Positive Outcome Of Clomiphene Citrate Treatment In Young Hypogonadal Men

Michael Scally MD

Doctor of Medicine
10+ Year Member
In conclusion, CC is an effective and safe alternative to testosterone supplementation therapy in hypogonadal men. The present study showed that there were significant improvements in testosterone levels with long-term CC therapy. Nearly all patients had improvement in at least one hypogonadal symptom on the ADAM questionnaire, with more than half improving in three symptoms. CC therapy has a role to play in the testosterone deficient man and should be incorporated into the clinician-patient discussion.


Katz DJ, Nabulsi O, Tal R, Mulhall JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int. Outcomes of clomiphene citrate treatment in young hypogonadal men - Katz - 2011 - BJU International - Wiley Online Library

Study Type - Therapy (case series) Level of Evidence 4
What's known on the subject? and
What does the study add?

Hypogonadism is a prevalent problem, increasing in frequency as men age. It is most commonly treated by testosterone supplementation therapy but in younger patients this can lead to testicular atrophy with subsequent exogenous testosterone dependency and may impair spermatogenesis. Clomiphene citrate (CC) may be used as an alternative treatment in these patients with hypogonadism when maintenance of fertility is desired. This study shows that CC is a safe and efficacious drug to use as an alternative to exogenous testosterone. Not only have we validated previous findings of other papers but have proven our findings over a much longer period (mean duration of treatment 19 months). This prospective study is the largest to date assessing both the objective hormone response to CC therapy as well as the subjective response based on a validated questionnaire.

OBJECTIVE: * To prospectively assess the andrological outcomes of long-term clomiphene citrate (CC) treatment in hypogonadal men.

PATIENTS AND METHODS: * We prospectively evaluated 86 men with hypogonadism (HG) as confirmed by two consecutive early morning testosterone measurements <300 ng/dL. * The cohort included all men with HG presenting to our clinic between 2002 and 2006 who, after an informed discussion, elected to have CC therapy. CC was commenced at 25 mg every other day and titrated to 50 mg every other day. The target testosterone level was 550 +/- 50 ng/dL. * Testosterone (free and total), sex hormone binding globulin, oestradiol, luteinizing hormone and follicle stimulating hormone were measured at baseline and during treatment on all patients. Once the desired testosterone level was achieved, testosterone/gonadotropin levels were measured twice per year. * To assess subjective response to treatment, the androgen deficiency in aging males (ADAM) questionnaire was administered before treatment and during follow-up.

RESULTS: * Patients' mean (standard deviation [sd]; range) age was 29 (3; 22-37) years. Infertility was the most common reason (64%) for seeking treatment. The mean (sd) duration of CC treatment was 19 (14) months. * At the last evaluation, 70% of men were using 25 mg CC every other day, and the remainder were using 50 mg every other day. * All mean testosterone and gonadotropin measurements significantly increased during treatment. * Subjectively, there was an improvement in all questions (except loss of height) on the ADAM questionnaire. More than half the patients had an improvement in at least three symptoms. * There were no major side effects recorded and the presence of a varicocele did not have an impact on the response to CC.

CONCLUSION: * Long-term follow-up of CC treatment for HG shows that it appears to be an effective and safe alternative to testosterone supplementation in men wishing to preserve their fertility.
 
So after this study were the patients able to taper off the cc and maintain there levels or did they require continious treatment? I was on TRT for a little over 2yrs and just got done doing a restart with cc @ 25mg EOD for 2months. I tappered off and after 2wks off my total T was at 231. Not bad considering the duration I was at 0. I decided to try it again only for a longer period of time hoping to reach the 500's and taper off to see if they hold. Even though thats a low # I feel tons better than I ever did on TRT. The only other thing I have considered is substituting Nolva instead.

Anybody else had success with a CC or Nolva restart of this sort.
 
