definitive.

Indication
The oral glucose tolerance test is used for the diagnosis of acromegaly and to determine the status of remission after pituitary surgery. In normal individuals, hyperglycemia suppresses growth hormone secretion.

Preparation
NPO for at least 8 hours prior to suppression test.

Procedure
1. Baseline serum growth hormone, somatomedin-C and glucose levels
2. Administer 100 g of glucola orally over 5 minutes
3. Serum glucose and growth hormone levels at 30, 60, 90 and 120 minutes

Interpretation
In normal individuals, growth hormone suppresses below 2 ng/ml after ingesting 100 g of glucola. More sensitive assays require a growth hormone level below 1 ng/ml to rule out acromegaly. False positive results can occur in patients with diabetes mellitus. anorexia, liver failure, tall adolescents, and individuals with growth hormone resistance disorders.
https://www.vanderbilthealth.com/pituitary/15472
 

Ashop

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I have not seen any studies to suggest that AIs can significantly increase IGF-1 in males.

TRT can increase IGF-1 levels a bit, but 79% above range is way too high for that. Would definitely follow up with a doctor. He/she will likely want to do a glucose suppression test, which is pretty definitive.


https://www.vanderbilthealth.com/pituitary/15472

Most studies I have seen have indeed been women but I doubt you
will find many ran in men.

https://www.ncbi.nlm.nih.gov/pubmed/9459192
 

sdstealth

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TRT can increase IGF-1 levels a bit, but 79% above range is way too high for that. Would definitely follow up with a doctor. He/she will likely want to do a glucose suppression test, which is pretty definitive.

Thanks. I'm having an OGTT tomorrow morning. Wish me luck!
 

sdstealth

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TRT can increase IGF-1 levels a bit, but 79% above range is way too high for that. Would definitely follow up with a doctor. He/she will likely want to do a glucose suppression test, which is pretty definitive.


Just to circle back on this, I got the results of my oral glucose tolerance test today. Completely normal at all time intervals on the test, with a fully-suppressed GH level. So whatever the cause of my elevated IGF-1, it doesn't seem to be a pituitary tumor secreting growth hormone. My body detects the rise in glucose levels and is able to both produce and respond to insulin and drop the levels of GH. The mystery deepens!
 

MyNameIsJeff

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Just to circle back on this, I got the results of my oral glucose tolerance test today. Completely normal at all time intervals on the test, with a fully-suppressed GH level. So whatever the cause of my elevated IGF-1, it doesn't seem to be a pituitary tumor secreting growth hormone. My body detects the rise in glucose levels and is able to both produce and respond to insulin and drop the levels of GH. The mystery deepens!
Glad to hear! But indeed quite puzzling. Is your doctor satisfied with this test or does he/she want to follow up? I presume an MRI could be justified to confirm. Otherwise I'd just retest the IGF-1 levels over the coming months to see where they are headed.
 

sdstealth

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Glad to hear! But indeed quite puzzling. Is your doctor satisfied with this test or does he/she want to follow up? I presume an MRI could be justified to confirm. Otherwise I'd just retest the IGF-1 levels over the coming months to see where they are headed.



Very puzzling indeed. I’m having a pituitary MRI today. I’ve found a few studies relating to patients with my presentation (elevated IGF-1, suppressable GH) who were followed for five years. Two even had MRI results that could have indicated microadenomas, but none developed active acromegaly over a five year period. I want to make sure we rule out any tumors elsewhere in the body (neuroendocrine, carcinoid) that could be hormone producing, but from what I can tell the GTT probably would have shown elevated GH if I had one of those. My liver enzymes were within range as well on a test from last month, so it’s also not clear what other diagnostics we might want to do since nothing is seeming abnormal besides the IGF-1.

The confounding factors are that I had been taking 50k IU/week of D2 for the last 8 months to correct a D deficiency, and I’ve seen some reports that connect D levels to the IGF system. I’m wondering if the high dose D combined with exemestane and TRT might have elevated the IGF outside of any disease process.

Beyond an MRI, anything else you’d suggest for further diagnostics?
 

MyNameIsJeff

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Very puzzling indeed. I’m having a pituitary MRI today. I’ve found a few studies relating to patients with my presentation (elevated IGF-1, suppressable GH) who were followed for five years. Two even had MRI results that could have indicated microadenomas, but none developed active acromegaly over a five year period. I want to make sure we rule out any tumors elsewhere in the body (neuroendocrine, carcinoid) that could be hormone producing, but from what I can tell the GTT probably would have shown elevated GH if I had one of those. My liver enzymes were within range as well on a test from last month, so it’s also not clear what other diagnostics we might want to do since nothing is seeming abnormal besides the IGF-1.

The confounding factors are that I had been taking 50k IU/week of D2 for the last 8 months to correct a D deficiency, and I’ve seen some reports that connect D levels to the IGF system. I’m wondering if the high dose D combined with exemestane and TRT might have elevated the IGF outside of any disease process.

Beyond an MRI, anything else you’d suggest for further diagnostics?
There's some evidence to suggest that VitD supplementation can increase IGF1. So with a mega dose like that, it may well have contributed. Assuming that the MRI turns out unremarkable, I would do the following: restrict VitD to 1000iu per day, ensure TRT and AI dose achieve T and E levels within normal range. Then retest IGF1 levels each month to hopefully see a normalization.
 

mujeriego

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There's some evidence to suggest that VitD supplementation can increase IGF1. So with a mega dose like that, it may well have contributed. Assuming that the MRI turns out unremarkable, I would do the following: restrict VitD to 1000iu per day, ensure TRT and AI dose achieve T and E levels within normal range. Then retest IGF1 levels each month to hopefully see a normalization.

