Menopause in the workplace: Challenges, impact, and next steps.

INTRODUCTION: Menopause is a natural part of a woman's life that coincides with a time when many women play significant roles in the workforce. Menopause symptoms, such as hot flashes, fatigue, and difficulty with concentration and memory, can have a negative effect on work productivity and efficiency. OBJECTIVES: This paper summarizes the impact of menopause in the workplace, with an emphasis on the impact of symptoms on employed women and how the workplace influences their experiences. It highlights economic implications, promotes awareness, and suggests potential next steps. METHODS: A search for papers was conducted between August and November 2023 in the PubMed and Medline databases. Papers were selected based on personal experience and interpretation of the findings. Recommendations for managing menopause symptoms in the workplace and guidance on an optimal workplace intervention strategy were provided. RESULTS: Women experiencing severe menopause symptoms are more likely to report adverse work outcomes, including absenteeism and job-related decisions such as quitting, retiring early, or declining promotions than women experiencing few symptoms. Factors such as a lack of awareness about menopause, inflexible work conditions, and high-stress jobs can exacerbate the severity of these symptoms. Additionally, unaddressed menopause symptoms contribute to both direct and indirect economic costs, including medical resource utilization and lost work productivity, resulting in a substantial economic burden. CONCLUSION: Menopause symptoms impair women's work experiences and productivity. In addition to dismantling the stigma associated with menopause, it is critical to create and implement menopause workplace policies and interventions aimed at supporting women in this universal life stage.

Weight Gain in Midlife Women.

PURPOSE OF REVIEW: To summarize the evidence and clinical implications of weight and body composition changes during midlife in women and provide an overview of weight gain prevention and management in this population. RECENT FINDINGS: Aging-related changes such as decreased energy expenditure and physical activity are important culprits for weight gain in midlife women. The hormonal changes of menopause also influence body adiposity distribution and increase central adiposity. These body changes can have health consequences including the development of cardiometabolic diseases, osteoarthritis, cancer, worsening in cognition, mental health, and menopause symptoms. Midlife women experience changes related to aging, menopause, and lifestyle which favor weight gain. Clinical practice should focus on early counseling and anticipatory guidance on the importance of dietary changes and physical activity to attenuate this phenomenon. Future research should focus on the longitudinal relationship between weight trends in midlife and health consequences and mortality.

Cardiometabolic outcomes in Kronos Early Estrogen Prevention Study continuation: 14-year follow-up of a hormone therapy trial.

OBJECTIVE: This study aimed to determine long-term cardiometabolic effects of hormone therapies initiated within 3 years of onset of menopause after a 14-year follow-up study of participants of the Kronos Early Estrogen Prevention Study (KEEPS). METHODS: KEEPS was a multisite clinical trial that recruited recently menopausal women with good cardiovascular health for randomization to oral conjugated equine estrogens (Premarin, 0.45 mg/d) or transdermal 17ß-estradiol (Climara, 50 µg/d) both with micronized progesterone (Prometrium, 200 mg/d) for 12 d/mo, or placebo pills and patch for 4 years. KEEPS continuation recontacted KEEPS participants 14 years after randomization and 10 years after the completion of the 4-year clinical trial to attend in-person clinic visits. RESULTS: Participants of KEEPS continuation (n = 299 of the 727 KEEPS participants; 41%) had an average age of 67 years (range, 58-73 y). Measurements of systolic and diastolic blood pressures, waist-to-hip ratio, fasting levels of glucose, insulin, lipid profiles, and homeostasis model assessment of insulin resistance were not different among the treatment groups at either KEEPS baseline or at KEEPS continuation visits, or for change between these two visits. The frequency of self-reported diabetes ( P = 0.007) and use of diabetes medications was higher in the placebo than the oral conjugated equine estrogens ( P = 0.045) or transdermal 17ß-estradiol ( P = 0.02) groups, but these differences were not supported by the laboratory measurements of glycemia or insulin resistance. CONCLUSIONS: There was no evidence of cardiovascular and/or metabolic benefits or adverse effects associated with 4 years use of oral or transdermal forms of hormone therapy by recently menopausal women with good cardiovascular health after 10 years.

