Sexual function in women with premature ovarian insufficiency (POI): Systematic review and meta-analysis.

Premature ovarian insufficiency (POI) is a rare condition characterized by loss of ovarian function before the age of 40. POI seems associated with mood disorders and sexual dysfunction. However, there is a lack of high-quality evidence relating to the impact of POI on sexual function. Therefore, we conducted a systematic review and meta-analysis to evaluate sexual function in women with POI compared to women without the condition. The following online databases were systematically searched up to January 2023: EMBASE, Medline (Ovid), Web of Science, Cochrane, PsychInfo, and Google Scholar. Random effects models were used for analyses, with data reported as Hedges' g and 95 % confidence interval, and the risk of heterogeneity was evaluated. The protocol of this study was registered with PROSPERO (CRD42023437203). A total of 10 studies were included in the systematic review and 5 studies involving 352 women with POI were included in the meta-analysis. Eight of the ten studies concluded that women with POI have reduced sexual function. An overall medium Hedges' g effect size of -0.72 was found (ranging between -0.20 and -1.29) in favor of control women, with moderate heterogeneity (I2 = 64 %). Stratified studies of women on systemic hormone replacement therapy (HRT) showed an even higher Hedges' g effect size, of -0.82 (95 % CI -1.18, -0.47). In conclusion, sexual function in women with POI is reduced compared with control women. Sexual function should be discussed with women with POI and they should be offered psychosexual counseling.

Bone mineral density in patients with primary ovarian insufficiency: A systematic review and Meta-Analysis.

INTRODUCTION: Premature menopause is a major complication of primary ovarian insufficiency (POI), and this loss is closely relates to bone mineral density (BMD). Previous research has indicated potential associations between BMD and POI. This study set out to provide the first systematic literature review and meta-analysison account of BMD content among women with POI. METHODS: Studies including women with POI and controls were eligible from PubMed, Embase, Cochrane Library and Web of Science databases (from their inception to April 2022). Two reviewers independently evaluated study eligibility. The meta-analysis was performed using the DerSimonian and Laird random effects model. RESULTS: Ten studies featuring 578 women with POI and 480 controls were selected. BMD content of femur neck (SMD:-0.76; 95 % CI: -1.20 to -0.31; P = 0.0008), the BMD content of nondominating forearm (SMD:-0.67; 95 % CI: -1.15 to -0.18; P = 0.007) were significantly decreased in women with POI. However, no differences were seen in other regions (lumbar spine, total hip, hipneck). DISCUSSION: The results of this study indicate that BMD content altered in patients with primary ovarian insufficiency. An implication of this is the possibility that hormone replacement therapy to minimize the prevalence of fracture morbidity and mortality associated with osteopenia in patients with POI.

Genitourinary symptoms and sexual function in women with primary ovarian insufficiency.

OBJECTIVE: There are limited studies on urogenital symptoms in women who experience menopause before the age of 40 years due to primary ovarian insufficiency (POI) or bilateral oophorectomy (surgical POI). This study aimed to compare the urogenital symptoms, including sexuality, of women with POI to those without the condition. METHODS: This cross-sectional study conducted was in seven Latin American countries, in which postmenopausal women (with POI and non-POI) were surveyed with a general questionnaire, the Menopause Rating Scale (MRS) and the six-item Female Sexual Function Index (FSFI-6). The association of premature menopause with more urogenital symptoms and lower sexual function was evaluated with logistic regression analysis. RESULTS: Women with POI experience more urogenital symptoms (MRS urogenital score: 3.54 ± 3.16 vs. 3.15 ± 2.89, p < 0.05) and have lower sexual function (total FSFI-6 score: 13.71 ± 7.55 vs. 14.77 ± 7.57 p < 0.05) than women who experience menopause at a normal age range. There were no significant differences in symptoms when comparing women based on the type of POI (idiopathic or surgical). After adjusting for covariates, our logistic regression model determined that POI is associated with more urogenital symptoms (odds ratio [OR]: 1.38, 95% confidence interval [CI] 1.06-1.80) and lower sexual function (OR: 1.67, 95% CI 1.25-2.25). CONCLUSION: POI, whether idiopathic or secondary to bilateral oophorectomy, is associated with symptoms that affect vaginal and sexual health.

