Clomiphene Citrate (CC or Clomid) – A Testosterone Therapy Alternative for Men with Low Testosterone Levels
Whether you are a 30, 50, 80 or even 110 year old man, having low testosterone levels (hypogonadism) is neither fun nor healthy. The symptoms of low testosterone in men range from lack of energy, depressed mood, loss of vitality, muscle atrophy (sarcopenia), muscles aches, low libido, erectile dysfunction, and weight gain…to bone loss (osteopenia), osteoporosis, mild anemia, increased risk of Alzheimer’s, increased risk of high-grade prostate cancer, and increased risk of death due to all causes.1
As you may know, low testosterone in men may be caused by problems in the testes (or gonads). This is called primary hypogonadism and can be brought on by the mumps, testicular trauma, or testicular cancer, etc., and can only be treated with testosterone replacement therapy. However, the more common causes of low testosterone/hypogonadism result from problems in the pituitary gland and/or hypothalamus in a man’s brain. Low testosterone levels caused by such “brain problems” are collectively described as secondary hypogonadism or hypogonadotropic hypogonadism and may result from depression/anxiety, head trauma, iron overload, anabolic steroid overdosing, diabetes, sleep deprivation, or some medications.
Traditionally, if low testosterone is diagnosed, testosterone replacement therapy is prescribed, and it most commonly comes in the form of a cream, gel, pellet, patch, and by injection. And although these types of therapy are effective, some methods are better than others, and there are side-effects with all of them. For example, testicular shrinkage, gynecomastia (breast enlargement), low sperm count/sterility, and polycythemia (overproduction of red blood cells) are common side-effects of testosterone replacement therapy (for many sufferers, these side-effects are mostly treatable or considered “worth it” by the patient).
However, specifically due to the sterility side-effect, such testosterone treatments aren’t a good option for men who want to have children. In these (usually young) hypogonadal men, clomiphene citrate (CC or Clomid) and/or human chorionic gonadotropin (HCG) have been used (by specialists) for decades to increase testosterone production, increase sperm production, and increase fertility. Both these therapies effectively help signal the testes to produce testosterone and thereby increase testosterone levels (assuming of course the cause of the initial problem is not in the testes’ ability to make testosterone). See “David” (below) for an oversimplified diagram of how clomiphene, HCG, and testosterone work within the hypothalamic-pituitary-testicular axis.
In a healthy male, the pituitary gland in the brain releases luteinizing hormone (LH) into the blood stream, which signals the testes to “GO” and produce testosterone. After testosterone has been produced it naturally converts to some estrogen (yes, there’s estrogen in men too) and this estrogen acts as a “STOP” signal to the pituitary to stop making LH. It is a delicate system of checks and balances which I have simplified here for our purposes.
Clomid works by blocking estrogen at the pituitary and hypothalamus. Thus, the usual estrogen message to “STOP” production of LH is essentially silenced, and therefore the pituitary makes more LH and there is an increased “GO” signal to produce testosterone in the testes. HCG works by mimicking LH, which also increases the “GO” signal to produce more testosterone in the testes. Prescribing testosterone for a man, however, does the opposite of what clomiphene and HCG do.
With traditional testosterone replacement therapy, the brain (hypothalamus and pituitary) gets the message that there is plenty of testosterone being made in the testes, so much so that it doesn’t need to make anymore. Subsequently, the pituitary stops producing LH, and the natural production of testosterone (and sperm) in the testes ceases, which is why traditional testosterone replacement results in testicular shrinkage and low sperm count…a man’s testosterone and sperm manufacturing plant is essentially shut off.
Clomiphene citrate (CC) and/or HCG do not turn off the testosterone manufacturing plant but rather turn it back on or reboot it. While some hypogonadal men require continuous use of clomiphene, for others it can be used for a 3-6 month time period and then discontinued. And, the checks and balances system is not interrupted, so there aren’t the testosterone replacement side-effects which occur due to intentional or unintentional testosterone overdosing. Most interestingly, although it used to be thought that clomiphene and/or HCG only worked on young men, in the past decade or so it has been used effectively in older men too.
The 5 Main Reasons Clomiphene Citrate (CC or Clomid) May be a Good Alternative to Testosterone Replacement Therapy in Men with Low Testosterone Due to Secondary Hypogonadism:
1. Clomiphene citrate stimulates the body’s own production of testosterone
2. Clomiphene citrate doesn’t interfere with the body’s checks and balances of testosterone
3. Clomiphene citrate comes as a pill easily administered by mouth
4. Clomiphene citrate is generic and very cheap2
5. Clomiphene citrate has little side-effects and low risk of developing these side-effects3
The 5 Main Reasons Clomiphene Citrate (CC or Clomid) is Not Usually Prescribed to Men with Low Testosterone Due to Secondary Hypogonadism:
1. Most doctors aren’t aware of the efficacy and safety of clomiphene use in men
2. Most doctors think of Clomid as a “women’s drug” to increase fertility
3. Clomid is FDA approved only for use in women
4. Clomid use in men is considered “off label”
5. Clomiphene citrate is now generic and really inexpensive so it’s not advertised very much
Note: HCG is more commonly known and prescribed for secondary hypogonadism in men but it involves injection and is expensive, so if clomiphene works alone I think that is preferred.
The 4 Main Risks of Using Clomiphene Citrate (CC or Clomid) in Men with Low Testosterone Due to Secondary Hypogonadism:
1. Very rarely, visual changes may occur which are reversible with discontinuation
2. In older men, there is a reported increased risk of pyospermia (a noninfectious increase in white blood cells in semen, with unseen detriment)
3. Clomiphene citrate is a drug which is not bioidentical. This means it’s molecular structure doesn’t mimic a compound naturally found in the human body. And, correspondingly, clomiphene citrate doesn’t have a known natural function in the human body and thus may at some point manifest a currently unknown side-effect in men. This latter, however, is a theoretical risk because for more than 40 years clomiphene use in men has only shown the risks above.
4. Clomiphene may not work…especially in older men who in addition to secondary hypogonadism may also have primary hypogonadism; or in men with an unresolved chronic disease4
In conclusion, in the appropriate male patient, clomiphene citrate (CC or Clomid) may be a good alternative to both short and long-term testosterone replacement therapy. Regardless, just like testosterone replacement, clomiphene citrate must be administered and monitored by a competent physician.
1. J Clin Endocrinol Metab. 2008 Jan;93(1):68-75.
2. J Sex Med. 2010 Jan;7(1 Pt 1):269-76.
3. BJU Int. 2012 Nov;110(10):1524-8.
4. Int J Impot Res. 2003 Jun;15(3):156-65.