Making sense of Clomid results

[FlemSnopes]

Cross-posted from the main forum:



My doctor put me on 50mg/day of Clomid. Initial results were decent: total testosterone jumped from 305 to 520 and free testosterone went from 70 to 170. However, a few months later, my free t had dropped to 150. Doctor told me to experiment with the dosage, so I cut it in half. After a month of 25mg/day, my total t had dropped to 420 and my free t was down to 100. I've since jumped back up to 50mg/day but don't feel anything like I did in the beginning.

What I found interesting were the LH results:
1) Baseline, pre-Clomid: 2.5 (Free T: 70)
2) Clomid, 50mg/day: 3.5 (Free T: 170)
3) Clomid, 25mg/day: 4.7 (Free T: 105)

I'm trying get to the meaning of these discrepancies, as my doctor seems uninterested. What could account for higher LH but lower testosterone numbers at the lower dosages?

I've asked everywhere on the internet about this and no one seems to have much of an answer. My best guess is that my pituitary just doesn't function well, even if allowed to produce as much LH as it can (by way of maximal estrogen blockage from the Clomiphene).

Any ideas?

[hammerheart]

It's not the LH the issue it's with clomid being a mixed estrogen agonist/antagonist. At the hypothalamus/pituitary you see an increase in LH leading to increase total test levels, but in the liver it will stimulate sex-hormone binding globulin (SHBG), a protein that binds testosterone and render it unavailable, hence free Test goes down.

You are not quite the first complaining about poor response to clomid despite actual elevation in total Test. Some weeks ago a guy posted some bw showing levels up to 1000 ng/dl and he didn't feel any better.

[FlemSnopes]

Yeah, I know a lot of guys feel the same or worse on clomid despite elevated Test levels.

I'm just confused because my free test initially went up by a larger margin than my total test. (305-520 vs. 70-170). That would indicate a depression of SHBG, rather than the typical elevation.

Then LH actually went up at the lower dosage, but total and free test both dropped severely. I was cutting at the time, but it was a very moderate cut so I don't know if it would have skewed the results.

[hammerheart]

Yeah, I know a lot of guys feel the same or worse on clomid despite elevated Test levels.

I'm just confused because my free test initially went up by a larger margin than my total test. (305-520 vs. 70-170). That would indicate a depression of SHBG, rather than the typical elevation.

Then LH actually went up at the lower dosage, but total and free test both dropped severely. I was cutting at the time, but it was a very moderate cut so I don't know if it would have skewed the results.

It's difficult to predict where your values will land at. Androgens (Test) will compete to down-regulate SHBG, but just like clomid the estrogen from LH stimulation can shift balance toward up-regulation.

[hammerheart]

Take a look here

https://www.nebido.com/tools/index.p...ree-calculator

If you input your data and play with values you can estimate SHBG at multiple points.

At baseline (tT 300, ft 7) it was 25. At (520, 17) it would have been 10.

[Mr.BB]

Cross-posted from the main forum:



My doctor put me on 50mg/day of Clomid. Initial results were decent: total testosterone jumped from 305 to 520 and free testosterone went from 70 to 170. However, a few months later, my free t had dropped to 150. Doctor told me to experiment with the dosage, so I cut it in half. After a month of 25mg/day, my total t had dropped to 420 and my free t was down to 100. I've since jumped back up to 50mg/day but don't feel anything like I did in the beginning.

What I found interesting were the LH results:
1) Baseline, pre-Clomid: 2.5 (Free T: 70)
2) Clomid, 50mg/day: 3.5 (Free T: 170)
3) Clomid, 25mg/day: 4.7 (Free T: 105)

I'm trying get to the meaning of these discrepancies, as my doctor seems uninterested. What could account for higher LH but lower testosterone numbers at the lower dosages?

I've asked everywhere on the internet about this and no one seems to have much of an answer. My best guess is that my pituitary just doesn't function well, even if allowed to produce as much LH as it can (by way of maximal estrogen blockage from the Clomiphene).

Any ideas?

You are looking at the results of bloodwork taken at specific dates, those values go up and down everyday. Hormones are released in pulsatile fashion, plus a lot of other variables can influence one single result. The day after results could have been completely different.

Still, the regulation seems to be working, your body adjusting the LH to the free T level.

[FlemSnopes]

Thanks. I knew that calculator existed, I just couldn't remember where it was.
I was just able to dig up my albumin results from earlier this year - 5.2 g/DL (Range: 3.5-5.2).
Assuming that's stayed the same since the early results, I'd be at:

February: 305 Total T, 7.0 Free T, 19 SHBG
April: 520 Total T, 17.0 Free T, 4 SHBG
August: 420 Total T, 10.5 Free T, 17 SHBG

That can't be right.

