Insulin resistance, secretion, and metabolism in users of oral contraceptives.

Godsland, Ian F.; Walton, Christopher; Felton, Carl V.; Proudler, Anthony J.; Patel, Ankit; Wynn,

doi:10.1210/jcem.74.1.1530790

Cited by 103 publications

(50 citation statements)

References 21 publications

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“…We assumed a background prevalence of 7% for PCOS among daughters of control women. None of the subjects was receiving hormonal (33), antihypertensive (34), or antidiabetic (35) medications, including 6 mothers with a history of diabetes and 27 with a history of hypertension.…”

Section: Methodsmentioning

confidence: 99%

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: 99%

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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“…50 However, supraphysiological doses of oestrogens, as achieved by administration of the oral contraceptive pill, increase insulin resistance. 51,52 Exogenous oestrogen increases SHBG concentrations, with studies in postmenopausal women demonstrating a larger increase with oral than with transdermal administration. 53 In postmenopausal women, oral oestrogen therapy is associated with a greater reduction in risk of developing type 2 DM than transdermal therapy.…”

Section: Shbg and Insulin Resistance: Cross-sectional Studiesmentioning

confidence: 99%

Sex hormone binding globulin and insulin resistance

Wallace

McKinley

Bell

et al. 2013

Clinical Endocrinology

202

146

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SummarySex hormone binding globulin (SHBG) is a glycoprotein composed of two 373-amino-acid subunits. The SHBG gene and a promotor region have been identified. The SHBG receptor has yet to be cloned but is known to act through a G-protein-linked second-messenger system following plasma membrane binding. The principal function of SHBG has traditionally been considered to be that of a transport protein for sex steroids, regulating circulating concentrations of free (unbound) hormones and their transport to target tissues. Recent research suggests that SHBG has functions in addition to the binding and transport of sex steroids. Observational studies have associated a low SHBG concentration with an increased incidence of type 2 diabetes mellitus (DM) independent of sex hormone levels in men and women. Genetic studies using Mendelian randomization analysis linking three single nucleotide polymorphisms of the SHBG gene to risk of developing type 2 DM suggest SHBG may have a role in the pathogenesis of type 2 DM. The correlation between SHBG and insulin resistance that is evident in a number of cross-sectional studies is in keeping with the suggestion that the association between SHBG and incidence of type 2 DM is explained by insulin resistance. Several potential mechanisms may account for this association, including the identification of dietary factors that influence SHBG gene transcription. Further research to characterize the SHBG-receptor and the SHBG second messenger system is required. An interventional study examining the effects on insulin resistance of altering SHBG concentrations may help in determining whether this association is causal.

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“…Many PCOS women are now believed to have insulin resistance (IR), and many studies have shown that oral contraceptives can cause deterioration of IR and several other metabolic, cardiovascular and inflammatory parameters. [1][2][3] Androgens themselves and the androgenic progestogen in many oral pills can induce or increase IR. 4,5 Pills containing antiandrogens, such as cyproterone acetate or drospirenone, are already available, but they are costly compared to the DSG-containing pill.…”

Section: Introductionmentioning

confidence: 99%