The association between chronic diseases and the age at natural menopause: a systematic review

Despite several existing studies on the age at natural menopause (ANM) and its related factors, epidemiologic data on the associations between chronic diseases and ANM are scarce with conflicting and inconclusive results. The aim of this systematic review was to summarize the results of the studies investigating the association between chronic disease and ANM. PubMed, Scopus, and Web of Science were searched for retrieving and summarizing studies published up to October 2020 investigating the association between chronic medical conditions and ANM. All types of observational studies published in the English language were eligible to be included in the systematic review. Studies needed to report the effect of at least one chronic disease on ANM. Studies with other designs, studies with unreliable and incomplete results, and those that assessed none of the chronic diseases as outcomes of interest were excluded. Of the 6294 records retrieved by searching the databases, a total of 28 observational studies were included for this review. According to the Newcastle-Ottawa scale, nine studies were classified as high-quality, fifteen studies as moderate, and four as low-quality. Among the five studies investigating the association between polycystic ovary syndrome (PCOS) and ANM, three studies reported that PCOS was associated with a later ANM, whereas others found no such association. Eight studies showed that diabetes was associated with an earlier ANM, whereas eight other studies found no such association. While only one study showed a younger age at the onset of menopause in patients with a history of hypertension, five studies did not report such an effect. Only one study assessed the effect of dyslipidemia on ANM and showed no association between these variables. While three studies documented the effects of cardiovascular diseases (CVD) and heart disease on earlier ANM, one study found no association between these diseases and ANM. Most included studies showed the association of mood disorders with earlier ANM. There were no sufficient data for assessing the effects of thyroid, skin, and autoimmune diseases on ANM. Chronic diseases particularly cardio-metabolic disturbances, cardiovascular events, and psycho-emotional disorders are associated with earlier menopause, whereas other diseases such as PCOS may lead to later menopause. Accordingly, early diagnosis and managing chronic medical conditions in women can potentially prevent early or late menopause.