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Impaired Glucose Tolerance in Pregnant Women With Polycystic Ovary Syndrome

From the Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Address reprint requests to: Michael J. McMahon, MD, MPH Department of Obstetrics and Gynecology University of North Carolina at Chapel Hill 214 MacNider Building, Campus Box 7570 Chapel Hill, NC 27599-7570 E-mail: mcmahon{at}med.unc.edu

	Abstract

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Objective: To determine whether women with polycystic ovary syndrome (PCOS) are more likely to develop gestational diabetes mellitus compared with age- and weight-matched controls.

Methods: This retrospective cohort study compared reproductive-age women with and without PCOS who received prenatal care at the University of North Carolina Hospitals between April 1989 and June 1998. We reviewed the medical charts of 22 women with PCOS diagnosis before pregnancy based on menstrual histories, elevated androgen levels, and LH-FSH ratios greater than 2. These women were compared with 66 women without PCOS matched for age and weight. Gestational diabetes mellitus (GDM) was diagnosed in women if they had abnormal results on a 50-g glucose screening test and at least two abnormal plasma glucose values during a 100-g glucose tolerance test. Medical complications of pregnancy, pregnancy complications, and birth outcomes were compared between women with and without PCOS.

Results: Nine of 22 women with PCOS also had GDM diagnosis, compared with two of 66 controls (odds ratio [OR] 22.2; 95% confidence interval [CI] 3.8, 170.0), and these women exhibited increased plasma glucose values for all measurements except fasting. Five of 22 women with PCOS developed preeclampsia compared with one of 66 controls (OR 15.0; 95% CI 1.9, 121.5).

Conclusion: Women with PCOS are at increased risk of glucose intolerance and preeclampsia during pregnancy.

Women with polycystic ovary syndrome (PCOS) often have associated reproductive and metabolic problems. Hyperinsulinemia in PCOS not only initiates and promotes hirsutism, but also causes diabetes and dyslipidemia.¹ Insulin-sensitizing agents have proved effective in treating not only ovulatory dysfunction and hyperandrogenemia,² but also dysfibrinolytic and lipid abnormalities.³ Immediate clinical concerns in this syndrome include reproductive problems related to infertility, hirsutism, and obesity. Preventive general health care also is necessary because of a predisposition to medical complications from noninsulin-dependent diabetes, hypertension, and cardiovascular disease in women with PCOS.⁴

Pregnancy is characterized by insulin resistance.⁵ Women with histories of gestational diabetes mellitus (GDM) have a 50% chance of developing noninsulin-dependent diabetes mellitus later in life.⁶ Because up to 80% of obese and 30% of lean women with PCOS demonstrate insulin resistance before conception and as many as 30% are affected by impaired glucose tolerance later in life, women with PCOS may be at an increased risk for glucose intolerance during pregnancy.⁷ Conflicting results regarding this association may simply reflect the different inclusion criteria that investigators use to study PCOS.⁸

Using age- and weight-matched controls and well-accepted criteria to define PCOS, we sought to determine retrospectively the risk of GDM in women with PCOS.

	Materials and Methods

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We performed a retrospective chart review approved by the institutional review board of the University of North Carolina. We used a computer search to identify all women 21–40 years of age who had a diagnosis of PCOS using the International Classification of Diseases, 9th revision, and had received prenatal care at our institution between April 1989 and June 1998. Inclusion criteria were clinical hirsutism and oligomenorrhea, defined as an intermenstrual interval in excess of 45 days, or fewer than eight menses per year. Women who received thyroid replacement were included only if they were euthyroid and still had irregular menses. All women with PCOS diagnosis had an elevated serum, free, or total testosterone concentration or a basal LH-FSH ratio greater than 2. Women were excluded if the diagnosis of PCOS had been made solely on the basis of sonographic or laparoscopic evidence of polycystic-appearing or sclerotic, enlarged ovaries.

Controls were selected from computer records of women who delivered at the University of North Carolina Hospitals during the same period and were age-and weight-matched to women with PCOS in a ratio of 3:1. Controls had not received ovulation induction. Cases and controls with histories of GDM or diabetes mellitus were excluded.

We recorded the number of women who had elevated serum or plasma glucose values 1 hour after a 50-g glucose load between 24 and 28 weeks’ gestation. In our clinics, a value greater than 140 mg/dL is considered elevated and prompts a 3-hour 100-g glucose tolerance test (GTT). Cases and controls with two or more elevated values on the oral GTT were considered to have GDM.

