Demographic, clinical and hormonal characteristics of patients with premature ovarian insufficiency and those of early menopause: data from two tertiary premature ovarian insufficiency centers in Greece.

The aim of the study was to compare demographic, hormonal and clinical parameters in patients with premature ovarian insufficiency (POI) and women with early menopause in Greece. One hundred thirty-nine women of Greek origin, aged 14-45 years, referring for oligomenorrhea and having elevated FSH concentrations were divided into three groups regarding the age of menstrual disturbances onset [POI1:

Serum anti-Mullerian hormone (AMH) concentration has limited prognostic value for density of primordial and primary follicles, questioning it as an accurate parameter for the ovarian reserve.

OBJECTIVES: To evaluate the prognostic value of anti-Mullerian hormone (AMH) levels in estimating the ovarian density of primordial and primary follicles, which can be assumed to reflect the real ovarian reserve. STUDY DESIGN: A total of 537 women, average age 30.4 years (range 8.0-43.7 years), underwent ovarian tissue cryopreservation prior to gonadotoxic therapies due to malignant diseases which do not affect ovarian reserve parameters. Standardized ovarian biopsies were obtained, and follicular density was analysed. The prognostic accuracy of serum AMH in estimating ovarian follicle density was evaluated. MAIN OUTCOME MEASURES: Histologically determined follicle density, AMH serum concentration and their correlation. RESULTS: In children, follicle density was high but AMH concentration was low. AMH concentration was predicted to be maximum at the age of 15.5 years. In women aged over 15.5 years, the relationship between AMH concentration and follicle density was evaluated. Crude analysis revealed that serum AMH levels and follicular density were moderately correlated (r = 0.34, p < 0.001). From the adjusted regression model the predicted value of follicle density of women aged 20, 30 and 40 years as well as the associated 50 % and 95 % prediction intervals (50 % PI and 95 % PI, respectively) were calculated. For example, for women aged 40 years with a serum AMH level of 1 ng/ml, a follicle density of 2.3/mm3 (50 %PI: [1.1, 4.6]; 95 %PI: [0.3, 18]) was predicted. These large prediction intervals demonstrate the low predictive value of serum AMH for the ovarian follicle density. CONCLUSIONS: Serum AMH levels have limited prognostic value for the follicle density and therefore for the real ovarian reserve.

Serum biomarker analysis in patients with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a primary ovarian defect characterized by premature depletion of ovarian follicles before 40 years of age. The disorder has been attributed to various causes, but the study of altered proteins in serum levels as the cause is rare. Additionally, identifying novel biomarkers can contribute to more accurate diagnosis or prognosis of POI. In the present study, a solid-phase antibody array simultaneously detecting multiple proteins was used to analyze POI serum with menopausal and healthy fertile subjects as control groups. As a result, compared to the menopause and healthy fertile groups, eleven proteins, including Neurturin, Frizzled-5, Serpin D1, MMP-7, ICAM-3, IL-17F, IFN-gamma R1, IL-29, IL-17R, IL-17C and Soggy-1, were uniquely down-regulated, and Afamin was particularly up-regulated in POI serum. More importantly, all of these factors were firstly found to be associated with POI in this study, suggesting that these proteins may participate in the pathogenesis of POI and may be novel serum biomarkers for POI.

Can Menopause Prediction Be Improved With Multiple AMH Measurements? Results From the Prospective Doetinchem Cohort Study.

CONTEXT: Anti-Müllerian hormone (AMH) levels are used worldwide as a screening tool for the duration of the female reproductive lifespan. Although AMH levels are associated with age at menopause, individual predictions of menopause with a single AMH measurement are unreliable. OBJECTIVE: This study investigated whether individual AMH decline patterns can improve the prediction of menopause compared with a single measurement. DESIGN: The study population comprised 2434 premenopausal women from the population-based Doetinchem Cohort Study. Participants were followed up every 5 years for a total of 20 years, and AMH was measured in 6699 plasma samples with the picoAMH assay. Longitudinal statistical modeling was combined with time varying Cox modeling, to integrate multiple AMH measurements per woman. RESULTS: The mean age at menopause was 50 years, and 7.4% of the women who reached menopause during follow-up did so before age 45 years. For a 25-year-old, the AMH decline rate between ages 20 and 25 years increased the C-statistic of menopause prediction from 0.64 to 0.69. Beyond that age, the AMH decline rate did not improve predictions of menopause or early menopause. For women younger than age 30 years, for whom menopause prediction is arguably most relevant, the models underestimated the risk of early menopause. CONCLUSION: These results suggest that knowledge of the AMH decline rate does not improve the prediction of menopause. Based on the low discriminative ability and underestimation of the risk of early menopause, the use of AMH as a screening method for the timing of menopause cannot currently be advocated.

