Association of infertility with type and timing of menopause: a prospective cohort study.

STUDY QUESTION: What is the association between past infertility and the type and timing of menopause in midlife women? SUMMARY ANSWER: Women with a history of infertility were more likely to experience surgical menopause overall and had elevated risk of earlier surgical menopause until age 43 years but experienced no differences in the timing of natural menopause. WHAT IS KNOWN ALREADY: Infertility is experienced by 12-25% of women and is thought to reveal a propensity for poor health outcomes, such as chronic illness, later in life. However, little is known about whether infertility is linked with characteristics of the menopausal transition as women age, despite possible shared underlying pathways involving ovarian function and gynecologic disease. STUDY DESIGN, SIZE, DURATION: Secondary analysis of a prospective cohort study of 13 243 midlife females recruited in Phase 1 of the Alberta's Tomorrow Project (Alberta, Canada) and followed approximately every 4 years (2000-2022). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected through standardized self-report questionnaires. History of infertility, defined as ever trying to become pregnant for more than 1 year without conceiving, was measured at baseline. Menopause characteristics were measured at each study follow-up. Menopause type was defined as premenopause, natural menopause, surgical menopause (bilateral oophorectomy), or indeterminate menopause (premenopausal hysterectomy with ovarian conservation). Timing of natural menopause was defined as the age at 1 full year after the final menstrual period, and timing of surgical and indeterminate menopause was defined as the age at the time of surgery. We used flexible parametric survival analysis for the outcome of menopause timing with age as the underlying time scale and multinomial logistic regression for the outcome of menopause type. Multivariable models controlled for race/ethnicity, education, parity, previous pregnancy loss, and smoking. Sensitivity analyses additionally accounted for birth history, menopausal hormone therapy, body mass index, chronic medical conditions, and age at baseline. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 18.2% of women reported a history of infertility. Past infertility was associated with earlier timing of surgical menopause exclusively before age 43 years (age 35: adjusted hazard ratio 3.13, 95% CI 1.95-5.02; age 40: adjusted hazard ratio 1.83, 95% CI 1.40-2.40; age 45: adjusted hazard ratio 1.13, 95% CI 0.87-1.46) as well as greater odds of experiencing surgical menopause compared to natural menopause (adjusted odds ratio 1.40, 95% CI 1.18-1.66). Infertility was not associated with the timing of natural or indeterminate menopause. LIMITATIONS, REASONS FOR CAUTION: Information on the underlying cause of infertility and related interventions was not collected, which precluded us from disentangling whether associations differed by infertility cause and treatment. Residual confounding is possible given that some covariates were measured at baseline and may not have temporally preceded infertility. WIDER IMPLICATIONS OF THE FINDINGS: Women with a history of infertility were more likely to experience early surgical menopause and may therefore benefit from preemptive screening and treatment for gynecologic diseases to reduce bilateral oophorectomy, where clinically appropriate, and its associated health risks in midlife. Moreover, the lack of association between infertility and timing of natural menopause adds to the emerging knowledge that diminishing ovarian reserve does not appear to be a primary biological mechanism of infertility nor its downstream implications for women's health. STUDY FUNDING/COMPETING INTEREST(S): Alberta's Tomorrow Project is only possible due to the commitment of its research participants, its staff and its funders: Alberta Health, Alberta Cancer Foundation, Canadian Partnership Against Cancer and Health Canada, and substantial in-kind funding from Alberta Health Services. The views expressed herein represent the views of the author(s) and not of Alberta's Tomorrow Project or any of its funders. This secondary analysis is funded by Project Grant Priority Funding in Women's Health Research from the Canadian Institutes of Health Research (Grant no. 491439). N.V.S. is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research. H.K.B. is supported by the Canada Research Chairs Program. E.A.B. is supported by an Early Career Investigator Award in Maternal, Reproductive, Child and Youth Health from the Canadian Institutes of Health Research. A.K.S. has received honoraria from Pfizer, Lupin, Bio-Syent, and Eisai and has received grant funding from Pfizer. N.V.S., H.K.B., and E.A.B. have no conflicts of interest to report. TRIAL REGISTRATION NUMBER: N/A.

Cannabis use during lactation may alter the composition of human breast milk.