So after this study were the patients able to taper off the cc and maintain there levels or did they require continious treatment? I was on TRT for a little over 2yrs and just got done doing a restart with cc @ 25mg EOD for 2months. I tappered off and after 2wks off my total T was at 231. Not bad considering the duration I was at 0. I decided to try it again only for a longer period of time hoping to reach the 500's and taper off to see if they hold. Even though thats a low # I feel tons better than I ever did on TRT. The only other thing I have considered is substituting Nolva instead.

Anybody else had success with a CC or Nolva restart of this sort.

For a restart, 25 mg/EOD for two months isn't very much. It would have been better to do a classic AAS restart, using Swale's restart protocol or something similar.

And, the time duration in the article was over a year on a constant dose.

I have done 3 bouts of clomiphene at 1 month, 1 month, and 2 months, spread out evenly every 3-4 months, over the last year and a half, using a dose of 50 mg/day.

It worked marginally at alleviating certain symptoms, but didn't come with a subjective mood increase.

If I were you, I'd get ready for the long haul. Get blood tests before, during, and after (>1-2 months) each bout of clomiphene treatment, like I did. Currently, I'm waiting to see if my 550 ng/dL total T will hold.
 
For a restart, 25 mg/EOD for two months isn't very much. It would have been better to do a classic AAS restart, using Swale's restart protocol or something similar.

And, the time duration in the article was over a year on a constant dose.

I have done 3 bouts of clomiphene at 1 month, 1 month, and 2 months, spread out evenly every 3-4 months, over the last year and a half, using a dose of 50 mg/day.

It worked marginally at alleviating certain symptoms, but didn't come with a subjective mood increase.

If I were you, I'd get ready for the long haul. Get blood tests before, during, and after (>1-2 months) each bout of clomiphene treatment, like I did. Currently, I'm waiting to see if my 550 ng/dL total T will hold.

Thanks for sharing. Im ready for the long haul. Im not a fan of big doses for a short time. An endo had me on 50mg 3x/wk (before any trt) and it brought me up to 574 but I felt like total shit, my e2 was at 60 thats why I tried half the dose. I know I didn't stay on long enough I just wanted to see if I would even respond after being shut down for so long. I am going back on at the same dose until I reach and maintain a 500+ level and then taper again. Please keep us informed if things hold for you best of luck.
 
The Adam questionarre was used in this study. One of the items is about "grumpy" moods. So I guess that in this study there was no singificant deterioration in mood due to the CC. Sorry that I could paste the questioairre here using my IPad.
 
that's interesting-question for you guys: if I took 12.5mg of clomid for one week-and my T increased from 178 to a 284, is it possible if I continued such protocol it would continue to increase? I didn't know if that surge was all I was working with naturally, or if longer treatment would further stimulate testicles. I appreciate your thoughts
 
I did 12 months of Tamoxifen Citrate therapy. 8 months at 20mg every day, 2 months at 10 mg every day , and 2 months at 5mg every day.

Pre therapy TT: 399

20mg TT: 1000-1500

10 mg TT: 1065

5mg TT: 1225

2 months off and my levels are now at 660. I felt completely back t0 normal when I was on 5 mg of Tamoxifen..Dont feel as well right now but just hoping my levels dont creep down anymore.
 
I did 12 months of Tamoxifen Citrate therapy. 8 months at 20mg every day, 2 months at 10 mg every day , and 2 months at 5mg every day.

Pre therapy TT: 399

20mg TT: 1000-1500

10 mg TT: 1065

5mg TT: 1225

2 months off and my levels are now at 660. I felt completely back t0 normal when I was on 5 mg of Tamoxifen..Dont feel as well right now but just hoping my levels dont creep down anymore.

Did you have this protocol prescribed to you, or was it based on an academically published and reviewed report, or did you just decide how to do this on your own?

I ask because I haven't seen any case studies done on secondary hypogonadal men using tamoxifen.

In my post, above, I used a study on clomiphene done using a significant amount of test subjects to guide my own self-treatment, which was only approved by an endocrinologist after I'd already undergone the entire 1.5 year long protocol.