Impact of ovarian insufficiency on bone health in childhood cancer survivors: Two cases.

PURPOSE: To investigate the skeletal phenotype of adolescent girls with premature ovarian insufficiency (POI). METHODS: Data are presented from two adolescent girls who participated in a clinical research protocol to evaluate axial bone mineral density (BMD) (via dual-energy x-ray absorptiometry, DXA) and appendicular bone density, microarchitecture, and strength (via high-resolution peripheral quantitative computed tomography, HRpQCT). Anthropometric data were also obtained, and pubertal staging was performed by a clinician. RESULTS: Both cases presented with an undetectable estradiol concentration and an elevated follicle stimulating hormone (FSH), meeting the criteria for POI. Each also received alkylating agents as part of their chemotherapy and radiotherapy, but in different locations as one presented with stage IV neuroblastoma and the other, metastatic medulloblastoma. Both had a low BMD of the axial and appendicular skeleton, as well as microarchitectural changes of the latter. The low BMD Z-score (<-2.0) seen when interpreting their DXA measurements for chronological age improved when adjusted for short stature, but it was not normalized. Lastly, most variables obtained by HRpQCT were abnormal for each participant, indicating that appendicular bone structure and strength were compromised. CONCLUSIONS: Chemotherapy and radiation affect growth, puberty, and bone accrual deleteriously. However, as these cases show, POI in an adolescent is not always classic primary ovarian insufficiency. Adolescents with brain cancer can present with signs of estrogen deficiency but may not be able to secrete FSH to the extent of elevation typically seen in long-term cancer survivors. Estrogen deficiency is almost universally present in either clinical setting and prompt recognition facilitates early provision of hormone replacement therapy that may then allow for a resumption of bone accrual as an adolescent approaches her peak bone mass.

Meibography and tear function alterations in premature ovarian failure.

PURPOSE: Premature ovarian failure (POF) is the deterioration of normal ovarian function before the age of 40. In the presence of chemotherapy, radiation, genetic factors, autoimmune conditions, hypoandrogenemia, hypoestrogenemia and increased gonadotropin hormones, dry eye with early menopause findings may be encountered. The goal of our study is to compare the tear film alterations and meibomian gland status of patients diagnosed with POF at the time of diagnosis with healthy volunteers. METHODS: In our study, 90 patients with POF and 60 control patients were evaluated. Complete ophthalmologic examinations of the patients, ocular surface disease index (OSDI) score, Oxford score for corneal and conjunctival involvement, Schirmer 1 and 2 tests, noninvasive tear break-up time (BUT), lower lid meibomian drop out grades with noncontact meibography, and meibomian gland distortion and shortening scores were compared between the two groups. RESULTS: The mean age was 29.49±2.92 years in the patient group and 29.37±2.85 years in the control group (P=0.830). OSDI scores were statistically significant higher in the patient group (32.11±18.88) compared to the control group (12.93±14.92) (P<0.001). On Oxford scoring, there was a significant increase in the patient group (P<0.001). There was no significant difference between the groups in terms of Schirmer 1 and 2 tests (P=0.195, P=0.117). NIBUT was significantly lower in the patient group (11.93±4.59) compared to the control group (18.72±5.38) (P<0.001). While there was no difference between the groups in terms of lower lid meiboscores or meibomian gland length (P>0.005), there was a significant deterioration in the patient group in the distortion grading showing the morphological evaluation of the meibomian glands (p=0.037). In the ROC analysis, OSDI score (AUC=0.816, P<0.0001) and NIBUT (AUC=0.820, P<0.0001) parameters showed high specifity and sensitivity for the disease. DISCUSSION: Ocular surface damage and dry eye symptoms are observed more frequently in patients with POF. We believe that hormonal insufficiency may cause deterioration in tear film composition, ocular surface damage with changes in tear homeostasis, and a change in the structure of the meibomian glands, starting with distortion at an early age.

