Women's Health Initiative

CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.

BACKGROUND: Fine particulate air pollution has been linked to cardiovascular disease, but previous studies have assessed only mortality and differences in exposure between cities. We examined the association of long-term exposure to particulate matter of less than 2.5 microm in aerodynamic diameter (PM2.5) with cardiovascular events. METHODS: We studied 65,893 postmenopausal women without previous cardiovascular disease in 36 U.S. metropolitan areas from 1994 to 1998, with a median follow-up of 6 years. We assessed the women's exposure to air pollutants using the monitor located nearest to each woman's residence. Hazard ratios were estimated for the first cardiovascular event, adjusting for age, race or ethnic group, smoking status, educational level, household income, body-mass index, and presence or absence of diabetes, hypertension, or hypercholesterolemia. RESULTS: A total of 1816 women had one or more fatal or nonfatal cardiovascular events, as confirmed by a review of medical records, including death from coronary heart disease or cerebrovascular disease, coronary revascularization, myocardial infarction, and stroke. In 2000, levels of PM2.5 exposure varied from 3.4 to 28.3 microg per cubic meter (mean, 13.5). Each increase of 10 microg per cubic meter was associated with a 24% increase in the risk of a cardiovascular event (hazard ratio, 1.24; 95% confidence interval [CI], 1.09 to 1.41) and a 76% increase in the risk of death from cardiovascular disease (hazard ratio, 1.76; 95% CI, 1.25 to 2.47). For cardiovascular events, the between-city effect appeared to be smaller than the within-city effect. The risk of cerebrovascular events was also associated with increased levels of PM2.5 (hazard ratio, 1.35; 95% CI, 1.08 to 1.68). CONCLUSIONS: Long-term exposure to fine particulate air pollution is associated with the incidence of cardiovascular disease and death among postmenopausal women. Exposure differences within cities are associated with the risk of cardiovascular disease.

CONTEXT: The timing of initiation of hormone therapy may influence its effect on cardiovascular disease. OBJECTIVE: To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began. DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate (CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998. MAIN OUTCOME MEASURES: Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials. RESULTS: In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [corrected] cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 (95% CI, 0.84-1.45); and 20 or more years, 1.28 (95% CI, 1.03-1.58) (P for trend = .02). The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years; for women 10 to 19 years since menopause began, 4 per 10,000 person-years; and for women 20 or more years from menopause onset, 17 per 10,000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 (95% CI, 0.65-1.33) and the absolute excess risk was -2 per 10,000 person-years; 60 to 69 years, 0.98 (95% CI, 0.79-1.21) and -1 per 10,000 person-years; and 70 to 79 years, 1.26 (95% CI, 1.00-1.59) and 19 per 10,000 person-years (P for trend = .16). Hormone therapy increased the risk of stroke (HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women (HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend = .06). CONCLUSIONS: Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.

Coronary heart disease (CHD), the commonest cause of death worldwide, is highly heritable, but the DNA sequence variations associated with elevated cardiovascular risk are largely unknown. The investigators planned a genome-wide associational study based on 100,000 single nucleotide polymorphisms and involving 3 sequential case-control comparisons made at a nominal significance threshold of P < 0.025. The study population included more than 23,000 participants from 4 Caucasian populations. Cases had severe, premature CHD starting before age 60 years and leading to coronary artery revascularization. Controls were healthy Caucasian men over age 65 and women over age 70 who lacked symptoms and a history of CHD. Individuals with diabetes or hypercholesterolemia were excluded. A 58-kilobase interval on chromosome 9p21 was consistently associated with CHD. The interval is near the CDKN2A and CDKN2B genes. It contains no annotated genes and is not associated with established CHD risk factors such as diabetes, plasma lipoproteins, or hypertension. Between 20% and 25% of Caucasians are homozygous for the risk allele, and they have an approximately 30%–40% increased risk of CHD. Mechanisms for the association between the risk allele and CHD remain incompletely understood. The allele might promote the development of atherosclerotic plaque, augment thrombogenesis, or increase the tendency of plaques to rupture. The association persisted after controlling for numerous possible confounding factors including age, gender, plasma lipid levels, blood pressure, diabetes, and plasma levels of C-reactive protein. The researchers believe that the effect of the risk allele on chromosome 9 on CHD is not mediated by established risk factors for cardiovascular disease. The present findings support the use of the whole-genome association approach for studying conditions as complex as CHD.

