Enzyme may flag baby girls for future PCOS

"Because PCOS can't be diagnosed until after puberty, we've been trying to look for early changes that may signal its development," says Andrea Dunaif. "We hope we may be able to develop early treatment or improved prevention, if we can catch it early." (Credit: iStockphoto)

The infant daughters of women with polycystic ovary syndrome show a higher level of an enzyme that activates testosterone. This may be an early sign of developing the complex genetic disease, according to a new study.

PCOS is one of the leading causes of hormonally related infertility and type 2 diabetes in young women. It affects about 5 million women in the US, and the daughters of affected women are at increased risk to develop PCOS.

A serious metabolic disorder, PCOS has long-term health risks throughout a woman’s lifespan, including obesity, pre-diabetes, and diabetes. Affected women also have other risk factors for heart disease.

Scientists have long sought the primary driver of the disease. Catching it early may enable the development of early treatment or improved prevention.

Testosterone exposure

The study shows infants whose mothers have PCOS have a higher level of an enzyme that activates androgens—the best known of which is testosterone—than infants whose mothers don’t have the disease. That could mean the girls are being exposed to higher levels of testosterone in utero and during infancy, both critical times for development.

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“Increased activity of this enzyme, called 5-alpha-reductase, would lead to a higher activation of and greater exposure to testosterone in these daughters, which could contribute to the development of PCOS,” says lead author Laura Torchen, assistant professor of pediatrics at Northwestern University Feinberg School of Medicine.

The enzyme 5-alpha-reductase is the most important for converting testosterone to the much more potent androgen, dihydrotestosterone (DHT). Increased levels of testosterone and DHT cause the symptoms of PCOS including excessive hair growth and fertility problems.

“We wondered, when do changes in hormone production or metabolism begin in these daughters?” Torchen says. In early infancy, the ovaries in infant girls are very active and produce sex hormones, Torchen notes.

Early signs

When female animals are exposed to testosterone early in development—in utero or early in infancy—they develop what looks like PCOS with insulin resistance, high testosterone levels, and irregular menstrual periods.

“Because PCOS can’t be diagnosed until after puberty, we’ve been trying to look for early changes that may signal its development,” says senior author Andrea Dunaif, professor of endocrinology and metabolism at Feinberg and a Northwestern Medicine endocrinologist. “We hope we may be able to develop early treatment or improved prevention, if we can catch it early.”

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Scientists measured 5-alpha-reductase activity in the urine of infant girls (1 to 3 years old), 21 of whose mothers had PCOS and 36 control girls. The goal was to determine if daughters of women with PCOS have altered androgen metabolism in early childhood. The study showed the daughters of women with PCOS had a 30 percent higher level of the enzyme activity.

The study appears in the Journal of Clinical Endocrinology & Metabolism.

The Eunice Kennedy Shriver National Institute of Child Health and Development of the National Institutes of Health, the Medical Research Council UK Research Training Fellowship, and the Wellcome Trust Project supported the work.

Source: Northwestern University