Clomid (and maybe more) with Defy

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Esq

Member
My latest round of labs have come back.
.
Testosterone, Serum: >1500 ng/dL (348-1197)
Testosterone, Free (Direct): 36.3 pg/mL (8.7-25.1)
SHBG, Serum: 58.1 nmol/L (16.5-55.9)
Estradiol (Sensitive): 53.2 pg/mL (8.0-35.0)
LH: 9.2 mIU/mL (1.7-8.6)
Vitamin D, 25-Hydroxy: 63.4 ng/mL (30.0-100.0)
Cortisol, 8am: 0.16 ug/dL (0.025-0.600)
Cortisol, noon: 0.097 ug/dL (<0.010-0.330)
Cortisol, 4pm: 0.059 ug/dL (0.010-0.200)
Cortisol, midnight: 0.054 ug/dL (<0.010-0.090)
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My observations: test numbers continue to climb even higher on clomid. Total testosterone literally is off the chart. Estradiol is down to 53.2 from the April reading of 68.3 after the introduction of 0.25mg anastrozole EOD. SHBG also is down, but also still elevated slightly. Cortisol numbers all are in range, but 8am is much lower than the April labs and midnight is much higher.
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I continue to feel generally the same. The high e2 symptoms seem to be gone, though I wonder whether e2 should be brought a little bit lower. I don't want to risk crashing it, so maybe its better left alone? Again, I'm feeling much the same since before clomid. I still haven't noticed any real, sustained changes, good or bad. I am somewhat surprised that my test levels have more than doubled without (apparently) any corresponding physical or psychological changes.
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My next consult with Dr. Saya is on July 11, so we'll see what comes next.
 
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Esq

Member
Quick follow-up - I heard from the Defy medical staff today and was advised to continue with anastrozole 0.25mg EOD, so no changes there. 53 is a little high, but they believe e2 could still be in the process of coming down and stabilizing so better to leave things alone until I speak with Dr. Saya next month.
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One small additional observation - since discontinuing rhodiola and ashwaganda and beginning licorice root about 6 weeks ago, I've had several bouts of insomnia. Insomnia is not something that historically has been an issue for me, and while I'm not experiecing it nightly, it does seem to hit roughly one night each week. Maybe it is unrelated to the adaptogen changes, but I did notice that with my April labs (taking rhodiola and ashwaganda, but not licorice), my midnight cortisol was <0.010. With my June labs (taking licorice but not rhodiola and ashwaganda), my midnight cortisol was 0.054. Similarly, 4pm cortisol was 0.023 in April and 0.059 in June.
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Just wondering if higher afternoon and evening cortisol levels could be contributing to the recent onset of sporadic insomnia. I haven't otherwise noticed any changes in energy levels throughout the day and they remain quite low, espcially in the late-morning and through the afternoon.
 

Esq

Member
Posting here just to vent a bit, but I think I am pretty close to deciding that clomid just is not going to resolve my symptoms. I'm now almost 5 months into clomid monotherapy, and despite my total and free testosterone increasing dramatically and my estradiol being mostly in check (though still a little high), I continue to struggle with the same symptoms that brought me here in the first place. In fact, the past two weeks I've been feeling even worse, struggling with periodic insomnia and a significant increase in lethargy and lack of motivation. I just feel very "off" right now, even compared to baseline.
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I don't think clomid is the answer. I'll continue on my prescribed treatment until my next consult in July with Dr. Saya, but hopefully we can discuss other options then. As a precaution, I am going to meet with a sleep specialist next week and possibly have a sleep study done to rule out sleep apnea (something Dr. Saya suggested I consider early on). I don't have the normal sleep apnea precursors (not overweight, only light snoring, generally in good shape, usually sleep well (except the last two weeks), etc.), but I want to confirm because the symptoms line up. I wouldn't want to transition to more aggressive treatment without being 100% sure sleep apnea is not an issue.
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Anyway, just venting. I'm feeling particularly frustrated today.
 
