Describing the case of a 16-year-old girl who had not yet menstruated, pediatric endocrinologist Ines Guttmann-Bauman noted that both the patient’s mother and maternal grandmother were “late bloomers” in reaching menarche, and that an aunt had been diagnosed with polycystic ovary syndrome, or PCOS. The patient’s BMI was in the 90th percentile, and lab tests showed slightly elevated testosterone but normal glucose, DHEAS (dehydroepinadrosterone sulfate) and lipids. The girl showed no signs of the excessive hairiness condition hirsutism, acne or acanthosis, a sign of insulin resistance in PCOS patients. So, Guttmann-Bauman asked the auditorium filled with pediatricians at Johns Hopkins annual Pediatric Endocrinology for the Primary Care Clinician conference in June, what would you tell a patient like this?
All appeared to agree that the girl needed to lose weight, but were uncertain as to whether she met the criteria for the hormonal condition PCOS. In potential cases of PCOS, the most common cause of infertility in women, Guttmann-Baumann explained, such presentations are typical and tricky to pin down, especially in adolescents.
“This is the kind of patient where you may want to talk about weight, and indicate that certain clinical features and family history may be predisposing the development of PCOS, but she is not yet meeting the criteria,” Guttmann-Bauman said. “How can you talk about oligoovulation (infrequent or irregular ovulation) in a child who has not yet reached menarche? It’s very slippery territory, and what makes it harder for us as pediatricians is that normal adolescence has certain features that are very similar to PCOS.”
Anovulation, or a menstrual cycle in which ovulation fails to occur, Guttmann-Bauman explained, is common in normal adolescents up to 3 years post menarche. But it’s important for pediatricians to remember that if the 24-35 day cycle is not established by 3 years after menarche, there’s a 50 percent chance of persistent irregular menses.
“The other thing that’s important,” she added, “is that a 90-day cycle, even in the first year of menarche, is in the 95th percentile. So if you have someone who has started menstruating and has had two periods in the course of a year, there’s a pretty good chance this will not turn out to be a normal cycle.”
The name of the condition itself is somewhat of a misnomer, Guttmann-Bauman said, because most patients don’t present with cysts. In the diagnosis of PCOS forged at the National Institute of Child Health and Human Development in 1990, the major criteria include hyperandrogenism and/or hyperandrogenemia, oligoovulation and exclusion of other known disorders, such as Cushing’s syndrome. In 2006 the diagnostic criteria for adolescents was expanded to include both biologic and clinical hyperandrogenism, as well as insulin resistance or hyperinsulinemia, and polcystic ovaries. Nonetheless, pediatricians are still puzzled over how to define hyperandrogenemia, Guttmann-Bauman said, because the levels of the male hormones (androgens) may be physiologically higher during normal puberty.
The prevalence of PCOS is about 6 to 10 percent of adult women, and 3 percent of adolescents. PCOS is more common in families, with 35 percent of mothers and 40 percent of sisters of PCOS patients affected. Long-term health consequences include up to a tenfold increase in the risk of type 2 diabetes, increased risk of dyslipidemia, hypertension, endothelial dysfunction and possibly increased cardiovascular morbidity and mortality. Also, obese women with PCOS are at risk of metabolic syndrome. Because of the risk of insulin resistance syndrome – up to 50 percent of teens with PCOS fulfill the criteria – all patients should be screened for diabetes by age 30.
What are the therapeutic goals? Treat hirsutism – often a very big concern of patients – regularize the menstrual cycle, improve fertility and prevent long-term consequences. But the chief concern, Guttmann-Bauman said, is weight loss. Studies have shown, she noted, that the loss of 15 percent of body weight results in lowered androgen levels and spontaneous resumption of ovulation in women with PCOS.
“I always tell the patient that medication is a Band-Aid and what you really need to do is lose weight,” Guttmann-Bauman said. “The idea is to get your body gets back into shape so that you’re capable of getting back on the cycle naturally.”
Medicines include oral contraceptives, which have been shown to restore regular menstrual cycles and normalize androgen levels, though they may adversely affect lipid profiles. For parents who resist oral contraceptives for their child, Provera, a form of progesterone, may be an option. Anti-androgens are an option, too, though in using those medications, Guttmann-Bauman stressed, pediatricians need to watch out for electrolyte imbalances.
Insulin-lowering medications like Metformin have been found to decrease hirsutism, hyperinsulinemia and hyperandrogenemia, and restore ovulation in 43 percent of women. Metformin has been approved for use in children, Guttmann-Bauman said, but there is controversy regarding who should receive it, and whether it adds any benefits to a patient already being treated with oral contraceptives. Also, Metformin has significant intestinal side effects like bloating and diarrhea, which a significant number of patients cannot tolerate, forcing them off the medication. But pointing to studies like “The Impact of Metformin, Oral Contraceptives and Lifestyle Modification on PCOS in Obese Adolescent Women in Two Randomized Controlled Clinical Trials” (Journal of Clinical Endocrinology & Metabolism, Aug. 8, 2008), Guttmann-Bauman said, “Metformin decreases BMI, improves testosterone levels, and improves menstrual cycles. It definitely has an impressive effect.”
When it comes to PCOS, Guttmann-Bauman noted, each cook tends to bring his or her own recipes. Regardless of the approach, she concluded, it should be tailored to the patient.
“You have to recognize that PCOS has a variety of symptoms that are expressed differently in different patients. So, the therapy should be directed at those manifestations individually."