PEAK TESTOSTERONE

Your Risk With Clomid

From what I have seen on the Peak Testosterone Forum, the popularity of Clomid (clomiphene citrate) seems to be growing.  Furthermore, it appears to be increasingly considered by young men as a viable long term solution for their low testosterone (hypogonadism).  And it is true:  Clomid can boost total testosterone levels easily to 500-600 ng/dl in most men with secondary hypogonadism from what I have seen.  (For details, see my link on Clomid and Testosterone.)

Futhermore, many physicians feel comfortable with Clomid overall and consider it to be a safe long term alternative.  Consider what one poster wrote:

"My doc says he's had guys on it 'for years.' There not that many (if any at all) studies on long term usage of clomid in men. Seems like most docs really feel/think it's fine, but still - that's what they *think.*" [1]

For years, eh? So what else is so great about Clomid and why is it so popular?

1. Convenience.  Just take a pill.  That's all you have to do with Clomid.  No messy gels. No driving to the doctors for injections or a pellet procedure.

2.  Inexpensive.  One recent study pointed out how cheap Clomid is compared to many of the brand testosterone-boosting alternatives: "The monthly cost of Testim 1% (5 gm daily) is $270, Androgel 1% (5 gm daily) is $265, and CC (50 mg every other day) is $83."  [Compounded testosterone products are much cheaper and are closer to Clomid in price.]

NOTE:  Standard testosterone injections and compounded creams are typically inexpensive as well.

3.  Fertility.  Clomid is used by many fertility physicians to boost fertility.  In fact Clomid can have a very powerful effect in this area:  one study on infertile men showed participants more than doubling their sperm counts! Another study found that within 2-6 months nnot only had sperm counts improved but also sperm motility (mobility/movement) as well.

4.  Testes and Pituitary Activation and Preservation. Traditional testosterone therapy can can lead to some testicular shrinkage especially if the doctor goes into the 800+ ng/dl range.  The shrinkage is actually not very much, depending on the man's testosterone levels and a few other factors, but many men are very sensitive about "the boys" getting smaller in any way and request HCG to overcome this. (See my link on Testosterone and HCG for more informatiion.) Because of #3, Clomid does not generally result in testicular shrinkage.

Put all this together and some men cannot understand why anyone would go on traditional testosterone therapy. (For some starter information, see my link on Hormone Replacement Therapy.) Clomid seems like the obvious alternative, especially for some of the younger guys wanting to preserve their fertility.  Furthermore, they are considering Clomid as a long term strategy.

The tragedy with this, though, is that these men forget that Clomid is a pharmaceutical and, as such, a synthetic substance that it does have side effects.  Yes, it's widely used by the fertility and steroid communities and, yes, it has been around for decades.  But that does NOT mean it is suitable for long term usage.

Always keep in mind that Bioidentical Testosterone is just what your body is expecting.  It is the exact molecule that your body needs and uses every day.  This is not the case with Clomid:  it is a synthetic molecule and is still not totally understood.  It has a powerful and poorly understood effect on many cells, affecting many pathways, including all-important calcium channeling.  Anytime you put a synthetic molecule into your body, you are taking risks and below we will discuss some of the potential lon term risks.

THE CRITICALITY OF LOW DOSE CLOMID:  Before I go on, it is important to note that some of the most famous and respected TRT / HRT physicians use low dose Clomid and they feel that it is safe provided the patient has no side effects.  Furthermore, some patients go on low dose clomid - which can be as low as 12.5 mg EOD - and feel fantastic.  These men will get a nice boost in testosterone and LH, and they feel as good as successful TRT men.  The reason this is so important is that virtually all of the side effects listed below are from men taking higher dosage Clomid or ignoring side effects.  So discuss with a knowledgeable physician:  perhaps low dose Clomid is viable option for you.  Keep in mind, though, that no long term studies have been done, and we do not have the extensive research that we have with testosterone replacement therapy.

1.  Mood.  Clomid can have a major impact on mood in particular and men can get "estrogen crash" symptoms, i.e. depression, moodiness and so on.  This sometimes manifests itself in a subtle fashion in men.  Clomid will double or triple their testosterone levels, which normally would greatly increase their libido.  However, the men find that they have no increase in lbido and may not even be thinking about sex at all.  Clearly the Clomid in these cases is generally conteracting their increased libido. Going on lower dosages, as mentioned above, helps lower the risk for this issue, but it still happens quite often.

