Identifying and addressing osteoporosis knowledge gaps in women with premature ovarian insufficiency and early menopause: A mixed‐methods study

Objective/Design Menopausal transition has been associated with a derangement of glucose metabolism. However, it is not known if early menopause (EM, defined as age at menopause <45 years) or premature ovarian insufficiency (POI, defined as age at menopause <40 years) are associated with increased risk of type 2 diabetes mellitus (T2DM). To systematically investigate and meta-analyze the best evidence regarding the association of age at menopause with the risk of T2DM. Methods A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to January 31, 2018. Data are expressed as odds ratio (OR) with 95% confidence intervals (CI). The I 2 index was employed for heterogeneity. Results Thirteen studies were included in the qualitative and quantitative analysis (191 762 postmenopausal women, 21 664 cases with T2DM). Both women with EM and POI were at higher risk of T2DM compared with those of age at menopause of 45–55 years (OR: 1.15, 95% CI: 1.04–1.26, P = 0.003; I 2: 61%, P < 0.002 and OR: 1.50, 95% CI: 1.03–2.19, P = 0.033; I 2: 75.2%, P < 0.003), respectively). Similar associations emerged when women with EM and POI were compared with those of age at menopause >45 years (OR: 1.12, 95% CI: 1.01–1.20, P < 0.02; I 2: 78%, P < 0.001 and OR: 1.53, 95% CI: 1.03–2.27, P = 0.035; I 2: 78%, P < 0.001), respectively). Conclusions Both EM and POI are associated with increased risk of T2DM.

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Premature and Early Menopause in Relation to Cardiovascular Disease

Seminars in Reproductive Medicine ◽

10.1055/s-0040-1722318 ◽

2021 ◽

Author(s):

Izaäk Schipper ◽

Yvonne V. Louwers

Keyword(s):

Cardiovascular Disease ◽

Postmenopausal Women ◽

Cardiovascular Events ◽

Premature Ovarian Insufficiency ◽

Premature Menopause ◽

Bilateral Oophorectomy ◽

Early Menopause ◽

Ovarian Insufficiency ◽

Age At Menopause ◽

Increased Risk

AbstractPostmenopausal women have an increased risk for cardiovascular diseases. It has been postulated that the loss of ovarian function and subsequent deficiency of endogenous estrogens after menopause contributes to this elevated risk of cardiovascular disease in postmenopausal women. Compared with woman entering menopause at the mean age of 51 years, in women with early menopause or premature ovarian insufficiency the risk for cardiovascular disease is even greater. These women lack the cardioprotective effect of endogenous estrogens for many more years than do women entering natural menopause. The majority of data assessing the risk of cardiovascular disease in relation to age at menopause and specifically premature menopause are derived from large epidemiological cohort studies. In addition, observations in women undergoing bilateral oophorectomy at an early age provide convincing evidence regarding association between early menopause or POI and the development of cardiovascular events and mortality. Moreover, genetic variants associated with earlier age at menopause have also been found to increase the risk of cardiovascular events in women. It has been substantiated that hormone replacement therapy (HRT) decreases the risk for ischemic heart disease and eliminates the increased cardiovascular disease mortality. It is therefore crucial to start HRT as soon as possible, particularly in women with premature ovarian insufficiency.

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Osteoporosis and premature ovarian insufficiency: geographic variation in clinicians’ and consumers’ knowledge gaps and barriers to care

Archives of Osteoporosis ◽

10.1007/s11657-020-00713-8 ◽

2020 ◽

Vol 15 (1) ◽

Cited By ~ 1

Author(s):

Alicia R. Jones ◽

Maylyn Goh ◽

Robyn Langham ◽

Jacqueline Boyle ◽

Frances Milat ◽

...

Keyword(s):

Geographic Variation ◽

Barriers To Care ◽

Premature Ovarian Insufficiency ◽

Knowledge Gaps ◽

Ovarian Insufficiency

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Association between premature ovarian insufficiency, early menopause, socioeconomic status in a nationally representative sample from Korea

Maturitas ◽

10.1016/j.maturitas.2018.12.004 ◽

2019 ◽

Vol 121 ◽

pp. 22-27 ◽

Cited By ~ 3

Author(s):

Young-Mee Lim ◽

Kyungah Jeong ◽

Sa Ra Lee ◽

Hye Won Chung ◽

Wanhyung Lee

Keyword(s):

Socioeconomic Status ◽

Representative Sample ◽

Premature Ovarian Insufficiency ◽

Early Menopause ◽

Ovarian Insufficiency ◽

Nationally Representative

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Rare deleterious BUB1B variants induce premature ovarian insufficiency and early menopause

Human Molecular Genetics ◽

10.1093/hmg/ddaa153 ◽

2020 ◽

Vol 29 (16) ◽

pp. 2698-2707 ◽

Cited By ~ 1

Author(s):

Qing Chen ◽

Hanni Ke ◽

Xuezhen Luo ◽

Lingbo Wang ◽

Yanhua Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Spindle Assembly Checkpoint ◽

Late Onset ◽

Missense Variant ◽

Premature Ovarian Insufficiency ◽

Ovarian Activity ◽

Loss Of Function ◽

Early Menopause ◽

Ovarian Insufficiency ◽

Natural Menopause

Abstract Losing of ovarian functions prior to natural menopause age causes female infertility and early menopause. Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity before 40 years of age. Known genetic causes account for 25–30% of POI cases, demonstrating the high genetic heterogeneity of POI and the necessity for further genetic explorations. Here we conducted genetic analyses using whole-exome sequencing in a Chinese non-syndromic POI family with the affected mother and at least four affected daughters. Intriguingly, a rare missense variant of BUB1B c.273A>T (p.Gln91His) was shared by all the cases in this family. Furthermore, our replication study using targeted sequencing revealed a novel stop-gain variant of BUB1B c.1509T>A (p.Cys503*) in one of 200 sporadic POI cases. Both heterozygous BUB1B variants were evaluated to be deleterious by multiple in silico tools. BUB1B encodes BUBR1, a crucial spindle assembly checkpoint component involved in cell division. BUBR1 insufficiency may induce vulnerability to oxidative stress. Therefore, we generated a mouse model with a loss-of-function mutant of Bub1b, and also employed D-galactose-induced aging assays for functional investigations. Notably, Bub1b+/− female mice presented late-onset subfertility, and they were more sensitive to oxidative stress than wild-type female controls, mimicking the clinical phenotypes of POI cases affected by deleterious BUB1B variants. Our findings in human cases and mouse models consistently suggest, for the first time, that heterozygous deleterious variants of BUB1B are involved in late-onset POI and related disorders.

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