Early menopause and premature ovarian insufficiency are associated with increased risk of dementia: A systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Among other risk factors, the decline in estrogen concentrations during menopause may compromise cognitive function. Whether early menopause (EM) is associated with an increased risk of dementia remains unclear. The purpose of this study was to systematically review and meta-analyze current evidence regarding the association between EM or premature ovarian insufficiency (POI) and the risk of dementia of any type. MATERIALS AND METHODS: A comprehensive literature search was conducted through the PubMed, Scopus and CENTRAL databases up to August 2022. Study quality was assessed using the Newcastle-Ottawa scale. Associations were calculated as odds ratio (OR) with 95 % confidence interval (CI). The I2 index was employed for heterogeneity. RESULTS: Eleven studies (nine assessed as of good and two as of fair quality) were included in the meta-analysis (n = 4,716,862). Women with EM demonstrated a greater risk of dementia of any type than women of normal age at menopause (OR 1.37, 95 % CI 1.22-1.54; I2 93%). However, after excluding a large retrospective cohort study, the results were altered (OR 1.07, 95 % CI 0.78-1.48; I2 94%). Increased risk of dementia was also found in women with POI (OR 1.18, 95 % CI 1.15-1.21; I2 0%). Subgroup analysis showed that this risk was mostly evident in cohort studies, and those which included women with natural menopause. CONCLUSIONS: Women with EM or POI may be at increased risk of dementia compared with women of normal age at menopause, but further research investigating that hypothesis is warranted.

Early menopause and premature ovarian insufficiency may increase the risk of sarcopenia: A systematic review and meta-analysis.

PURPOSE: Menopausal transition, resulting from a decline in estrogen concentrations, may compromise musculoskeletal health. However, it is unclear if early menopause (defined as age at menopause <45 years) and premature ovarian insufficiency (defined as age at menopause <40 years) are associated with increased risk of sarcopenia. The aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and risk of sarcopenia. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 December 2022. Data were expressed as standardized mean difference with 95 % confidence intervals. The I2 index was employed to evaluate heterogeneity. RESULTS: Six studies were included in the qualitative and quantitative analysis, with a total of 18,291 post-menopausal women. Compared with women of normal age at menopause (>45 years), women with early menopause demonstrated lower muscle mass, assessed by appendicular skeletal muscle mass/body mass index [standardized mean difference (SMD) -0.14, 95 % confidence interval (CI) -0.20 to -0.07, p < 0.001; I2 0%]. However, no differences in muscle strength, assessed by handgrip strength (SMD -0.15, 95 % CI -0.31 to 0.01, p = 0.071; I2 72%), and muscle performance, assessed by gait speed (SMD -0.11, 95 % CI -0.29 to 0.05, p = 0.18; I2 79%), were found. Women with premature ovarian insufficiency had lower handgrip strength (SMD -0.3, 95 % CI -0.58 to -0.01, p = 0.04; I2 74.6 %) and gait speed (SMD -0.13, 95 % CI -0.23 to -0.04, p = 0.004; I2 0%) compared with women of normal age at menopause. CONCLUSION: Early menopause is associated with reduced muscle mass and premature ovarian insufficiency with reduced muscle strength and performance compared with normal age at menopause.

Penetrance of pathogenic genetic variants associated with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) affects 1% of women and is a leading cause of infertility. It is often considered to be a monogenic disorder, with pathogenic variants in ~100 genes described in the literature. We sought to systematically evaluate the penetrance of variants in these genes using exome sequence data in 104,733 women from the UK Biobank, 2,231 (1.14%) of whom reported at natural menopause under the age of 40 years. We found limited evidence to support any previously reported autosomal dominant effect. For nearly all heterozygous effects on previously reported POI genes, we ruled out even modest penetrance, with 99.9% (13,699 out of 13,708) of all protein-truncating variants found in reproductively healthy women. We found evidence of haploinsufficiency effects in several genes, including TWNK (1.54 years earlier menopause, P = 1.59 × 10-6) and SOHLH2 (3.48 years earlier menopause, P = 1.03 × 10-4). Collectively, our results suggest that, for the vast majority of women, POI is not caused by autosomal dominant variants either in genes previously reported or currently evaluated in clinical diagnostic panels. Our findings, plus previous studies, suggest that most POI cases are likely oligogenic or polygenic in nature, which has important implications for future clinical genetic studies, and genetic counseling for families affected by POI.

