Importance
Menopause is defined as the cessation of a person's menstrual cycle. It is defined retrospectively, 12 months after the final menstrual period. Perimenopause, or the menopausal transition, is the few-year time period preceding a person's final menstrual period and is characterized by increasing menstrual cycle length variability and periods of amenorrhea, and often symptoms such as vasomotor dysfunction. The prevalence and incidence of most chronic diseases (eg, cardiovascular disease, cancer, osteoporosis, and fracture) increase with age, and US persons who reach menopause are expected on average to live more than another 30 years.


Objective
To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal persons and whether outcomes vary by age or by timing of intervention after menopause.


Population
Asymptomatic postmenopausal persons who are considering hormone therapy for the primary prevention of chronic medical conditions.


Evidence Assessment
The USPSTF concludes with moderate certainty that the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons with an intact uterus has no net benefit. The USPSTF concludes with moderate certainty that the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy has no net benefit.


Recommendation
The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy. (D recommendation).

/pdf/hormone-therapy-for-the-primary-prevention-of-chronic-vleyct6m.pdf

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: US Preventive Services Task Force Recommendation Statement.

Importance
It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers.


Objective
To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions.


Data Sources
PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022.


Study Selection
English-language randomized clinical trials and prospective cohort studies of fair or good quality.


Data Extraction and Synthesis
Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available.


Main Outcomes and Measures
Morbidity and mortality related to chronic conditions; health-related quality of life.


Results
Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year.


Conclusions and Relevance
Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance
Current prevalence of obstructive sleep apnea (OSA) in the US is not well established; however, based on cohort and survey data, in 2007-2010 the estimated prevalence of at least mild OSA (defined as an apnea-hypoxia index [AHI] ≥5) plus symptoms of daytime sleepiness among adults aged 30 to 70 years was 14% for men and 5% for women, and the estimated prevalence of moderate to severe OSA (defined as AHI ≥15) was 13% for men and 6% for women. Severe OSA is associated with increased all-cause mortality. Other adverse health outcomes associated with untreated OSA include cardiovascular disease and cerebrovascular events, type 2 diabetes, cognitive impairment, decreased quality of life, and motor vehicle crashes.


Objective
To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for OSA in adults.


Population
Asymptomatic adults (18 years or older) and adults with unrecognized symptoms of OSA.


Evidence Assessment
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for OSA in the general adult population.


Recommendation
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for OSA in the general adult population. (I statement).

Screening for Obstructive Sleep Apnea in Adults: US Preventive Services Task Force Recommendation Statement.

Objectives This study assessed the effects of obstructive sleep apnea (OSA) on mental health, health-related quality of life (HRQoL), and multimorbidity in Korean adults. Methods The study included 8030 participants from the Korea National Health and Nutrition Examination Survey Ⅷ (2019–2020). The risk of OSA was assessed using STOP-BANG questionnaire. Depression was measured using the Patient Health Questionnaire-9 (PHQ-9), and stress was measured using a questionnaire. HRQoL was determined by EuroQol 5-dimension (EQ-5D) and Health-related Quality of Life Instrument with 8 Items (HINT-8) scores. Multimorbidity was defined as the presence of 2 or more chronic diseases. A complex sample multivariate logistic regression analysis was conducted. Results Participants with a high OSA risk were more likely to a have high PHQ-9 score (OR 4.31, 95% confidence interval [CI] 2.80–6.65), total depression (OR 4.07, 95% CI 2.67–6.19) stress (OR 2.33, 95% CI 1.85–2.95), lower EQ-5D (OR 2.88, 95% CI 2.00–4.15) and HINT-8 scores (OR 2.87, 95% CI 1.65–4.98), and multimorbidity (OR 2.62, 95% CI 2.01–3.41) than participants with low OSA risk. High OSA risk was significantly associated with all EQ-5D and HINT-8 items. Conclusions This study adds to the few population-based studies showing associations between mental health, HRQoL, and multimorbidity using nationwide data. OSA prevention might be helpful for good mental health, improving HRQoL, and comorbidity burdens. The results provide novel insights regarding the association between sleep apnea and multimorbidity.