Nutty possibility: the nurse drawing my blood in April was hot and I was sporting a stiffy during the test. Results skewed? The August results make more sense than the April results.

[Mr.BB]

but in the liver it will stimulate sex-hormone binding globulin (SHBG), a protein that binds testosterone and render it unavailable

SHBG is an hormone on its own, it even has specific receptors.

We need it as much as any other hormone, although it is very misunderstood.

Trying to clear some misunderstandings here: Interactions of sex hormone-binding globulin with target cells

[FlemSnopes]

SHBG is an hormone on its own, it even has specific receptors.

We need it as much as any other hormone, although it is very misunderstood.

Trying to clear some misunderstandings here:

Thanks, I'll read that. Does SHBG fluctuate as wildly as my results would indicate? Bizarro's post indicates that there's competition for up-regulating and down-regulating, meaning it should presumably stay within some confined range. And, indeed, my August results are pretty close to my February - pre-Clomid - results for SHBG. The April one is wayyyyy out of range.

I got more blood drawn yesterday, back at 50mg/day. I'll find out today or tomorrow if the results are more like April or August.

[FlemSnopes]

Oops, just ran across my life insurance bloodwork results from May - lower albumin score in that of 4.4. Assuming my April albumin is more like May than February, my results would look like:


February: 305 Total T, 7.0 Free T, 19 SHBG (confirmed albumin of 5.2)
April: 520 Total T, 17.0 Free T, 11 SHBG (assumed albumin of 4.4)
August: 420 Total T, 10.5 Free T, 22 SHBG (assumed albumin of 4.4 again)


If this is more accurate, then it looks like the August results show an elevated of SHBG at 25mg/day of clomid (from the 19 SHBG baseline). The April results are still crazy but not quite as crazy.

[Mr.BB]

Thanks, I'll read that. Does SHBG fluctuate as wildly as my results would indicate? Bizarro's post indicates that there's competition for up-regulating and down-regulating, meaning it should presumably stay within some confined range. And, indeed, my August results are pretty close to my February - pre-Clomid - results for SHBG. The April one is wayyyyy out of range.

I got more blood drawn yesterday, back at 50mg/day. I'll find out today or tomorrow if the results are more like April or August.

I dont understand your doubts, the results are logic to me.

Higher free T, lower LH. Lower free T, higher LH. Pretty much how it works (in a rudimentary way of explaining it).

[FlemSnopes]

I dont understand your doubts, the results are logic to me.

Higher free T, lower LH. Lower free T, higher LH. Pretty much how it works (in a rudimentary way of explaining it).

They just seem inconsistent. You're clearly really well-informed on this stuff, so I'm not doubting what you're saying for a second, Mr.BB . But, to me, it looks like this:

February: LH of 2.5, Free T of 70, Total T of 305
April: LH of 3.5, Free T of 170, Total T of 520
August: LH of 4.7, Free T of 105, Total T of 420

So from February to April (baseline to Clomd 50mg/day) there's higher LH and higher Free T AND higher Total T.
From April to August (50mg to 25mg), there's higher LH and lower Free T and lower Total T.

So, to me, it appears that your rudimentary explanation (+Free T, -LH) works when looking at April to August, but not from February to April. I am assuming that clomid's primary causal role vis a vis testosterone production is an increase in LH.

[hammerheart]

SHBG is an hormone on its own, it even has specific receptors.

We need it as much as any other hormone, although it is very misunderstood.

Trying to clear some misunderstandings here: Interactions of sex hormone-binding globulin with target cells

What for?

We found that adding dihydrotestosterone or estradiol to SHBG that was already bound to LNCaP cells caused a rapid rise in intracellular cAMP, However in human prostatic explants, estradiol but not dihydrotestosterone was active in generating cAMP. The agonist activity of estradiol was exceeded by that of 5a-androstant-3a,17b-diol , a steroid formed in prostate by the 3a reduction of dihydrotestosterone. These surprising results showed not only the steroid specificity of the SHBG-RSHBG second messenger system, but also a lack of response to the prostate’s most active androgen dihydrotestosterone. That this response was not mediated by the estrogen receptor (ER) was shown by a lack of effect of diethylstilbestrol (which does not bind to SHBG) and the inability of a classic ER blocker, tamoxifen, to modulate the response.

The only evidence is prostate cancer cells need SHBG as a catalyst for estradiol to GROW.

The article also points out that these effects are mediated in a autocrine fashion ie. intracellular SHBG, likely synthesized there - not plasma SHBG.

Higher sex hormone-binding globulin and lower bioavailable testosterone are related to prostate cancer detection on prostate biopsy.

[Mr.BB]

Yes, I'm excluding the baseline, no treatment, clearly your HPTA was not functioning properly.

And I'm also excluding the clomid dosage, most drugs after reaching the saturation dosage dont add that much.