BACKGROUND: Cannabis is often used by women to manage symptoms of morning sickness during pregnancy, and postpartum stress and anxiety. While exclusive breastfeeding has been recommended for the first 6 months of an infant's life, the presence of cannabinoids in the milk of cannabis users complicates this recommendation. The objective of this study was to investigate the effect of maternal cannabis use on changes in the levels of macronutrients and bioactive factors in breast milk. METHODS: Milk was collected from women who were 6-8 weeks postpartum and were either using cannabis post-delivery, had used cannabis during pregnancy, or were non-users. Levels of cannabinoids, macronutrients, lactose, and SIgA were assessed in the milk of all subjects. RESULTS: THC was detected in the milk of women who reported cannabis use during lactation (n = 13, median: 22 ng/mL). Carboxy-THC, 11-hydroxy-THC, CBD, and CBN were also detected in the milk of women who used cannabis postpartum. Relative to non-users (n = 17), lactose levels were higher and SIgA levels were significantly lower in the milk of subjects who used cannabis during lactation (n = 14). CONCLUSIONS: The presence of cannabinoids, along with altered lactose and SIgA levels in the milk of cannabis users, may have implications for infant health. IMPACT: Metabolites of cannabis are found in breast milk and can accumulate in higher concentrations with ongoing consumption, which is concerning for potential exposure among infants born to mothers who consume cannabis. This work reports that lactose levels are increased and SIgA levels are decreased in the breast milk of cannabis users, relative to the milk of non-users. Change in levels of lactose and SIgA in the milk of cannabis users may have significant implications on infant health, which must be investigated in the future to better inform mothers.

Impact of lifetime lactation on the risk and duration of frequent vasomotor symptoms: A longitudinal dose-response analysis.

OBJECTIVE: To examine the association between lifetime lactation and risk and duration of frequent vasomotor symptoms (VMS). DESIGN: Prospective cohort. SETTING: USA, 1995-2008. SAMPLE: 2356 parous midlife women in the Study of Women's Health Across the Nation. METHODS: Lifetime lactation was defined as the duration of breastfeeding across all births in months. We used generalised estimating equations to analyse risk of frequent VMS and Cox regression to analyse duration of frequent VMS in years. MAIN OUTCOME MEASURES: Frequent VMS (hot flashes and night sweats) were measured annually for 10 years, defined as occurring ≥6 days in the past 2 weeks. RESULTS: Overall, 57.1% of women reported hot flashes and 43.0% reported night sweats during follow-up. Lifetime lactation was inversely associated with hot flashes plateauing at 12 months of breastfeeding (6 months: adjusted odds ratio [AOR] 0.85, 95% confidence interval (CI) 0.75-0.96; 12 months: AOR 0.78, 95% CI 0.65-0.93) and was inversely associated with night sweats in a downward linear fashion (6 months: AOR 0.93, 95% CI 0.81-1.08; 18 months: AOR 0.82, 95% CI 0.67-1.02; 30 months: AOR 0.73, 95% CI 0.56-0.97). Lifetime lactation was associated with shorter duration of hot flashes and night sweats in a quadratic (bell-shaped) fashion. The association was strongest at 12-18 months of breastfeeding and significant for hot flashes (6 months: adjusted hazard ratio [AHR] 1.35, 95% CI 1.11-1.65; 18 months: AHR 1.54, 95% CI 1.16-2.03; 30 months: AHR 1.18, 95% CI 0.83-1.68). CONCLUSIONS: Longer lifetime lactation is associated with decreased risk and duration of frequent VMS.

Prenatal cannabis use and its impact on offspring neuro-behavioural outcomes: A systematic review.

