The effect of conjugated equine oestrogen on diabetes incidence: the Women’s Health Initiative randomised trial

Bonds, Denise E.; Lasser, Norman L.; Qi, Lihong; Brzyski, Robert G.; Caan, Bette J.; Heiss, Gerardo; Limacher, Marian C.; Liu, J. H.; Mason, Ellen; Oberman, Albert; OʼSullivan, Mary J.; Phillips, Lawrence S.; Prineas, Ronald J.; Tinker, Lesley F.

doi:10.1007/s00125-005-0096-0

Cited by 181 publications

(126 citation statements)

References 36 publications

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“…Another possibility is that a shift towards android obesity in women indicates a change in hormonal state as is observed in post-menopausal women and in women with polycystic ovarian syndrome or Turner's syndrome, which can elevate type 2 diabetes risk. Oestrogen replacement among post-menopausal women is associated with a lower incidence of type 2 diabetes [28,29]. The reason for the interaction with sex with regard to hip circumference is unclear.…”

Section: Resultsmentioning

confidence: 99%

Anthropometric measures and glucose levels in a large multi-ethnic cohort of individuals at risk of developing type 2 diabetes

et al. 2010

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Aims/hypotheses We determined: (1) which of BMI, waist circumference, hip circumference and WHR has the strongest association and explanatory power for newly diagnosed type 2 diabetes and glucose status; and (2) the impact of considering two measures simultaneously. We also explored variation in anthropometric associations by sex and ethnicity. Methods We performed cross-sectional analysis of 22,293 men and women who were from five ethnic groups and 21 countries, and at risk of developing type 2 diabetes. Standardised anthropometric associations with type 2 diabetes and AUC of glucose status from OGTT (AUC OGTT ) were determined using multiple regression. Explanatory power was assessed using the c-statistic and adjusted r 2 . Results An increase in BMI, waist circumference or WHR had similar positive associations with type 2 diabetes, AUC OGTT and explanatory power after adjustment for age, sex, smoking and ethnicity (p <0.01). However, using BMI and WHR together resulted in greater explanatory power than with other models (p< 0.01). Associations were strongest when waist circumference and hip circumference were used together, a combination that had greater explanatory power than other models except for BMI and WHR together (p<0.01). Results were directionally similar according to sex and ethnicity; however, significant variations in associations were observed among these subgroups. Conclusions/interpretation The combination of BMI and WHR, or of waist circumference and hip circumference has the best explanatory power for type 2 diabetes and glucose status compared with a single anthropometric measure. Measurement of waist circumference and hip circumference is required to optimally identify people at risk of type 2 diabetes and people with elevated glucose levels.

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Section: Resultsmentioning

confidence: 99%

Anthropometric measures and glucose levels in a large multi-ethnic cohort of individuals at risk of developing type 2 diabetes

et al. 2010

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“…A decreased peripheral blood flow may limit insulin delivery and promote insulin resistance. Results of the WHI trial suggested that a decrease in insulin resistance, induced by the MHT, may have been responsible for the lower incidence of diabetes observed in the women who received the active treatment [13,14]; these results were confirmed in a meta-analysis [15]. As in a recent study [36], the relationship was no longer significant after discontinuation of MHT use, when the model was adjusted for BMI during follow-up.…”

Section: Discussionmentioning

confidence: 73%

“…Though our study is the first to consider the effect of different types of MHT combination on diabetes risk, several authors have reported the impact of different types of hormone therapy on intermediate risk factors. In the WHI trial, conjugated equine oestrogen combined with MPA was found to improve insulin sensitivity [14]. Low-dose dydrogesterone associated with oestradiol may lead to a decrease in the concentration of circulating insulin [38].…”

Section: Discussionmentioning

confidence: 99%

“…Two randomised trials, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative (WHI) trial, examined the effects of 0.625 mg conjugated equine oestrogen alone or combined with 2.5 mg medroxyprogesterone acetate (MPA) on diabetes incidence [12][13][14]. These trials found a significant reduction in the incidence of diabetes of 20% to 30% in users of combined MHT [12,13], and of 12% in users of oestrogen alone [14].…”

Section: Introductionmentioning

confidence: 99%

“…These trials found a significant reduction in the incidence of diabetes of 20% to 30% in users of combined MHT [12,13], and of 12% in users of oestrogen alone [14]. There was also a significant fall in insulin resistance during the first year of follow-up in women treated with combined MHT or oestrogens alone [13,14]. Similarly, a recent meta-analysis examining components of the metabolic syndrome, which included 107 randomised controlled trials of at least 8 weeks' duration, showed that MHT reduced the risk of new-onset diabetes [15].…”

Section: Introductionmentioning

confidence: 99%

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Menopausal hormone therapy and new-onset diabetes in the French Etude Epidemiologique de Femmes de la Mutuelle Générale de l’Education Nationale (E3N) cohort

et al. 2009

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Aims/hypothesis Two US randomised trials found a lower incidence of type 2 diabetes in women treated by menopausal hormone therapy (MHT) with oral conjugated equine oestrogen combined with medroxyprogesterone acetate. The purpose of this study was to evaluate the influence of various MHTs, according to their formulation and route of administration, on new-onset diabetes in a cohort of postmenopausal French women. Methods The association between MHT use and new-onset diabetes was investigated by Cox regression analysis in 63,624 postmenopausal women in the prospective French cohort of the Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N). Cases of diabetes were identified through self-reporting or drugreimbursement record linkage, and further validated. Results 1,220 new-onset diabetes cases were validated. We observed a lower risk of new-onset diabetes among women who had ever used MHT (HR 0.82 [95% CI 0.72-0.93]), compared with those who had never used MHT. Adjustment for BMI during follow-up (rather than according to baseline BMI) did not substantially modify this association.An oral route of oestrogen administration was associated with a greater decrease in diabetes risk than a cutaneous route (HR 0.68 [95% CI 0.55-0.85] vs 0.87 [95% CI 0.75-1.00], p for homogeneity = 0.028). We were not able to show significant differences between the progestagens used in combined MHT. Conclusions/interpretation Use of MHT appeared to be associated with a lower risk of new-onset diabetes. This relationship was not mediated by changes in BMI. Further studies are needed to confirm the stronger effect of oral administration of oestrogen compared with cutaneous administration.

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Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative

Culver¹

2012

Arch Intern Med

387

255

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The effect of conjugated equine oestrogen on diabetes incidence: the Women’s Health Initiative randomised trial

Cited by 181 publications

References 36 publications

Anthropometric measures and glucose levels in a large multi-ethnic cohort of individuals at risk of developing type 2 diabetes

Anthropometric measures and glucose levels in a large multi-ethnic cohort of individuals at risk of developing type 2 diabetes

Menopausal hormone therapy and new-onset diabetes in the French Etude Epidemiologique de Femmes de la Mutuelle Générale de l’Education Nationale (E3N) cohort

Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative

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