Posting here just to vent a bit, but I think I am pretty close to deciding that clomid just is not going to resolve my symptoms. I'm now almost 5 months into clomid monotherapy, and despite my total and free testosterone increasing dramatically and my estradiol being mostly in check (though still a little high), I continue to struggle with the same symptoms that brought me here in the first place. In fact, the past two weeks I've been feeling even worse, struggling with periodic insomnia and a significant increase in lethargy and lack of motivation. I just feel very "off" right now, even compared to baseline.
.
I don't think clomid is the answer. I'll continue on my prescribed treatment until my next consult in July with Dr. Saya, but hopefully we can discuss other options then. As a precaution, I am going to meet with a sleep specialist next week and possibly have a sleep study done to rule out sleep apnea (something Dr. Saya suggested I consider early on). I don't have the normal sleep apnea precursors (not overweight, only light snoring, generally in good shape, usually sleep well (except the last two weeks), etc.), but I want to confirm because the symptoms line up. I wouldn't want to transition to more aggressive treatment without being 100% sure sleep apnea is not an issue.
.
Anyway, just venting. I'm feeling particularly frustrated today.

Hi ESQ, I certainly agree with the sleep study as you stated. To rule out, if for nothing else, as sleep apnea not only presents many longterm health risks but will always inhibit subjective response.

I'd like to see your E2 lower, particularly on clomid. My office should be contacting you to arrange a change in your regimen prior to our July consult. There won't be adequate time to allow retesting of sensitive E2 (as it takes a week, sometimes two to result), but will be more interested in any subjective changes at that time (and also to follow-up on sleep study results).
 

Esq

Member
Hi ESQ, I certainly agree with the sleep study as you stated. To rule out, if for nothing else, as sleep apnea not only presents many longterm health risks but will always inhibit subjective response.

I'd like to see your E2 lower, particularly on clomid. My office should be contacting you to arrange a change in your regimen prior to our July consult. There won't be adequate time to allow retesting of sensitive E2 (as it takes a week, sometimes two to result), but will be more interested in any subjective changes at that time (and also to follow-up on sleep study results).

Thanks, Dr. Saya. I look foward to hearing from them.
 

Esq

Member
Chatted with Defy a few minutes ago, and they want me to switch from 0.25mg anastrozole EOD to 12.5mg exemestane twice/week. Exemestane should arrive sometime middle of next week, and I'll make the switch.
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Dr. Saya - if you happen to read this (and I should have asked Sam this question on the phone), should I discontinue the anastrozole for any length of time before switching to exemestane? For example, if I take anastrozole on Tuesday can I take the first exemestane on Wednesday, or should I discontinue the anastrozole sooner?
 
Chatted with Defy a few minutes ago, and they want me to switch from 0.25mg anastrozole EOD to 12.5mg exemestane twice/week. Exemestane should arrive sometime middle of next week, and I'll make the switch.
.
Dr. Saya - if you happen to read this (and I should have asked Sam this question on the phone), should I discontinue the anastrozole for any length of time before switching to exemestane? For example, if I take anastrozole on Tuesday can I take the first exemestane on Wednesday, or should I discontinue the anastrozole sooner?

Discontinue the anastrozole 2 days prior to beginning exemestane.
 

SJTrance

New Member
I'm closely following this thread. I've just started my treatment of anastrozole a few weeks ago and I've been on chlomid for about 3 months. I've also had a quick boost in symptom relief in the 3rd or 4th week and then went down again.
 

Esq

Member
I'm closely following this thread. I've just started my treatment of anastrozole a few weeks ago and I've been on chlomid for about 3 months. I've also had a quick boost in symptom relief in the 3rd or 4th week and then went down again.

Wishing you good results! Some certainly seem to benefit greatly, unfortunately that has not been the case for me so far. I haven't noticed any improvement after switching from anastrozole to exemestane to manage E2 better, although it has only been a week since the switch.

Unfortunately, I continue with the same symptoms, and things have progressively gotten worse over the last 3 weeks or so. Lack of energy, lack of motivation, difficulty concentrating, and low libido really have spiked of late. In short, my journey with clomid can be characterized by early and significant but short-lived improvement, return to baseline for a few months, and now an apparent worsening of symptoms.
 

CoastWatcher

Moderator
Wishing you good results! Some certainly seem to benefit greatly, unfortunately that has not been the case for me so far. I haven't noticed any improvement after switching from anastrozole to exemestane to manage E2 better, although it has only been a week since the switch.

Unfortunately, I continue with the same symptoms, and things have progressively gotten worse over the last 3 weeks or so. Lack of energy, lack of motivation, difficulty concentrating, and low libido really have spiked of late. In short, my journey with clomid can be characterized by early and significant but short-lived improvement, return to baseline for a few months, and now an apparent worsening of symptoms.
It's been three months, and then some, hasn't it? No one can say you've not given it a full-on, good-faith, effort.
 