Introduction: Cannabis is a widely used substance in pregnancy, yet there is a paucity of literature addressing the neuro-behavioural consequences for prenatally exposed children. Our systematic review synthesizes currently available data for the impact of prenatal cannabis use on offspring intelligence and cognitive functioning. Methods: MEDLINE, EMBASE, PsychINFO, CINAHL, and Clinicaltrials.gov were searched. Observational studies comparing prenatal cannabis use to controls were included. Offspring neuro-behavioural outcomes were grouped in prespecified domains of (1) intelligence and (2) cognitive functioning. Random-effect models were performed for meta-analyses when at least three studies reported the same outcome. All others were summarized qualitatively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework was used to assess evidence certainty. Results: Of the 1982 reviewed studies (n = 523,107 patients), 28 were included. Significant heterogeneity and cohort redundancy limited meta-analysis. Very low-quality evidence from pooled analyses showed no significant associations between prenatal cannabis exposure and attention [standardized mean difference = -0.27 (95% CI = -0.60 to 0.07)], global intelligence quotient [-0.16 (-0.42 to 0.10)], reading [-0.05 (-0.29 to 0.20)], written comprehension [-0.09 (-0.40 to 0.22)], spelling [-0.04 (-0.26 to 0.17)], and mathematics [-0.01 (-0.15 to 0.13)]. No significant associations were found between prenatal cannabis exposure for all other outcomes. Individual studies reported significant differences between the heavy use groups and non-exposed, although this did not prove to be significant when outcomes were pooled. Conclusions: The current review did not find a clear association between prenatal cannabis use and offspring neuro-behavioural outcomes. However, evidence was low quality and heterogenous. Further prospective investigation is needed to elucidate any potential association between prenatal cannabis use and long-term neuro-developmental outcomes.

How are Canadian cannabis dispensaries counselling breastfeeding consumers?

Objectives: This study aimed to identify recommendations given to breastfeeding individuals by Canadian cannabis dispensary employees, since the legalization of recreational cannabis in 2018. Methods: This was a nationwide cross-sectional study conducted from November 2020 to January 2021. A mystery caller approach was used to identify recommendations given to breastfeeding individuals seeking a product for "relaxation." This study was modelled on similar studies which assessed recommendations given to pregnant women looking for cannabis products to manage nausea and vomiting (Vastis V, Shea AK, Vincent S, Metz TD. 275: Are canadian cannabis dispensaries counselling pregnant women appropriately? Am. J. Obstet. Gynecol. 2020;222: S187.(Abst). Lusero I, Paltrow LM, Rosenbloom N. Recommendations from cannabis dispensaries about first-trimester cannabis use Obstet Gynecol 2018;132:781-2.). The primary outcome was the recommendation of a cannabis product. Secondary outcomes included stated benefits of cannabis, recommended discussion with health care provider, length of call, rationale for recommendation, and reported source of information on which the recommendation was based. Results: The majority (79.4%) of employees of the 714 Canadian dispensaries contacted recommended against a cannabis product for "relaxation" while breastfeeding. The recommendations from dispensary employees were often (80%) provided without a specific reason, whereas a minority referenced published research (2%) and opinion (17.6%). Cannabis products were rarely (3.3%) classified as safe in breastfeeding. Approximately 76.6% of dispensary employees recommended contacting a health care provider, while 2.4% recommended against. Conclusions: Although a high proportion of dispensary employees recommended against using a cannabis product during lactation, there were still 20.6% that did recommend use, which contrasts the current public health guidelines and is not supported by the paediatric and obstetric societies. These findings highlight the need for further education about the safety of cannabis products while breastfeeding.

Guideline No. 422c: Menopause: Mood, Sleep, and Cognition.

OBJECTIVE: Provide strategies for improving the care of perimenopausal and postmenopausal women based on the most recent published evidence. TARGET POPULATION: Perimenopausal and postmenopausal women. BENEFITS, HARMS, AND COSTS: Target population will benefit from the most recent published scientific evidence provided via the information from their health care provider. No harms or costs are involved with this information since women will have the opportunity to choose among the different therapeutic options for the management of the symptoms and morbidities associated with menopause, including the option to choose no treatment. EVIDENCE: Databases consulted were PubMed, MEDLINE, and the Cochrane Library for the years 2002-2020, and MeSH search terms were specific for each topic developed through the 7 chapters. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: physicians, including gynaecologists, obstetricians, family physicians, internists, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; pharmacists; medical trainees, including medical students, residents, fellows; and other providers of health care for the target population. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique n° 422c : Ménopause : Humeur, sommeil et cognition.

