Clomiphene Citrate (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. 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 pill, 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).

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 (clomiphene citrate, or CC pill) 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 pill) 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 pill, or Clomid) May be a Good Alternative to Testosterone Replacement Therapy in Men with Low Testosterone Due to Secondary Hypogonadism:

1. Clomiphene citrate (CC pill) stimulates the body's own production of testosterone
2. Clomiphene citrate (CC pill) doesn't interfere with the body's checks and balances of testosterone
3. Clomiphene citrate (CC pill) comes as a pill easily administered by mouth
4. Clomiphene citrate (CC pill) is generic and very cheap2
5. Clomiphene citrate (CC pill) has little side-effects and low risk of developing these side-effects

The 5 Main Reasons Clomiphene Citrate (CC pill, 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 (CC pill) 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 pill, 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 (CC pill) 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 (CC pill) 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 disease

In conclusion, in the appropriate male patient, clomiphene citrate (CC pill, or Clomid) may be a good alternative to both short and long-term testosterone replacement therapy. Regardless, just like testosterone replacement, clomiphene citrate (CC pill) must be administered and monitored by a competent physician.

Endocrinologist Groups Reject FDA's Testosterone Therapy Position

Two endocrinologist societies have issued a joint position statement recommending that the decision to prescribe testosterone replacement therapy (TRT) to hypogonadal men should be guided by signs and symptoms and testosterone levels rather than the underlying cause, as recommended by the FDA in response to concerns about cardiovascular risks associated with TRT. In the position statement, the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) say the evidence for increased cardiovascular risks associated with testosterone use is weak. Two retrospective studies raised concern that testosterone therapy increases cardiovascular risk, but these studies have major flaws “precluding meaningful conclusions to be drawn,” according to the statement.

The statement, which was published recently in Endocrine Practice (2015;21:1066-1073), was prepared by Neil Goodman, MD, of the University of Miami Miller School of Medicine, and other members of the AACE Reproductive Endocrinology Scientific Committee.

“Epidemiologic studies strongly support the association of low testosterone concentrations and hypogonadism with cardiovascular events and all-cause mortality, especially in elderly men,” the position statement reads. “However, low testosterone could be a marker of illness and not a causal factor.”

The statement also pointed out that TRT “favorably changes many cardiovascular risk factors. It decreases fat mass, increases muscle mass, decreases insulin resistance and can reverse metabolic syndrome in some men.”

In March, the FDA issued a statement that read, “Health care professionals should prescribe testosterone therapy only for men with low testosterone levels caused by certain medical conditions and confirmed by laboratory tests.” According to the FDA, testosterone “should not be used to relieve symptoms in men who have low testosterone for no reasons other than aging.”

The AACE/ACE statement recommends that TRT be considered “for symptomatic men who have unequivocally low total and/or free testosterone levels that are assayed on at least 2 samples drawn before 10 am.” All men being considered for TRT must undergo a thorough diagnostic work-up.

“Since the risk/benefit ratio of TRT is not well established in aging-associated hypogonadism, we advise the practicing clinician to be extra cautious in the symptomatic elderly with demonstrably low testosterone levels prior to embarking on replacement therapy and to avoid treatment of the frail elderly altogether.”

Hormone Tests for Women

Modern medicine has led us to believe that, for most medical issues, there's a single test that will confirm a clear and concise diagnosis. This is about as helpful as a 6-minute doctor visit, and springs from the same limited thinking. Women are especially hurt by this kind of medical approach to hormonal imbalance. That's because hormone panels and other tests aren't as helpful as you might wish. But in the hands of a skilled doctor who will take the time to "connect the dots", the tests can be very meaningful. Here's a general overview of the basic hormone tests and what they mean to your health and hormonal balance. When is hormone testing helpful? By dividing women into three generalized groups it will help you understand who benefits from hormone testing and who may not.

Women with fertility issues. For women in this category, hormone panels are key, both as a diagnostic and a therapeutic tool. So many fertility problems can be traced to irregularities in the menstrual cycle, and your practitioner needs to understand what's wrong in order to give you the right support.

Women with ordinary symptoms of hormonal imbalance. Women often ask us: is there a test to tell whether I'm in menopause? The short answer is no. You're menopausal when you haven't had a period for a year. Hormone tests are not required for this largest group of women. The symptom patterns are very individual, but the first line therapy is mostly the same: build a nutritional foundation, take the right basic supplements to restore balance, and make meaningful lifestyle changes.

Women with severe symptoms of hormonal imbalance. For women with debilitating or intractable symptoms, a hormone panel is essential. When dealing with PCOS, fibroids, diagnosed alopecia (hair loss), and other more severe hormone issues, your practitioner simply can't treat you without knowing where your hormones are.

Key tests in a hormone panel When it comes to key tests in a hormone panel, what they measure and what the results mean, levels and ranges will vary from lab to lab. This chart gives you a very general idea of what high or low levels of a particular hormone may indicate.

Female Hormone Panel