Specifics of infertility treatment in women with premature ovarian failure.

Premature ovarian failure (POF, POI - premature ovarian insufficiency) is a serious situation for a woman with reproductive plans that more or less precludes having her own bio-logical child. In addition to the lack of functional oocytes in the ovaries, it is also a premature lack of sex hormones, which has an overall negative effect on health. The article guides us through care both in the clinic of the gynecologist and through treatment in the center of reproductive medicine. The dia-gnosis and treatment of POF illustrates some endocrinological principles and connections.

Family building after diagnosis of premature ovarian insufficiency: a cross-sectional survey in 324 women.

OBJECTIVE: The diagnosis of premature ovarian insufficiency (POI) is a traumatic event for many patients that involves poor fertility prognosis. After such diagnosis, spontaneous pregnancies are rare. The alternatives for building a family are oocyte donation, embryo donation, and adoption. However, we have few information on how many women with POI finally built a family after the diagnosis and which alternative they chose. DESIGN: We performed a cross-sectional, descriptive study. METHODS: We conducted a survey of all the women who consulted for POI in the department of endocrinology and reproductive medicine at la Pitié Salpêtrière between May 31, 1991, and January 12, 2021. We included patients who continued to be followed up regularly by our department or were contacted by mail or phone between June and September 2021. We excluded patients with Turner syndrome and POI secondary to oncological treatment and patients under 18 at the time of the survey. RESULTS: 985 patients were referred to the department for POI, and 324 patients were finally analyzed. 41% of the women who wanted to build a family had children after the diagnosis: 53.9% by oocyte donation, 1 woman by embryo donation, 5.6% after ovarian stimulation, 13.5% by adoption, and 25.8% who had spontaneous pregnancy after a mean time of 2.5 years. Spontaneous pregnancy rate was 8.6% in the whole cohort. CONCLUSIONS: Having children after a diagnosis of POI is not uncommon but more often results from oocyte donation. This study will provide enlightened information for newly diagnosed women on the possibilities to build a family after POI diagnosis.

Premature ovarian insufficiency and infertility.

BACKGROUND: Premature ovarian insufficiency (POI) is the loss of ovarian function before the age of 40 years and can be spontaneous or iatrogenic. It is an important cause of infertility, and the diagnosis should be considered in any woman presenting with oligo/amenorrhoea, even in the absence of menopausal symptoms suchas hot flushes. OBJECTIVE: The aim of this article is to provide an overview of the diagnosis of POI and its management with respect to infertility. DISCUSSION: Diagnostic criteria for POI are follicle-stimulating hormone levels >25 IU/L on two occasions at least one month apart following 4-6 months of oligo/amenorrhoea, with exclusion of secondary causes of amenorrhoea. Approximately 5% of women will have a spontaneous pregnancy after a POI diagnosis; however, most women with POI will require a donor oocyte/embryo for pregnancy. Some women may elect to adopt or live childfree. Fertility preservation should be considered for those at risk of POI.

The risk of depressive and anxiety symptoms in women with premature ovarian insufficiency: a systematic review and meta-analysis.

Premature ovarian insufficiency (POI) appears to be associated with depressive and anxiety symptoms. However, there is a lack of high-quality evidence relating to the risk of patients with POI developing depression or anxiety. Therefore, we conducted a systematic review and meta-analysis to quantify the risk of depressive and anxiety symptoms in women with POI. We searched English and Chinese databases to evaluate the risk of depression and anxiety disorders in patients with POI. The final search date was November 2021. The risk was quantified using meta-analysis, with an estimation of pooled odds ratio (OR) and 95% confidence interval (CI). Sources of heterogeneity were explored by subgroup analysis. A total of seven primary studies with 1316 individuals were included, five of which were related to depression and six to anxiety disorders. All included articles were case-control studies of high quality. Patients with POI were associated with a higher odds of depression and anxiety (depression: OR = 3.33, 95% CI = 2.31-4.81, P < 0.001; anxiety: OR = 4.89, 95% CI = 3.28-7.30, P < 0.001). Subgroup analysis also indicated that patients with POI are at a higher risk of anxiety and depression. POI appears to be associated with a high risk of depression and anxiety. Early psychosocial assessment and regular screening of patients with POI are also necessary. In addition, it is important to consider the mental health of patients with POI.