More stories like yours, mine, and the ops are the future of alternatives to TRT, in my opinion.

There is, however, a new compound (peptide, Triptorelin) being investigated that supposedly mimics gonadotropin releasing hormone, and can cause a restart after only one small administration.
 
Did you have this protocol prescribed to you, or was it based on an academically published and reviewed report, or did you just decide how to do this on your own?

I ask because I haven't seen any case studies done on secondary hypogonadal men using tamoxifen.

In my post, above, I used a study on clomiphene done using a significant amount of test subjects to guide my own self-treatment, which was only approved by an endocrinologist after I'd already undergone the entire 1.5 year long protocol.

More stories like yours, mine, and the ops are the future of alternatives to TRT, in my opinion.

There is, however, a new compound (peptide, Triptorelin) being investigated that supposedly mimics gonadotropin releasing hormone, and can cause a restart after only one small administration.

This was prescribed to me
 
Apparently, a follow-up study. I do not have the full-text.

Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. Clomiphene citrate is safe and effective for long-term management of hypogonadism - Moskovic - 2012 - BJU International - Wiley Online Library

Study Type - Therapy (population cohort)

Level of Evidence 2a

What's known on the subject? and What does the study add?

Clomiphene citrate (CC) has previously been documented to be efficacious in the treatment of hypogonadism. However little is known about the long term efficacy and safety of CC. Our study demonstrates that CC is efficacious after 3 years of therapy. Testosterone levels and bone mineral density measurement improved significantly and were sustained over this prolonged period. Subjective improvements were also demonstrated. No adverse events were reported.

OBJECTIVE:
* To assess the efficacy and safety of long-term clomiphene citrate (CC) therapy in symptomatic patients with hypogonadism (HG).

PATIENTS AND METHODS:
* Serum T, oestradiol and luteinizing hormone (LH) were measured in patients who were treated with CC for over 12 months.
* Additionally, bone densitometry (BD) results were collected for all patients. Demographic, comorbidity, treatment and Androgen Deficiency in Aging Men (ADAM) score data were also recorded.
* Comparison was made between baseline and post-treatment variables, and multivariable analysis was conducted to define predictors of successful response to CC.
* The main outcome measures were predictors of response and long-term results with long-term CC therapy in hypogonadal patients.

RESULTS:
* The 46 patients (mean age 44 years) had baseline serum testosterone (T) levels of 228 ng/dL.
* Follow-up T levels were 612 ng/dL at 1 year, 562 ng/dL at 2 years, and 582 ng/dL at 3 years (P < 0.001).
* Mean femoral neck and lumbar spine BD scores improved significantly.
* ADAM scores (and responses) fell from a baseline of 7 to a nadir of 3 after 1 year.
* No adverse events were reported by any patients.

CONCLUSIONS:
* Clomiphene citrate is an effective long-term therapy for HG in appropriate patients.
* The drug raises T levels substantially in addition to improving other manifestations of HG such as osteopenia/osteoporosis and ADAM symptoms.
 
Apparently, a follow-up study. I do not have the full-text.

Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. Clomiphene citrate is safe and effective for long-term management of hypogonadism - Moskovic - 2012 - BJU International - Wiley Online Library

Study Type - Therapy (population cohort)

Level of Evidence 2a

What's known on the subject? and What does the study add?

Clomiphene citrate (CC) has previously been documented to be efficacious in the treatment of hypogonadism. However little is known about the long term efficacy and safety of CC. Our study demonstrates that CC is efficacious after 3 years of therapy. Testosterone levels and bone mineral density measurement improved significantly and were sustained over this prolonged period. Subjective improvements were also demonstrated. No adverse events were reported.

OBJECTIVE:
* To assess the efficacy and safety of long-term clomiphene citrate (CC) therapy in symptomatic patients with hypogonadism (HG).