Primary ovarian insufficiency: a toolkit for the busy clinician.

Primary ovarian insufficiency (sometimes known as premature ovarian insufficiency) is a result of loss of ovarian follicular activity before the age of 40 years. It is an endocrine deficiency state in women, characterized by premature estrogen deprivation. In the absence of estrogen replacement, women experience bothersome menopause symptoms and a predisposition to accelerated aging and multimorbidity accumulation. Unless a true contraindication exists, estrogen therapy is recommended at least until the age of natural menopause. This Practice Pearl summarizes the clinical manifestations, diagnostic evaluation, and management of primary ovarian insufficiency.

Association between obesity and female sexual dysfunction: a review.

INTRODUCTION: Obesity is a global health crisis that has been growing over the past few decades. The economic burden associated with obesity is substantial as it is associated with multiple disabling chronic diseases, such as cardiovascular disease, certain cancers, osteoarthritis, chronic pain, and mental illness. Obesity is known to be a risk factor for sexual dysfunction in men, but this association is less well understood in women. AIMS: To provide a narrative review of the available literature on the relationship between overweight/obesity and female sexual dysfunction, elaborate on the possible mechanisms explaining this association, and discuss the effects of weight loss on sexual function in those with obesity. METHODS: A search of the medical literature was carried out in PubMed and Medline, focusing on original research and systematic reviews of original research on obesity and sexual function in women. RESULTS: The relationship between obesity and female sexual function is not consistent across studies. While women with obesity are more likely to have worse sexual function and avoid sexual activity, many studies have failed to identify these associations. Lifestyle changes resulting in weight loss lead to better sexual function, and bariatric surgery has been shown to improve sexual function in the first couple of years following the procedure; yet, the long-term effects of weight loss and bariatric surgery are still uncertain. CONCLUSIONS: The evidence on the relationship between obesity and female sexual function is mixed. Nevertheless, weight loss has been shown to improve sexual function in women with obesity. The impact of weight loss medications and the long-term effect of bariatric surgery on female sexual function require further study.

Functional Hypothalamic Amenorrhea: Recognition and Management of a Challenging Diagnosis.

Functional hypothalamic amenorrhea is responsible for approximately a third of the cases of secondary amenorrhea. The condition is a result of disturbances in gonadotropin-releasing hormone pulsatile secretion at the level of the hypothalamus, which in turn disrupts gonadotropin secretion. It is due to psychosocial stress, disordered eating, and/or excessive exercise. Often, however, it is a combination of more than one etiology, with a possible role for genetic or epigenetic predisposition. The dysfunctional gonadotropin-releasing hormone release leads to the cessation of ovarian function, resulting in amenorrhea, infertility, and a long-term impact on affected women's bone health, cardiovascular risk, cognition, and mental health. Functional hypothalamic amenorrhea is a diagnosis of exclusion, and treatment involves identifying and reversing the underlying cause(s). The aim of this concise review is to summarize the current knowledge of functional hypothalamic amenorrhea, review its pathophysiology and the adverse health consequences, and provide recommendations for diagnosis and management of this condition. Furthermore, this review will emphasize the gaps in research on this common condition impacting women of reproductive age all over the world.

Long-term effects of premenopausal bilateral oophorectomy with or without hysterectomy on physical aging and chronic medical conditions.

