Elevated Testosterone and Estrogen Levels May Increase the Risk for Uterine Fibroids

In contrast, women with high estrogen or high levels of both testosterone and estrogen were at lower risk for fibroid recurrence

With Jennifer Lee MD, PhD, Richard Legro MD, and Jason Wong ScD 

Uterine fibroids.

Women who have high levels of both testosterone and estrogen in midlife may be at greater risk of developing uterine fibroids than women with low levels of these hormones, according to a 13-year epidemiologic study published in the Journal of Clinical Endocrinology & Metabolism.

“Our research suggests women undergoing the menopausal transition who have higher testosterone levels have an increased risk of developing fibroids, particularly if they also have higher estrogen levels,” said lead author Jason Y.Y. Wong, ScD, of Stanford University School of Medicine, in a statement to the press. “This study is the first longitudinal investigation of the relationship between androgen and estrogen levels and the development of uterine fibroids.”

The Study of Women’s Health Across the Nation (SWAN) included 3,240 women aged 45 to 52 years who were premenopausal (52.3%) or early perimenopausal (45.3%) and were seen at one of 7 sites across the United States. Less than half of the original group (43.6%) completed the 13-year follow-up. At near-annual visits, the women’s sex hormone levels were measured, and they were asked whether they had been diagnosed with or treated for uterine fibroids.

Hormones showed conflicting effects on the risk for incident versus recurrent fibroids
A total of 512 women reported incident fibroids, and 478 women reported recurrent fibroids during the follow-up period. Participants who had high levels of bioavailable testosterone in the blood were 1.33 times more likely to develop a single incidence of fibroids than women who had low levels of testosterone (P=0.04). Women who had high levels of both bioavalable testosterone and estrogen were at even greater risk for incident fibroids compared to women with low levels of both hormones (adjusted odds ratio [OR], 1.52 P=0.02).

In contrast, women with high estrogen or high levels of both testosterone and estrogen were at lower risk for fibroid recurrence (adjusted OR= 0.61 and 0.50, respectively; P=0.04 for both).

Further research is needed to confirm findings
“Our findings are particularly interesting because testosterone was previously unrecognized as a factor in the development of uterine fibroids,” said senior author Jennifer S. Lee, MD, PhD, of Stanford University School of Medicine and Veterans Affairs Palo Alto Health Care System in Palo Alto, CA. “The research opens up new lines of inquiry regarding how fibroids develop and how they are treated. 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.”

“The effects were modest from a clinical standpoint and not present at baseline; they were only teased out over time with repeated measures and a large sample size,” commented Richard S. Legro, MD Professor in the Department of Obstetrics and Gynecology and Public Health Sciences at Penn State University College of Medicine in Hershey, PA and Co-Leader of the Clinical Services Core (CSC). Dr. Legro called the findings “tantalizing” but noted that replication of the study findings and further research is needed.

“The results are perplexing,” Dr. Legro added. “How can a combination of high testosterone and estradiol be associated positively with the formation of first fibroids and negatively with their recurrence? The findings lack biologic plausibility. That is not unusual for epidemiological studies, which identify associations and not cause and effect.”

“The next step is further research to find a mechanism that would address the disparate findings,” Dr. Legro said.

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