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Article 3 SSRI Research
2004-04-07 08:41:44

WSU Spokane Scientists Launch Clinical Research

Adding to the growing cluster of biotechnology activities in the Terabyte Triangle, the National Institute of Child Health and Human Development (NIH) awarded a $143,000 grant to WSU Spokane researchers Joanna Ellington and Clarke St. Dennis to study the effects of antidepressants on male reproductive health. Ellington, DVM, PhD, is associate professor and director of biomedical development at the Health Research and Education Center, and she is also CEO of Bio~OriGyn LLC. St. Dennis, PhD, BCPP, is assistant professor of pharmacotherapy at WSU Spokane, and a psychopharmacology specialist at Sacred Heart Medical Center. Bio~OriGyn’s offices are in the Metropolitan Financial Center building.

In the post-thalidomide era, many harbor suspicions that psychoactive drugs might have negative affects on human reproduction. In this case, preliminary evidence exists indicating a class of drugs prescribed for clinical depression may cause sperm function abnormalities including chromatin (DNA) damage. The class of drugs is selective serotonin reuptake inhibitors (SSRIs), and includes Prozac, Zoloft, Effexor and Paxil.

One of the first clues was that nearly half of the estimated 4 million US men taking SSRIs experienced sexual dysfunction. According to Dr. Ellington, libido and erectile function are not as disrupted, but these men have a high incidence of delayed or failed orgasm. Other studies have suggested that SSRI induced hormone imbalances may be the cause. Specifically, SSRIs are the number one cause of clinically high prolactin levels in men. Excess prolactin confuses the normally functioning male body into believing that its testosterone levels are completely normal, according to Ellington, and that no more testosterone needs to be produced. Adequate testosterone is mandatory for healthy sperm. Insufficient testosterone can cause sperm chromatin damage. So, when prolactin interferes, it fools the body into believing that testosterone is normal, and this lowers the testosterone level causing DNA chromatin damage in the sperm. Chromatin is the genetic material the sperm incorporates with the egg’s genetic material to create a baby.

Ellington and St Dennis developed their hypothesis based on a previous observation that a normal sperm donor’s sperm chromatin assay showed a sudden doubling of chromatin damage following a two-month-old prescription use of the SSRI Prozac. Additionally, evidence was found in animal studies where injecting prolactin caused sperm DNA breakage. The hypothesis is that the SSRIs are causing sperm damage, and the NIH granted the WSU researchers funding to investigate.

The ramifications of sperm chromatin damage manifest itself in the offspring, Ellington states. Sperm itself is nothing more than DNA surrounded by a membrane with a tail attached. The damaged sperm looks and acts exactly like healthy sperm so it is fully capable of fertilizing an egg. When the new cell starts reading the DNA, it comes upon a break in the double-helix chain that causes incorrect reading of the biological map. The several possible results are all tragic. Results include: early embryonic death, miscarriage, a live birth of a child prone to severe illness including cancer, and birth defects. Between 15 and 20% of all childhood cancer cases are reportedly the result of sperm DNA damage.

Subjects are being enrolled to take part in the two-year study. Subjects will include men with clinical depression either beginning SSRI therapy or psychotherapy. Each subject will be enrolled through his personal psychologist or physician who will prescreen the individual for suitability in the study. Each subject will make a six-month commitment, and will be paid for his participation. Over the six-month period, the subject will submit blood samples for hormone level testing and semen samples for sperm chromatin assay. All findings are, of course, confidential.

“Many factors cause sperm chromatin (DNA) damage,” Ellington stated. Those factors include smoking, antihistamines, anabolic steroids, environmental pollutants, and hormones in the food supply. “Probably the single greatest cause of transient sperm chromatin damage is overheated testicles,” said Ellington, “and that can happen in your hot tub.” For this reason, it is not a forgone conclusion that SSRIs cause sperm chromatin damage or if so, how much damage they cause. Much more conclusive evidence will be available at the end of the study. “In the meantime,” Ellington cautions, “anyone wanting to begin a pregnancy may want to consider other forms of antidepressant medication.”

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