Medical charts, prenatal records, and laboratory results were reviewed for each woman. Medical complications during pregnancy, including hematologic, pulmonary, cardiac, coagulation, connective-tissue, gastrointestinal, and psychiatric disorders, were compared between the groups. Preeclampsia was diagnosed if a woman presented with relevant signs and symptoms including a persistently elevated blood pressure of at least 140/90 mmHg and proteinuria. Delivery complications included shoulder dystocia; vaginal, cervical, or perineal lacerations; uterine rupture; and uterine inversion. The incidence of preeclampsia, mode of delivery, delivery complications, birth weight, and Apgar scores were collected from the charts. Both groups included women who conceived by means of clomiphene citrate, gonadotropins, or in vitro fertilization. Only singleton pregnancies were included.

Data entry and statistical analyses were done using STATA software (STATA, College Station, TX) and EPI Info, Version 6 (Centers for Disease Control and Prevention, Atlanta, GA). Categoric data were compared using the ² test and continuous data using the t test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.

	Results

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Demographic characteristics of the groups were similar, with an expected decrease in gravidity in women with PCOS (Table 1). There were no significant differences between the groups in race, marital status, alcohol or tobacco use, or the incidence of medical complications during pregnancy.

	Discussion

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Estimating conservatively, 5–10% of reproductive-age women have PCOS.⁹ The current diagnostic criteria for PCOS are controversial, but hyperandrogenism and chronic ovulatory disturbances are key characteristics. Polycystic ovary morphology is consistent with the diagnosis, but not essential. Gonadotropin abnormalities, with characteristic increases in LH pulse amplitude and frequency, have long been recognized as contributing to the elevation of LH/FSH.¹⁰ In a 1990 National Institute of Child Health and Human Development conference, 69% of the participants agreed that insulin resistance was a possible diagnostic criterion for PCOS.¹¹ Based on the prevalence of glucose intolerance, it can be extrapolated that PCOS-related insulin resistance contributes to approximately 10% of glucose intolerance in premenopausal women. It has been estimated that up to 30% of premenopausal women with the syndrome will develop impaired glucose tolerance.¹² Hyperinsulinemia is also noted in nonobese women with PCOS, so this syndrome may be as important a risk factor for GDM as is a history of macrosomia, advanced maternal age, glucosuria, and obesity.¹³ In addition, an increased prevalence of polycystic-appearing ovaries has been noted postpartum in women with GDM.¹⁴ Because polycystic-appearing ovaries are noted in normal ovulatory women,¹⁵ women with hypothalamic amenorrhea,¹⁶ and women with congenital adrenal hyperplasia,¹⁷ previous reports may have inaccurately estimated the prevalence of GDM in women with PCOS.

Data conflict regarding the prevalence of impaired glucose tolerance in gravidas with PCOS, which likely reflects the criteria used to diagnose the syndrome. Using well-defined criteria, we retrospectively determined that age- and weight-matched women with PCOS had a significantly higher risk of impaired glucose tolerance. Among women who underwent a 3-hour oral GTT, significantly higher glucose values were noted in women with PCOS, except for the fasting value. This observation suggests that the hyperinsulinemic state of pregnancy in women with PCOS fails to respond adequately to immediate glucose loads. Pancreatic beta-cell dysfunction has been demonstrated in women with this syndrome, as shown by decreased meal-related insulin secretory responses.¹⁸

Women who have undergone wedge resection of their ovaries for hyperandrogenic, chronic anovulation have a higher incidence of cardiovascular disease.¹³ Dyslipidemias and dysfibrinolytic disorders of reproductive-age women with PCOS reflect their hyperinsulinemic state. The increased occurrence of preeclampsia in our cases may indicate early impaired vascular reactivity. It is interesting that there was no difference in birth weights between the groups. Perhaps placental vascular compromise may counterbalance the usual effects of impaired glucose tolerance on increasing birth weight.¹⁹

In conclusion, it appears that women with PCOS are at increased risk for glucose intolerance during pregnancy. Whether early screening is beneficial in this group of women is debatable. Careful monitoring should be undertaken in pregnancy for the development of preeclampsia.

	Footnotes

 
PII S0029-7844(99)00252-5

Received October 1, 1998. Received in revised form December 28, 1998. Accepted January 28, 1999.

	References

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