Serum androgen profiles in women with premature ovarian insufficiency: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to investigate serum androgen profiles (testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin) in women with premature ovarian failure and to establish if there is evidence of diminished androgen levels in these women. METHODS: Various Internet sources of PubMed, Cochrane library, and Medline were searched systematically until February, 2018. Out of a pool of 2,461 studies, after applying the inclusion/exclusion criterion, 14, 8, 10, and 9 studies were chosen for testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin, respectively, for this meta-analysis. The effect measure was the standardized mean difference with 95% confidence interval (95% CI) in a random-effects model. RESULTS: The testosterone concentrations in premature ovarian insufficiency were compared with fertile controls: stamdard mean difference (IV, random, 95% CI) -0.73 [-0.99, -0.46], P value < 0.05. The dehydroepiandrosterone sulfate concentrations in premature ovarian insufficiency compared to fertile controls: standard mean difference (IV, random, 95% CI) -0.65 [-0.92, -0.37], P value < 0.05. Androstenedione in premature ovarian insufficiency were compared with fertile controls: standard mean difference (IV, random, 95% CI) -1.09 [-1.71, -0.48], P value < 0.05. Sex hormone-binding globulin levels did not show statistical significance. The dehydroepiandrosterone sulfate levels were reduced in premature ovarian insufficiency cases, but still showed a higher level than in postmenopausal women. CONCLUSIONS: Women with premature ovarian insufficiency are at risk for decreased concentrations of testosterone, dehydroepiandrosterone sulfate, and androstenedione. Dehydroepiandrosterone sulfate levels were more reduced in postmenopausal controls when compared with premature ovarian insufficiency cases.

A prospective study of inflammatory biomarker levels and risk of early menopause.

OBJECTIVE: Early menopause, the cessation of ovarian function before age 45, has consequences for fertility and cardiovascular health. Evidence from studies of women with autoimmune conditions and genetic studies supports a role for inflammation in early menopause, but the association of inflammatory markers and risk has not been directly evaluated. METHODS: We assessed the relation of the soluble fraction of tumor necrosis factor alpha receptor 2 (sTNFR2), C-reactive protein, interleukin-6 (IL6) levels with incident early menopause among Nurses' Health Study II participants who provided a premenopausal blood sample in 1996 to 1999. Cases (n = 328) were women reporting natural menopause between blood collection and age 45.Controls (n = 492) included (1) 328 women with menopause after age 47, matched 1:1 with cases on age at blood collection and other factors; and (2) 164 additional women with menopause after age 45. RESULTS: In multivariable models comparing cases and n = 492 controls, we observed a significant association of sTNFR2 levels and risk of early menopause (P = 0.002). Compared with women with the lowest sTNFR2 levels, odds ratios (95% CIs) for quartiles 2 to 4 were 0.60 (0.38-0.95), 0.93 (0.61-1.43), and 1.40 (0.93-2.11). Results further adjusting for antimüllerian hormone levels were similar in magnitude, as were results from sensitivity analyses of matched cases and controls (n = 328 pairs), nonsmokers, and leaner women. C-reactive protein and IL6 levels were unrelated to risk. CONCLUSIONS: The observation of lower risk of early menopause among women with moderate sTNFR2 levels compared with women with lower and higher levels warrants further prospective study.

Cholesterol profile in women with premature menopause after risk reducing salpingo-oophorectomy.

