DECEMBER 15, 2004

Testosterone emasculates the male immune system

The battle of the sexes probably began when first two gender-specific creatures crawled out of the primordial sludge. Biologically, women have proven to outperform men in at least one aspect — they're immune systems are stronger. This difference has baffled scientists for some time but we're getting closer to uncovering the secret. In fact, testosterone — that distinctly manly hormone — may be the culprit holding back the male immune system, according to research published in the November 15 issue of the Journal of Immunology.

"What we are showing is that testosterone seems to impede immunity," said Dr Eugene Kwon, a urologist and immunology researcher at the Mayo Clinic in Rochester, MN. "When testosterone is withdrawn, you get an increased host immune response indicated by the rising numbers of immune cells that are available to participate."

Research has already noted that the immune system's B-cells multiply and lymph nodes swell upon androgen deprivation or upon removal of testosterone from the body. The researchers were also hoping to find the mechanism through which androgens like testosterone interact with the immune system. This study examined the effect of androgen deprivation on T-cell counts and efficacy.

Male mice were either surgically castrated or sham-castrated, where pericordal fat was removed instead of the testicles. T-cell expression was measured under several conditions including antigen stimulation, chemotherapy, thymus glands removal and in cell culture.

Androgen deprivation caused the T-cells to multiply and become more reactive to antigenic stimulation, confirming that testosterone affects T-cell numbers and function. However, adding testosterone back into androgen deprived T-cell cultures didn't decrease the number of T-cells or change the cells' characteristics. This means that testosterone isn't directly interacting with the immune cells to hinder their growth.

But when testosterone is away, other hormones may play. Since testosterone suppresses the production of prolactin, luteinizing hormone, estradiol and other hormones, an increase in one of these could be causing the enhanced immune response. More research is needed to establish a cause-and-effect relationship between the presence of various sex hormones and the potency of the immune response.

Once that relationship is found it could lead to a new way for doctors to hasten the recovery of the immune system after immunosuppression resulting from chemotherapy, burn injuries and blood loss. As the authors wrote, "These studies may have implications for enhancing immune responses to immunotherapy, for improving immune system recovery following chemotherapy, and for establishing a mechanistic basis whereby gonadal steroid hormones modulate autoimmunity."



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