Of those, six articles were excluded, due to the following reasons: (i) No data on T2DM according to menopausal age ( n = 1) (ii) No data on EM ( n = 3) (iii) Non-English language ( n = 1) (iv) Referral to another paper already included in the analysis ( n = 1). The initial search provided 1851 results, after excluding duplicates, 19 of which were assessed as full texts for eligibility ( Fig. The following comparisons were made according to the incidence or prevalence of T2DM: (i) Women with EM compared with those with menopausal age of >45 years (ii) Women with EM compared with those with menopausal age of 45–55 years (iii) Women with POI compared with those with menopausal age of >45 years (iv) Women with POI compared with those with menopausal age of 45–55 years (v) Women with late menopause compared with those with menopausal age of 45–55 years. Parameters such as mean age of the participants at study entry, mean BMI, the percentage of women with surgical menopause, the method of T2DM diagnosis, smoking status and physical activity were also recorded. The following data were extracted and recorded: (i) First author (ii) Year of publication (iii) Country in which the study was conducted (iv) Study design (case–control or cohort) (iv) Duration (available in cohorts) (v) Total number of participants (vi) Number of women with EM (vii) Number of women with POI (viii) Number of women with normal menopause (subdivided in those with menopausal age between 45 and 55 years and those with a menopausal age >45 years (ix) Number of women with late menopause (>55 years) (x) Number of cases with T2DM in each of these categories. Two researchers (K C and A M A) reviewed all eligible studies. Any discrepancy was solved by consultation of an investigator, not involved in the initial procedure (P A and D G G). The main search was completed independently by two investigators (K C and A M A). To identify eligible studies, the main search was conducted in the electronic databases MEDLINE, Scopus and Cochrane (CENTRAL) covering the period from conception until January 31, 2018, and using the following search strings: ("menopause, premature" OR "primary ovarian insufficiency" OR “ovarian insufficiency” OR “ovarian failure” OR ((menopause OR menopause OR menopausal OR climacteric OR postmenopausal OR post-menopausal) AND (early OR premature OR age OR years OR time))) AND ("diabetes mellitus, Type 2" OR (diabet* AND (“non-insulin dependent” OR “non-insulin-dependent” OR type-2 OR “type 2” OR “type II”)) OR diabetes OR diabetic) NOT (Animal NOT Human) NOT (letter OR comment OR editorial OR Review OR "practice guideline" OR "case reports"). The following PICO (Population, Intervention or exposure, Comparison, Outcome) elements were applied as inclusion criteria for the systematic review: (i) Population: postmenopausal women (ii) Intervention: early age at menopause, either EM or POI (iii) Comparison group: women with natural menopause (iv) Outcome: T2DM. The aim of this study was to systematically investigate and meta-analyze the best evidence regarding the association of menopausal age with the risk of developing T2DM. However, whether EM or POI per se is associated with increased risk of T2DM is unknown. The association of T2DM with increased CVD risk has been well documented in both genders, although women with T2DM seem to be at a higher relative CVD risk compared with their male counterparts ( 15). With respect to glucose metabolism, the true effect of endogenous hormonal milieu during menopause on T2DM risk is controversial, since some, but not all, studies have shown a possible association between EM and increased risk of T2DM ( 11, 12, 13, 14). Except the vasomotor symptoms affecting the woman’s quality of life, transition to menopause has also been associated with a potential higher cardiovascular (CVD) risk, mainly attributed to a more atherogenic lipid profile, central adiposity and glucose intolerance ( 5, 6, 7, 8).īoth early menopause (EM) and POI have been associated with increased risk of death and CVD in recent meta-analyses ( 9, 10). About 1% of women enter menopause under the age of 40 (0.1% under the age of 30), a condition termed ‘premature ovarian insufficiency’ (POI) ( 3, 4). However, approximately 10% of the female population enter menopause before 45 years, a condition termed ‘early’ or ‘premature’ menopause ( 3). The average age at menopause is 50–52 years ( 2). It is the consequence follicular depletion leading to estrogen deficiency ( 1). Menopause is chronically determined by the completion of 12 months after the final menstrual period.
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