Loss of muscle mass in women with premature ovarian insufficiency as compared with healthy controls.

OBJECTIVE: Menopausal transition has been known to be associated with the loss of muscle mass. However, muscle health in women with premature menopause, that is, premature ovarian insufficiency (POI), remains unclear. We aimed to investigate and compare muscle mass parameters and the prevalence of low muscle mass between patients with spontaneous POI and healthy controls. METHODS: In this cross-sectional study, 59 women with spontaneous POI and 57 premenopausal controls with normal ovarian function were enrolled at the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) from June 17, 2020, to August 20, 2021. Muscle mass parameters were measured by dual-energy x-ray absorptiometry, and low muscle mass was diagnosed using the Asian Working Group for Sarcopenia criteria. In addition, participants provided their sociodemographic data, menstrual and reproductive history, lifestyle factors, and medical history. Multivariate linear regression analysis was conducted. RESULTS: Muscle mass parameters, including appendicular skeletal muscle mass (ASM), ASM/height2, ASM/weight, ASM/body mass index, total skeletal muscle mass (TSM), and TSM/weight, were significantly lower in women with POI as compared with healthy controls (ASM: 14.62 ± 2.08 vs 15.97 ± 1.78, P < 0.001; ASM/height2: 5.71 ± 0.64 vs 6.15 ± 0.62, P < 0.001; ASM/weight: 0.27 [0.25, 0.28] vs 0.28 [0.27, 0.29], P = 0.002; ASM/BMI: 0.68 ± 0.07 vs 0.73 ± 0.06, P = 0.001; TSM: 33.85 ± 4.08 vs 36.43 ± 3.56, P < 0.001; TSM/weight: 0.63 [0.59, 0.65] vs 0.64 [0.61, 0.67], P = 0.02). The prevalence of low muscle mass in POI patients was significantly higher than that in controls (32.20% vs 8.77%, χ2 = 9.70, P = 0.002). Furthermore, multivariate linear regression analyses demonstrated that POI status was an independent risk factor for ASM (ß = -1.13; 95% CI, -1.62 to -0.65), ASM/height2 (-0.35, -0.47 to -0.22), ASM/weight (-0.01, -0.02 to -0.009), ASM/BMI (-0.05, -0.07 to -0.02), TSM (-2.16, -3.14 to -1.17), and TSM/weight (-0.03, -0.04 to -0.02). CONCLUSIONS: Women with POI exhibit significant loss of muscle mass as compared with healthy controls. Early diagnosis and long-term health management in POI patients are important.

Reproductive health in Turner syndrome: A narrative review.

Turner syndrome (TS), a common chromosomal abnormality affecting females, is associated with partial or complete loss of the second sex chromosome. Although the classic karyotype is 45, X, the detection of mosaic TS is increasing. TS is a multi-system disorder with significant endocrine, cardiovascular and reproductive impacts. Accelerated ovarian follicular loss leads to primary amenorrhoea or premature ovarian insufficiency and infertility. Early diagnosis and counselling regarding hormone replacement therapy and future reproductive capacity, including fertility preservation, are essential to improve reproductive outcomes. Pubertal induction or estrogen replacement is usually required to optimise long-term health outcomes; however, initiation may be delayed due to delayed diagnosis. Spontaneous pregnancy occurs in a small number of women; however, many require donor oocytes and assisted reproductive technology to achieve a pregnancy. Pregnancy is a high risk especially when associated with congenital heart disease. Prepregnancy counselling by the multidisciplinary team (MDT) to identify contraindications and optimise pre-existing health issues is essential. Pregnancy management should be led by a maternal-fetal medicine unit with input from the MDT. This review examines reproductive health outcomes in women with TS and how best to manage them to reduce health risks and improve maternal and neonatal outcomes.

