Prevalence of cytogenetic abnormalities and FMR1 gene premutation in a Portuguese population with premature ovarian insufficiency

Introduction: Chromosome abnormalities contribute to about 10% of cases of premature ovarian insufficiency. Most are associated with X chromosome. Fragile mental retardation 1 (FMR1) gene premutation has an estimated prevalence of 1% - 7% in sporadic cases and up to 13% in familial cases. Our aim was to describe the clinical characteristics, cytogenetic and FMR1 testing of a Portuguese population with premature ovarian insufficiency.Material and Methods: Women diagnosed with premature ovarian insufficiency in a Portuguese tertiary centre were retrospectivelyanalysed. Data were retrieved from electronic medical records including clinical characteristics, cytogenetic and FMR1 testing. The main outcome measures were the prevalence of chromosome abnormalities and FMR1 premutation in a Portuguese population with premature ovarian insufficiency.Results: Ninety-four patients were included, with a median age at menopause of 36 years. The prevalence of chromosome abnormalities was 16.5% (14/85) and most were X chromosome related (78.6%). The prevalence of FMR1 premutation was 6.7% (6/90). The prevalence of karyotypic abnormalities or FMR1 premutation did not differ significantly between familial and sporadic cases. Neither chromosome abnormalities nor FMR1 premutation influenced age at menopause or follicle stimulating hormone levels at diagnosis in premature ovarian insufficiency patients.Discussion: This is the first study describing the clinical characteristics and both cytogenetic and FMR1 testing in a Portuguese population with premature ovarian insufficiency. The rate of chromosome abnormalities in our sample was higher than in other populations, while the prevalence of FMR1 premutation was similar to previous reports.Conclusion: Our results underline the importance of genetic screening in premature ovarian insufficiency patients in both etiological study and genetic counselling.

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Clinical characteristics and genetic analysis in women with premature ovarian insufficiency

Maturitas ◽

10.1016/j.maturitas.2012.09.017 ◽

2013 ◽

Vol 74 (1) ◽

pp. 61-67 ◽

Cited By ~ 20

Author(s):

Eleonora Ferrarini ◽

Laura Russo ◽

Franca Fruzzetti ◽

Patrizia Agretti ◽

Giuseppina De Marco ◽

...

Keyword(s):

Genetic Analysis ◽

Clinical Characteristics ◽

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency

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Genetics of premature ovarian insufficiency and the association with X-autosome translocations

Reproduction ◽

10.1530/rep-20-0338 ◽

2020 ◽

Vol 160 (4) ◽

pp. R55-R64

Author(s):

Adriana Di-Battista ◽

Mariana Moysés-Oliveira ◽

Maria Isabel Melaragno

Keyword(s):

X Chromosome ◽

Molecular Mechanisms ◽

Ovarian Function ◽

Single Gene ◽

Position Effect ◽

Gene Mutations ◽

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency ◽

Functional Consequences ◽

Critical Regions

Premature ovarian insufficiency (POI) is the cessation of menstruation before the age of 40 and can result from different etiologies, including genetic, autoimmune, and iatrogenic. Of the genetic causes, single-gene mutations and cytogenetic alterations, such as X-chromosome aneuploidies and chromosome rearrangements, can be associated with POI. In this review, we summarize the genetic factors linked to POI and list the main candidate genes. We discuss the association of these genes with the ovarian development, the functional consequences of different mutational mechanisms and biological processes that are frequently disrupted during POI pathogenesis. Additionally, we focus on the high prevalence of X-autosome translocations involving the critical regions in Xq, known as POI1 and POI2, and discuss in depth the main hypotheses proposed to explain this association. Although the incorrect pairing of chromosomes during meiosis could lead to oocyte apoptosis, the reason for the prevalence of X-chromosome breakpoints at specific regions remains unclear. In most cases, studies on genes disrupted by balanced structural rearrangements cannot explain the ovarian failure. Thus, the position effect has emerged as a putative explanation for genetic mechanisms as translocations possibly result in changes in overall chromatin topology due to chromosome repositioning. Given the tremendous impact of POI on women’s quality of life, we highlight the value of investigations in to the interplay between ovarian function and gene regulation to deepen our understanding of the molecular mechanisms related to this disease, with the ultimate goal of improving patients’ care and assistance.

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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

Acta Endocrinologica ◽

10.1530/eje-18-0602 ◽

2019 ◽

Vol 180 (1) ◽

pp. 41-50 ◽

Cited By ~ 20

Author(s):

Panagiotis Anagnostis ◽

Konstantinos Christou ◽

Aikaterini-Maria Artzouchaltzi ◽

Nifon K Gkekas ◽

Nikoletta Kosmidou ◽

...