2. Stomach and Headaches.  Clomid can also give nasty headaches and stomach aches as well.  One of our Forum Posts stated "I do get some nausea but not that bad." Not that bad?? What is 10+ years of mild nausea going to do for you?  For one thing it may be effecting your vitamin and mineral absorption.

3. Vision. On this page I want to focus on the potential long term risk to your vision.  First of all, there have been studies of a year with no major visual issues discovered.  And, yes, there was a study on women that found the following comforting news about Clomid:

"We found no differences between the washout and clomiphene citrate conditions for color vision, visual acuity, contrast sensitivity, and visual fields. The only statistically significant difference was found for foveal flicker sensitivity at 32 Hz in the right eye, with a similar trend in the left eye and at 8 Hz in both eyes."

That said, there are many case reports and some research summaries have been done and here are just a few examples:

a) Vascular Sludging and Vision Loss.  How does Clomid sometimes effect vision and damage the eye? One issue is that it "gunks up" blood flow to the eye. One woman lost vision in one eye due to this. [5]

b) Uveitis. Several cases of uveitis have been reported, which is an inflammation of certain visual tissues. One study reported the case of a woman who lost vision from uveitis after initiating Clomid therapy, then recovered her vision and then lost her vision again when she repeated Clomid therapy. [6]

c) Retinal Blood Vessel Damage.  Other case reports include injury to retinal blood vessels. [7]

4.  Cytotoxicity.  Clomid is known to be cytotoxic (cell-killing) to many types of cells in vitro.  One of these studies looked at rabbit corneal epitheal cells and found that "at concentrations of 0.5 20 M, clomiphene killed cells in a concentration-dependent manner." [8] In my mind, this is the biggest risk of Clomid.  Is there a chance that it is pro-aging and not antiaging?  Dosage is everything and so maybe this is not an issue and, unfortunately, it is very unlikely to receive funding, because using Clomid to boost fertility and testosterone in men is off label and not particuarly profitable for anyone.

CONCLUSION.  Does it really happen in real life?  You bet it does.  One of our long term member on the Peak Testosterone Forum wrote the following: "When I first saw Shippen he put me on Clomid to test for secondary or primary. And I could have stayed on it but I have a side affect of eye blurriness."

Again, I think it may be a BIG assumption to think you can take Clomid for 10, 20 or 30 years without risk to your vision. Talk to your doctor about this potential long term issue. (The PDE5 Inhibitors are also notorious for affecting vision and disturbing blood flow to the optic nerve.  Men taking both Clomid and Levitra, Cialis or Viagra should probably be doubly careful.)

So, if you are looking to use Clomid long term, I would definitely disciss the vision issue with your doctor.

REFERENCES:

1)   http://peaktestosterone.com/forum/index.php?topic=682.msg6258#msg6258

2) J Sex Med, 2010 Jan, 7(1 Pt 1):269-76, "Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost"

3) International Journal of Andrology, Dec 1980, 3(1-6):479-486, "The Effect of Clomiphene Citrate on Different Sperm Parameters and Serum Hormone Levels in Preselected Infertile Men: A Controlled Double-Blind Cross-Over Study"

4) Fertility and Sterility, 1977, 28(7):741-745, "Clomiphene treatment in oligospermic infertile males"

5) Fertility and Sterility, 1994, 61(2):390-391, "Optic neuropathy associated with clomiphene citrate therapy."

6) Ocular Immunology and Inflammation, 2008, 16(1-2):23-24, "Bilateral Anterior Uveitis Associated with Clomiphene Citrate"

7) Fertility and Sterility, Nov 2008, 90(5), "Central retinal vein occlusion associated with clomiphene-induced ovulation"

8) Drug Development Research, Aug 2008, 69(5):272 278, "Effect of clomiphene on [Ca2+]i rises and cell viability in rabbit corneal epithelial cells"

9) Fertility and Sterility, Mar 2010, 93(4):1169-1172, "An investigation of the visual disturbances experienced by patients on clomiphene citrate"