Bit OT, but I've seen some other people suggesting on another forum I frequent that dht compounds such as proviron, mast, primo etc may have an affect on lowering igf levels. Especially from exogenous hgh use. What do you make of this? would there be any relation at all?
 

sdstealth

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There's some evidence to suggest that VitD supplementation can increase IGF1. So with a mega dose like that, it may well have contributed. Assuming that the MRI turns out unremarkable, I would do the following: restrict VitD to 1000iu per day, ensure TRT and AI dose achieve T and E levels within normal range. Then retest IGF1 levels each month to hopefully see a normalization.

I just got my MRI report. They only used a 1.5T magnet (vs the higher resolution 3T magnet), but there was no large/apparent tumor of any kind and the pituitary and sella appear normal. Here's what that section says: "The pituitary gland size is within normal limits. There is slightly heterogeneous enhancement with no definitive lesion identified. The infundibulum is midline. The suprasellar cistern is patent. The cavernous sinuses enhance symmetrically. The visualized paranasal sinuses are clear."

So either I have a microadenoma small enough that it couldn't be resolved on a 1.5T magnet, or there's no pituitary tumor.

The mystery continues to deepen.
 

Stewie

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Throwing this out there. What was your IGF-1 levels?

Are you taking any extra biotin? If so, ask your primary to check the immunoassay used to see if it's a "Biotinylated immunoassays". This may cause interference with the results showing false-high levels.
 

sdstealth

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Throwing this out there. What was your IGF-1 levels?

Are you taking any extra biotin? If so, ask your primary to check the immunoassay used to see if it's a "Biotinylated immunoassays". This may cause interference with the results showing false-high levels.

Thanks for the reply, much appreciated. Not taking any biotin that I'm aware of.

Here are my IGF-1 and IGFBP-3 results, the first one was done at LabCorp and the 2nd one (and binding protein) done at ARUP Labs (local lab sent it out).
  • First
  • IGF-1 419 ng/mL 83-233[/INDENT]
  • Second
  • Prolactin 5.9 ng/mL Range: 2.1 - 17.7 ng/mL
  • IGF-1 397 ng/mL Range: 83 - 240 ng/mL
  • IGFBP-3 6840 ng/mL Range: 2474 - 5208 ng/mL

Everything else-- blood glucose levels, liver enzymes, etc-- all were normal/within range. Up until a few months ago I was using some Masteron as an adjunct to my TRT but stopped in early June. These labs were done in July. I was still using 50,000 IU/week of Vitamin D2 during these labs as well as exemestane to manage E2. Since I've had a clear-ish MRI (the -ish being the heterogeneous enhancing area) and a normal OGTT, I'm wondering whether the combo of Vit D, exemestane, and testosterone contributed to this increased IGF-1? Hard to say. It's all very weird.

I have found a few case reports of people with a similar presentation to me (elevated IGF-1, normal OGTT) finding tiny microadenomas (~3mm) on high-resolution 3T MRIs. In those cases their IGF-1 normalized after surgery. In one case, the woman had a tiny microadenoma on MRI, the surgeon couldn't find it during surgery, they removed 1/3rd of her pituitary in the region where the MRI showed the tumor, and her IGF-1 normalized after surgery.

In the absence of any symptoms other than heat intolerance and sleep apnea, I think I'm going to ask my endocrinologist to re-test in a few months and do a 3T MRI if IGF-1 is still elevated. Thoughts? Ideas?
 

MyNameIsJeff

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Thanks for the reply, much appreciated. Not taking any biotin that I'm aware of.

Here are my IGF-1 and IGFBP-3 results, the first one was done at LabCorp and the 2nd one (and binding protein) done at ARUP Labs (local lab sent it out).
  • First
  • IGF-1 419 ng/mL 83-233[/INDENT]
  • Second
  • Prolactin 5.9 ng/mL Range: 2.1 - 17.7 ng/mL
  • IGF-1 397 ng/mL Range: 83 - 240 ng/mL
  • IGFBP-3 6840 ng/mL Range: 2474 - 5208 ng/mL

Everything else-- blood glucose levels, liver enzymes, etc-- all were normal/within range. Up until a few months ago I was using some Masteron as an adjunct to my TRT but stopped in early June. These labs were done in July. I was still using 50,000 IU/week of Vitamin D2 during these labs as well as exemestane to manage E2. Since I've had a clear-ish MRI (the -ish being the heterogeneous enhancing area) and a normal OGTT, I'm wondering whether the combo of Vit D, exemestane, and testosterone contributed to this increased IGF-1? Hard to say. It's all very weird.

I have found a few case reports of people with a similar presentation to me (elevated IGF-1, normal OGTT) finding tiny microadenomas (~3mm) on high-resolution 3T MRIs. In those cases their IGF-1 normalized after surgery. In one case, the woman had a tiny microadenoma on MRI, the surgeon couldn't find it during surgery, they removed 1/3rd of her pituitary in the region where the MRI showed the tumor, and her IGF-1 normalized after surgery.

In the absence of any symptoms other than heat intolerance and sleep apnea, I think I'm going to ask my endocrinologist to re-test in a few months and do a 3T MRI if IGF-1 is still elevated. Thoughts? Ideas?
Sounds like a plan.
 

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