CONTEXT: Hypoactive sexual desire disorder (HSDD) is one of the most common sexual problems reported by women, but few studies have been conducted to evaluate treatments for this condition. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of a testosterone patch in surgically menopausal women with HSDD. DESIGN: The design was a randomized, double-blind, parallel-group, placebo-controlled, 24-wk study (the Intimate SM 1 study). SETTING: The study was performed at private or institutional practices. PATIENTS: The subjects studied were women, aged 26-70 yr, with HSDD after bilateral salpingo-oophorectomy who were receiving concomitant estrogen therapy. Placebo (n = 279) or testosterone 300 microg/d (n = 283) was administered. There were 19 patients who withdrew due to adverse events in the placebo group and 24 in the 300 mug/d testosterone group. INTERVENTION: Testosterone (300 microg/d) or placebo patches were applied twice weekly. MAIN OUTCOME MEASURE(S): The primary end point was the change in the frequency of total satisfying sexual activity at 24 wk. Secondary end points included other sexual functioning end points and safety assessments. RESULTS: At 24 wk, there was an increase from baseline in the frequency of total satisfying sexual activity of 2.10 episodes/4 wk in the testosterone group, which was significantly greater than the change of 0.98 episodes/4 wk in the placebo group (P = 0.0003). The testosterone group also experienced statistically significant improvements in sexual desire and a decrease in distress. The overall safety profile was similar in both treatment groups. CONCLUSION: In the Intimate SM 1 study, the testosterone patch improved sexual function and decreased distress in surgically menopausal women with HSDD and was well tolerated in this trial.

McKinney, Jessica PT, MS; Keyser, Laura DPT, MPH; Clinton, Susan PT, DSc; Pagliano, Carrie PT, DPT Author Information

OBJECTIVES: To evaluate the association between protein intake and incident frailty. DESIGN: Prospective cohort study. SETTING: Subset of the Women's Health Initiative Observational Study conducted at 40 clinical centers. PARTICIPANTS: Twenty-four thousand four hundred seventeen women aged 65 to 79 who were free of frailty at baseline with plausible self-reported energy intakes (600-5,000 kcal/day) according to the Food Frequency Questionnaire (FFQ). MEASUREMENTS: Baseline protein intake was estimated from the FFQ. Calibrated estimates of energy and protein intake were corrected for measurement error using regression calibration equations estimated from objective measures of total energy expenditure (doubly labeled water) and dietary protein (24-hour urinary nitrogen). After 3 years of follow-up, frailty was defined as having at least three of the following components: low physical function (measured using the Rand-36 questionnaire), exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models estimated associations for uncalibrated and calibrated protein intake. RESULTS: Of the 24,417 eligible women, 3,298 (13.5%) developed frailty over 3 years. After adjustment for confounders, a 20% increase in uncalibrated protein intake (%kcal) was associated with a 12% (95% confidence interval (CI)=8-16%) lower risk of frailty, and a 20% increase in calibrated protein intake was associated with a 32% (95% CI=23-50%) lower risk of frailty. CONCLUSION: Higher protein consumption, as a fraction of energy, is associated with a strong, independent, dose-responsive lower risk of incident frailty in older women. Using uncalibrated measures underestimated the strength of the association. Incorporating more protein into the diet may be an intervention target for frailty prevention.

BACKGROUND: Increasing evidence supports a role for inflammation in the atherosclerotic process. The role of the leukocyte count as an independent predictor of risk of a first cardiovascular disease (CVD) event remains uncertain. Our objective was to describe the relation between the baseline white blood cell (WBC) count and future CVD events and mortality in postmenopausal women. METHODS: In this prospective cohort study set in 40 US clinical centers, the study population comprised 72 242 postmenopausal women aged 50 to 79 years, free of CVD and cancer at baseline, enrolled in the Women's Health Initiative Observational Study. Main outcome measures included incident fatal coronary heart disease (CHD), nonfatal myocardial infarction, stroke, and total mortality. RESULTS: At baseline, the mean +/- SD age of the women was 63 +/- 7.3 years, 84% were white, 4% had diabetes, 35% had hypertension, and 6% were current smokers. The mean WBC count was 5.8 +/- 1.6 x 10(9) cells/L. During a mean of 6.1 years of follow-up, there were 187 CHD deaths, 701 nonfatal myocardial infarctions, 738 strokes, and 1919 deaths from all causes. Compared with women with WBC counts in the first quartile (2.5-4.7 x 10(9) cells/L), women in the fourth quartile (6.7-15.0 x 10(9) cells/L) had over a 2-fold elevated risk for CHD death (hazard ratio, 2.36; 95% confidence interval, 1.51-3.68), after multivariable adjustment for age, race, diabetes, hypertension, smoking, hypercholesterolemia, body mass index, alcohol intake, diet, physical activity, aspirin use, and hormone use. Women in the upper quartile of the WBC count also had a 40% higher risk for nonfatal myocardial infarction, a 46% higher risk for stroke, and a 50% higher risk for total mortality. In multivariable models adjusting for C-reactive protein, the WBC count was an independent predictor of CHD risk, comparable in magnitude to C-reactive protein. CONCLUSIONS: The WBC count, a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, is an independent predictor of CVD events and all-cause mortality in postmenopausal women. A WBC count greater than 6.7 x 10(9) cells/L may identify high-risk individuals who are not currently identified by traditional CVD risk factors.

