ContextAlthough postmenopausal hormone replacement therapy (HRT) is widely
used in the United States, new evidence about its benefits and harms requires
reconsideration of its use for the primary prevention of chronic conditions.ObjectiveTo assess the benefits and harms of HRT for the primary prevention of
cardiovascular disease, thromboembolism, osteoporosis, cancer, dementia, and
cholecystitis by reviewing the literature, conducting meta-analyses, and calculating
outcome rates.Data SourcesAll relevant English-language studies were identified in MEDLINE (1966-2001),
HealthSTAR (1975-2001), Cochrane Library databases, and reference lists of
key articles. Recent results of the Women's Health Initiative (WHI) and the
Heart and Estrogen/progestin Replacement Study (HERS) are included for reported
outcomes.Study Selection and Data ExtractionWe used all published studies of HRT if they contained a comparison
group of HRT nonusers and reported data relating to HRT use and clinical outcomes
of interest. Studies were excluded if the population was selected according
to prior events or presence of conditions associated with higher risks for
targeted outcomes.Data SynthesisMeta-analyses of observational studies indicated summary relative risks
(RRs) for coronary heart disease (CHD) incidence and mortality that were significantly
reduced among current HRT users only, although risk for incidence was not
reduced when only studies that controlled for socioeconomic status were included.
The WHI reported increased CHD events (hazard ratio [HR], 1.29; 95% confidence
interval [CI], 1.02-1.63). Stroke incidence but not mortality was significantly
increased among HRT users in the meta-analysis and the WHI. The meta-analysis
indicated that risk was significantly elevated for thromboembolic stroke (RR,
1.20; 95% CI, 1.01-1.40) but not subarachnoid or intracerebral stroke. Risk
of venous thromboembolism among current HRT users was increased overall (RR,
2.14; 95% CI, 1.64-2.81) and was highest during the first year of use (RR,
3.49; 95% CI, 2.33-5.59) according to a meta-analysis of 12 studies. Protection
against osteoporotic fractures is supported by a meta-analysis of 22 estrogen
trials, cohort studies, results of the WHI, and trials with bone density outcomes.
Current estrogen users have an increased risk of breast cancer that increases
with duration of use. Endometrial cancer incidence, but not mortality, is
increased with unopposed estrogen use but not with estrogen with progestin.
A meta-analysis of 18 observational studies showed a 20% reduction in colon
cancer incidence among women who had ever used HRT (RR, 0.80; 95% CI, 0.74-0.86),
a finding supported by the WHI. Women symptomatic from menopause had improvement
in certain aspects of cognition. Current studies of estrogen and dementia
are not definitive. In a cohort study, current HRT users had an age-adjusted
RR for cholecystitis of 1.8 (95% CI, 1.6-2.0), increasing to 2.5 (95% CI,
2.0-2.9) after 5 years of use.ConclusionsBenefits of HRT include prevention of osteoporotic fractures and colorectal
cancer, while prevention of dementia is uncertain. Harms include CHD, stroke,
thromboembolic events, breast cancer with 5 or more years of use, and cholecystitis.

