Early Menopause and Cardiovascular Disease Risk in Women With or Without Type 2 Diabetes: A Pooled Analysis of 9,374 Postmenopausal Women

Abstract

OBJECTIVE Early menopause may be associated with higher cardiovascular disease (CVD) risk. Type 2 diabetes mellitus (T2DM), coupled with early menopause, may result in even greater CVD risk in women. We examined CVD risk in women with early compared with normal-age menopause, with and without T2DM overall, and by race/ethnicity. RESEARCH DESIGN AND METHODS We pooled data from the Atherosclerosis Risk in Communities study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. We included women with data on menopausal status, menopausal age, and T2DM, excluding pre- or perimenopausal women and those with prevalent CVD. Outcomes included incident coronary heart disease (CHD), stroke, heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD) (CHD or stroke). We estimated the risk associated with early (<45 years) compared with normal-age menopause using Cox proportional hazards models. Covariates included age, race/ethnicity, education, BMI, blood pressure, cholesterol, smoking, alcohol consumption, antihypertensive medication, lipid-lowering medication, hormone therapy use, and pregnancy history. RESULTS We included 9,374 postmenopausal women for a median follow-up of 15 years. We observed 1,068 CHD, 659 stroke, 1,412 HF, and 1,567 ASCVD events. T2DM significantly modified the effect of early menopause on CVD risk. Adjusted hazard ratios for early menopause and the outcomes were greater in women with T2DM versus those without (CHD 1.15 [95% CI 1.00, 1.33] vs. 1.09 [1.03, 1.15]; stroke 1.21 [1.04, 1.40] vs. 1.10 [1.04, 1.16]; ASCVD 1.29 [1.09, 1.51] vs. 1.10 [1.04, 1.17]; HF 1.18 [1.00, 1.39] vs. 1.09 [1.03, 1.16]). The modifying effect of T2DM on the association between early menopause and ASCVD was only statistically significant in Black compared with White women. CONCLUSIONS Early menopause was associated with an increased risk for CVD in postmenopausal women. T2DM may further augment the risk, particularly in Black women.

Menopausal status, age at natural menopause and risk of diabetes in China: a 10-year prospective study of 300,000 women

“…As ovaries are considered the main source of female hormones, great public health concerns have been raised on the health consequences of menopause. In literature, the post-menopausal status coincided with increased risks for multiple chronic conditions among women [ 7 ], and moreover, findings suggested that the earlier and later age at menopause was associated with higher risk of cardiovascular diseases [ 8 ] and cancers (e.g., breast and endometrium cancer) [ 9 , 10 ], respectively.…”

Fisetin attenuates doxorubicin‐induced cardiotoxicity by inhibiting the insulin‐like growth factor II receptor apoptotic pathway through estrogen receptor‐α/‐β activation

“…Menopause‐related estrogen insufficiency can lead to left ventricular hypertrophy and systolic dysfunction, both of which have been associated with an increase in cardiac apoptosis and heart failure (Lin et al, 2018; Pedram et al, 2008; Yoshida et al, 2021). Postmenopause is a risk factor that may increase the chance of developing DOX‐induced cardiomyopathy in patients (Chen et al, 2022; Muñoz‐Castañeda et al, 2006).…”

Reducing Unnecessary Oophorectomies for Benign Ovarian Neoplasms in Pediatric Patients

“…5,6 Patients who have early menopause also have impaired sexual health, with worse body image, lower desire and arousal, and higher rates of dyspareunia, as well as a higher prevalence of cardiovascular disease. 7,8 Additionally, after unilateral oophorectomy, patients have a shorter reproductive life span with a less robust response to in vitro fertilization in terms of number of follicles, concentration of estradiol, number of oocytes retrieved, and requirement for higher doses of gonadotropins. 9 Furthermore, patients with benign ovarian neoplasms have an increased risk for developing a second neoplasm in the contralateral ovary.…”

“…Oophorectomy can lead to premature ovarian failure, early menopause, and associated increased risks of cognitive impairment, osteopenia, impaired sexual health, and cardiovascular disease. [2][3][4][5][6][7][8][9][10][11] Furthermore, patients with benign ovarian neoplasms are at increased risk of developing a contralateral second neoplasm. 4,[12][13][14] This may result in unintentional castration due to potential contralateral torsion or surgical castration if oophorectomy is ultimately required for malignant disease.…”