Early postnatal alterations in follicular stress response and survival in a mouse model of Classic Galactosemia.

Primary ovarian insufficiency is characterized by accelerated loss of primordial follicles, which results in ovarian failure and concomitant menopause before age 40. About 1-3% of females in the general population are diagnosed with POI; however, greater than 80% of females with the inherited disease Classic Galactosemia will develop POI. Classic Galactosemia is caused by mutations in the GALT gene encoding the enzyme galactose-1 phosphate uridylyltransferase. While dietary restriction of galactose is lifesaving in the neonatal period, the development of complications including primary ovarian insufficiency is not mitigated. Additionally, the pattern(s) of follicle loss have not been completely characterized. The chronic accumulation of aberrant metabolites such as galactose-1-phosphate and galactitol are suspected culprits in the development of the sequelae, yet the mechanisms remain elusive.Our group uses a GalT gene-trapped mouse model to study the pathophysiology of primary ovarian insufficiency in Classic Galactosemia. We recently showed that differences in the Integrated Stress Response pathway occur in mutant ovaries that likely contribute to their primary ovarian insufficiency phenotype. Using immunofluorescent staining of histological sections of ovaries at progressive ages, we saw evidence of altered Integrated Stress Response activity in granulosa cells and primordial oocytes consistent with accelerated primordial follicle growth activation, aberrant DNA damage and/or repair, and increased cellular stress/death. Overall, our findings indicate that abnormal Integrated Stress Response in the Classic Galactosemia model ovary results in accelerated primordial follicle growth activation, sometimes referred to as "burnout." These aberrant early events help further clarify when/how the primary ovarian insufficiency phenotype arises under galactosemic conditions.

Chronic and Cumulative Adverse Life Events in Women with Primary Ovarian Insufficiency: An Exploratory Qualitative Study.

Background and Purpose: Primary ovarian insufficiency (POI) has serious physical and psychological consequences due to estradiol deprivation, leading to increased morbidity and mortality. However, the causes of most POI cases remain unknown. Psychological stress, usually caused by stressful life events, is known to be negatively associated with ovarian function. It is important to explore high-frequency adverse life events among women with POI for future interventions. Methods: Forty-three women (mean age=33·8 years) were recruited who were newly- diagnosed with idiopathic POI (FSH levels >40 IU/L) to participate in semi-structured interviews through convenience sampling. The main questions covered by the topic guide were designed to explore adverse life events prior to POI diagnosis. Interviews were audio recorded, transcribed and analyzed thematically. Data were analyzed from June 2019 to August 2020. Results: Among the women with POI, mean age at diagnosis of POI was 33·8 years (range from 19 to 39 years), and the average time between the onset of irregular menstruation and POI diagnosis was 2.3 years. These women with POI had a relatively normal menstrual cycle before the diagnosis. A number of stressful life events prior to POI diagnosis were discussed by them as important factors influencing their health. Four core themes emerged: 1) persistent exposure to workplace stress, 2) persistent exposure to family-related adverse life events, 3) sleep problem/disturbance existed in women with POI before diagnosis, and 4) participants' general cognition and concerns about POI. Conclusions: Persistent exposures to adverse life events related to work stress, family stress and sleep problem existed in women with POI. Our findings are consistent with the hypothesis that adverse life events play a role in the development of POI. Future research should investigate how social environmental factors influence POI disease risks, and whether provision of tailored interventions (i.e. preventing or mitigating impact of adverse life events) aimed at high-risk populations may help prevent new POI cases and improve conditions of women with POI. We gained an in-depth understanding of the experiences of these women via 1:1 qualitative method, and find adverse life events are frequent in women with POI prior to the diagnosis.

Is premature ovarian insufficiency associated with mortality? A three-decade follow-up cohort.