OBJECTIF: Proposer des stratégies fondées sur les plus récentes données publiées pour améliorer les soins aux femmes ménopausées ou en périménopause. POPULATION CIBLE: Les femmes ménopausées ou en périménopause. BéNéFICES, RISQUES ET COûTS: La population cible bénéficiera des plus récentes données scientifiques publiées communiquées par leurs fournisseurs de soins de santé. Aucun coût ni préjudice ne sont associés à cette information, car les femmes seront libres de choisir parmi les différentes options thérapeutiques, y compris le statu quo, pour la prise en charge des symptômes et morbidités associés à la ménopause. DONNéES PROBANTES: Les auteurs ont interrogé les bases de données PubMed, MEDLINE et Cochrane Library pour extraire des articles publiés entre 2002 et 2020 en utilisant des termes MeSH spécifiques à chacun des sujets abordés dans les 7 chapitres. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant l'approche d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: gynécologues, obstétriciens, médecins de famille, internistes, urgentologues, infirmières (autorisées et praticiennes), pharmaciens, stagiaires (étudiants en médecine, résidents, moniteurs cliniques) et autres fournisseurs de soins de santé pour la population cible. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Are Canadian Cannabis Dispensaries Counselling Pregnant Women Appropriately?

Our objective was to examine the recommendations that Canadian dispensary employees are giving to women regarding cannabis use for nausea and vomiting of pregnancy (NVP) since the legalization of recreational cannabis in 2018. We conducted a nationwide cross-sectional study of licensed cannabis dispensaries in 2019, wherein a mystery caller stated they were 8 weeks pregnant and experiencing nausea and vomiting and asked for recommendations about cannabis. Our research was modeled after the primary study done in Colorado by Dickson and colleagues in 2018. An overwhelming majority of dispensaries (93%) in our study recommended against the use of a cannabis product for NVP, which contrasted significantly to the findings of the Colorado study, in which 70% of dispensaries recommended a cannabis product. These findings suggest that Canadian dispensary employees have been adequately educated about the dangers of cannabis use during pregnancy and are helpful from a public health lens.

Do Maternal Pharmacogenetics Impact the Neonatal Abstinence Syndrome Following In Utero Exposure to Antidepressant Medications?

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the most commonly used medications for mood and anxiety disorders in women. Many women need to continue or initiate these medications during pregnancy, but there is concern about potential withdrawal effects in the newborn, referred to as neonatal abstinence syndrome (NAS). The reason why some infants remain asymptomatic while others are affected has not been elucidated. The objective of this study was to examine whether genetic differences in maternal drug metabolism influence the incidence of NAS. METHODS: Women who took Selective serotonin reuptake inhibitors s/SNRIs during pregnancy were recruited from obstetrical clinics. DNA was extracted from saliva samples for genetic analyses of cytochrome P450 (CYP) enzyme polymorphisms. Delivery and NAS data were collected from electronic medical records. RESULTS: Ninety-five women participated. The overall NAS rate was 16.2%. Mild NAS was seen in 13.8% of neonates and severe NAS, in 2%. One-quarter (25%) of the neonates with mild withdrawal symptoms were born to mothers with polymorphisms associated with slower metabolism of their particular antidepressant, but this association was not statistically significant. CONCLUSION: Importantly, the overall rate of NAS in our study was lower than previously reported. Maternal CYP polymorphisms did not affect the rate of NAS in neonates exposed to SSRIs/SNRIs in utero. This study lends added assurance to patients requiring SSRIs or SNRIs during pregnancy.

Pregnant Canadians' Perceptions About the Transmission of Cannabis in Pregnancy and While Breastfeeding and the Impact of Information From Health Care Providers on Discontinuation of Use.

OBJECTIVE: Rates of cannabis use during pregnancy and while breastfeeding are increasing in Canada. Some observational studies have found associations between cannabis use in pregnancy and low birthweight, preterm labour, and admission to the intensive care unit. This study aimed to evaluate women's perceptions about transmission of cannabis to the fetus, and whether receiving information from a health care provider influenced their decision to stop using cannabis during pregnancy. METHODS: Pregnant women presenting to obstetrical, midwifery, and family practice clinics in the greater Hamilton, Ontario area were asked to complete an anonymous survey. Chi-square tests were used to investigate whether patient knowledge was influenced by health care providers or by self-directed learning and if this information influenced their decision to discontinue cannabis use. RESULTS: Of the 478 women surveyed, the vast majority perceived that cannabis is transmitted to the fetus during pregnancy and to the infant while breastfeeding (94.3% and 91.2%, respectively). The majority of women (99%) indicated that the advent of cannabis legalization did not influence their choice to use cannabis in pregnancy. Women who continued to use cannabis during pregnancy were more likely to report receiving information on cannabis from a health care provider (52%) than those who chose to discontinue use in pregnancy (35%) (P = 0.035). CONCLUSIONS: In our study, the proportion of pregnant women who understood that cannabis could be transmitted to the fetus in utero and to the infant via breastmilk was high. Despite this, 4.2% of women reported that they continued to use cannabis in pregnancy. More work is needed to understand why some women continue to use cannabis in pregnancy despite being informed of its risks.

