Testosterone Replacement Therapy (TRT) has boomed in the past decade with the positive benefits of increased energy, muscle mass, libido and sleep in those with sub-optimal levels. However, there are alternative strategies to boost Testosterone without actually taking the hormone itself.

By using exogenous testosterone in either injectable format, cream/gel or pellet insertion, there is a negative feedback in the brain which essentially turns “off” the natural production in the body. Under normal circumstances in men, the testis produce testosterone via the Cells of Leydig. The stimulus for this production is from the pituitary gland secreting hormone called Luteinizing Hormone (LH). Estrogen is the signal to pituitary gland to stop producing LH. Therefore, by blocking the receptors in the pituitary gland with clomiphene citrate, from interacting with circulating estrogen, we can essentially stop the off signal and continue the signal from pituitary to testis.

The neuro-endrocine system of the body works very much like the common thermostat and air conditioner (here in sunny Miami). When the temperature rises, the thermostat sends a signal to the A/C compressor to cool the room. When the desired temperature is achieved, the signal is decreased or ceased. By manipulating these pathways we can alter hormone production.

 

Estrogen receptors in the pituitary gland (brain) are the target of Clomid

Clomiphene Citrate Preserves Testis Size

Since clomiphene citrate blocks the estrogen receptors in the brain, the pituitary gland continues to send the LH (and FSH) signal to the testis to produce testosterone. The un-interrupted signal does not cause atrophy of the testis like testosterone does. An additional benefit of Clomid is that sperm production is increased via FSH (Follicle Stimulating Hormone) and is often used to boost fertility.

FDA Approved?

 

Clomiphene citrate is FDA approved for use in Women, but not Men. This does not mean that it cannot be prescribed, but however is considered off-label.

Side Effects

Clomid in women is known to cause moodiness, but the incidence in men is much less. Acne may be experienced and surprisingly low libido in certain individuals. The pathophysiology of this is unknown and seems counterintuitive if it raises testosterone. Weight gain is also a side-effect.

Although Clomid seems to be a magic bullet, in clinical practice we find that it simply doesn’t achieve the serum testosterone levels or desired symptoms that actual injectable testosterone does in the majority of the patients, although some respond very well. This is consistent with a 2017 study in the Indian Journal of Urology, Testosterone versus Clomiphene Citrate in Managing Symptoms of Hypogonadism in Men.

For those strong responders, estrogen must also be monitored since higher levels of testosterone increases the possibility of conversion to estrogen in a process called aromatization. 

Every individual responds differently and has different goals. These should be discussed with your provider to determine optimal outcomes while minimizing negative side effects.

 

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