OBJECTIVE: We examined the long-term effects of premenopausal bilateral oophorectomy (PBO) with or without concurrent or preceding hysterectomy on physical and cognitive function and on odds of chronic conditions. METHODS: We enrolled 274 women with PBO with or without concurrent or preceding hysterectomy and 240 referents aged 55 years and older who were residents of Olmsted County, MN as of the PBO or index date. Chronic conditions were assessed via medical record abstraction. Cognitive diagnoses were based on neurocognitive testing. A physical function assessment included measures of strength and mobility. Multivariable regression models compared characteristics for women with PBO <46 years, PBO 46-49 years, and referent women with adjustments for age and other confounders. RESULTS: The clinical visits (median age, 67 years) were a median of 22 years after the PBO or index date. Of 274 women with PBO, 161 (59%) were <46 years at PBO and 113 (41%) were 46-49 years. Compared with referents, women with a history of PBO <46 years had increased odds of arthritis (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.06-2.55), asthma (OR, 1.74; 95% CI, 1.03-2.93), obstructive sleep apnea (OR, 2.00; 95% CI, 1.23-3.26), and bone fractures (OR, 2.86; 95% CI, 1.17-6.98), and walked a shorter mean distance on a 6-minute walk test ( b = -18.43; P = 0.034). Compared with referents, women with a history of PBO at age 46-49 years had increased odds of arthritis (OR, 1.92; 95% CI, 1.16-3.18) and obstructive sleep apnea (OR, 2.21; 95% CI, 1.33-3.66). There were no significant differences in cognitive status in women with PBO compared with referents. CONCLUSIONS: Women with a history of PBO with or without concurrent or preceding hysterectomy, especially at age <46 years, have more chronic conditions in late mid-life compared with referents.

Associations between childhood adversity and age at natural menopause.

OBJECTIVE: Adverse childhood experiences (ACEs) are reported in more than half of the women in the United States and have been shown to negatively impact the menopause experience. The objective of this study was to evaluate the association between ACEs and age at natural menopause. METHODS: This is a cross-sectional study conducted among participants of the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The registry included women who were seen for consultations in the women's health clinic at Mayo Clinic, Rochester, between May 2015 and December 2016. Only postmenopausal women were included in this analysis. Childhood adversity was assessed with the validated ACE questionnaire. Age at natural menopause was self-reported. The association between ACEs and age at menopause was evaluated using a multivariable linear regression model adjusting for multiple confounders. RESULTS: A total of 350 women were evaluated. The mean age was 59.2 years, and a majority were White (92.9%), married/partnered (82%), and educated (91.2% with at least some college education). Women with a history of at least four ACEs were estimated to reach natural menopause 1.3 years sooner than women with no ACE in multivariable analysis, but the results were not statistically significant (95% confidence interval, -3.2 to 0.6; P = 0.18). CONCLUSIONS: Although stressful life experiences such as ACEs may negatively influence health for midlife women, this study did not find an association with the age at natural menopause.

The effect of genetic variation in estrogen transportation and metabolism on the severity of menopause symptoms: A study from the RIGHT 10K cohort.

OBJECTIVE: The severity of menopause-related symptoms varies considerably among women. The determinants of this variation are incompletely understood. The aim of this study was to assess the association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms. METHODS: This was a cross-sectional study of 60 peri- and postmenopausal women in the Mayo Clinic RIGHT study (which involved sequencing of genes involved in drug metabolism and transport), who had also been evaluated in the Women's Health Clinic at Mayo Clinic in Rochester, MN. All participants completed the Menopause Rating Scale (MRS) for assessment of menopause symptoms, including hot flashes. The association between severity of menopause symptoms and the variation in genes encoding 8 enzymes and transporters involved in estrogen metabolism was evaluated. RESULTS: Lower CYP3A4 activity and higher COMT activity were associated with lower severity of somatic menopause symptoms (p = 0.04 and 0.06, respectively). These associations did not persist after adjustment for hormone therapy use. No differences in MRS scores or hot flash severity were noted among other genetic variant groups. Age at natural menopause was not affected by variations in the genes studied. CONCLUSION: The current study did not show an association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms. Further studies with larger sample sizes may be required to understand this potentially complex association.

History of infertility and sexual dysfunction in midlife women: Is there a link?