The effect of maternal antidepressants on third trimester uteroplacental hemodynamics and the neonatal abstinence syndrome: a retrospective cohort study.

The objective of this study is to determine whether maternal antidepressant use during pregnancy influences uteroplacental hemodynamics, thereby affecting fetal growth and gestational age at delivery. The secondary aim was to determine the incidence of neonatal abstinence syndrome (NAS) among infants exposed to antidepressant medications. The charts of women who received obstetrical care and had a history of depression from January 2014 to December 2016 at Mount Sinai Hospital in Toronto, Canada, were reviewed. Exclusion criteria were substance abuse; narcotic or lithium use at the time of delivery.In total, 205 women met the inclusion criteria (92 took antidepressants; 113 women did not). There were no significant differences in umbilical artery pulsatility index (PI), gestational age at delivery, or birth weight when comparing women based on antidepressant use. A small proportion (18%) of neonates had mild withdrawal symptoms; one baby had a score (≥ 8) consistent with severe NAS. In women with a history of depression, there was no difference in uteroplacental hemodynamics as measured by third trimester Doppler ultrasonography when comparing women who took antidepressant medication versus those who did not. The large majority of babies who were exposed to antidepressants in utero did not show withdrawal symptoms. These results lend support for the relative safety of antidepressants during pregnancy.

Pregnancy Outcomes of Women Admitted to a Tertiary Care Centre with Short Cervix.

OBJECTIVE: Our aim was to characterize the management and outcome of women admitted to a tertiary high-risk obstetrics unit with a short cervix (≤25 mm), measured on transvaginal ultrasound (TVS), and to determine the latency period from diagnosis to delivery. METHODS: A retrospective chart review of women admitted to the High Risk Obstetrics Unit at Sunnybrook Health Sciences Centre between 2005-2011 with an ultrasound-identified short cervix was done. RESULTS: A total of 110 women admitted for a short cervix between 2005-2011 (N = 56 singletons; N = 54 twin gestations) met the inclusion criteria. The mean latency to delivery was 62.6 days; mean GA at delivery was 33.9 weeks. Following 7 and 14 days of admission, 5.5% and 11.8% of women had delivered, respectively. Preterm birth occurred in 70% of all women. Cervical length was a significant factor in predicting latency among singletons, whereas the length of stay in hospital for activity restriction was not. CONCLUSIONS: Although many women with a short cervix delivered preterm, only a small proportion delivered within 2 weeks of admission. Although it is not clear whether inpatient management improves the pregnancy outcome, these findings have implications for both patient care and health resources.

The association of depressive symptoms and female sexual functioning in the menopause transition: a cross-sectional study.

OBJECTIVE: Sexual dysfunction is very common among middle-aged females. Several factors are considered to influence sexual functioning, including reproductive aging and associated physiological changes as well as life stressors, mental health, and other socioeconomic influences. The objectives of this study are to evaluate the effect of current depressive symptoms on sexual functioning during menopause and to further analyze whether socioeconomic status, age, and antidepressant usage impact this association. METHODS: Perimenopausal and postmenopausal women aged 40 to 65 years seeking treatment from a specialized menopause clinic completed a self-report survey with the main outcome measure being the 19-item Female Sexual Function Index quantifying sexual dysfunction. We used the 10-item Center for Epidemiological Studies Depression Scale to estimate a major depressive episode. Statistical analyses were completed to assess the potential associations of socioeconomic factors, age, and antidepressant usage. RESULTS: Of the 269 participants, 61.3% met criteria for a major depressive episode and 67.0% had low sexual function. As predicted, women currently experiencing depressive symptoms had a greater risk of low sexual function during perimenopause and postmenopause. Antidepressant usage, low household income, being postmenopausal, and age also predicted low sexual function. CONCLUSIONS: Among perimenopausal and postmenopausal women, current depressive symptoms were associated with low sexual function. A biopsychosocial approach should be considered when exploring effective treatment strategies for sexual concerns among midlife women.

Does menopause hormone therapy improve symptoms of depression? Findings from a specialized menopause clinic.