This cross-sectional study aimed to investigate the effect of premenopausal risk reducing salpingo-oophorectomy (RRSO) on the cholesterol profile of women at increased ovarian cancer risk and to assess possible effects of age at and time since RRSO. We included 207 women who underwent RRSO before menopausal age (52 years) attending the family cancer clinic of an academic hospital and 828 age-matched women from a general population cohort (PREVEND). Participants filled out a questionnaire on socio-demographic characteristics, lifestyle and medical history, had anthropometric measurements and provided blood samples for assessment of serum levels of total cholesterol, HDL-cholesterol and non-HDL-cholesterol. The correlation between RRSO and cholesterol profile was assessed with logistic regression. Furthermore, subgroup analyses were performed to explore a possible effect of age at and time since RRSO. At a median time of 5.9 years (range 2.3-25.2) after surgery, RRSO was associated with low (< 60 mg/dl) HDL-cholesterol (OR 9.74, 95% CI 5.19-18.26) and high (≥ 160 mg/dl) non-HDL-cholesterol (OR 1.85, 95% CI 1.21-2.82) when adjusting for body mass index, hormone therapy, participation on sports and previous chemotherapy. The observed association was not dependent on age or time since RRSO. The RRSO group had less smokers (19.3 vs. 25.8%) and more participation on sports (45.4 vs. 22.0%). Our results suggest that RRSO is associated with a more atherogenic cholesterol profile, despite a lower prevalence of smoking and higher prevalence of participation on sports as compared to controls. This observation can be useful for physicians involved in the counselling and follow-up of women having RRSO.

Anti-Müllerian hormone levels and incidence of early natural menopause in a prospective study.

STUDY QUESTION: Are anti-Müllerian hormone (AMH) levels assessed in women aged 32-44 associated with risk of incident early natural menopause? SUMMARY ANSWER: We observed strong, significant associations between lower AMH levels and higher risk of early menopause. WHAT IS KNOWN ALREADY: The ability to predict risk early menopause, defined as menopause before age 45, prior to fertility decline would improve options for family planning and cardiovascular disease prevention. Though AMH is an established marker of menopause timing in older reproductive-aged women, whether AMH is associated with risk of early menopause has not been evaluated. STUDY DESIGN, SIZE, DURATION: We assessed these relations in a nested case-control study within the prospective Nurses' Health Study II cohort. Premenopausal blood samples were collected in 1996-1999. Participants were followed until 2011 for early natural menopause, with follow-up rates >94%. PARTICIPANTS/MATERIALS, SETTING, METHODS: Early menopause cases (n = 327) were women reporting natural menopause between blood collection and age 45. Controls (n = 491) experienced menopause after age 45 and included 327 cases matched to controls on the basis of age at blood draw (±4 months) and other factors. AMH levels up to 12 years before early menopause were assayed in 2016. MAIN RESULTS AND THE ROLE OF CHANCE: In multivariable conditional logistic regression models adjusting for matching factors, body mass index, smoking, parity, oral contraceptive use, and other factors, each 0.10 ng/ml decrease in AMH was associated with a 14% higher risk of early menopause (95% confidence interval (CI) 1.10 to 1.18; P < 0.001). In polynomial regression models including linear and quadratic terms for AMH, odds ratios for early menopause for women with AMH levels of 1.5, 1.0 and 0.5 ng/ml compared to 2.0 ng/ml were 2.6, 7.5 and 23 (all P < 0.001). Significant associations were observed irrespective of smoking status, adiposity, infertility history and menstrual cycle characteristics. Furthermore, models assessing the predictive ability of AMH showed high concordance, and C-statistics were high, ranging from 0.68 (age ≤35) to 0.93 (age 42). LIMITATIONS, REASONS FOR CAUTION: Our population was relatively homogenous with respect to race/ethnicity. Further work in more ethnically diverse populations is needed. WIDE IMPLICATION OF THE FINDINGS: To our knowledge, this is the first prospective study to evaluate whether AMH levels are associated with early menopause. These findings support the utility of AMH as a clinical marker of early menopause in otherwise healthy women. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by UM1CA176726, R01CA67262, and R01HD078517 from the U.S. Department of Health and Human Services, National Institutes of Health. No competing interests declared.

Brain-derived neurotrophic factor (BDNF) plasma concentration in patients diagnosed with premature ovarian insufficiency (POI).