PATIENTS AND METHODS:
* Serum T, oestradiol and luteinizing hormone (LH) were measured in patients who were treated with CC for over 12 months.
* Additionally, bone densitometry (BD) results were collected for all patients. Demographic, comorbidity, treatment and Androgen Deficiency in Aging Men (ADAM) score data were also recorded.
* Comparison was made between baseline and post-treatment variables, and multivariable analysis was conducted to define predictors of successful response to CC.
* The main outcome measures were predictors of response and long-term results with long-term CC therapy in hypogonadal patients.

RESULTS:
* The 46 patients (mean age 44 years) had baseline serum testosterone (T) levels of 228 ng/dL.
* Follow-up T levels were 612 ng/dL at 1 year, 562 ng/dL at 2 years, and 582 ng/dL at 3 years (P < 0.001).
* Mean femoral neck and lumbar spine BD scores improved significantly.
* ADAM scores (and responses) fell from a baseline of 7 to a nadir of 3 after 1 year.
* No adverse events were reported by any patients.

CONCLUSIONS:
* Clomiphene citrate is an effective long-term therapy for HG in appropriate patients.
* The drug raises T levels substantially in addition to improving other manifestations of HG such as osteopenia/osteoporosis and ADAM symptoms.

If anyone can find the full text of this (I am interested in the dosage used) I would appreciate it.
 
I did 12 months of Tamoxifen Citrate therapy. 8 months at 20mg every day, 2 months at 10 mg every day , and 2 months at 5mg every day.

Pre therapy TT: 399

20mg TT: 1000-1500

10 mg TT: 1065

5mg TT: 1225

2 months off and my levels are now at 660. I felt completely back t0 normal when I was on 5 mg of Tamoxifen..Dont feel as well right now but just hoping my levels dont creep down anymore.

Any updates on this? Thanks.
 
Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. Clomiphene citrate is safe and effective for long-term management of hypogonadism - Moskovic - 2012 - BJU International - Wiley Online Library

Study Type - Therapy (population cohort)

Level of Evidence 2a

What's known on the subject? and What does the study add?

Clomiphene citrate (CC) has previously been documented to be efficacious in the treatment of hypogonadism. However little is known about the long term efficacy and safety of CC. Our study demonstrates that CC is efficacious after 3 years of therapy. Testosterone levels and bone mineral density measurement improved significantly and were sustained over this prolonged period. Subjective improvements were also demonstrated. No adverse events were reported.

OBJECTIVE:
* To assess the efficacy and safety of long-term clomiphene citrate (CC) therapy in symptomatic patients with hypogonadism (HG).

PATIENTS AND METHODS:
* Serum T, oestradiol and luteinizing hormone (LH) were measured in patients who were treated with CC for over 12 months.
* Additionally, bone densitometry (BD) results were collected for all patients. Demographic, comorbidity, treatment and Androgen Deficiency in Aging Men (ADAM) score data were also recorded.
* Comparison was made between baseline and post-treatment variables, and multivariable analysis was conducted to define predictors of successful response to CC.
* The main outcome measures were predictors of response and long-term results with long-term CC therapy in hypogonadal patients.

RESULTS:
* The 46 patients (mean age 44 years) had baseline serum testosterone (T) levels of 228 ng/dL.
* Follow-up T levels were 612 ng/dL at 1 year, 562 ng/dL at 2 years, and 582 ng/dL at 3 years (P < 0.001).
* Mean femoral neck and lumbar spine BD scores improved significantly.
* ADAM scores (and responses) fell from a baseline of 7 to a nadir of 3 after 1 year.
* No adverse events were reported by any patients.

CONCLUSIONS:
* Clomiphene citrate is an effective long-term therapy for HG in appropriate patients.
* The drug raises T levels substantially in addition to improving other manifestations of HG such as osteopenia/osteoporosis and ADAM symptoms.
 
Since Clomiphene citrate's half life approximates SIX days, there's no reason
to suspect QD, QOD or splint daily dosing, especially of a period of several months, would make any difference in efficacy.
 
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