Medical Therapy

Medical therapy for male infertility consists of using medications to manipulate the male endocrine (hormone) system. Typically, the goal is to increase the bioavailable testosterone and decrease the estradiol. The medications used to do this are either clomiphene citrate or Clomid, which is used “off label” in the male as it is FDA approved only for use in women, anastrazole or arimidex and hCG or hMG. All of these except hCG and hMG, which must given as injections, are taken as oral medications. It may be helpful to review the male endocrine system schematic link to male anatomy page prior to reading the descriptions of how these drugs work. All of these drugs have side effects; we will go over the specific side effects of these drugs, should you need them, at the time of your consultation with us. For a general overview of our initial evaluation and our rationale for how we prescribe these drugs see Figure 1. Note that QD is daily and QOD means every other day.

Figure 1: Initial Evaluation of the Infertile Male and Data Driven Use of Medications

initial evaluationtreat bioavailable

Clomiphene Citrate/Clomid

Clomiphene citrate, or Clomid, works by blocking the action of estrogen on the pituitary. Normally, estrogen provides negative feedback to the pituitary. This means that estrogen causes the pituitary to produce less LH and FSH, resulting in decreased testosterone and suboptimal spermatogenesis or sperm production. Clomiphene citrate works by blocking this negative feedback, causing the pituitary to increase the LH and FSH it is producing and also the testosterone. Side effects of clomiphene include, but are not limited to, pectoral (or breast muscle) tenderness, irritability, possible ability to accelerate prostate cancer growth if cancer is present, mild acne, and, very rarely, visual field disturbances caused by pituitary swelling. All of these side effects are reversible if the clomiphene is stopped; please stop taking clomiphene and notify us immediately if you experience any of these side effects. Further, most men notice positive side effects from the clomiphene citrate such as improved erections, increased sex drive, increased muscle mass, more energy, and weight loss.

hCG & hMG

A small percentage of men will not respond to clomiphene citrate. We put these men on hCG or hMG. While these drugs are delivered by injection, they have very similar side effect profiles to clomiphene citrate. They work by directly stimulating the testes to make testosterone and improve spermatogenesis. We do not start with these drugs because they mandate injections, which most patients would rather avoid.


Anastrazole or arimidex is a drug that was originally developed for breast cancer that has become an excellent drug for specific groups of men with male factor infertility. Arimidex blocks the conversion of testosterone to estradiol in the peripheral tissues. Specifically, it blocks the action of aromatase, the enzyme (or biochemical machine) that converts testosterone to estradiol. The optimal conditions for sperm production are a bioavailable testosterone > 155 ng/dl as well as a testosterone: estradiol ratio of greater than 10:1. If the estradiol is significantly elevated and the testosterone is low (a low testosterone to estradiol ratio), we typically use anastrazole or arimidex, which will decrease the estradiol and decrease the testosterone.

Medication Monitoring

We request that patients on any of these medications return after two weeks for laboratory testing and a clinic visit to ensure the medications are working properly. We then have patients see us every four months for the first year of medication use and then annually there after. We obtain a PSA, hemoglobin and testosterone at each of these visits to ensure the medication is working appropriately and that there are no adverse side effects.

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