Premature ovarian insufficiency (POI) is defined as a cessation of function of ovaries in women younger than 40 years old. Brain-derived neurotrophic factor (BDNF) is a protein critically involved in neuronal growth and metabolism. BDNF also has been shown to be important regulator of oocyte maturation. Recent data show that BDNF can be potentially involved in POI pathology. The aim of the study was to assess the BDNF plasma concentrations in patients diagnosed with idiopathic POI. 23 women diagnosed with POI (age 31 ± 7 years) and 18 (age 31 ± 3) controls were included to the study, matched according to age and body mass index. The BDNF concentrations were measured using competitive enzyme-linked immunosorbent assay (ELISA). Hormonal and metabolic parameters were measured in all individuals, in controls in late follicular phase. The POI group demonstrated lower mean plasma concentrations of BDNF (429.25 ± 65.52 pg/ml) in comparison to healthy controls (479.75 ± 34.75 pg/ml, p = 0.0345). The BDNF plasma concentration correlated negatively (R = -0.79, p < 0.001) with number of months since last menstrual period. There was a positive correlation between BDNF and progesterone in controls. In conclusion, POI patients show significantly lower BDNF plasma concentration and it correlates with the duration of amenorrhea. This observation brings important potential insights to the pathology of POI.

Use of antimüllerian hormone to predict the menopausal transition in HIV-infected women.

BACKGROUND: HIV infection has been associated with early menopausal onset, which may have adverse long-term health consequences. Antimüllerian hormone, a biomarker of ovarian reserve and gonadal aging, is reduced in HIV-infected women. OBJECTIVE: We sought to assess the relationship of antimüllerian hormone to age of menopause onset in HIV-infected women. STUDY DESIGN: We used antimüllerian hormone levels measured in plasma in 2461 HIV-infected participants from the Women's Interagency HIV Study to model the age at final menstrual period. Multivariable normal mixture models for censored data were used to identify factors associated with age at final menstrual period. RESULTS: Higher antimüllerian hormone at age 40 years was associated with later age at final menstrual period, even after multivariable adjustment for smoking, CD4 cell count, plasma HIV RNA, hepatitis C infection, and history of clinical AIDS. Each doubling of antimüllerian hormone was associated with a 1.5-year increase in the age at final menstrual period. Median age at final menstrual period ranged from 45 years for those in the 10th percentile of antimüllerian hormone to 52 years for those in the 90th percentile. Other factors independently associated with earlier age at final menstrual period included smoking, hepatitis C infection, higher HIV RNA levels, and history of clinical AIDS. CONCLUSION: Antimüllerian hormone is highly predictive of age at final menstrual period in HIV-infected women. Measuring antimüllerian hormone in HIV-infected women may enable clinicians to predict risk of early menopause, and potentially implement individualized treatment plans to prevent menopause-related comorbidities and to aid in interpretation of symptoms.

Early menopause: A hazard to a woman's health.

Early menopause or premature ovarian insufficiency (POI) is a common cause of infertility in women and affects about one per cent of young women. This disorder has significant psychological sequelae and major health implications. Its relevance has increased in recent years due to the fact that age of motherhood is being delayed in developed countries, with the risk of having either primary ovarian insufficiency or less possibilities of pregnancy. The main characteristics are absence of ovulation, amenorrhoea and high levels of serum gonadotropins (hypergonadotropic hypogonadism). Although the aetiology remains uncertain in most cases, several rare specific causes have been elucidated. Potential causes for POI are iatrogenic (ovarian surgery, radiotherapy or chemotherapy), environmental factors, viral infections, metabolic and autoimmune diseases, and genetic alterations. Because of the association with other autoimmune diseases, close follow up is recommended in patients with POI. The traditional indicators to evaluate ovarian ageing are age, serum hormonal levels, anti-Mullerian hormone, antral follicle count, and ultrasonography of ovaries. Hormone replacement therapy remains the mainstay of treatment, and the best chance of achieving a pregnancy is through oocyte donation. This article aims to present an overview of potential causes, clinical manifestations, and treatment options of POI.

Vitamin D and conjugated equine estrogen: the association with coronary artery atherosclerosis in cynomolgus monkeys.