BACKGROUND: Infertility has been linked with an increased risk of sexual dysfunction in reproductive-aged women, with longer periods of infertility associated with a greater risk. AIM: The study's aim was to examine whether a history of infertility treatment in women is linked to sexual dysfunction during midlife. METHODS: The cross-sectional study was conducted among sexually active women, between the ages of 45 and 65 years, who sought consultation at the women's health clinics at a US tertiary care center. History of infertility treatment was assessed with a single question that asked participants if they were treated for infertility in the past. The association between a history of infertility treatment and sexual dysfunction-which was diagnosed by a combination of Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale-Revised score ≥11-was assessed in a multivariable logistic regression model that adjusted for multiple confounders. OUTCOMES: The primary outcome was sexual dysfunction in midlife women. RESULTS: The analysis included 5912 women, with a mean age of 54.1 years. Nearly 16% of women reported receiving treatment for infertility. More than half the women (55%) had sexual dysfunction: 56.3% of those with previous fertility treatments and 54.4% of those without any fertility treatment (P = .3). Receiving treatment for infertility in the younger years did not significantly increase the odds of sexual dysfunction in midlife in univariate (odds ratio, 1.08; 95% CI, 0.94-1.24; P = .3) and multivariable analyses (odds ratio, 1.11; 95% CI, 0.96-1.29; P = .17). CLINICAL IMPLICATIONS: While infertility is known to be predictive of sexual dysfunction in women during their reproductive years, there was no association between a history of infertility treatment and sexual dysfunction in midlife women in the current study. STRENGTHS AND LIMITATIONS: The study used validated questionnaires accounting for sexual complaints and distress and adjusted for multiple confounding factors. Limitations include the selection bias introduced by the study of women presenting for evaluation of sexual dysfunction, which may have been a result of factors stronger than the influence of infertility. Other limitations include the study's cross-sectional nature with suboptimal racial and ethnic representation. CONCLUSION: Although infertility is commonly associated with female sexual dysfunction in women of reproductive age, the association was not present in midlife women in the current study.

Association of Migraine and Vasomotor Symptoms.

OBJECTIVE: To further examine a potential link between migraine and vasomotor symptoms as well as hypertension as a cardiovascular disease risk factor, potentially explaining the association in midlife women. PATIENTS AND METHODS: We conducted a cross-sectional analysis from the Data Registry on Experiences of Aging, Menopause, and Sexuality using questionnaire data from women aged 45 to 60 years seen in women's clinics at a tertiary care center from May 15, 2015, through January 31, 2022. A history of migraine was self-reported; menopause symptoms were assessed with the Menopause Rating Scale. Associations between migraine and vasomotor symptoms were evaluated utilizing multivariable logistic regression models adjusting for multiple factors. RESULTS: Of 5708 women included in the analysis, 1354 (23.7%) reported a migraine history. The total cohort had a mean age of 52.8 years, most (5184 [90.8%]) were White, and 3348 (58.7%) were postmenopausal. In adjusted analysis, women with migraine were significantly more likely to have severe/very severe hot flashes vs no hot flashes compared with women without migraine (odds ratio, 1.34; 95% CI, 1.08 to 1.66; P=.007). Migraine was associated with a diagnosis of hypertension in adjusted analysis (odds ratio, 1.31; 95% CI, 1.11 to 1.55; P=.002). CONCLUSION: This large cross-sectional study confirms an association between migraine and vasomotor symptoms. Migraine also was associated with hypertension, potentially providing a link with cardiovascular disease risk. Given the high prevalence of migraine in women, this association may help identify those at risk for more severe menopause symptoms.

Impact of Menopause Symptoms on Women in the Workplace.