/pdf/obstructive-sleep-apnea-related-to-mental-health-health-1inasd37.pdf

Obstructive sleep apnea related to mental health, health-related quality of life and multimorbidity: A nationwide survey of a representative sample in Republic of Korea

Over the past 2 decades, the US Preventive Services Task Force (USPSTF) has issued 5 updates to its recommendation on menopausal hormone therapy (MHT), each time recommending against use of estrogen with or without a progestin for prevention of chronic conditions such as coronary heart disease (CHD). The first of these appeared in 2002, shortly after the first Women’s Health Initiative (WHI) trial enrolling more than 16 000 US women aged 50 to 79 years from 40 clinical centers reported an unfavorable overall benefit-to-risk ratio of postmenopausal estrogen with progestin for primary prevention of chronic diseases,1 followed by another update in 2005 after the WHI estrogen-only trial enrolling more than 10 000 additional women drew similar conclusions for unopposed estrogen.2 The next was in 2012, after findings from longerterm follow-up and subgroup analyses from the WHI3,4 and other smaller trials supported the same conclusions. In 2017, the task force reissued its recommendation, again based on substantially the same evidence.5 Now in 2022, after additional review of only 2 additional modest-sized trials6,7 as well as ancillary analyses of previous trials, the USPSTF has, for the fifth time, reiterated its guideline.8 After all this time, some may wonder why a repeat statement of this same recommendation is necessary. Isn’t enough, enough? Are there still clinicians who believe, despite the preponderance of evidence to the contrary, that MHT offers a net preventive benefit for postmenopausal persons? Do any important questions about MHT as a preventive intervention remain? Arguably not. Some menopausal women and their clinicians continue to ask whether MHT may offer preventive benefits in younger postmenopausal patients, even if the net harms outweighed benefits for older women such as those enrolled in the WHI and similar trials. Most of these persistent questions center on the potential implications of timing of MHT, namely, whether the use of hormones in the first few years after menopause may offer beneficial preventive effects, even if continued use more than 5 or 10 years after menopause may result in net harm. But as the updated review of evidence supporting the 2022 USPSTF recommendation update indicates,9 there is little rigorous evidence to support this timing hypothesis. Women in the WHI trials who were aged 50 to 59 years did not have a statistically significant increased risk of CHD events (hazard ratio, 0.93 [95% CI, 0.65-1.33]) or stroke (hazard ratio, 1.13 [95% CI, 0.73-1.76]), but the numbers of these events in this subgroup of younger women were small, and no statistically significant differences in event rates by age were detected (P values for trend, 0.16 to 0.62).10 The 2 most recent trials that were added to the USPSTF evidence base, focusing primarily on the question of cognitive effects of MHT, were modest in size compared with the WHI, focused on surrogate end points rather than clinical events, and have yielded inconsistent findings.6,7 And for other conditions such as cancer, analyses of WHI data suggest that use of estrogen worsens cancer risk when initiated in the early rather than later postmenopausal years.11 Even if new and robust evidence were to emerge that MHT offers a net preventive benefit when used exclusively within a short period after menopause, the medical community would still be in a quandary. How could clinicians and patients navigate use of an intervention that might initially offer protection against CHD only to reverse its effects at some uncertain (and probably impossible to precisely identify) future time? No precedent exists for starting a preventive medication in a large cross-section of the general population with the expectation of discontinuing it before its effects change diametrically to worsen the same health problems it was designed to prevent. At the same time, it is important to recognize that the USPSTF, faithful to its mandate, has focused its recommendation on use of MHT for chronic disease prevention, not for treatment of symptoms of menopause. And yet its recommendations, along with the study results on which they are based, have made many women and their clinicians reluctant to consider MHT for treatment of menopausal symptoms.12 These include vasomotor symptoms (hot flashes and night sweats), which affect up to three-fourths of US menopausal women, persist for more than 10 years in up to 10% of women,13 and have detrimental effects on sleep, day-to-day activities, mood, and well-being. Despite the efforts of the USPSTF to draw a clear distinction between MHT for prevention vs symptom management, many patients and clinicians conflate these 2 different indications. The notion that “the net harms of MHT outweigh the benefits,” originally intended to explain the limitations of MHT for routine prevention, is now widely adopted as a rationale for forgoing MHT for symptomatic treatment. For prevention, a pillar of the USPSTF recommendation is that for major chronic conditions for which MHT does offer benefits (such as prevention of osteoporosis), there are effective and safe alternatives (such as bisphosphonates). But for menopausal symptoms like hot flashes and night sweats, nonhormonal treatments that are as efficacious as MHT have not yet been identified. Furthermore, the approach to weighing risks should differ when MHT is used for symptom relief in acutely afflicted individuals as opposed to disease prevention Related articles pages 1740 and 1747 and JAMA Patient Page page 1780 Opinion