Journal of Women's HealthVol. 29, No. 4 CommentaryFree AccessSex and Gender Disparities in the COVID-19 PandemicJewel Gausman and Ana LangerJewel GausmanWomen & Health Initiative, Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Search for more papers by this author and Ana LangerAddress correspondence to: Ana Langer, MD, Women & Health Initiative, Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 651 Huntington Avenue, FXB Building 6th Floor Office 643B, Boston, MA 02115 E-mail Address: [email protected]Women & Health Initiative, Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Search for more papers by this authorPublished Online:17 Apr 2020https://doi.org/10.1089/jwh.2020.8472AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail In the case of the ongoing COVID-19 pandemic, sex-disaggregated data suggest that fewer women are dying from the disease than men.1 However, taking this observation at face value oversimplifies the biological, behavioral, and social and systemic factors that may cause differences to emerge with regard to how women and men experience both the disease and its consequences. As governments react with swift and severe measures in their ongoing fight to control the pandemic's spread, it is important to understand how these actions may disproportionately increase the risks for women both directly and indirectly with regard to sex and gender.Pregnant women are often among the most vulnerable groups during public health emergencies. In some cases, pregnant women face increased biological susceptibility to adverse health outcomes, as in the case of some respiratory infections. With other emergent coronaviruses, such as those responsible for severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), pregnant women who became infected were found to be more likely than nonpregnant women to experience severe complications.2 It is still too early to tell whether this will be the case with COVID-19.In the ongoing pandemic, other factors may have a ripple effect that put women at increased risk even if the disease itself does not. As made clear during the 2014 Ebola outbreak, the consequences of large-scale infectious disease outbreaks on uninfected pregnant women can be dire. Routine prenatal care appointments, if not interrupted or discontinued, may put women at increased risk of exposure to the virus. Overwhelmed hospitals struggling to function with staff and supply shortages may not be able to provide the high quality of care that all pregnant women and their newborns deserve, let alone respond to emergency obstetric complications. Furthermore, there is also a risk that life-saving treatments or vaccines will be denied to pregnant women over concern for fetal safety or a lack of data.3,4The fear of infection, concern for the well-being of friends and loved ones, uncertainty, disruption, and social isolation that have become part and parcel of daily life for many around the world will undoubtedly have profound effects on mental health on the population at large, but being pregnant during a global pandemic is likely to be even more frightening for many women. Although containment strategies, such as those that require women to deliver without a companion present, including partners and doulas, that have already been put into place in some cities in the United States,5 or those that separate newborns from their mothers immediately after birth if the mother is infected with COVID-196 may be clinically important to reduce transmission, they may also have profound short- and long-term mental health implications for women. Among women who have young children, previous research in Ethiopia, India, and Vietnam found that women who experience family-related stressful life events, such as illness or death within the household and financial uncertainty, are more likely to experience episodes of severe mental distress.7 With the ongoing need to social distance, family and community networks may struggle and pregnant and postpartum women may feel even more vulnerable and isolated over a lack of social support.The adverse effects of the pandemic in relation to women's reproductive health are not limited to pregnancy or motherhood. As movement restrictions are put into place, supply chains are disrupted, and businesses are shuttered, some women may be at increased risk of unintended pregnancy should it become difficult to obtain their regular contraceptive method or emergency contraceptives, if needed. Furthermore, some states within the United States have begun to impose restrictions on certain medical procedures that they deem to be elective, including abortion, suggesting they must be delayed until after the pandemic is over.8 Spikes in domestic violence during times of crisis are another area of grave concern for women's health, and as governments continue to put into place more extreme measures to enforce social distancing, for some women, more time at home may mean more time spent with an abusive partner. Fewer social interactions may also mean less accountability for perpetrators and fewer opportunities for others to intervene.Gender-related factors may also increase the impact of the COVID-19 pandemic on women globally. Women constitute a disproportionately high percentage of caregivers in both the formal and informal sectors.9 A large proportion of frontline health care professionals (nurses, community health workers, health technicians, etc.) is women who face a higher risk of infection, morbidity, and death as a result of their profession.9 At the same time, women more frequently serve as the primary caregivers within a household, which may further increase their risk of exposure. In the United States, 65% of unpaid family caregivers are estimated to be women and 80% of them care for someone aged 50 years or older.10 Outside of their caregiving role, women are overrepresented in the informal employment sector. In low-and middle-income countries, two-thirds of women who work do so as part of the informal economy with limited access to health care for themselves and their families.9 Containment and mitigation policies that limit women's ability to perform their duties without offering effective alternatives, such as closing of daycare facilities for their children or not providing paid sick leave, may result in unnecessary exposure to disease and increased family vulnerability.It is urgent that we adopt a gender lens to study the pandemic and its effects, including the policies and actions that are put into place at the global, country, and local levels. This may be especially important in disadvantaged populations and resource-poor communities, where women are especially vulnerable. The