OBJECTIVE: Depressive symptoms are commonly reported during the perimenopause and in the early postmenopausal years. Although menopausal hormone therapy (MHT) is considered the most effective treatment option for vasomotor symptoms, its effect on mood-related symptoms is less established. This study aims to assess interval change in depressive symptoms after initiation of MHT treatment in women seeking care at a Canadian specialized menopause clinic. METHODS: Women and female-presenting people attending the St. Joseph's Healthcare Menopause Clinic in Hamilton, Ontario, were invited to participate in this study. Participants (n = 170) completed a self-report questionnaire, which included their medical history as well as validated tools for bothersome symptoms at their initial visit. A shortened version was administered at the follow-up visit 3 to 12 months later with the same validated tools. We sought to examine interval changes on the Center for Epidemiological Studies Depression Scale based on type of treatment used and MHT dose, while controlling for relevant demographic variables (smoking, education level, age). RESULTS: There was a high rate of depressive symptoms in those seeking specialized menopause care (62%). MHT use was associated with significantly improved depressive symptoms, both alone and in addition to an antidepressant medication ( P < 0.001). Younger age, lower education attainment, and smoking were all associated with higher depression scores. CONCLUSION: This study supports the use of MHT to improve depressive symptoms experienced by those seeking specialized menopause care. Further investigation into timing of treatment initiation may facilitate a personalized treatment approach to improve quality of life of women in the peri- and postmenopausal years.

The association between primary ovarian insufficiency and increased multimorbidity in a large prospective cohort.

OBJECTIVE: To describe the prevalence of multimorbidity among individuals with premature ovarian insufficiency (POI) and early menopause, in comparison to average age of menopause. DESIGN: Prospective cohort SUBJECTS: This prospective cohort encompassed female postmenopausal individuals from the Canadian Longitudinal Study on Aging (CLSA). The CLSA collected cross-sectional data from 50,000 community-dwelling Canadians aged 45 to 85 between 2010 and 2015. EXPOSURE: The primary exposure was primary ovarian insufficiency (defined by onset of menopause younger than 40 years). Comparators included average age of menopause (age 46 to 55 years), early menopause (40-45 years), late onset menopause (56-65 years), and those who underwent a hysterectomy. MAIN OUTCOME MEASURES: The primary outcome was multimorbidity, which was defined as two or more chronic conditions. The secondary outcome was severe multimorbidity (defined as three or more chronic conditions) as well as frequencies of specific chronic conditions among a comprehensive list of 15 individual conditions. We assessed the association between multimorbidity and age at menopause using logistic regression and odds ratios, with confidence intervals set at 95%. Odds ratios were adjusted for known predictors of multimorbidity, including age, menopause hormone therapy (MHT), education, ethnicity, self-reported loneliness, living alone, BMI, smoking habits, nutritional risk, social participation, and physical activity. RESULTS: A total of 12,339 postmenopausal participants were included, of which 374 (3.0%) experienced POI and 1396 (11.3%) experienced early menopause. The prevalence of multimorbidity was 64.8% and 51.1% among those with POI and early menopause respectively. In contrast, only 43.9% of individuals with average age of menopause (age 46 to 55 years) had multimorbidity. The OR for multimorbidity in the POI population was 2.5 (95% CI 2.0-3.1) in comparison to those who underwent the average age of menopause. This relationship was maintained after adjustment for confounders (aOR 2.0, 95% CI: 1.5-2.5). The prevalence of severe multimorbidity was also double in the POI group in comparison in the average age group (39.2% versus 21.1%). There was significantly increased risk of ischemic heart disease (aOR 2.8, 95% CI: 1.7-4.7), gastric ulcers (aOR 1.6, 95% CI: 1.1-2.3) and osteoporosis (aOR 1.6, 95% CI: 1.2-2.1) in the POI group. CONCLUSIONS: Individuals with POI and early menopause experience increased multimorbidity in comparison to those undergoing menopause at an average age. This trend persists even after adjusting for significant multimorbidity risk factors.

Fetal serotonin reuptake inhibitor antidepressant exposure: maternal and fetal factors.

Prenatal serotonin reuptake inhibitor exposure is common and neonatal outcomes vary greatly, often leading to confusion about whether to use or even continue antenatal use of these antidepressants. Importantly, some but not all infants are affected, which raises questions about how maternal drug metabolism contributes to fetal drug exposure. To address this key question, our paper reviews the role of key maternal, fetal, and placental pharmacokinetic, metabolic, and genetic factors that affect the extent of fetal drug exposure. Considering the role of these factors may further our understanding of variables that may assist in optimizing maternal psychopharmacotherapy during pregnancy and neonatal outcomes.