Menopausal Hormone Therapy for Prevention of Chronic Conditions: When Is Enough, Enough?

Importance
Obstructive sleep apnea (OSA) is associated with adverse health outcomes.


Objective
To review the evidence on screening for OSA in asymptomatic adults or those with unrecognized OSA symptoms to inform the US Preventive Services Task Force.


Data Sources
PubMed/MEDLINE, Cochrane Library, Embase, and trial registries through August 23, 2021; surveillance through September 23, 2022.


Study Selection
English-language studies of screening test accuracy, randomized clinical trials (RCTs) of screening or treatment of OSA reporting health outcomes or harms, and systematic reviews of treatment reporting changes in blood pressure and apnea-hypopnea index (AHI) scores.


Data Extraction and Synthesis
Dual review of abstracts, full-text articles, and study quality. Meta-analysis of intervention trials.


Main Outcomes and Measures
Test accuracy, excessive daytime sleepiness, sleep-related and general health-related quality of life (QOL), and harms.


Results
Eighty-six studies were included (N = 11 051). No study directly compared screening with no screening. Screening accuracy of the Multivariable Apnea Prediction score followed by unattended home sleep testing for detecting severe OSA syndrome (AHI ≥30 and Epworth Sleepiness Scale [ESS] score >10) measured as the area under the curve in 2 studies (n = 702) was 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90). Five studies assessing the accuracy of other screening tools were heterogeneous and results were inconsistent. Compared with inactive control, positive airway pressure was associated with a significant improvement in ESS score from baseline (pooled mean difference, -2.33 [95% CI, -2.75 to -1.90]; 47 trials; n = 7024), sleep-related QOL (standardized mean difference, 0.30 [95% CI, 0.19 to 0.42]; 17 trials; n = 3083), and general health-related QOL measured by the 36-Item Short Form Health Survey (SF-36) mental health component summary score change (pooled mean difference, 2.20 [95% CI, 0.95 to 3.44]; 15 trials; n = 2345) and SF-36 physical health component summary score change (pooled mean difference, 1.53 [95% CI, 0.29 to 2.77]; 13 trials; n = 2031). Use of mandibular advancement devices was also associated with a significantly larger ESS score change compared with controls (pooled mean difference, -1.67 [95% CI, 2.09 to -1.25]; 10 trials; n = 1540). Reporting of other health outcomes was sparse; no included trial found significant benefit associated with treatment on mortality, cardiovascular events, or motor vehicle crashes. In 3 systematic reviews, positive airway pressure was significantly associated with reduced blood pressure; however, the difference was relatively small (2-3 mm Hg).


Conclusions and Relevance
The accuracy and clinical utility of OSA screening tools that could be used in primary care settings were uncertain. Positive airway pressure and mandibular advancement devices reduced ESS score. Trials of positive airway pressure found modest improvement in sleep-related and general health-related QOL but have not established whether treatment reduces mortality or improves most other health outcomes.

Manny Schwimmer

Papers

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Screening for Obstructive Sleep Apnea in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.