OBJECTIVE: To analyze vitamin D3 plasma concentrations among monkeys randomized to oral conjugated equine estrogen (CEE) versus control and the association with coronary artery atherosclerosis (CAA). METHODS: Surgically postmenopausal monkeys (N = 50) were fed an atherogenic diet containing a woman's equivalent of 1000 IU/day of vitamin D3. The monkeys were randomized at baseline to receive CEE (equivalent of 0.45 mg/d, n = 25) or placebo (n = 25). 25-hydroxyvitamin D3 (25OHD3) was measured at baseline and 20 months later. At 20 months, CAA evidence of coronary artery remodeling, and American Heart Association (AHA) severity scores were assessed. RESULTS: The percent change in 25OHD3 concentrations from baseline to 20 months postrandomization was inversely correlated with plaque area of the right coronary artery (P = 0.048), left circumflex artery (P = 0.039), left anterior descending artery (P = 0.017), and AHA severity score (AHA LADmax) (P = 0.016). Those with increased 25OHD3 concentrations who were taking CEE also had significantly lower AHA scores compared with those who were not taking CEE and did not have an increase in 25OHD3 (P = 0.01). CONCLUSIONS: Monkeys with increases in 25OHD3 concentrations had significantly less severe CAA. Those with increases in 25OHD3 with CEE were associated with significantly decreased AHA lesion scores, decreased plaque, and greater coronary artery remodeling. If these findings are present in women, achieving higher 25OHD3 concentrations (or being a vitamin D supplementation "responder") may be associated with cardioprotection, and further studies to evaluate a synergistic effect with CEE and vitamin D on cardiovascular health are needed.

[Influence of Selected Reproductive Factors and Smoking on Age at Menopause]. / Einfluss ausgewählter Reproduktionsfaktoren sowie des Rauchens auf das Alter bei Eintreten der Menopause.

Introduction: Early menopause may be associated with serious health risks resulting from, for example, decreased oestrogen levels. This may occur despite hormone replacement therapy. Aim: The aim of this study was the determination of the effect of selected reproductive factors and smoking on age at the onset of menopause in women from Szczecin and surrounding areas. Material and Methods: 305 women after natural menopause were asked to complete a questionnaire, and blood samples were collected from them to test for the levels of follicle stimulating hormone (FSH) and oestradiol (E2). Results: Smoking women experienced menopause on average more than a year earlier than non-smokers, but this difference was not statistically significant. There was no statistically significant effect of age at menarche or first birth on age at the last menstrual period. Conclusions: Age at menarche and first birth were not related to age at menopause. In smoking women, menopause occurred earlier but the difference was not statistically significant.

Chemotherapy-Related Amenorrhea and Menopause in Young Chinese Breast Cancer Patients: Analysis on Incidence, Risk Factors and Serum Hormone Profiles.

PURPOSE: In this prospective cross-sectional study on young premenopausal breast cancer patients, the objectives were to: determine the incidences of chemotherapy-related amenorrhea (CRA) and menopause (CRM); identify associated factors; and assess plasma levels of estradiol (E2) and follicular stimulating hormone (FSH) among patients who developed menopause. METHODS: Eligibility criteria include Chinese stage I-III breast cancer patients, premenopausal, age ≤45 at breast cancer diagnosis, having received adjuvant chemotherapy, within 3-10 years after breast cancer diagnosis. Detailed menstrual history prior to and after adjuvant treatment was taken at study entry. Patients' background demographics, tumor characteristics and anti-cancer treatments were collected. The rates of CRA and CRM were determined. Analysis was conducted to identify factors associated with CRM. For postmenopausal patients, levels of E2 and FSH were analyzed. RESULTS: 286 patients were recruited; the median time from breast cancer diagnosis to study entry was 5.0 years. 255 patients (91.1%) developed CRA. Of these, 66.7% regained menstruation. At the time of study entry, 137 (48.9%) had developed CRM, amongst whom 84 were age ≤45. On multivariate analysis, age was the only associated factor. Among patients with CRM, the median FSH was 41.0 IU/L; this was significantly lower in those who were taking tamoxifen compared to those who were not (20.1 vs. 59.7 IU/L, p<0.0001). The E2 level was <40 pmol/L; there was no difference between those who were still on tamoxifen or not. CONCLUSION: After adjuvant chemotherapy, the majority of young Chinese breast cancer patients developed CRA; ~50% developed CRM, with 61% at age ≤45. Age at diagnosis is the only factor associated with CRM. FSH level may be affected by tamoxifen intake.

