Stopping Testosterone Injections for Enclomiphene

Cataceous

Well-Known Member
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If enclomiphene is really estrogen ANTAgonist everywhere in the body, including bones, it can lead to osteoporosis because it will then block the action of estrogen on bones. That applies to men too, not only to women.
But the point of enclomiphene is that it is selective. It does not antagonize all estrogen receptors equally. Regarding bone health in particular, this study measures osteocalcin and carboxy‐terminal collagen as a proxies. The authors conclude that "Treatment with enclomiphene citrate did not significantly affect levels of ... bone markers."
 

sammmy

Active Member
Cataceous, the study is excellent in terms of terms of measurements.
However, the authors conclusion misrepresents the change in bone markers, which can be found in Table 4:

Table4.JPG

It is clear that bone formation markers carboxyterminal collagen and osteocalcin decreased in ALL enclomiphene groups and osteocalcin increased ONLY in the transdermal testosterone group.
The authors conclude that these changes are "not significant" because their treatment groups are rather small (~12 people each), and with such small samples it is not possible to discern such changes in the markers from random sampling fluctuations. However, if you take into account the fact that you see a consistent DECREASE of the two markers in all enclomiphene groups, the probability for random fluctuations to all align in the same direction 6 times is rather small (it's like flipping a coin 6 times and getting 6 heads).

The correct conclusion should have been "although the mean bone formation markers were reduced in all enclomiphene groups, these changes did not reach statistical significance due to the small sample sizes".

Medical people always make that error. "No (statistically) significant difference/change/effect" does not mean that there is no change. It means that the study could not prove a change, either because there really isn't one or because the sample size was too small and the study does not have the statistical power to claim the observed change is not random, which is what I think is happening in this study.
 
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Cataceous

Well-Known Member
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The correct conclusion should have been "although the mean bone formation markers were reduced in all enclomiphene groups, these changes did not reach statistical significance due to the small sample sizes".
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If you want to instead assume they are statistically significant then look at the magnitudes. The decline of all values averages 11%. A normal range for osteocalcin is 8-32 ng/mL. If you are average then enclomiphene may reduce osteocalcin from 20 to 18 ng/mL. That is minor, and is not going to push guys into osteoporosis, just as a drop in total testosterone from 680 ng/dL to 600 is not going to cause hypogonadism. The same applies to the CTx marker.

These data give me no reason to worry about osteoporosis.
 

sammmy

Active Member
You are right. I am not familiar with these markers but from what I see online, actually a decline in them means less probability for osteoporosis. That was probably related to the increased circulating estradiol that the study didn't measure.

It is strange why osteocalcin increased in the transdermal testosterone group but that could be easily attributed to a random fluctuation.
 

Cataceous

Well-Known Member
I'm getting the sense that low or high levels of either marker may be associated with osteoporosis. [R][R]

One hour of exercise, 3 times per week for 12 weeks, increased osteocalcin levels and bone mineral density in 29 women with osteoporosis (with an age range of 71 to 78) [25].
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High osteocalcin levels indicate higher bone turnover.
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These ... can be caused by:
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  • Osteoporosis [42]
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What Do Low C-Telopeptide Blood Test Results Mean?
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... The most common reason for a low test result is because of age-related osteoporosis. Secondary osteoporosis is also an option, which occurs when there is an underlying condition that is contributing to bone loss. ...
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What Do High C-Telopeptide Blood Test Results Mean?
Having high levels of bone markers in the blood or urine could suggest the presence of elevate[d] bone resorption and this may be an indicator of osteoporosis as well. ...
 

sammmy

Active Member
I looked at Anastrozole as a good example of a drug that induces osteoporosis due to reduction of estrogen activity in the body (due to reduced estrogen production). This is a model of what could happen if enclomiphene blocks the estrogen receptors in bones i.e. reduces the estrogen activity there despite the elevated circulating estrogen.

Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates:
In the surveillance group, anastrozole induced after 1 year of treatment a marked bone loss at the spine (mean ± S.E.M., [95% confidence interval]) − 3.3 ± 0.4% [− 4.1 to − 2.5]), and hip (2.8 ± 0.4% [− 3.6 to − 2]) that was significantly greater than in controls (p < 0.0001). Anastrozole induced an increase in bone remodelling: osteocalcin (+ 36.6%, p < 0.0001) and CTX (+ 34%, p < 0.0001).
So in this case, an increase of the bone markers CTX and osteocalcin is correlated with bone loss.
 
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goolapsh

Member
As a side question does anyone know how long it takes for defy to ship the ordered medication. I ordered last Wednesday and they still haven’t shipped it. So far I’m not impressed with the follow through from the company but I like the doctor.
 