public health community must ensure that existing health and social services meant to support women in the face of their unique needs do not disappear in lieu of the all-encompassing focus on stopping the pandemic. Furthermore, we argue that special attention needs to be paid to ensure that informal caregivers are supported, informed, and protected. To avoid making existing gender disparities larger as a result of the pandemic, a special body at the U.S. Centers of Disease Control and Prevention is urgently needed to track sex disaggregated data and analyze policies related to COVID-19 using a gender lens.Author Disclosure StatementNo competing financial interests exist.Funding InformationNo funding was received for this article.References1. Cai H. Sex difference and smoking predisposition in patients with COVID-19. Lancet Respir Med 2020;pii: S2213-2600(20)30117-X. Medline, Google Scholar2. Favre G, Pomar L, Musso D, Baud D. 2019-nCoV epidemic: What about pregnancies? Lancet 2020;395:e40. Crossref, Medline, Google Scholar3. Rasmussen SA, Smulian JC, Lednicky JA, Wen TS, Jamieson DJ. Coronavirus disease 2019 (COVID-19) and pregnancy: What obstetricians need to know. Am J Obstet Gynecol 2020;pii: S0002-9378(20)30197-6. Medline, Google Scholar4. Weigel G. Novel coronavirus "COVID-19": Special considerations for pregnant women. Available at: https://www.kff.org/womens-health-policy/issue-brief/novel-coronavirus-covid-19-special-considerations-for-pregnant-women/?utm_source=Global+Health+NOW+Main+List Accessed March 17, 2020. Google Scholar5. Caron C, Syckle KV. Laboring alone: Some hospitals bar partners because of virus fears. The New York Times. 2020. Google Scholar6. American College of Obstetricians and Gynecologists. Practice advisory: Novel coronavirus 2019 (COVID-19). Available at: https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Novel-Coronavirus2019?IsMobileSet=false Accessed March 13, 2020. Google Scholar7. Gausman J, Austin SB, Subramanian S, Langer A. Adversity, social capital, and mental distress among mothers of small children: A cross-sectional study in three low and middle-income countries. PLoS One 2020;15:e0228435. Crossref, Medline, Google Scholar8. Tavernise S. Texas and Ohio include abortion as medical procedures that must be delayed. The New York Times. 2020. Google Scholar9. Langer A, Meleis A, Knaul FM, et al. Women and health: The key for sustainable development. Lancet 2015;386:1165–1210. Crossref, Medline, Google Scholar10. Feinberg L, Reinhard SC, Houser A, Choula R. Valuing the invaluable: 2011 update, the growing contributions and costs of family caregiving. Washington, DC: AARP Public Policy Institute, 2011:32. 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Public Health, Vol. 19, No. 19Syndemic aspects between COVID-19 pandemic and social inequalitiesWorld Journal of Methodology, Vol. 12, No. 5Impact of Social and Personal Factors on Psychological Distress in the Spanish Population in the COVID-19 Crisis9 September 2022 | The British Journal of Social Work, Vol. 28(Suppl 1)Levels of Depression and Anxiety Among Informal Caregivers During the COVID-19 Pandemic: A Study Based on the Canadian Longitudinal Study on Aging12 February 2022 | The Journals of Gerontology: Series B, Vol. 77, No. 9Knowledge, attitudes, and practices [KAP] toward COVID-19: A cross-sectional study in the New York Metropolitan Area and California Bay Area10 August 2022 | PLOS ONE, Vol. 17, No. 8Examining the impact of sex differences and the COVID-19 pandemic on health and health care: findings from a national cross-sectional study28 September 2022 | JAMIA Open, Vol. 5, No. 3Combination of cycle threshold time, absolute lymphocyte count and neutrophil:lymphocyte ratio is predictive of hypoxia in patients with SARS-CoV-2 infection11 December 2021 | Transactions of The Royal Society of Tropical Medicine and Hygiene, Vol. 116, No. 7Conflicto trabajo-familia de mujeres en situación de teletrabajo a partir de la contingencia sanitaria por COVID-19 en Chile15 June 2022 | Investigaciones Feministas, Vol. 13, No. 1Impact of COVID-19 restrictions on mental health and physical activity among LGBQAP and heterosexual adults21 December 2021 | Journal of Gay & Lesbian Mental Health, Vol. 26, No. 3Women's Use and Abuse of the News Media during the COVID-19 Pandemic on Mumsnet2 September 2021 | Digital Journalism, Vol. 10, No. 6COVID-19 effects on women's home and work life, family violence and mental health from the Women's Health Expert Panel of the American Academy of NursingNursing Outlook, Vol. 70, No. 4Perceived risk, political polarization, and the willingness to follow COVID-19 mitigation guidelinesSocial Science & Medicine, Vol. 305Racial and Ethnic Disparities in Postpartum Care in the Greater Boston Area During the COVID-19 Pandemic23 June 2022 | JAMA Network Open, Vol. 5, No. 6Access to contraception during the Covid-19 pandemic: barriers and perspectives1 June 2022 | Cadernos Saúde Coletiva, Vol. 30, No. 2Disparities by Sex in COVID-19 Risk and Related Harms Among People with Opioid Use Disorder Caitlin E. Martin, Bhushan Thakkar, DaShaunda D.H. Taylor, and Derek A. Chapman16 May 2022 | Journal of Women's Health, Vol. 31, No. 5Vision 2020: How and for E. A. E. S. and May 2022 | Journal of Women's Health, Vol. 31, No. of women in clinical A for and Clinical Vol. and urban towards pandemic May 2022 | Vol. the The of during a January 2022 | & Psychology, Vol. 32, No. and During the and of the COVID-19 Pandemic in April 2022 | Frontiers in Vol. to Greater With the COVID-19 and to Journal of Health Psychology, Vol. 29, No. of to the of SARS-CoV-2 With Anxiety and A Study of March 2022 | International Journal of Public Health, Vol. in the Impact of COVID-19 Pandemic in in The Gender in Vol. No. 3Women's health and access COVID-19 Outlook, Vol. 70, No. of to COVID-19 Outcomes in a Longitudinal of February 2022 | Vol. No. as March 2022 | Saúde Vol. No. COVID-19 wave in during the of and its with higher February 2022 | PLOS ONE, Vol. 17, No. well-being and during the COVID-19 pandemic in the United A February 2022 | The Social Science Vol. to and February 2022 | Psychology, Vol. women's during the COVID-19 pandemic in June 2021 | and An International Vol. No. an and at the same in work and during the coronavirus April 2021 | International Journal of Psychology, Vol. No. and local A in the time of November 2021 | International Journal of Psychology, Vol. No. and the During June 2021 | & Vol. 26, No. of Medical Care among in the United States during the COVID-19 May 2022 | Journal of Public Health Research, Vol. 11, No. the Gender Disparities in COVID-19 and January 2022 | & Vol. with public health for COVID-19: a study of mothers with young children in the United February 2022 | Journal of in Vol. No. Perspectives on January and Among Adults During the to COVID-191 February in and and during the COVID-19 pandemic health and and Vol. in the COVID‐19 Effects of on December 2021 | British Journal of Vol. No. effects of the on for an emerging January 2022 | & Vol. No. Distress among Dental during the COVID-19 December 2021 | International Journal of Environmental Research and Public Health, Vol. 19, No. physical and social of health during the COVID-19 lockdown: a for of depression, and stress in the population during social isolation to the COVID-19 a cross-sectional study28 April 2021 | BMC Vol. No. and but same mortality of severe disease in March 2021 | BMC Medicine, Vol. No. Factors with and among community October 2021 | and Health, Vol. 17, No. differences in a of COVID-19 patients during the first and pandemic August 2021 | of Sex Vol. 12, No. in December 2021 | Journal of Clinical Medicine, Vol. 10, No. November 2021 | of Coronavirus Anxiety in Women on and Birth One of Coronavirus October 2021 | Journal of and Research, Vol. No. in and among Young Adults During Social to March 2021 | The Journal of Sex Research, Vol. No. of COVID-19 short- and long-term Disparities in and October 2021 | PLOS ONE, Vol. 16, No. analysis of on 2021 | Journal of in Medicine, Vol. No. of and Among COVID-19 by States in Women An September 2021 | and Vol. No. of COVID-19 using Public Gender and COVID-19: a Social Media of 2021 | Journal of Research, Vol. 5, No. for COVID-19 and its impact on in the Research on and Economics, Vol. No. differences in mental health of Canadian during the COVID-19 of and Health, Vol. No. Use and Relationship to Stress, and Perceived During the COVID-19 Pandemic in August 2021 | Frontiers in Public Health, Vol. and Lessons for August 2021 | PLOS ONE, Vol. 16, No. in How women in the United States in of of during the pandemic of March 2021 | Journal of Psychology, Vol. No. of in severe COVID-19 and Vol. No. the gender June 2021 | Journal of Perinatal Medicine, Vol. No. and the Related Factors in for COVID-19 at 2021 | International Journal of Health and Sciences, Vol. No. Gender Disparities and A Vol. No. impact of COVID‐19 on women to A of December | & Vol. No. of the and During the Covid-19 2021 | Frontiers in Psychology, Vol. in a January 2021 | Vol. No. responses to COVID-19 to Abuse & Vol. in and Practice During Social Among Young Adults in the May 2021 | Medicine, Vol. No. SARS-CoV-2 pandemic: A Health, Vol. and and after the pandemic April 2021 | Clinical and Research, Vol. No. on in August | Vol. 13, No. An to COVID-19 February 2022 | Journal of Women and Social Vol. No. in the and Outcomes of With May 2021 | Journal of Medicine, Vol. 16, No. of COVID-19: and May 2021 | Frontiers in Public Health, Vol. in the of February 2022 | Journal of Human Vol. No. and of the COVID-19 pandemic from the of in May 2021 | Journal of Social Work, Vol. No. the Pandemic: December April health disparities in vulnerable populations of psychiatric patients during the COVID-19 Journal of Vol. 11, No. 4The Gender of to in March 2021 | Feminist Economics, Vol. No. in Risk Factors and Mental Health During the of the COVID-19 Pandemic: A of U.S. Women A. E. E. and April 2021 | Journal of Women's Health, Vol. 30, No. and of and in March 2021 | Medicine, Vol. No. impact of COVID-19 on the mental health of and Science & Medicine, Vol. of and with in April 2021 | Vol. 12, No. health and well-being of staff during the coronavirus disease 2019 4 and in an March 2021 | Journal of Vol. of Gender in the and of Coronavirus Disease 2019 An of Health and and March 2021 | Journal of Women's Health, Vol. 30, No. of the COVID-19 pandemic on and Vol. of COVID-19 and of and Public Health, Vol. No. cross-sectional study of the of and with perceptions of to March 2021 | Open, Vol. 11, No. research and social of health: at the of of impact on and of Clinical Medicine, Vol. 17, No. differences in responses to SARS-CoV-2 in patients with January 2021 | Reports, Vol. No. and to COVID-19 in and January 2021 | Policy and Practice, Vol. impact of COVID-19 among and of November | & Health, Vol. 26, No. in case and mortality of coronavirus disease 2019 (COVID-19) among states in the United November | of Medicine, Vol. No. and pandemic risk and fear among September 2021 | Health and Behavioral Medicine, Vol. No. June 2021 | Vol. No. of and with of Coronavirus Related September 2021 | Vol. a January 2021 | Cadernos de Saúde Vol. No. and Among Vol. of Psychological Distress and Factors among During the COVID-19 Pandemic at in March 2021 | Disease and Vol. and on During the COVID-19 Pandemic in of Social Media October 2021 | Journal of Medical Research, Vol. 23, No. and and attitudes, and practices toward COVID-19 among birth of and Health Vol. 10, No. the of in COVID-19 October | Health Vol. No. in the of COVID-19 and political Vol. services in times of in of quality care for pregnant women and their October | Health Care for Women Vol. No. social support in the face of the December | Journal of & Vol. 12, No. with fear and during the COVID-19 pandemic in October | and Health, Vol. 16, No. and of People from by December | Journal of in Health, and Education, Vol. 10, No. is in gender and age for COVID-19 A December | Journal of and Vol. No. of SARS-CoV-2 Among Nursing and in September | Journal of Medicine, Vol. No. role of in the severity of learned from Vol. on gender disparities in the impact of the U.S. COVID-19 Research, Vol. Gender Women's Health and October | Frontiers in Global Women's Health, Vol. and the risk to and women during Journal of Vol. No. With Disparities in COVID-19 Outcomes in an Health Care October | JAMA Network Open, Vol. No. in the time of in August | Vol. 17, No. de la en en por September | Vol. No. de la COVID-19 en la de September | Vol. No. Perspectives to Health Research and Prevention During the COVID-19 | and Health Vol. 24, No. and Disease Disparities in the United in Vol. No. for a to | Global Public Health, Vol. No. and of in September | Vol. 11, No. and What is the Vol. No. we in Covid-19 women and men Vol. in of COVID-19: Insights a Vol. No. will The need to for the research on and the role of and and Vol. Impact and Factors During the of the Coronavirus (COVID-19) Pandemic Among the Population in June | Frontiers in Psychology, Vol. and of and the in SARS-CoV-2 to the in May | International Journal of Sciences, Vol. No. Coronavirus Disease 2019 the of August | Vol. Gender of to in January | Vol. Social of Vol. of of and Digital Vol. this Gausman and Ana and Gender Disparities in the COVID-19 of Women's in April 17,

