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Middle-aged women with higher testosterone levels were 33% more likely to develop uterine fibroids than those with lower levels, according to a study published in the .

However, high testosterone was not associated with increased risk for recurrent fibroids in women who had a history at baseline, reported senior study author , of the Stanford University School of Medicine in California, and colleagues.

The study also found that higher levels of testosterone and estrogen together were associated with a higher risk of incident fibroids, but a lower risk of recurrent fibroids.

While high estrogen levels are already known to be linked to fibroid risk, "To our knowledge, this study is the first longitudinal investigation of the relationship between serum androgen and estrogen levels and the development of uterine fibroids," Lee and colleagues wrote.

"Our findings are particularly interesting because testosterone was previously unrecognized as a factor in the development of uterine fibroids," Lee said in a statement. "The research opens up new lines of inquiry regarding how fibroids develop and how they are treated."

The study included 3,240 pre- or early perimenopausal women with an intact uterus, age 45-52, enrolled in the prospective Study of Women's Health Across the Nation (SWAN). Approximately 44% of the women completed the 13-year follow-up. There were 512 incident and 478 recurrent cases of uterine fibroids during the study period.

The investigators measured participants' serum levels of bioavailable testosterone (T) and estrogen (E2) about every year. These levels were dichotomized at the median as "high" versus "low," and analyzed for relationships with incident and recurrent fibroid risk.

Key results with respect to incident fibroids were as follows:

• Women with high bioavailable testosterone had increased risk of incident fibroids compared to women with low testosterone (odds ratio 1.33; 95% CI 1.01-1.76; P=0.04)
• Women with both high testosterone and estrogen had an even greater risk for incident fibroids (OR 1.52; 95% CI 1.07-2.17; P=0.02)
• Estrogen level alone was not significantly associated with incident fibroid risk

Results for recurrent fibroids included:

• Testosterone level alone was not significantly associated with recurrent fibroid risk
• However, women with high estrogen were at decreased risk for recurrent fibroids compared with women with low estrogen (OR 0.61; 95% CI 0.38-0.98; P=0.04)
• Women with both high bioavailable estrogen and testosterone had an even lower risk of fibroid recurrence compared to women with low levels of both hormones (OR 0.50; 95% CI 0.26-0.96; P=0.04)

"In summary, findings from this longitudinal study of midlife women suggest that higher levels of both bioavailable T and E2 is related to an increased risk of incident fibroids in the ensuing years in women who never previously reported them, but is related to a decreased risk of recurrent fibroids in women who previously reported them," Lee and colleagues wrote.

Why the opposite relationship with incident versus recurrent fibroids? One reason may be differences in the expression of estrogen and androgen receptors in the myometrium of women with and without prior fibroids, the investigators hypothesized.

Lee and colleagues also suggested that testosterone and estrogen may act on receptors in undetected fibroids, whose distributions are different between women with and without prior fibroids at baseline.

"Considering the individual and joint effects of circulating T and E2 levels on fibroid risk could help in identifying high-risk midlife women and developing personalized nonsurgical therapeutic options," the investigators concluded.

Said Lee in the prepared statement, "Given that managing uterine fibroids costs an estimated $34.4 billion in annual medical expenditures nationwide, it is important to identify new ways to better treat this common condition."

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