TLawyer

Member
As a side question does anyone know how long it takes for defy to ship the ordered medication. I ordered last Wednesday and they still haven’t shipped it. So far I’m not impressed with the follow through from the company but I like the doctor.
I think it's more on the pharmacy than Defy. Usually takes a week for me to get mine.
 

goolapsh

Member
What is the significance of Enclomiphene reducing Igf-1 levels? What side effects does that cause. Btw I started Enclomiphene 25mg Daily (doctor prescribed this amount for me) four days ago and it’s disrupting my sleep and draining my energy just like clomid did. I’m so sensitive to pharmaceuticals. Don’t know how long I will stay on it now but ain’t lookin good at the moment.
 

TLawyer

Member
What is the significance of Enclomiphene reducing Igf-1 levels? What side effects does that cause. Btw I started Enclomiphene 25mg Daily (doctor prescribed this amount for me) four days ago and it’s disrupting my sleep and draining my energy just like clomid did. I’m so sensitive to pharmaceuticals. Don’t know how long I will stay on it now but ain’t lookin good at the moment.
That seems like a high daily amount, especially if you are experiencing side effects. Defy started me on 12.5 mg daily and so far so good.
 

goolapsh

Member
That seems like a high daily amount, especially if you are experiencing side effects. Defy started me on 12.5 mg daily and so far so good.
Doctor from defy changed me from 12.5mg clomid to 25mg enclomid. Not sure why? Maybe he’s seen that the potency isn’t as strong as clomid. But even at 12.5mg clomid I was having this issue. It causes me to have poor sleep and then I’m groggy the next day with a headache. I’m gonna keep taking it for another week or so and see if I can push through this. My job is demanding so I can’t really afford bad sleep.
 

Cataceous

Well-Known Member
is this in conjunction with testosterone?
do you notice any benefits?
Yes, it was with TRT, used to ensure pituitary activation in this experiment. The subjective results were good, with improvements in libido, etc. It is a complicated protocol, however. More recently I am finding that the enclomiphene may not be necessary, at least with a low enough TRT dose.
 

camygod

Member
Yes, it was with TRT, used to ensure pituitary activation in this experiment. The subjective results were good, with improvements in libido, etc. It is a complicated protocol, however. More recently I am finding that the enclomiphene may not be necessary, at least with a low enough TRT dose.
what do you think is necessary with low enough dose ? hcg?
 

Cataceous

Well-Known Member
what do you think is necessary with low enough dose ? hcg?
In the experiment GnRH is used in place of hCG. GnRH acts at the pituitary to stimulate production of LH and FSH. However, at the pituitary there is negative feedback from estrogens, which reduces its responsiveness to GnRH. What I don't know is the relative strength of this negative feedback. In a normal HPTA there is also negative feedback at the hypothalamus from both androgens and estrogens. The three types of negative feedback act to regulate our testosterone. Given that by using exogenous GnRH we bypass negative feedback at the hypothalamus, it's possible that a greater amount of exogenous testosterone may be tolerated before suppression at the pituitary becomes significant. So to answer your question, a low enough TRT dose is probably that which would give you serum testosterone levels comparable to what you'd have if your HPTA were functioning properly. And even a higher dose may work if the suppressive action at the pituitary is small relative to that at the hypothalamus.
 
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camygod

Member
In the experiment GnRH is used in place of hCG. GnRH acts at the pituitary to stimulate production of LH and FSH. However, at the pituitary there is negative feedback from estrogens, which reduces its responsiveness to GnRH. What I don't know is the relative strength of this negative feedback. In a normal HPTA there is also negative feedback at the hypothalamus from both androgens and estrogens. The three types of negative feedback act to regulate our testosterone. Given that by using exogenous GnRH we bypass negative feedback at the hypothalamus, it's possible that a greater amount of exogenous testosterone may be tolerated before suppression at the pituitary becomes significant. So to answer your question, a low enough dose is probably that which would give you serum testosterone levels comparable to what you'd have if your HPTA was functioning properly. And even a higher dose may work if the suppressive action at the pituitary is small relative to that at the hypothalamus.
fair play sounds intresting but complicated hope in the future we will have a better idea of how to make things optimal for each man
 

CKO

New Member
I'm on week six of enclomiphene and it hasn't been a positive experience. I can go into the labs and details later, but I figured I'd throw my two cents in this conversation. I went from using chlomid and HCG (local clinic) to enclomiphene, 12.5 daily, with Defy. My labs look great but I haven't noticed any benefits physically or mentally from it. Side effects include: insomnia, moodiness/anxiety, loss of libido, and eye floaters. I actually felt better on clomid and HCG. I personally can't wait to get off this or switch to a different treatment.
 

goolapsh

Member
I'm on week six of enclomiphene and it hasn't been a positive experience. I can go into the labs and details later, but I figured I'd throw my two cents in this conversation. I went from using chlomid and HCG (local clinic) to enclomiphene, 12.5 daily, with Defy. My labs look great but I haven't noticed any benefits physically or mentally from it. Side effects include: insomnia, moodiness/anxiety, loss of libido, and eye floaters. I actually felt better on clomid and HCG. I personally can't wait to get off this or switch to a different treatment.
That’s funny you mentioned the insomnia. I feel like shit on this drug and can’t sleep.
 
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