New drug could treat low testosterone with fewer side effects

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In fertility treatment, what's good for the goose apparently is good for the gander. A new study shows that a drug similar to one used to help women ovulate can raise testosterone levels and sperm counts in men.

The drug, called enclomiphene citrate, may prove to be more effective in treating men with low testosterone than the testosterone gels and injections currently prescribed. That's because the medicine helps the body produce its own testosterone and may be cheaper and more convenient to use.

The new study, a phase II clinical trial, will appear in an upcoming issue of the journal Fertility and Sterility. A phase II clinical trial is the second of four phases used to test a drug for safety and effectiveness before it is submitted to the Food and Drug Administration for approval.

Low testosterone, or hypogonadism, affects millions of U.S. men, according to the Centers for Disease Control and Prevention. Symptoms of the condition include fatigue, loss of muscle mass, an increase in body fat, depression, erectile dysfunction and low libido. Testosterone levels in men drop naturally after about age 30, but lower-than-normal levels are also associated with obesity, diabetes and circulatory disease.

The definition of a normal testosterone level is hotly debated, because it varies so greatly among individuals. However, in general, doctors treat men with low testosterone mainly using testosterone injections and gels. The treatments are expensive, and once they are stopped, testosterone levels plummet. [5 Myths About the Male Body]

"This is a complicated problem that requires expert consultation before embarking on treatment," said Dr. Lawrence Ross, a urologist and professor emeritus at the University of Illinois at Chicago, who did not work on the new study.

Testosterone up, but sperm down

One perhaps surprising side effect of current testosterone drugs is low sperm count. The influx of externally produced testosterone causes the brain to tell the testicles to produce less testosterone, which compromises sperm production.

Many primary care physicians do not know about this effect, however, and they readily prescribe testosterone to male patients who have low testosterone and also wish to have a child, said Ross, who wrote an editorial accompanying the new study in the journal. A survey by the American Urological Association found that 25 percent of urologists said they would use testosterone to treat infertile men pursuing pregnancy.

The medicine, enclomiphene citrate, used in the new study is a derivative of clomiphene citrate, which is marketed under the name Clomid as a female infertility treatment. The researchers from Repros Therapeutics in The Woodlands, Texas, and from Baylor College of Medicine in Houston treated 73 men with "secondary hypogonadism." In this condition, low testosterone results from a problem in the hypothalamus or the pituitary gland, as opposed to the testes.

In the study, that drug increased levels of testosterone produced by the testes, as well as levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) produced by the pituitary gland, two other hormones important for reproduction.

However, the medicine didn't lower the men's sperm counts because testosterone production in the testes was never compromised.

Clomid can produce similar results, and some doctors may prescribe it "off-label" (meaning it is used to treat people with a condition other than the one the medicine was approved for) to men to treat low testosterone, said Dr. Ron Wiehle of Repros Therapeutics, the study's lead author. "Still, it seems that Clomid works inconsistently, and [some] physicians are wary of its use," Wiehle said. And no groups are pushing for its use, either. "No drug company will champion Clomid since its patent lapsed a long time ago," he said.

But enclomiphene citrate, which Repros Therapeutics hopes to market as Androxal, has been tweaked in a way that makes it more effective than Clomid in raising testosterone levels, Wiehle added.

Ross, in his editorial, noted that enclomiphene citrate or its broader family, called selective estrogen receptor modulators has the potential to help men who have postponed fatherhood into their 40s or 50s and now suffer from low testosterone.