https://jamanetwork.com/journals/jama/articlepdf/195214/JSR20014.pdf

Postmenopausal Hormone Replacement Therapy: Scientific Review

OBSTRUCTIVE SLEEP APNEA (OSA) is a sleep disorder characterized by intermittent complete and partial airway collapse, resulting in frequent episodes of apnea and hypopnea. The breathing pauses cause acute adverse effects, including oxyhemoglobin desaturation, fluctuations in blood pressure and heart rate, increased sympathetic activity, cortical arousal, and sleep fragmentation. The condition has received increasing attention during the past 3 decades. Until 1981, the only effective treatment for OSA was tracheostomy. The advent of continuous positive air pressure therapy, an effective noninvasive treatment, was a turning point, and clinical interest began to increase in tandem with the accumulation of research linking OSA to cognitive, behavioral, cardiovascular, and cerebrovascular morbidities (FIGURE). Findings from large population studies in different countries during the last decade have contributed to a better understanding of the epidemiology of OSA. In most population studies, OSA status has been indicated by the frequency of apnea and hypopnea events per hour of sleep (apnea-hypopnea index) as determined by polysomnography (a continuous overnight recording of sleep, breathing, and cardiac parameters). The apnea-hypopnea index cutpoints of 5, 15, and 30 (with or without daytime sleepiness) are commonly used to indicate mild, moderate, and severe OSA, respectively. These studies have demonstrated that OSA is highly prevalent in adults (TABLE). Approximately 1 in 5 adults has at least mild OSA and 1 in 15 adults has OSA of moderate or worse severity. In the United States, 75% to 80% of OSA cases that could benefit from treatment remain undiagnosed. Associations of OSA with serious morbidity have raised concern that untreated OSA is a substantial but underappreciated public health threat. Primary care physicians are currently being encouraged to be alert to OSA symptoms of disruptive snoring, breathing pauses, and excessive daytime sleepiness in their patients. It is important that physicians also recognize that not all OSA patients are “Pickwickian” (ie, male, obese, sleepy, snoring, and middle-aged), a stereotype that emerged from clinical observations of the highly selective patient populations observed in earlier years. The goal of this article is to review recent findings from populationbased epidemiology studies on risk factors for OSA in adults.

Risk Factors for Obstructive Sleep Apnea in Adults

ContextObservational studies have suggested that postmenopausal hormone treatment
may improve cognitive function, but data from randomized clinical trials have
been sparse and inconclusive The Women's Health Initiative Memory Study (WHIMS)
is an ancillary study of the Women's Health Initiative (WHI) hormone therapy
trials On July 8, 2002, the estrogen plus progestin therapy in the WHI trial
was discontinued because of certain increased health risks for womenObjectiveTo determine whether estrogen plus progestin therapy protects global
cognitive function in older postmenopausal womenDesign, Setting, and ParticipantsA randomized, double-blind, placebo-controlled clinical trial, WHIMS
is an ancillary study of geographically diverse, community-dwelling women
aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen
plus progestin trial that started in June 1995 Of 4894 eligible postmenopausal
women aged 65 years or older and free of probable dementia at baseline, 4532
(926%) were enrolled in the estrogen plus progestin component of WHIMS A
total of 4381 participants (967%) provided at least 1 valid cognitive function
score between June 1995 and July 8, 2002InterventionsParticipants received either 1 daily tablet containing 0625 mg of conjugated
equine estrogen with 25 mg of medroxyprogesterone acetate (n = 2145) or matching
placebo (n = 2236)Main Outcome MeasureGlobal cognitive function measured annually with the Modified Mini-Mental
State ExaminationResultsThe Modified Mini-Mental State Examination mean total scores in both
groups increased slightly over time (mean follow-up of 42 years) Women in
the estrogen plus progestin group had smaller average increases in total scores
compared with women receiving placebo (P = 03),
but these differences were not clinically important Removing women by censoring
them after adjudicated dementia, mild cognitive impairment, or stroke, and
nonadherence to study protocol, did not alter the findings Prior hormone
therapy use and duration of prior use did not affect the interpretation of
the results, nor did timing of prior hormone therapy initiation with respect
to the final menstrual period More women in the estrogen plus progestin group
had a substantial and clinically important decline (≥2 SDs) in Modified
Mini-Mental State Examination total score (67%) compared with the placebo
group (48%) (P = 008)ConclusionsAmong postmenopausal women aged 65 years or older, estrogen plus progestin
did not improve cognitive function when compared with placebo While most
women receiving estrogen plus progestin did not experience clinically relevant
adverse effects on cognition compared with placebo, a small increased risk
of clinically meaningful cognitive decline occurred in the estrogen plus progestin
group

https://jamanetwork.com/journals/jama/articlepdf/196627/JOC30764.pdf

Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.