OBJECTIVE: This study was designed to propose a classification scheme for platforms of surgical delivery in low- and middle-income countries (LMICs) and to review the literature documenting their effectiveness, cost-effectiveness, sustainability, and role in training. Approximately 28 % of the global burden of disease is surgical. In LMICs, much of this burden is borne by a rapidly growing international charitable sector, in fragmented platforms ranging from short-term trips to specialized hospitals. Systematic reviews of these platforms, across regions and across disease conditions, have not been performed. METHODS: A systematic review of MEDLINE and EMBASE databases was performed from 1960 to 2013. Inclusion and exclusion criteria were defined a priori. Bibliographies of retrieved studies were searched by hand. Of the 8,854 publications retrieved, 104 were included. RESULTS: Surgery by international charitable organizations is delivered under two, specialized hospitals and temporary platforms. Among the latter, short-term surgical missions were the most common and appeared beneficial when no other option was available. Compared to other platforms, however, worse results and a lack of cost-effectiveness curtailed their role. Self-contained temporary platforms that did not rely on local infrastructure showed promise, based on very few studies. Specialized hospitals provided effective treatment and appeared sustainable; cost-effectiveness evidence was limited. CONCLUSIONS: Because the charitable sector delivers surgery in vastly divergent ways, systematic review of these platforms has been difficult. This paper provides a framework from which to study these platforms for surgery in LMICs. Given the available evidence, self-contained temporary platforms and specialized surgical centers appear to provide more effective and cost-effective care than short-term surgical mission trips, except when no other delivery platform exists.