OBJECTIVE: To evaluate the impact of menopause symptoms on work outcomes and to assess the estimated economic impact. PATIENTS AND METHODS: Women aged 45 to 60 years receiving primary care at 1 of the 4 Mayo Clinic sites were invited to participate in a survey study (Hormones and ExpeRiences of Aging) from March 1 through June 30, 2021. A total of 32,469 surveys were sent, with 5219 responses (16.1% response rate). Of the 5219 respondents, 4440 (85.1%) reported current employment information and were included in the study. The primary outcome was self-reported adverse work outcomes related to menopause symptoms assessed by the Menopause Rating Scale (MRS). RESULTS: The mean age of the 4440 participants was 53.9±4.5 years, with the majority being White (4127 [93.0%]), married (3398 [76.5%]), and educated (2632 [59.3%] college graduate or higher); the mean total MRS score was 12.1, signifying moderate menopause symptom burden. Overall, 597 women (13.4%) reported at least one adverse work outcome due to menopause symptoms; 480 women (10.8%) reported missing work in the preceding 12 months (median, 3 days missed). The odds of reporting an adverse work outcome increased with increasing menopause symptom severity; women in the highest quartile of total MRS scores were 15.6 (95% CI, 10.7 to 22.7; P<.001) times more likely to have an adverse work outcome vs those in the first quartile. Based on workdays missed due to menopause symptoms, we estimate an annual loss of $1.8 billion in the United States. CONCLUSION: This large cross-sectional study identified a major negative impact of menopause symptoms on work outcomes and the need to improve medical treatment for these women and make the workplace environment more supportive. Additional studies are needed to confirm these findings in larger and more diverse groups of women.

Adverse childhood experiences and sexual dysfunction in midlife women: Is there a link?

BACKGROUND: One in 3 children has had at least 1 adverse childhood experience (ACE), and ACEs have been associated with multiple medical and psychiatric morbidities in women later in life, including greater menopause symptom burden. AIM: To evaluate the association between ACEs and female sexual dysfunction (FSD) in midlife women. METHODS: A cross-sectional analysis from DREAMS-the Data Registry on Experiences of Aging, Menopause, and Sexuality-was conducted with questionnaires completed by women aged 40 to 65 years who presented to a women's health clinic at Mayo Clinic in Rochester, Minnesota, from May 2015 to December 2016. History of ACEs was obtained with the validated ACE questionnaire. FSD was assessed by the Female Sexual Function Index and the Female Sexual Distress Scale-Revised. OUTCOMES: The association between ACEs and FSD (defined as Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale-Revised score ≥11) was evaluated via a multivariable logistic regression model, adjusting for age, menopause status, hormone therapy use, anxiety, depression, relationship satisfaction, hot flash severity, and history of abuse in the past year. RESULTS: Women (N = 1572) had a mean age of 53.2 years. Overall 59% reported having at least 1 ACE. When compared with no ACEs, a history of ≥4 ACEs significantly increased the odds of not being sexually active (odds ratio, 1.83; 95% CI, 1.30-2.57; P < .001). Among sexually active women, the proportion of women with FSD increased sequentially as the number of ACEs increased. In the univariate analysis, a history of ≥4 ACEs significantly increased the odds of FSD as compared with no ACEs (odds ratio, 2.12; 95% CI, 1.50-2.99; P < .001). The association remained statistically significant in the multivariable analysis after adjusting for confounders (odds ratio, 1.75; 95% CI, 1.15-2.68; P = .009). CLINICAL IMPLICATIONS: The findings highlight an opportunity for clinicians to screen for ACEs in women with sexual dysfunction and offer appropriate treatment and counseling as indicated. STRENGTHS AND LIMITATIONS: Strengths of the study include the large cohort, the use of validated tools for assessment of ACEs and FSD, and the adjustment for multiple potential confounding factors. Limitations include the cross-sectional study design, recall bias in reporting ACEs and recent abuse, and the low representation of racially and ethnically diverse women in the cohort. CONCLUSION: The study demonstrates an increased risk of sexual inactivity and sexual dysfunction in midlife women who experienced childhood adversity. The sexual dysfunction in women with ACEs seems to be independent of other factors that potentially affect female sexual function in midlife.

