Early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: a systematic review and meta-analysis

Anagnostis, Panagiotis; Christou, Konstantinos; Artzouchaltzi, Aikaterini-Maria; Gkekas, Nifon K; Kosmidou, Nikoletta; Siolos, Pavlos; Paschou, Stavroula Α.; Potoupnis, Michael; Kenanidis, Eustathios; Tsiridis, Eleftherios; Lambrinoudaki, Ιrene; Stevenson, John C.; Goulis, Dimitrios G.

doi:10.1530/eje-18-0602

Cited by 133 publications

(85 citation statements)

References 48 publications

(126 reference statements)

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“…The protective role of endogenous oestrogens in women is evidenced by the deleterious impact of the menopause on body composition and glucose homeostasis, leading to an increased incidence of metabolic disorders vs premenopausal women [12]. Early menopause and premature ovarian insufficiency are associated with an increased risk of type 2 diabetes as compared with premenopausal women, while a 21-35% reduction in diabetes incidence has been reported in menopausal women receiving oestrogen-based hormonal therapy vs placebo [13][14][15]. Further demonstrating the contribution of the oestrogen pathway to diabetes susceptibility in humans, rare loss-of-function mutations in the gene encoding either aromatase (the enzyme that converts androgens into oestrogens) or oestrogen receptor α (ERα) result in dysmetabolic phenotypes in individuals of both sexes [16].…”

Section: A Critical Role For Sex Steroid Hormones In Diabetes Susceptmentioning

confidence: 99%

Sex differences in metabolic regulation and diabetes susceptibility

et al. 2019

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Gender and biological sex impact the pathogenesis of numerous diseases, including metabolic disorders such as diabetes. In most parts of the world, diabetes is more prevalent in men than in women, especially in middle-aged populations. In line with this, considering almost all animal models, males are more likely to develop obesity, insulin resistance and hyperglycaemia than females in response to nutritional challenges. As summarised in this review, it is now obvious that many aspects of energy balance and glucose metabolism are regulated differently in males and females and influence their predisposition to type 2 diabetes. During their reproductive life, women exhibit specificities in energy partitioning as compared with men, with carbohydrate and lipid utilisation as fuel sources that favour energy storage in subcutaneous adipose tissues and preserve them from visceral and ectopic fat accumulation. Insulin sensitivity is higher in women, who are also characterised by higher capacities for insulin secretion and incretin responses than men; although, these sex advantages all disappear when glucose tolerance deteriorates towards diabetes. Clinical and experimental observations evidence the protective actions of endogenous oestrogens, mainly through oestrogen receptor α activation in various tissues, including the brain, the liver, skeletal muscle, adipose tissue and pancreatic beta cells. However, beside sex steroids, underlying mechanisms need to be further investigated, especially the role of sex chromosomes, fetal/neonatal programming and epigenetic modifications. On the path to precision medicine, further deciphering sex-specific traits in energy balance and glucose homeostasis is indeed a priority topic to optimise individual approaches in type 2 diabetes prevention and treatment.

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Section: A Critical Role For Sex Steroid Hormones In Diabetes Susceptmentioning

confidence: 99%

Sex differences in metabolic regulation and diabetes susceptibility

et al. 2019

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“…Most studies suggest that the menopausal transition [47] or premature menopause [48] is associated with increased risks of developing insulin resistance, the metabolic syndrome, and type 2 diabetes. This may be mediated by metabolically adverse changes in body composition and by the direct effect of estrogens on insulin sensitivity and pancreatic β -cells.…”

Section: Effects Of Endocrine Therapy On Cardiometabolic Outcomesmentioning

confidence: 99%

Cardiometabolic Effects of Endocrine Treatment of Estrogen Receptor–Positive Early Breast Cancer