Effect of age at menopause on disease presentation in early rheumatoid arthritis: results from the Canadian Early Arthritis Cohort.

OBJECTIVE: Studies suggest that hormonal states affect disease characteristics in women with rheumatoid arthritis (RA). This study investigated how age at menopause affects disease in women presenting with early RA. METHODS: This was a cross-sectional study of postmenopausal women with early RA under age 65 years at time of enrollment in the Canadian Early Arthritis Cohort. RA-related disease characteristics in women who had early age at menopause (EM; age at menopause <45 years) were compared to those who had usual age at menopause (age at menopause ≥45 years). The t-test was applied to continuous variables and the chi-square test to categorical variables. Multivariate logistic regression analysis was used to adjust for age at menopause, smoking, and use of exogenous hormones. RESULTS: A total of 534 women were included; 93 were in the EM group. The age at RA onset was similar between groups. The EM group had higher mean patient global and pain scores and was more likely to be rheumatoid factor (RF) positive and meet the 1987 American College of Rheumatology criteria for RA. Using multivariate logistic regression, the EM group was more likely to be RF positive (odds ratio 2.2 [95% confidence interval 1.3-3.8], P = 0.005). Symptom duration, joint counts, Disease Activity Score in 28 joints, Health Assessment Questionnaire scores, and inflammatory markers did not differ between groups. CONCLUSION: These data suggest that early age at menopause, compared to usual age at menopause, is associated with seropositivity in women with early RA.

Association of menopause age and N-terminal pro brain natriuretic peptide: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Menopause age can affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before age 45 y) and menopause age with N-terminal pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure. METHODS: Our cross-sectional study included 2,275 postmenopausal women, aged 45 to 85 years and without clinical CVD (2000-2002), from the Multi-Ethnic Study of Atherosclerosis. Participants were classified as having or not having early menopause. NT-proBNP was log-transformed. Multivariable linear regression was used for analysis. RESULTS: Five hundred sixty-one women had early menopause. The median (25th-75th percentiles) NT-proBNP value was 79.0 (41.1-151.6) pg/mL for all participants, 83.4 (41.4-164.9) pg/mL for women with early menopause, and 78.0 (40.8-148.3) pg/mL for women without early menopause. The mean (SD) age was 65 (10.1) and 65 (8.9) years for women with and without early menopause, respectively. No significant interactions between menopause age and ethnicity were observed. In multivariable analysis, early menopause was associated with a 10.7% increase in NT-proBNP levels, whereas each 1-year increase in menopause age was associated with a 0.7% decrease in NT-proBNP levels. CONCLUSIONS: Early menopause is associated with greater NT-proBNP levels, whereas each 1-year increase in menopause age is associated with lower NT-proBNP levels, in postmenopausal women.

The progressive reduction in the ovarian reserve in young women after anticancer treatment.

Anticancer treatment can disturb gonadal function and deplete the primordial follicle pool, leading to premature menopause. We made a prospective analysis of serum hormone levels in young female cancer survivors who had been treated during childhood and adolescence. Serum anti-Müllerian hormone (AMH) as a marker of ovarian reserve, FSH, LH, and estradiol were measured in 33 women treated previously (6-11 years earlier) for Hodgkin Lymphoma, solid tumours, and after bone marrow transplantation, and in 34 healthy controls. The group of survivors was divided according to the risk of gonadotoxicity into the low risk and median risk group (LR+MR), and into the high risk (HR) group. The measurements were repeated after 5 years. In the HR group, AMH levels were significantly lower than in controls (p=0.001) and in the LR+MR group (p=0.006) at the time of the first examination fell progressively after 5 years (p=0.03), whereas elevated FSH values (p=0.053) increased (p=0.001). Unchanged LH values in the first measurement rose in the second one (p=0.001). In the LR+MR group, the levels of AMH and FSH were normal (compared to the control) at baseline, but after 5 years serum AMH decreased (p=0.027) and FSH increased (p=0.008). Our findings indicate that anticancer treatment during childhood and adolescence is associated with a serious, progressive risk of ovarian failure. It is necessary to inform female cancer survivors, especially the high risk patients, about the risk of premature menopause.