Esq

Member
It's been three months, and then some, hasn't it? No one can say you've not given it a full-on, good-faith, effort.

A little over 4 months, actually, so I'm content that I've given it a chance. I still have almost a week until my next consult so the exemestane has a little more time to do its thing, but absent a dramatic turnaround over the next 6 days, I struggle to see any compelling reason to continue with clomid.
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I'm also scheduled for a home sleep study week after next to rule out sleep apnea, so we'll see how that turns out.
 

Esq

Member
any update?

Thanks for checking in. My consult was this morning and pleasant as always. I'm going to discontinue clomid immediately, continue the exemestane for two more doses, and then retest levels in six weeks to see how things look with clomid out of my system. My sleep study is next week, and I should have the results the first week of August.
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I'll speak again with Dr. Saya in about 8 weeks. If sleep apnea is ruled out, I have the option of trying traditional TRT to see if it helps. I'm undecided on whether to try it, and I'm going to wait to really think about it until after my sleep study. If apnea is an issue, I'll address that first and see what happens. If not, I have a tough decision to make.
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Dr. Saya also gave me the option of lowering the clomid dose while continuing with the exemestane to see if getting e2 lower might help, which I appreciated, but I just don't think clomid is going to do it for me and I don't have the patience to give it at least another 6-8 weeks after about 5 months on it. My e2 was very high in April, but it's been slowly coming down since then and yet I feel worse than ever over the last 4 weeks. Time to move on and try something different.
 

Esq

Member
I had my post-sleep study consult with the sleep specialist this morning, and I've been diagnosed with moderate obstructive sleep apnea. The sleep study showed a respiratory event index of 6 (mild) and oxygen saturation of 83% (moderate, borderline severe). That means that, on average, I have 6 occurences per hour of stopping breathing for at least 10 seconds. The oxygen saturation rates apparently are approaching low enough to cause significant health issues, including premature death. The doctor has prescribed a CPAP machine which I should get set up with this week hopefully.
.
The diagnosis, while a bit of a surprise (I'm 36 years old and 165 pounds), also is somewhat of a relief. So many of my symptoms can be explained by sleep apnea, and I'm hopeful that treating the OSA will relieve them. I probably should have gotten tested for that first, but until doing research (and Dr. Saya recommending I consider getting tested) I just assumed OSA was an issue for older, overweight people.
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I'm scheduled for follow-up blood work with Defy at the end of this month and another consult with Dr. Saya in early September, but I'm considering pushing both of those events out another 6-8 weeks so I can see if treating the OSA relieves my symptoms. Dr. Saya, if you happen to see this, I would welcome your thoughts on that. The next appointment was to be the one where we decided whether to give traditional TRT a go, and I"d rather wait to have that conversation until after I've given the CPAP some time to do its thing.
 
Last edited:
I had my post-sleep study consult with the sleep specialist this morning, and I've been diagnosed with moderate obstructive sleep apnea. The sleep study showed a respiratory event index of 6 (mild) and oxygen saturation of 83% (moderate, borderline severe). That means that, on average, I have 6 occurences per hour of stopping breathing for at least 10 seconds. The oxygen saturation rates apparently are approaching low enough to cause significant health issues, including premature death. The doctor has prescribed a CPAP machine which I should get set up with this week hopefully.
.
The diagnosis, while a bit of a surprise (I'm 36 years old and 165 pounds), also is somewhat of a relief. So many of my symptoms can be explained by sleep apnea, and I'm hopeful that treating the OSA will relieve them. I probably should have gotten tested for that first, but until doing research (and Dr. Saya recommending I consider getting tested) I just assumed OSA was an issue for older, overweight people.
.
I'm scheduled for follow-up blood work with Defy at the end of this month and another consult with Dr. Saya in early September, but I'm considering pushing both of those events out another 6-8 weeks so I can see if treating the OSA relieves my symptoms. Dr. Saya, if you happen to see this, I would welcome your thoughts on that. The next appointment was to be the one where we decided whether to give traditional TRT a go, and I"d rather wait to have that conversation until after I've given the CPAP some time to do its thing.

As we discussed, ESQ, this makes a lot of sense which is why I recommended the study for you. It truly can tie together many of the pieces for you including the adrenal function. Get on the CPAP ASAP and give it a little time to work its magic. Will be very interested to discuss on follow up.
 