Study objective Most but not all epidemiologic evidence suggests a female predisposition of insomnia. We applied meta-analytic methods to investigate sex differences in the risk of insomnia among the published epidemiologic studies. Design Meta-analysis with Comprehensive Meta-Analysis (Englewood, NJ); 9 different analyses were performed to investigate the sex difference of insomnia among different conditions. Setting A comprehensive search of the medical literature databases was performed to identify epidemiologic studies of insomnia. A rolling snowball method was also used. Participants General population. Interventions N/A. Result Thirty-one related papers were found, but 2 studies only reported the subtype prevalence of insomnia. All other studies (1,265,015 participants, female/male: 718,828/546,187) were included in the overall analysis of insomnia. A risk ratio of 1.41 [95% confidence interval: 1.28-1.55] for female versus male was found. The female excess in the risk of insomnia in large and quality studies was much higher than that of small and nonquality studies. The trend of female predisposition was consistent and progressive across age, with more significance in the elderly. The use of various criteria and frequency and duration of insomnia did not influence the predisposition of female in the risk of developing insomnia. Although obvious female excess in the risk of insomnia exists among different regions, there was a relatively lower female excess in East Asia. Conclusion This meta-analysis confirmed a female predisposition of insomnia. Further studies will be needed to examine the roles of different factors in leading to the sex difference of insomnia.

/pdf/sex-differences-in-insomnia-a-meta-analysis-1hztp2jllg.pdf

Sex differences in insomnia: a meta-analysis.

The 2017 Hormone Therapy Position Statement of The North American Menopause Society (NAMS) updates the 2012 Hormone Therapy Position Statement of The North American Menopause Society and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women's health and menopause was recruited by NAMS to review the 2012 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees. Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM) and has been shown to prevent bone loss and fracture. The risks of HT differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized to identify the most appropriate HT type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing HT. For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome VMS and for those at elevated risk for bone loss or fracture. For women who initiate HT more than 10 or 20 years from menopause onset or are aged 60 years or older, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS or bone loss, with shared decision making and periodic reevaluation. For bothersome GSM symptoms not relieved with over-the-counter therapies and without indications for use of systemic HT, low-dose vaginal estrogen therapy or other therapies are recommended. This NAMS position statement has been endorsed by Academy of Women's Health, American Association of Clinical Endocrinologists, American Association of Nurse Practitioners, American Medical Women's Association, American Society for Reproductive Medicine, Asociacion Mexicana para el Estudio del Climaterio, Association of Reproductive Health Professionals, Australasian Menopause Society, Chinese Menopause Society, Colegio Mexicano de Especialistas en Ginecologia y Obstetricia, Czech Menopause and Andropause Society, Dominican Menopause Society, European Menopause and Andropause Society, German Menopause Society, Groupe d’etudes de la menopause et du vieillissement Hormonal, HealthyWomen, Indian Menopause Society, International Menopause Society, International Osteoporosis Foundation, International Society for the Study of Women's Sexual Health, Israeli Menopause Society, Japan Society of Menopause and Women's Health, Korean Society of Menopause, Menopause Research Society of Singapore, National Association of Nurse Practitioners in Women's Health, SOBRAC and FEBRASGO, SIGMA Canadian Menopause Society, Societa Italiana della Menopausa, Society of Obstetricians and Gynaecologists of Canada, South African Menopause Society, Taiwanese Menopause Society, and the Thai Menopause Society. The American College of Obstetricians and Gynecologists supports the value of this clinical document as an educational tool, June 2017. The British Menopause Society supports this Position Statement.

The 2017 hormone therapy position statement of The North American Menopause Society.

Today, prolonged wakefulness is a widespread phenomenon. Nevertheless, in the field of sleep and wakefulness, several unanswered questions remain. Prolonged wakefulness can be due to acute total sleep deprivation (SD) or to chronic partial sleep restriction. Although the latter is more common in everyday life, the effects of total SD have been examined more thoroughly. Both total and partial SD induce adverse changes in cognitive performance. First and foremost, total SD impairs attention and working memory, but it also affects other functions, such as long-term memory and decision-making. Partial SD is found to influence attention, especially vigilance. Studies on its effects on more demanding cognitive functions are lacking. Coping with SD depends on several factors, especially aging and gender. Also interindividual differences in responses are substantial. In addition to coping with SD, recovering from it also deserves attention. Cognitive recovery processes, although insufficiently studied, seem to be more demanding in partial sleep restriction than in total SD.

Päivi Polo-Kantola

Papers

Sleep deprivation: Impact on cognitive performance

When does estrogen replacement therapy improve sleep quality

Women's sleep in health and disease

The effect of short-term estrogen replacement therapy on cognition: a randomized, double-blind, cross-over trial in postmenopausal women.

Sleep problems in midlife and beyond