In the Journals

Hormone levels may predict PCOS in premenarchal girls

Daughters of women with polycystic ovary syndrome exhibit a distinctive reproductive phenotype before puberty that can predict PCOS risk when compared with normal-weight girls and girls with obesity, according to findings published in The Journal of Clinical Endocrinology & Metabolism.

“PCOS can only be diagnosed in girls after the start of menses,” Andrea Dunaif, MD, professor of molecular medicine and system chief of the division of endocrinology, diabetes and bone disease at the Icahn School of Medicine and Mount Sinai Health System, told Endocrine Today. “However, increased testosterone levels are present before the onset of menstrual cycles in daughters of women with PCOS. Obese girls who are not daughters of women with PCOS also have elevated testosterone levels before menarche. ... However, we found that only daughters of women with PCOS have elevated anti-Müllerian hormone (AMH) levels, a marker of changes in ovarian follicle development characteristic of PCOS, compared to obese girls. These findings suggest that daughters, who have inherited PCOS risk genes from their affected mothers, may be at risk to develop PCOS after menarche.”

Dunaif and colleagues analyzed data from 48 premenarchal daughters of women with PCOS (mean age, 10 years; 80th BMI percentile), 30 girls with obesity (mean age, 10 years; 99th BMI percentile; mothers reported regular menses every 27 to 35 days and no androgen excess) and 22 normal-weight girls who served as controls (mean age, 10 years; 50th BMI percentile), all aged 8 to 12 years. Girls underwent a physical exam and provided a fasting morning blood sample to assess levels of AMH, testosterone, estradiol, dehydroepiandrosterone sulfate (DHEAS) and androstenedione.

Researchers observed no between-group differences in total testosterone (P = .53), DHEAS (P = .34) or androstenedione levels (P = .52), whereas free testosterone levels were similarly increased in both daughters of women with PCOS (P = .01) and in girls with obesity (P = .0001) when compared with normal-weight girls. Mean levels of free testosterone were 0.13 ng/dL in daughters of women with PCOS, 0.22 ng/dL in girls with obesity and 0.1 ng/dL in controls.

AMH levels were higher among daughters of women with PCOS vs. girls with obesity (P < .0001), and researchers observed a trend toward higher AMH levels in daughters of women with PCOS vs. controls (P = .1). Across groups, mean AMH levels were 3.28 ng/mL for daughters of women with PCOS, 1.22 ng/mL for girls with obesity and 2.08 ng/mL for controls, according to researchers. In addition, 31% of daughters of women with PCOS who had elevated AMH levels also had elevated free testosterone.

In subgroup analyses stratifying daughters of women with PCOS by obesity status, researchers found that elevated AMH levels persisted in the daughters of women with PCOS who had obesity when compared with girls with obesity whose mothers did not have PCOS (P = .03).

“In contrast, obese girls may not develop PCOS because they lack evidence for changes in ovarian follicle development,” Dunaif said. “Our findings suggest that testosterone and AMH levels could be used to predict risk for PCOS in premenarchal daughters of women with PCOS. This would permit early interventions to prevent disease progression.” – by Regina Schaffer

For more information:

Andrea Dunaif, MD, can be reached at the Icahn School of Medicine and Mount Sinai Health System, Atran Building, 1428 Madison Ave., Fourth Floor, Room 4-36, One Gustave L. Levy Place, Box 1055, New York, NY 10029; email: andrea.dunaif@mssm.edu.

Disclosures: The authors report no relevant financial disclosures.

Daughters of women with polycystic ovary syndrome exhibit a distinctive reproductive phenotype before puberty that can predict PCOS risk when compared with normal-weight girls and girls with obesity, according to findings published in The Journal of Clinical Endocrinology & Metabolism.

“PCOS can only be diagnosed in girls after the start of menses,” Andrea Dunaif, MD, professor of molecular medicine and system chief of the division of endocrinology, diabetes and bone disease at the Icahn School of Medicine and Mount Sinai Health System, told Endocrine Today. “However, increased testosterone levels are present before the onset of menstrual cycles in daughters of women with PCOS. Obese girls who are not daughters of women with PCOS also have elevated testosterone levels before menarche. ... However, we found that only daughters of women with PCOS have elevated anti-Müllerian hormone (AMH) levels, a marker of changes in ovarian follicle development characteristic of PCOS, compared to obese girls. These findings suggest that daughters, who have inherited PCOS risk genes from their affected mothers, may be at risk to develop PCOS after menarche.”

Dunaif and colleagues analyzed data from 48 premenarchal daughters of women with PCOS (mean age, 10 years; 80th BMI percentile), 30 girls with obesity (mean age, 10 years; 99th BMI percentile; mothers reported regular menses every 27 to 35 days and no androgen excess) and 22 normal-weight girls who served as controls (mean age, 10 years; 50th BMI percentile), all aged 8 to 12 years. Girls underwent a physical exam and provided a fasting morning blood sample to assess levels of AMH, testosterone, estradiol, dehydroepiandrosterone sulfate (DHEAS) and androstenedione.

Researchers observed no between-group differences in total testosterone (P = .53), DHEAS (P = .34) or androstenedione levels (P = .52), whereas free testosterone levels were similarly increased in both daughters of women with PCOS (P = .01) and in girls with obesity (P = .0001) when compared with normal-weight girls. Mean levels of free testosterone were 0.13 ng/dL in daughters of women with PCOS, 0.22 ng/dL in girls with obesity and 0.1 ng/dL in controls.

AMH levels were higher among daughters of women with PCOS vs. girls with obesity (P < .0001), and researchers observed a trend toward higher AMH levels in daughters of women with PCOS vs. controls (P = .1). Across groups, mean AMH levels were 3.28 ng/mL for daughters of women with PCOS, 1.22 ng/mL for girls with obesity and 2.08 ng/mL for controls, according to researchers. In addition, 31% of daughters of women with PCOS who had elevated AMH levels also had elevated free testosterone.

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In subgroup analyses stratifying daughters of women with PCOS by obesity status, researchers found that elevated AMH levels persisted in the daughters of women with PCOS who had obesity when compared with girls with obesity whose mothers did not have PCOS (P = .03).

“In contrast, obese girls may not develop PCOS because they lack evidence for changes in ovarian follicle development,” Dunaif said. “Our findings suggest that testosterone and AMH levels could be used to predict risk for PCOS in premenarchal daughters of women with PCOS. This would permit early interventions to prevent disease progression.” – by Regina Schaffer

For more information:

Andrea Dunaif, MD, can be reached at the Icahn School of Medicine and Mount Sinai Health System, Atran Building, 1428 Madison Ave., Fourth Floor, Room 4-36, One Gustave L. Levy Place, Box 1055, New York, NY 10029; email: andrea.dunaif@mssm.edu.

Disclosures: The authors report no relevant financial disclosures.