Association of lifetime lactation and age at natural menopause: a prospective cohort study.

OBJECTIVE: The aim of this study was to examine the association between duration of lifetime lactation and age at natural menopause. METHODS: In this prospective cohort study, we analyzed parous premenopausal women in the multiethnic Study of Women's Health Across the Nation who were followed approximately annually for 10 years (1995-2008). Lifetime lactation was defined as the duration of breastfeeding across all births in months. Age at natural menopause was defined as age in years after 12 consecutive months of amenorrhea after the final menstrual period for no other reported cause. We used Cox proportional hazard models to analyze time to natural menopause with age as the underlying time scale. Multivariable models controlled for education, race/ethnicity, parity, smoking, body mass index, and oral contraceptive use. RESULTS: Among 2,377 women, 52.6% experienced natural menopause during follow-up and reported a valid final menstrual period date. The small, crude association between lifetime lactation up to 24 months and later age at natural menopause attenuated to nonsignificance in adjusted models (6 months: adjusted hazard ratio [AHR], 0.96; 95% confidence interval (CI), 0.87-1.06; 12 months: AHR, 0.95; 95% CI, 0.82-1.11; 18 months: AHR, 0.96; 95% CI, 0.82-1.13; 24 months: AHR, 0.99; 95% CI, 0.84-1.16). CONCLUSIONS: Duration of lifetime lactation was not associated with age at natural menopause after controlling for sociodemographic characteristics.

Behavioral interventions for improving sleep outcomes in menopausal women: a systematic review and meta-analysis.

IMPORTANCE: Perimenopausal and postmenopausal women commonly report sleep disruption and insomnia. Behavioral interventions may be safe alternatives for patients who are unwilling to begin pharmacological treatments because of adverse effects, contraindications, or personal preference. OBJECTIVE: The primary objective is to assess the efficacy of behavioral interventions on sleep outcomes among perimenopausal and postmenopausal women, as measured using standardized scales and objective methods (polysomnography, actigraphy). The secondary objective is to evaluate the safety of these methods through occurrence of adverse events. EVIDENCE REVIEW: Searches were performed within MEDLINE (OVID interface, 1946 onward), Embase (OVID interface, 1974 onward), Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Web of Science (Core collection) using a search strategy developed in consultation with a health sciences librarian. Title/abstract and full-text screenings were performed in duplicate, and relevant studies were selected based on inclusion and exclusion criteria set to identify randomized controlled trials evaluating the effects of behavioral interventions on sleep quality. Risk of bias assessments were done using the Cochrane Risk of Bias 2 tool, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of the body of evidence. Data were pooled in a meta-analysis using a random-effects model. FINDINGS: Nineteen articles reporting results from 16 randomized controlled trials were included, representing a total of 2,108 perimenopausal and postmenopausal women. Overall, behavioral interventions showed a statistically significant effect on sleep outcomes (standardized mean difference [SMD], -0.62; 95% confidence interval [CI], -0.88 to -0.35; I2 = 93.4%). Subgroup analyses revealed that cognitive behavioral therapy (SMD, -0.40; 95% CI, -0.70 to -0.11; I2 = 72.7%), physical exercise (SMD, -0.57; 95% CI, -0.94 to -0.21; I2 = 94.0%), and mindfulness/relaxation (SMD, -1.28; 95% CI, -2.20 to -0.37; I2 = 96.0%) improved sleep, as measured using both subjective (eg, Pittsburg Sleep Quality Index) and objective measures. Low-intensity (SMD, -0.91; 95% CI, -1.59 to -0.24; I2 = 96.8) and moderate-intensity exercise (SMD, -0.21; 95% CI, -0.34 to -0.08; I2 = 0.0%) also improved sleep outcomes. No serious adverse events were reported. Overall risk of bias ranged from some concern to serious, and the certainty of the body of evidence was assessed to be of very low quality. CONCLUSIONS AND RELEVANCE: This meta-analysis provides evidence that behavioral interventions, specifically, cognitive behavioral therapy, physical exercise, and mindfulness/relaxation, are effective treatments for improving sleep outcomes among perimenopausal and postmenopausal women.