Cheung

Ramchand

Yeo

et al. 2019

Journal of the Endocrine Society

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Estrogen receptor–positive early breast cancer is common and has a relatively good prognosis. It shares risk factors with cardiovascular disease, and cardiovascular disease is an important competing cause of mortality. Adjuvant endocrine therapy with aromatase inhibitors (requiring concomitant ovarian suppression in premenopausal women) or selective estrogen receptor modulators (usually tamoxifen) exert oncologic benefits by respectively inhibiting estradiol synthesis or breast estrogen receptor signaling. Aromatase inhibitors cause systemic estradiol depletion. Tamoxifen has mixed agonistic/antagonistic effects in a tissue-dependent fashion. Given that estrogens modulate cardiometabolic risk, a review of the effects of endocrine therapy on cardiometabolic outcomes is pertinent. The current, but limited, evidence suggests that tamoxifen treatment, although associated with increases in body fat, hepatic steatosis, serum triglycerides, and diabetes risk, modestly reduces low-density lipoprotein cholesterol and lipoprotein(a) and may have favorable effects on markers of subclinical atherosclerosis. Tamoxifen is associated with either no effect on, or a reduction in, cardiovascular events, and it is associated with an increase in venous thromboembolic events. Aromatase inhibitors, although fewer studies are available and often confounded by comparison with tamoxifen, have not been consistently associated with adverse changes in cardiometabolic risk factors or increases in cardiovascular events. Further clinical trials designed to evaluate cardiometabolic outcomes are needed to more accurately determine the effects of endocrine therapy on cardiovascular risks, to inform individualized decisions regarding choice and duration of endocrine therapy, and to implement evidence-based strategies to mitigate cardiometabolic risks. In the meantime, although breast cancer–specific evidence for benefit of lifestyle measures is available and recommended routinely, proactive monitoring and treatment of cardiovascular risk factors should follow general population recommendations.

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“…Data from the InterLACE consortium indicate that in the general female population of high-income countries, the prevalence of premature menopause is 2% (range 1-3%) and of early menopause is 7.6% (range 5-10%), suggesting that almost one in 10 women have premature or early menopause [5]. Recent reviews have concluded that premature or early menopause is associated with an increased risk of all-cause mortality, cardiovascular disease, type 2 diabetes, depression, osteoporosis and fracture [6][7][8][9][10][11]. There is some evidence that premature menopause is associated with greater than average cognitive decline in later life [12], but current studies do not support a consistent association between early menopause and dementia risk [13].…”

Section: Introductionmentioning

confidence: 99%

EMAS position statement: Predictors of premature and early natural menopause

et al. 2019

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Introduction: While the associations of genetic, reproductive and environmental factors with the timing of natural menopause have been extensively investigated, few epidemiological studies have specifically examined their association with premature (< 40 years) or early natural menopause (40-45 years). Aim: The aim of this position statement is to provide evidence on the predictors of premature and early natural menopause, as well as recommendations for the management of premature and early menopause and future research. Materials and methods: Literature review and consensus of expert opinion. Results and conclusions: Strong genetic predictors of premature and early menopause include a family history of premature or early menopause, being a child of a multiple pregnancy and some specific genetic variants. Women with early menarche and nulliparity or low parity are also at a higher risk of experiencing premature or early menopause. Cigarette smoking (with a strong dose-response effect) and being underweight have been consistently associated with premature and early menopause. Current guidelines for the management of premature and early menopause mainly focus on early initiation of hormone therapy (HT) and continued treatment until the woman reaches the average age at menopause (50-52 years). We suggest that clinicians and health professionals consider the age at menopause of the relevant region or ethnic group as part of the assessment for the timing of HT cessation. In addition, there should be early monitoring of women with a family history of early menopause, who are a child of a multiple pregnancy, or who have had early menarche (especially those who have had no children). As part of preventive health strategies, women should be encouraged to quit smoking (preferably before the age of 30 years) and maintain optimal weight in order to reduce their risk of premature or early menopause.

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Early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: a systematic review and meta-analysis

Cited by 133 publications

References 48 publications

Sex differences in metabolic regulation and diabetes susceptibility

Sex differences in metabolic regulation and diabetes susceptibility

Cardiometabolic Effects of Endocrine Treatment of Estrogen Receptor–Positive Early Breast Cancer

EMAS position statement: Predictors of premature and early natural menopause

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