Abstract The historical development of program theory evaluation, current variations in theory and practice, and pressing issues are discussed.

OBJECTIVE: To assess the safety, effectiveness, and reliability of a tubal occlusion microinsert for permanent contraception, as well as to document patient recovery from the placement procedure and overall patient satisfaction. METHODS: A cohort of 518 previously fertile women seeking sterilization participated in this prospective, phase III, international, multicenter trial. Microinsert placement was attempted in 507 women. Microinserts were placed bilaterally into the proximal fallopian tube lumens under hysteroscopic visualization in outpatient procedures. RESULTS: Bilateral placement of the microinsert was achieved in 464 (92%) of 507 women. The most common reasons for failure to achieve satisfactory placement were tubal obstruction and stenosis or difficult access to the proximal tubal lumen. More than half of the women rated the average pain during the procedure as either mild or none, and 88% rated tolerance of device placement procedure as good to excellent. Average time to discharge was 80 minutes. Sixty percent of women returned to normal function within 1 day or less, and 92% missed 1 day or less of work. Three months after placement, correct microinsert placement and tubal occlusion were confirmed in 96% and 92% of cases, respectively. Comfort was rated as good to excellent by 99% of women at all follow-up visits. Ultimately, 449 of 518 women (87%) could rely on the microinsert for permanent contraception. After 9620 woman-months of exposure to intercourse, no pregnancies have been recorded. CONCLUSION: This study demonstrates that hysteroscopic interval tubal sterilization with microinserts is well tolerated and results in rapid recovery, high patient satisfaction, and effective permanent contraception.