Esq

Member
Just thought I'd update this thread. It's been almost 4 weeks since stopping the clomid and AI, and I'd say I'm more or less feeling back to my pre-clomid baseline. That is to say that some of the negative effects I had been feeling during my last 2-3 weeks on it have gone away, but the old symptoms persist for the most part.
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I go for my CPAP mask fitting next week and should be all set up on that soon (a bit longer than I expected because of insurance pre-auth requirements and sleep clinic scheduling delays). I called Defy today and pushed my next consult out another 6 weeks, so that is set for mid-October now instead of September. I'll have labs done 2 or 3 weeks prior to that. That also wil give me a full 2 months with the CPAP machine so I hope to know by then whether it is resolving my issues. I'll also be interested to see where my hormones land - by then I will have been off clomid for 3 months.
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The journey continues...
 

Esq

Member
I just realized it's been almost 2 months since I've posted here, and thought an update was in order. To summarize where I am now, I stopped taking the clomid in mid-July, and then soon after was diagnosed with mild- to moderate sleep apnea. I decided to give everything a few months to (1) allow my levels to settle after the clomid and (2) give the CPAP machine a chance to see if I started to feel any better, and then re-evalute my options.
.
I've now been on the CPAP for two months and don't feel even remotely better. My AHI numbers are good and I'm sleeping fine, but my symptoms persist. My sleep doctor is content that the CPAP is controlling my apnea, but is perplexed as to why I don't feel any better. He even asked whether I have considered getting my hormones tested because he thinks the symptoms could be a low T issue. I told him I've been working on that on a parallel path.
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I had my most recent Defy labs done last week, and am pretty surprised by the numbers. These labs were done 82 days after my last dose of clomid.
.
Testosterone, Serum: 550 ng/dL (range 264-916)
Testosterone, Free (Direct): 15.1 (range 8.7-25.1)
Estradiol (Sensitive): 28.1 (range 8.0-35.0)
LH: 5.6 mIU/mL (1.7-8.6)
.
For comparion's sake, in September 2015, before any treatment, total T was 783 and free was 20.6. In early 2017, pre-clomid, total T was 702 and free was 17.5. Now, I'm at 550 total T and 15.1 free. In two years, my total T has gone from 783 to 550, and my free from 20.6 to 15.1.
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My next consult with Dr. Saya is next week, and after seeing these numbers (and the fact that the CPAP isn't alleviating my symptoms), I'm leaning heavily towards giving TRT a go. My numbers seem to be in a constant state of decline, and I'm pretty comfortable that I've exhausted other options.
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Am I missing anything?
 
I just realized it's been almost 2 months since I've posted here, and thought an update was in order. To summarize where I am now, I stopped taking the clomid in mid-July, and then soon after was diagnosed with mild- to moderate sleep apnea. I decided to give everything a few months to (1) allow my levels to settle after the clomid and (2) give the CPAP machine a chance to see if I started to feel any better, and then re-evalute my options.
.
I've now been on the CPAP for two months and don't feel even remotely better. My AHI numbers are good and I'm sleeping fine, but my symptoms persist. My sleep doctor is content that the CPAP is controlling my apnea, but is perplexed as to why I don't feel any better. He even asked whether I have considered getting my hormones tested because he thinks the symptoms could be a low T issue. I told him I've been working on that on a parallel path.
.
I had my most recent Defy labs done last week, and am pretty surprised by the numbers. These labs were done 82 days after my last dose of clomid.
.
Testosterone, Serum: 550 ng/dL (range 264-916)
Testosterone, Free (Direct): 15.1 (range 8.7-25.1)
Estradiol (Sensitive): 28.1 (range 8.0-35.0)
LH: 5.6 mIU/mL (1.7-8.6)
.
For comparion's sake, in September 2015, before any treatment, total T was 783 and free was 20.6. In early 2017, pre-clomid, total T was 702 and free was 17.5. Now, I'm at 550 total T and 15.1 free. In two years, my total T has gone from 783 to 550, and my free from 20.6 to 15.1.
.
My next consult with Dr. Saya is next week, and after seeing these numbers (and the fact that the CPAP isn't alleviating my symptoms), I'm leaning heavily towards giving TRT a go. My numbers seem to be in a constant state of decline, and I'm pretty comfortable that I've exhausted other options.
.
Am I missing anything?

On the contrary ESQ, I don't think you're missing anything, but rather have covered a lot of ground and have been diligent with the entire process of attempting to uncover a culprit. Look forward to our talk.
 
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