Younger age of menopause in women with cerebral aneurysms.

BACKGROUND: The incidence of subarachnoid hemorrhage in women surges following menopause. Estrogen fluctuations have been implicated in cerebral aneurysm formation, growth and rupture and are thought to explain the well-known gender disparity. The aim of this study was to examine the association between age at menopause, which can determine lifetime estrogen exposure, and the presence of cerebral aneurysms. METHODS: A retrospective case-control study was conducted by interviewing postmenopausal women with intradural cerebral aneurysms about their basic medical and gynecologic histories. This information was compared with the same data points collected from 4682 women contacted through random digit phone dialing in the National Institute of Child Health and Human Development-sponsored Contraceptive and Reproductive Experiences Study published in 2002. RESULTS: Among 76 consecutive postmenopausal women with cerebral aneurysms who were treated by a single physician and interviewed, multivariate logistic regression showed that later menopause age (OR 0.79, CI 0.63 to 0.996, p=0.046) was significantly associated with a lower aneurysm incidence. Premature menopause (<40 years) was seen in 26% of cases and 19% of controls (p=0.15). Each categorical increase in menopause age (<40, 40-44, 45-49, 50-54, ≥55 years) decreased the likelihood by 21%. Despite a trend towards earlier mean age at menopause in the case group, the difference was not statistically significant. CONCLUSION: There is a trend showing that an earlier age at menopause is associated with the presence of a cerebral aneurysm. This suggests that loss of estrogen earlier in a woman's life may contribute to the pathogenesis of cerebral aneurysm. These data may identify a risk factor for cerebral aneurysm pathogenesis and also a potential target for future therapies.

Therapy with climara in surgical menopause.

UNLABELLED: Hormone replacement therapy in surgical menopause is a prophylactic measure that is used for preventing the short and long term effects of the lack of ovarian hormones. MATERIAL AND METHODS: This is a retrospective study conducted between 2004 and 2006 at the Iasi "Elena-Doamna" Hospital of Obstetrics and Gynecology on two series of patients: 46 patients with surgical menopause who received treatment with transdermal estradiol (Climara), and 20 surgical menopause patients not receiving this treatment who served as controls. RESULTS: A decreases in the average levels of total cholesterol, triglycerides and LDL cholesterol and an increase in the HDL cholesterol level were identified in the series receiving Climara compared to the controls. The climacteric symptoms improved in the patients receiving treatment. CONCLUSIONS: Transdermal therapy with estradiol (Climara) is an effective method of treatment in surgically induced menopause.

[Diagnosis of premature menopause measuring circulating anti-Müllerian hormone]. / Diagnóstico de menopausia prematura usando la medición de la hormona anti-mülleriana circulante.

The production of anti-müllerian hormone for the ovarian follicles begins near the puberty and the circulating levels begin to descend progressively in the stage of the pre-menopause coinciding with the depletion follicular and in consequence the menstrual cycles become irregular, frequently anovulatories. Therefore, concentration of anti-müllerian hormone shows a close correlation with follicular reserve and reproductive capacity, more than FSH and estradiol measurements. We described two patients that developed premature ovarian failure without previous diagnosis and therefore just were treated pharmacologically with estrogen-progestagen to induce menstrual bleeding. In blood of both patients was found low levels (< or = 4 ng/mL) of anti-müllerian hormone, and by means of sonography the absence of follicles was demonstrated in the ovaries. Has intended that premature ovarian failure could be of a chromosomal dysfunction, similar to other gonadal dysgenesias, another explanation of the mechanism is that it could be for development of some autoimmunity dysfunction. Therefore, the combined hormonal substitution of estrogen with progestagen should stay during several years to avoid the complications for the lack of estrogens; in some cases, could be informed on offering the pregnancy possibility by means of the attended fertilization using ovules donor.