Insulin Resistance in the Sisters of Women with Polycystic Ovary Syndrome: Association with Hyperandrogenemia Rather Than Menstrual Irregularity

Legro, Richard S.; Bentley‐Lewis, Rhonda; Driscoll, Deborah A.; Wang, Steve C.; Dunaif, Andrea

doi:10.1210/jcem.87.5.8513

Cited by 169 publications

(82 citation statements)

References 63 publications

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“…Three mothers did not report menstrual history and were assigned unknown menstrual status and excluded from all analyses based on menstrual history. Hyperandrogenemia in mothers was defined by the same criteria used in the probands with PCOS (11,17). We did not record self-reported hirsutism because we have found that such self-assessments are unreliable (unpublished observations), an observation that has also been confirmed by other investigators (36).…”

Section: Methodsmentioning

confidence: 87%

“…1). When hyperandrogenemia was defined categorically (11,17), 3% of mothers fulfilled the National Institute of Child Health and Human Development diagnostic criteria for PCOS (18), and 6% of mothers had hyperandrogenemia with a history of regular menses.…”

Section: Resultsmentioning

confidence: 99%

“…Written informed consent was obtained from all participants. We used the National Institute of Child Health and Human Development diagnostic criteria for PCOS (18): no more than six menses per year and either total T Ͼ 2.0 nmol͞liter or nonsex hormone-binding globulin-bound T (uT) Ͼ0.5 nmol͞liter, levels greater than two standard deviations above the mean value that we have established in reproductively normal women aged 18 -40 years in the early follicular phase of the menstrual cycle (11,17). Other causes of anovulation and hyperandrogenemia were excluded by appropriate tests (11,17).…”

Section: Methodsmentioning

confidence: 99%

“…Height, weight, blood pressure, and waist measurements were obtained as previously reported for the on-site subjects (11,17). For the off-site subjects, the height and weight were selfreported as previously validated (11,17).…”

Section: Methodsmentioning

confidence: 99%

“…For the off-site subjects, the height and weight were selfreported as previously validated (11,17). Waist circumference was self-reported for 31% of mothers, who were provided with a calibrated tape measure for this determination.…”

Section: Methodsmentioning

confidence: 99%

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Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome

Sam

Legro²,

Essah

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Dyslipidemia is a feature of polycystic ovary syndrome (PCOS), but its pathogenesis remains controversial. We performed this study of mothers of women with PCOS to test the hypothesis that dyslipidemia is a heritable trait in families of women with PCOS and to investigate the impact of age on reproductive and metabolic phenotypes. Fasting blood was obtained in 215 non-Hispanic white mothers of women with PCOS and 62 control women. The prevalence of metabolic syndrome was compared with that in nonHispanic white women of comparable age from the National Health and Nutrition Examination Survey III. Mothers had higher total (P < 0.001) and low-density lipoprotein (LDL) cholesterol levels (P ‫؍‬ 0.007), whereas high-density lipoprotein and triglyceride levels did not differ compared with control women. The only predictors of LDL levels in mothers were their daughters' LDL levels (r 2 ‫؍‬ 0.11, P < 0.001) and their own unbound testosterone levels (r 2 ‫؍‬ 0.04, P ‫؍‬ 0.03). The prevalence of metabolic syndrome was increased in obese (body mass index > 30 kg͞m 2 ) mothers compared with obese non-Hispanic white women from the National Health and Nutrition Examination Survey III (P ‫؍‬ 0.04). Thirty-one percent of mothers reported a history of menstrual irregularity. These mothers had higher androgen levels, markers of insulin resistance, and LDL levels than mothers with regular menses. LDL levels are increased in mothers of women with PCOS, suggestive of a heritable trait. A history of menstrual irregularity identifies mothers with features of PCOS. Obese mothers have a very high prevalence of metabolic syndrome. These findings suggest that both the reproductive and metabolic abnormalities persist with age in PCOS.hyperandrogenemia ͉ hypertriglyceridemia ͉ insulin resistance ͉ low-density lipoprotein cholesterol ͉ menstrual irregularity P olycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women (1) characterized by disordered gonadotropin secretion and hyperandrogenism (2). Women with PCOS frequently have substantial insulin resistance (3) and are at increased risk for type 2 diabetes mellitus (DM2) (4, 5). Affected women also have other risk factors for cardiovascular disease, including obesity and dyslipidemia (6-8). Studies of women with PCOS, by definition, have been limited to women in their reproductive years, and little is known about the reproductive or metabolic phenotypes as these women age. Paradoxically, the only controlled study of older women with PCOS suggested that lipid abnormalities normalize in the fifth decade of life as the prevalence of these changes increases in the normal population (7). The long-term health consequences of PCOS are of considerable importance because of the well established increase in cardiovascular disease risk conferred by DM2 and the emerging data on risk conferred by other disorders associated with insulin resistance. Moreover, the full burden of these associated disorders may not become evident until affected women are in their sixth to eighth d...

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Section: Methodsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome

Sam

Legro²,

Essah

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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A 27-Year-Old Woman With a Diagnosis of Polycystic Ovary Syndrome

Legro

2007

JAMA

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Background: Polycystic ovary syndrome and oligomenorrhea which is one of its complications are considered as the most common causes of menstrual disorders which increases the risk of depression and psychological effects complications. The prevalence of oligomenorrhea is predicted to be 12 to 15 percent. This syndrome occurs with symptoms such as obesity, impaired glucose metabolism, dysmenorrhea, oligomenorrhea and other symptoms. In addition, incidence of decreased libido, painful sexual intercourse and decreased libido are also observed in the patients concurrently which must be considered during the treatment. Case Presentation: The case is a 27 year old woman married 2 years ago without children, unprotected, housewife who has been referred to the clinic of traditional medicine in June 2016 with palpitation complaints, dizziness, extreme tiredness, poor sleep, fatigue, darkening of skin along with syncopal attacks. She was the candidate for standard treatment for depression with diagnosis of depression by a psychiatrist. Based on the history of the patient, she has experienced delayed period for up to three months, severe pain prior to and during menstruation, dyspareunia and fear of sexual intercourse, decreased libido and progressive lack of sexual satisfaction over the past two years. She suffered from epileptic attack every 7-10 days without falling resulting in organ and head damage. After taking history, medical tonic treatment of ovarian and treatment using sitz-bath and training for sexual intercourse were conducted simultaneously from the perceptive of modern and Iranian medicine and menstruation was regulated in the first three months and sexual intercourse gradually became possible in the next three months and patient experienced regular menstruation and complete sexual intercourse with sexual pleasure at the end of six months. Conclusion: Treatment of this patient by modification of her uterus and ovaries function, creation of menstrual regularity and possibility of sexual intercourse along with sexual pleasure based on sexual pleasure highlights the necessity of more attention to the connection between the different organs in the human body. A woman's uterus and femininity functions make her sick in the case of disorder, one of such is termed strangulation of uterus (Ekhtenagh in Persian) in Iranian medicine.

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Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys

Abbott

Tarantal

Dumesic³

2009

American J Primatol

145

114

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Old World monkeys provide naturally-occurring and experimentally-induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally-induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia, and increased incidence of type 2 diabetes that characterize early gestated-exposed PA adults.These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin-glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood.

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Insulin Resistance in the Sisters of Women with Polycystic Ovary Syndrome: Association with Hyperandrogenemia Rather Than Menstrual Irregularity

Cited by 169 publications

References 63 publications

Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome

Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome

A 27-Year-Old Woman With a Diagnosis of Polycystic Ovary Syndrome

Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys

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