Insulin sensitivity is decreased in normal women by doses of ethinyl estradiol used in oral contraceptives

Kojima, Tetsuya; Lindheim, Steven R.; Duffy, Daniel M.; Vijod, Marcela A.; Stanczyk, Frank Z.; Løbo, Rogerio A.

doi:10.1016/0002-9378(93)90432-i

Cited by 36 publications

(12 citation statements)

References 21 publications

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“…Prior studies (1,2) noted increased IR with higher-dose EE preparations; however, results have been inconsistent. In non-PCOS subjects, higher doses of estrogen (50 g) have reduced glucose clearance while lower doses (20 g) have not (27). Current findings (10,12) significantly support prior small, largely uncontrolled, shorterduration studies suggesting that highdose OCPs increase IR in PCOS.…”

Section: Conclusion -In Women Withsupporting

confidence: 73%

Effects of Medical Therapy on Insulin Resistance and the Cardiovascular System in Polycystic Ovary Syndrome

2007

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OBJECTIVE -We aimed to determine the impact of medical therapy for symptom management on insulin resistance, metabolic profiles, and surrogate markers of cardiovascular disease in polycystic ovary syndrome (PCOS), an insulin-resistant pre-diabetes condition. RESULTS -All treatments similarly and significantly improved symptoms including hirsutism and menstrual cycle length. Insulin resistance was improved by metformin and worsened by the high-dose OCP. Arterial stiffness worsened in the higher-dose OCP group (PWV 7.46 vs. 8.03 m/s, P Ͻ 0.05), related primarily to the increased insulin resistance. RESEARCH DESIGN AND METHODS -One hundred overweight women (BMI Ͼ27kgCONCLUSIONS -In overweight women with PCOS, metformin and low-and high-dose OCP preparations have similar efficacy but differential effects on insulin resistance and arterial function. These findings suggest that a low-dose OCP preparation may be preferable if contraception is needed and that metformin should be considered for symptomatic management, particularly in women with additional metabolic and cardiovascular risk factors. Diabetes Care 30:471-478, 2007I t is well recognized that polycystic ovary syndrome (PCOS) has both reproductive and metabolic features. Insulin resistance (IR), the primary underlying abnormality, affects the majority of women with PCOS (1,2). In general populations, IR independently predicts cardiovascular risk (3,4), underlies the metabolic syndrome, and increases the risk of type 2 diabetes (1,2).Type 2 diabetes also potently increases cardiovascular risk, especially in women. Furthermore, treating IR improves the metabolic profile, reduces progression to type 2 diabetes, and decreases cardiovascular risk in general populations. In PCOS, IR is increased, cardiovascular risk factors are elevated, type 2 diabetes risk is increased four-to sevenfold, and the risk of cardiovascular disease is also likely to be increased (2,5). We postulate that IR per se is an important target in the treatment of this condition, especially when considering long-term health implications in PCOS.Lifestyle modification is first-line therapy for IR in PCOS, and a loss of 5-10% of body weight improves IR and increases ovulation (6,7). As long-term weight loss is not feasible or sustainable in the majority (8), additional medical therapy is usually required. The oral contraceptive (OCP) is first-line medical therapy in PCOS, when fertility is not desired, in regulating cycles and controlling hyperandrogenism. Yet, in both PCOS and non-PCOS populations, the OCP increases IR, albeit inconsistently (1,9 -12).The increased IR appears to be estrogen dose related (13,14). The metabolic effects of OCP preparations have not been adequately studied in PCOS, and optimal preparations and doses remain unclear.Alternatively, medical therapy can directly target IR in PCOS. Glitazones are considered inappropriate in reproductive-age women until concerns over teratogenicity are clarified (1). Metformin, supported by a Cochrane review (15), has a legitimate adjuvant...