OBJECTIVE: To evaluate the association between premature ovarian insufficiency (POI) and mortality. MATERIALS AND METHODS: This was a secondary analysis of a long-term cohort of Chilean women who received preventive health care between 1990 and 1993. The exposure variable was POI and the outcome was death, and follow-up time was 30 years. Patient data were extracted from medical records. Data related to deaths were obtained from the records of the official government registry as of January 2021. Cox regression proportional hazard models were used to estimate crude and adjusted hazard ratios (HR) and 95 % confidence intervals (CI). RESULTS: Data for a total of 1119 women were included in the analysis. Median age was 47 years (interquartile range: 44-52). The baseline prevalence of POI was 6.7 %. At the end of the follow-up, 34.7 % of women with POI had died, compared with 19.3 % of women without the condition (p < 0.001). A larger proportion of women with POI died from cardiovascular disease (12.0 % vs. 5.1 %; OR: 2.55, 95 % CI: 1.21-5.39) whereas there was no significant difference in cancer mortality (6.7 % vs. 7.7 %; OR: 0.86, 95 % CI: 0.34-2.19). In the adjusted Cox model, POI was among the main factors associated with mortality (hazard ratio [HR] 1.60, 95 % CI: 1.03-2.47), after diabetes (HR 2.51, 95 % CI: 1.40-4.51) and arterial hypertension (HR 1.75, 95 % CI: 1.29-2.37). CONCLUSION: Although POI affects a small group of women, its association with mortality seems to be relevant; hence it is necessary to implement measures that reduce this risk.

Sleep, depression, anxiety and fatigue in women with premature ovarian insufficiency.

PURPOSE: To assess sleep disturbances, levels of anxiety, depression and fatigue in women with premature ovarian insufficiency (POI). MATERIALS AND METHODS: The study included 62 women with POI and 62 age-matched controls. Women in both groups completed questionnaires. Pittsburgh Sleep Quality Index, Insomnia severity index, Epworth Sleepiness Scale, Hospital Anxiety and Depression Scale and Fatigue Severity Scale were used. RESULTS: We found poor sleep quality, higher levels of insomnia in women with POI than in controls. Depression was much more prevalent and severe in POI women. Total anxiety score, the severity of anxiety and fatigue did not differ significantly between the groups. According to the multivariable logistic regression analysis, being married and having POI were associated with worse quality of sleep, and having more children was associated with an increase in depression levels in the whole cohort. Backward analysis showed that when POI status was taken as a reference, married women were at 6.5 fold increased risk of poor sleep quality. CONCLUSIONS: Women with premature ovarian failure are more likely to suffer from poor sleep quality, insomnia and depression than healthy women.

Management of cardiovascular disease in women with premature ovarian insufficiency: critical quality appraisal of clinical guidelines and algorithm development.

OBJECTIVES: 1) To assess the methodological quality of clinical practice guidelines (CPGs) associated with cardiovascular disease (CVD) in women with premature ovarian insufficiency (POI); 2) to formulate an algorithm to foster the implementation of guidelines by clinicians. METHODS: A systematic search for CPGs in English and Chinese languages published between 2015 and 2020 was conducted. Assessment was conducted by two reviewers respectively via the Appraisal of Guidelines for Research and Evaluation II instrument. The interappraisal agreement was evaluated. Recommendations pertaining to the management of CVD in women with POI were extracted from high-score CPGs and developed into an algorithm, which was refined on the basis of expert feedback. RESULTS: A total of 14 CPGs were included. Three CPGs were evaluated as "high quality," with five "average" and six considered "low quality." The consistency of agreement between reviewers was considered as substantial agreement to almost perfect agreement (0.72-0.90). The algorithm consisted of three categories: initial evaluation, management, and subsequent monitoring of CVD in POI. Only "management" had recommendations from all three high-quality CPGs. CONCLUSIONS: The overall methodological quality of most CPGs regarding CVD in women with POI is moderate to poor. A management algorithm with a clear implementation strategy was developed from high-scoring CPGs. Further research is needed to provide evidence-based health care in this field.