Keyword(s):

Type 2 Diabetes ◽

Meta Analysis ◽

Premature Ovarian Insufficiency ◽

Early Menopause ◽

Ovarian Insufficiency ◽

Pubmed Central ◽

Age At Menopause ◽

Increased Risk ◽

Comprehensive Search

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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Prevalence of premature ovarian insufficiency and its determinants in Iranian populations: Tehran lipid and glucose study

BMC Women s Health ◽

10.1186/s12905-021-01228-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Marzieh Rostami Dovom ◽

Razieh ‌Bidhendi-Yarandi ◽

Kazem Mohammad ◽

Maryam Farahmand ◽

Fereidoun Azizi ◽

...

Keyword(s):

Failure Time ◽

Population Based ◽

Normal Weight ◽

Influential Factors ◽

Reproductive Age ◽

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency ◽

Natural Menopause ◽

Age At Menopause ◽

Aft Model

Abstract Background Premature ovarian insufficiency (POI) considered as a concerning health issue for women of reproductive age. In this study we aim to estimate the prevalence of POI and assessing the influential factors. Methods Data was obtained from Tehran lipid and glucose study (TLGS). All eligible post-menarcheal female participants of the TLGS, ages 20–65, were recruited (n = 6521). Participants were followed for the event of menopause, and age at menopause was recorded. Kaplan Meier analysis was applied to estimate mean and median for age at menopause. Weibull accelerated failure time survival regression model (AFT), was applied to assess influential determinants of POI. Conditional probability approach was used to provide estimation for prevalence of POI. Results In this population-based study, the prevalence of POI (menopause age < 40 years) and early menopause (menopause age < 45 years) were estimated 3.5% and 24.6%, respectively. AFT model showed that in comparison to normal weight women, time to menopause was decreased by − 0.09 year (95% CI − 0.27, − 0.01, p = 0.023) and − 0.03 year (95% CI − 0.05, − 0.02, p = 0.000) in underweight and overweight women, respectively. Moreover, time to natural menopause was increased by 0.12 year (95% CI 0.07 to 0.17, p = 0.000) in women used oral contraceptives for > 6 months. Conclusion About one quartile of Iranian women experienced menopause at an age less than 45, especially the non-normal weight ones; this high prevalence is a critical public health concerns that needs to be addressed by health policy makers.

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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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Complex X chromosome rearrangement delineated by array comparative genome hybridization in a woman with premature ovarian insufficiency

Fertility and Sterility ◽

10.1016/j.fertnstert.2011.03.082 ◽

2011 ◽

Vol 95 (7) ◽

pp. 2433.e9-2433.e15 ◽

Cited By ~ 4

Author(s):

Melanie E. Ochalski ◽

Natalie Engle ◽

Anthony Wakim ◽

Britt J. Ravnan ◽

Lori Hoffner ◽

...

Keyword(s):

X Chromosome ◽

Chromosome Rearrangement ◽

Premature Ovarian Insufficiency ◽

Comparative Genome Hybridization ◽

Ovarian Insufficiency ◽

Comparative Genome ◽

Array Comparative Genome Hybridization

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Molecular Characterization of FMR1 Gene by TP-PCR in Women of Reproductive Age and Women with Premature Ovarian Insufficiency

Molecular Diagnosis & Therapy ◽

10.1007/s40291-017-0305-9 ◽

2017 ◽

Vol 22 (1) ◽

pp. 91-100 ◽

Cited By ~ 3

Author(s):

Deepika Delsa Dean ◽

Sarita Agarwal ◽

Deepa Kapoor ◽

Kuldeep Singh ◽

Chandra Vati

Keyword(s):

Molecular Characterization ◽

Reproductive Age ◽

Fmr1 Gene ◽

Premature Ovarian Insufficiency ◽

Women Of Reproductive Age ◽

Ovarian Insufficiency

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Prevalence and Risk Factors of Premature Ovarian Insufficiency/Early Menopause

Seminars in Reproductive Medicine ◽

10.1055/s-0040-1722317 ◽

2021 ◽

Author(s):

Rinky Giri ◽

Amanda J. Vincent

Keyword(s):

Risk Factors ◽

Premature Ovarian Insufficiency ◽

Health Impacts ◽

Ovarian Activity ◽

Risk Minimization ◽

Early Menopause ◽

Ovarian Insufficiency ◽

Age At Menopause ◽

Social Environmental ◽

Underlying Mechanisms

AbstractPremature ovarian insufficiency (POI) and early menopause, defined as loss of ovarian activity prior to 40 years or menopause between the ages of 40 and 45 years, respectively, is associated with significant adverse health impacts. Recent data indicate that the prevalence of POI and early menopause is greater than was previously thought, affecting more than 10% of women. Biopsychosocial risk factors including genetic, autoimmune, reproductive, lifestyle, early-life, social/environmental, and iatrogenic have been associated with POI/early menopause or earlier age at menopause. However, establishing a causal role and the underlying mechanisms remains elusive. Understanding and clarification of these risk factors will facilitate prevention and risk minimization strategies to optimize women's health.

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