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Section: Conclusion -In Women Withsupporting

confidence: 73%

Effects of Medical Therapy on Insulin Resistance and the Cardiovascular System in Polycystic Ovary Syndrome

2007

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“…Similar observations were made earlier with oral levonorgestrel during OGTTs [11]. The estrogen component of COCs is also implicated in lowering insulin sensitivity; among others authors, Kojima et al [12] using an insulin tolerance test, showed that even low hormone doses, such as 20 µg (EE) administered alone, causes a reduction in insulin sensitivity. The effect of different combined OCs on overall glucose tolerance has accordingly been postulated to be a result of a combination of estrogen-induced insulin resistance and progestin-associated changes in insulin half-life or pancreatic secretion [13].…”

Section: Discussionsupporting

confidence: 76%

Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism

Lüdicke¹,

Gaspard²,

Demeyer³

et al. 2002

Contraception

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This study compared the impact on carbohydrate metabolism of two combinedoral contraceptives (COCs). This open-label, single-center trial enrolled participants for a total of 15 cycles. Thirty-six women were randomized to receive either 20 µg ethinyl estradiol (EE) and 75 µg gestodene (GSD) or 20 µg ethinyl estradiol and 150 µg desogestrel (DSG) daily for 21 days out of 28. A glucose tolerance test was performed at baseline and cycles 6 and 13. The area under the curve (AUC) for glucose increased in both study groups. The change was statistically significant (p = 0.036) for the 20 EE/75 GSD group at cycle 6 versus baseline. Fasting blood glucose at cycle 13 was significantly (p < 0.01) higher for both treatment groups compared to baseline. No changes were found for fasting insulin and fasting C-peptide levels or for the AUCs of insulin or C-peptide. Both regimens were well tolerated. Gestodene and desogestrel in combination with 20-µg ethinyl estradiol induce similar changes in carbohydrate metabolism which are smaller than those described earlier for COCs containing higher estrogen doses or more androgenic progestins such as levonorgestrel.

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“…Exercise and insulin sensitivity in PM women Although results of previous studies have been inconsistent, HRT has been shown to influence glucose and insulin metabolism (8,13,24,(31)(32)(33)(34)41). We found a significant relationship between HRT use and both fasting plasma insulin levels and K G .…”

mentioning

confidence: 45%

Insulin sensitivity in postmenopausal women: independent and combined associations with hormone replacement, cardiovascular fitness, and body composition.

et al. 2000

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Insulin Sensitivity in Postmenopausal WomenIndependent and combined associations with hormone replacement, cardiovascular fitness, and body compositionOBJECTIVE -The effects of combined physical activity and hormone replacement therapy (HRT) on insulin sensitivity in postmenopausal (PM) women are unclear. The purpose of the study was to test the following hypotheses: 1) PM women who have undergone vigorous exercise training have greater insulin sensitivity than PM women who are physically active and PM women who are sedentary, and 2) PM women using HRT have greater insulin sensitivity than PM women not using HRT. We also sought to determine whether body composition or cardiovascular fitness was the stronger predictor of insulin sensitivity in these women.RESEARCH DESIGN AND METHODS -Three groups of PM women classified as sedentary (n = 18), physically active (n = 19), and athletic (n = 23) underwent an insulin-modified frequently sampled intravenous glucose tolerance test to determine the insulin sensitivity index (S I ) and dual-energy X-ray absorptiometry to determine body composition.RESULTS -There was a significant association between both physical activity (P = 0.036) and HRT (P = 0.007) and fasting plasma insulin levels. The athletic PM women had the lowest plasma insulin levels and the highest S I . Across all physical activity levels, PM women using HRT (n = 29) had significantly lower fasting plasma insulin levels and a lower S I than PM women not using HRT (n = 31). HRT was significantly (P = 0.025) associated with intravenous glucose tolerance (K G ); the women not using HRT had a higher K G than the PM women using HRT (0.83 ± 0.08 vs. 0.60 ± 0.05% per minute). Percent body fat (r = Ϫ0.37, P = 0.004) and VO 2max (r = 0.35, P = 0.007) were similar predictors of S I .CONCLUSIONS -We conclude that, although overall HRT was associated with an attenuated S I , vigorous exercise training was independently associated with the greatest S I . In addition, PM women using HRT may benefit from having lower plasma insulin levels, but they may also have a lower S I .

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Insulin sensitivity is decreased in normal women by doses of ethinyl estradiol used in oral contraceptives

Cited by 36 publications

References 21 publications

Effects of Medical Therapy on Insulin Resistance and the Cardiovascular System in Polycystic Ovary Syndrome

Effects of Medical Therapy on Insulin Resistance and the Cardiovascular System in Polycystic Ovary Syndrome

Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism

Insulin sensitivity in postmenopausal women: independent and combined associations with hormone replacement, cardiovascular fitness, and body composition.

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