Premature Ovarian Insufficiency.

Natural menopause typically occurs between the ages of 46 to 55 years. Premature ovarian insufficiency or premature menopause refers to compromised ovarian follicular activity, occurring spontaneously or because of medical interventions, prior to the age of 40 years. The premature loss of estrogen leads to bothersome menopause symptoms and predisposes the women to multiple long-term health risks including a higher mortality risk. Hormone replacement therapy used until the natural age of menopause can help manage the symptoms effectively and can mitigate the long-term risk of estrogen deprivation to some extent. However, hormone replacement therapy is underutilized in this population due to the inappropriate extrapolation of potential risks that have been demonstrated with hormone therapy use in women after natural menopause. There is a large unmet need for educating patients and providers regarding the impact of premature ovarian insufficiency and the compelling need for its appropriate management.

Synergistic interactions of obesity with sex, education, and smoking and accumulation of multi-morbidity (MM) across the lifespan.

Objectives: Obesity is a potentially modifiable risk factor that has been consistently associated with the development and progression of multi-morbidity (MM). However, obesity may be more problematic for some persons compared to others because of interactions with other risk factors. Therefore, we studied the effect of interactions between patient characteristics and overweight and obesity on the rate of accumulation of MM. Methods: We studied 4 cohorts of persons ages 20-, 40-, 60-, and 80-years residing in Olmsted County, Minnesota between 2005 and 2014 using the Rochester Epidemiology Project (REP) medical records-linkage system. Body mass index, sex, race, ethnicity, education, and smoking status were extracted from REP indices. The rate of accumulation of MM was calculated as the number of new chronic conditions accumulated per 10 person years through 2017. Poisson rate regression models were used to identify associations between characteristics and rate of MM accumulation. Additive interactions were summarized using relative excess risk due to interaction, attributable proportion of disease, and the synergy index. Results: Greater than additive synergistic associations were observed between female sex and obesity in the 20- and 40-year cohorts, between low education and obesity in the 20-year cohort (both sexes), and between smoking and obesity in the 40-year cohort (both sexes). Conclusions: Interventions targeted at women, persons with lower education, and smokers who also have obesity may result in the greatest reduction in the rate of MM accumulation. However, interventions may need to focus on persons prior to mid-life to have the greatest effect.

Frequency and type of premature or early menopause in a geographically defined American population.

OBJECTIVE: There is limited information on the prevalence of premature and early menopause. Therefore, we studied the frequency and type of premature (age < 40 years) or early (age 40-44 years) menopause in a geographically-defined American population. METHODS: We studied a random sample of women aged 18 to 50 years who resided in Olmsted County, MN between 1988 and 2007. Women were followed through December 2021, and age at cessation of menses was assessed via review of the medical records included in a medical records-linkage system. Menopause was defined as cessation of menses due to spontaneous or induced ovarian insufficiency. RESULTS: 1015 women (71.3 %) underwent spontaneous menopause, 138 (9.7 %) underwent bilateral oophorectomy, 17 (1.2 %) had antecedent chemotherapy or radiation therapy, and 254 (17.8 %) underwent hysterectomy or endometrial ablation. The median age at cessation of menses was 51.0 years (IQR, 49.0-52.0) for spontaneous menopause, 46.0 years (IQR, 41.0-49.0) for menopause induced by oophorectomy, chemotherapy, or radiation therapy, and 38.0 years (IQR, 33.0-44.0) for hysterectomy. Considering both spontaneous and induced menopause, the frequency was 3.1 % (95 % CI, 2.2-4.2) for premature and 6.2 % (95 % CI, 5.0-7.8) for early menopause. Considering only spontaneous menopause, the frequency reduced to 0.4 % (95 % CI, 0.2-1.0) for premature and 5.2 % (95 % CI, 4.0-6.8) for early menopause. However, considering all types of cessations of menses, the frequency was 12.2 % (95 % CI, 10.6-14.0) for premature and 9.7 % (95 % CI, 8.3-11.3) for early cessation of menses. DISCUSSION: Approximately 3 % of women in the general population experienced either spontaneous or induced premature menopause. The most common cause of premature menopause was bilateral oophorectomy.