Have to say again that this hormones have pulsatile patterns, so looking at "snapshots" can sometimes be misleading.

[FlemSnopes]

Yes, I'm excluding the baseline, no treatment, clearly your HPTA was not functioning properly.

And I'm also excluding the clomid dosage, most drugs after reaching the saturation dosage dont add that much.

Have to say again that this hormones have pulsatile patterns, so looking at "snapshots" can sometimes be misleading.

Yeah, the snapshot problem is one reason I've gone back for more bloodwork. I'll post it here as soon as I get it.

[Mr.BB]

What for?



The only evidence is prostate cancer cells need SHBG as a catalyst for estradiol to GROW.

The article also points out that these effects are mediated in a autocrine fashion ie. intracellular SHBG, likely synthesized there - not plasma SHBG.

Higher sex hormone-binding globulin and lower bioavailable testosterone are related to prostate cancer detection on prostate biopsy.

Yes, clearly more studies are needed on SHBG, like the study points out. My point was that there is a role for SHBG, which is not only to regulate the free portion of sex hormones.

Personally not really interested in it, as there are no Rshbg in skeletal muscles

[FlemSnopes]

Last thing I post before I get my results:

I'm apparently hypothyroidal. My TSH is at 4.7 on a 0.4-4.5 range.
My limited understanding of the effects of hypothyroidism is that it causes an underresponsiveness of LH production when exposed to gnrh. Might that explain the relatively modest boost in LH - a baseline of 2.5 up to a max of 4.7? I've seen some guys on Clomid go up to +10 on LH from levels near my baseline.

[Mr.BB]

Last thing I post before I get my results:

I'm apparently hypothyroidal. My TSH is at 4.7 on a 0.4-4.5 range.
My limited understanding of the effects of hypothyroidism is that it causes an underresponsiveness of LH production when exposed to gnrh. Might that explain the relatively modest boost in LH - a baseline of 2.5 up to a max of 4.7? I've seen some guys on Clomid go up to +10 on LH from levels near my baseline.

So, your low T is caused by hypothyroidism?

No free T3 and free T4 values? Have you tested thyroid antibodies?

[FlemSnopes]

So, your low T is caused by hypothyroidism?

No free T3 and free T4 values? Have you tested thyroid antibodies?

Free T4 was tested in February at 1.2 on a 0.8-1.8 range. No T3 numbers as far as I see.
I met with a urologist for my Testosterone stuff. Maybe I need to see an Endo instead.

[FlemSnopes]

I know I said I was going to zip up until I got more results, but this got me thinking:

Should I delay my planned cycle until after seeing an endo? I was really hoping to run testosterone + anavar for my recreational track season, with an 8 week cycle going from November to January. First cycle, don't want to go testosterone only, reasons discussed in separate thread.

If my HTPA is already functioning poorly, would shutting down for 8 weeks be a terrible idea? I guess what I'm asking is this:
* If my hypothyroidism is inhibiting LH production (when exposed to GNRH), thus causing hypogonadism
* THEN is my HTPA at some special risk of being further impaired by a shutdown - moreso than the average guy?

If I can run my cycle and PCT, wait till the competitions are over, then go to an endo for thyroid medication to clear it all up, I'd be pretty pleased. Don't know if that's unnecessarily risky though.

[Mr.BB]

If you dont feel good you need to treat the thyroid, and find a balance between thyroid and sex hormones.

So, yes, I would postpone blasting.

[hammerheart]

Get thyroid fixed first. Testosterone augments thyroid hormone requirements, if dysfunction is present this can wreak havoc on your system, though yours only appear to be minimal. You won't need more than 25-50mg levothyroxine.

[FlemSnopes]

Thanks for the advice, guys. I will try to see an endo around here, but all of them appear to require a referral from another doctor. My primary care physician doesn't think 305 total testosterone is low, so I'm not sure she'll think I need to see an endo at all. My urologist is a good guy and might be willing to.

[FlemSnopes]

Unless, of course, there's any chance the uro himself would prescribe the levothyroxine. I have no idea if urologists ever prescribe something like that.

[FlemSnopes]

Finally got results - 50mg ED from August to mid-October brought me to

Total T: 556
Free T: 13.7
LH: 6

There's the snapshot thing about LH.

Doctor wouldn't give a script for HCG (which he sometimes referred to as "BCG") on the theory that it's too expensive (?). Wouldn't put me on TRT because I want kids. He did get me referral to an endo....whose waiting list is 6 months long.

[The_Crawfish]

Doctor wouldn't give a script for HCG (which he sometimes referred to as "BCG") on the theory that it's too expensive (?). Wouldn't put me on TRT because I want kids. He did get me referral to an endo....whose waiting list is 6 months long.

Run away from him for your trt needs...this paragraph proves he doesn't know what he's talking about