Vasomotor Symptoms During Menopause: A Practical Guide on Current Treatments and Future Perspectives.

Vasomotor symptoms affect as many as 80% of midlife women, but only about one in four women receive treatment due to many factors. Menopausal hormone therapy remains the most effective treatment for vasomotor symptoms, and current professional guidelines conclude that the benefits of treatment typically outweigh the risks for healthy, symptomatic women under age 60 years and those within 10 years from their final menstrual period. For women with medical comorbidities, an individualized approach to treatment is recommended. For women who cannot use or choose not to use menopausal hormone therapy, there are many evidence-based non-hormonal options available including pharmacologic therapies. This review aims to summarize treatment options for bothersome vasomotor symptoms to guide clinicians caring for midlife women.

Migraine and sleep quality: does the association change in midlife women?

OBJECTIVE: The aim of this study was to compare the association between migraine and sleep quality in premenopausal versus perimenopausal women. METHODS: A cross-sectional analysis from the Data Registry on the Experiences of Aging, Menopause and Sexuality was conducted using questionnaire data from premenopausal and perimenopausal women seen at women's health clinics at 3 geographic locations from 2015 to 2021. Sleep quality and duration were assessed with the Pittsburgh Sleep Quality Index. Associations between poor sleep quality (Pittsburgh Sleep Quality Index >5) and self-reported migraine history (Y/N) were evaluated using a multivariable logistic regression model, adjusting for body mass index, anxiety, depression, and vasomotor symptoms. RESULTS: Of 2,067 women (mean age 43.2 years) included in the analysis, 594 (28.7%) reported a migraine history. Women were mostly white (92.2%), partnered (75.1%), and educated (86% with at least some college); 46.5% (n = 962) were premenopausal, 53.5% (n = 1,105) were perimenopausal, and 71.2% met the criteria for poor sleep. In univariate analysis, migraine history predicted poor sleep in both premenopausal and perimenopausal women ( P = 0.005 and P = 0.004, respectively). However, in multivariable analysis, migraine history remained associated with poor sleep in premenopausal women ( P = 0.044), but not in perimenopausal women ( P = 0.46). CONCLUSIONS: A migraine history was associated with poor sleep in premenopausal women. The relationship in perimenopausal women seemed to be influenced by confounding factors that are more prevalent during the menopause transition and are known to affect the frequency of migraine and sleep disturbances, such as anxiety, depression, and vasomotor symptoms. These conditions may need to be the focus of management in migraineurs with sleep disturbances during the menopause transition.

Oral Delivery of Nucleic Acid Therapies for Local and Systemic Action.

Nucleic acid (NA) therapy has gained importance over the past decade due to its high degree of selectivity and minimal toxic effects over conventional drugs. Currently, intravenous (IV) or intramuscular (IM) formulations constitute majority of the marketed formulations containing nucleic acids. However, oral administration is traditionally preferred due to ease of administration as well as higher patient compliance. To leverage the benefits of oral delivery for NA therapy, the NA of interest must be delivered to the target site avoiding all degrading and inhibiting factors during its transition through the gastrointestinal tract. The oral route presents myriad of challenges to NA delivery, making formulation development challenging. Researchers in the last few decades have formulated various delivery systems to overcome such challenges and several reviews summarize and discuss these strategies in detail. However, there is a need to differentiate between the approaches based on target so that in future, delivery strategies can be developed according to the goal of the study and for efficient delivery to the desired site. The goal of this review is to summarize the mechanisms for target specific delivery, list and discuss the formulation strategies used for oral delivery of NA therapies and delineate the similarities and differences between local and systemic targeting oral delivery systems and current challenges.