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11)), GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.

For half a century, it has been known that some patients experience neurocognitive dysfunction after cardiac surgery; however, defining its incidence, course, and causes remains challenging and controversial. Various terms have been used to describe neurocognitive dysfunction at different times after cardiac surgery, ranging from "postoperative delirium" to "postoperative cognitive dysfunction or decline." Delirium is a clinical diagnosis included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Postoperative cognitive dysfunction is not included in the DSM-5 and has been heterogeneously defined, though a recent international nomenclature effort has proposed standardized definitions for it. Here, the authors discuss pathophysiologic mechanisms that may underlie these complications, review the literature on methods to prevent them, and discuss novel approaches to understand their etiology that may lead to novel treatment strategies. Future studies should measure both delirium and postoperative cognitive dysfunction to help clarify the relationship between these important postoperative complications.

BACKGROUND: In many countries, rates of facility-based childbirth have increased substantially in recent years. However, insufficient attention has been paid to the acceptability and quality of maternal health services provided at facilities and, consequently, maternal health outcomes have not improved as expected. Disrespect and abuse during childbirth is increasingly being recognized as an indicator of overall poor quality of care and as a key barrier to achieving improved maternal health outcomes, but little evidence exists to describe the scope and magnitude of this problem, particularly in urban areas in low-income countries. METHODS: This paper presents findings from an assessment of the prevalence of disrespectful and abusive behaviors during facility-based childbirth in one large referral hospital in Dar es Salaam, Tanzania. Client reports of disrespect and abuse (D&A) were obtained through postpartum interviews immediately before discharge from the facility with 1914 systematically sampled women and from community follow-up interviews with 64 women four to six weeks post-delivery. Additionally, 197 direct observations of the labor, delivery, and postpartum period were conducted to document specific incidences of disrespect and abuse during labor and delivery, which we compared with women's reports. RESULTS: During postpartum interviews, 15 % of women reported experiencing at least one instance of D&A. This number was dramatically higher during community follow-up interviews, in which 70 % of women reported any experience of D&A. During postpartum interviews, the most common forms of D&A reported were abandonment (8 %), non-dignified care (6 %), and physical abuse (5 %), while reporting for all categories of D&A, excluding detention and non consented care, was above 50 % during community follow-up interviews. Evidence from direct observations of client-provider interactions during labor and delivery confirmed high rates of some disrespectful and abusive behaviors. CONCLUSIONS: This study is one of the first to quantify the prevalence of disrespect and abuse during facility-based childbirth in a large public hospital in an urban setting. The difference in respondent reports between the two time periods is striking, and more research is needed to determine the most appropriate methodologies for measuring this phenomenon. The levels and types of disrespect and abuse reported here represent fundamental violations of women's human rights and are symptomatic of failing health systems. Action is urgently needed to ensure acceptable, quality, and dignified care for all women.

The rapid aging of populations around the world presents an unprecedented set of challenges: shifting disease burden, increased expenditure on health and long-term care, labor-force shortages, dissaving, and potential problems with old-age income security. We view longer life spans, particularly longer healthy life spans, as an enormous gain for human welfare. The challenges come from the fact that our current institutional and social arrangements are unsuited for aging populations and shifting demographics; our proposed solution is therefore to change our institutions and social arrangements. The first section of this essay provides a statistical overview of global population aging and its contributing factors. The second section outlines some of the major challenges associated with widespread population aging. Finally, the third section of the essay describes various responses to these challenges, both current and prospective, facing individuals, businesses, institutions, and governments.

UNLABELLED: Further analyses from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture. INTRODUCTION: The Women's Health Initiative provided evidence that conjugated equine estrogen (CEE) can significantly reduce fracture risk in postmenopausal women. Additional analysis of the effects of CEE on BMD and fracture are presented. MATERIALS AND METHODS: Postmenopausal women 50-79 years of age with hysterectomy were randomized to CEE 0.625 mg daily (n = 5310) or placebo (n = 5429) and followed for an average 7.1 years. Fracture incidence was assessed by semiannual questionnaire and verified by adjudication of radiology reports. BMD was measured in a subset of women (N = 938) at baseline and years 1, 3, and 6. A global index was used to examine whether the balance of risks and benefits differed by baseline fracture risk. RESULTS: CEE reduced the risk of hip (hazard ratio [HR], 0.65; 95% CI, 0.45-0.94), clinical vertebral (HR, 0.64; 95% CI, 0.44-0.93), wrist/lower arm (HR, 0.58; 95% CI, 0.47-0.72), and total fracture (HR, 0.71; 95% CI, 0.64-0.80). This effect did not differ among strata according to age, oophorectomy status, past hormone use, race/ethnicity, fall frequency, physical activity, or fracture history. Total fracture reduction was less in women at the lowest predicted fracture risk in both absolute and relative terms (HR, 0.86; 95% CI, 0.68-1.08). CEE also provided modest but consistent positive effects on BMD. The HRs of the global index for CEE were relatively balanced across tertiles of summary fracture risk (lowest risk: HR, 0.81; 95% CI, 0.62-1.05; mid risk: HR, 1.09; 95% CI, 0.92-1.30; highest risk: HR, 1.04; 95% CI, 0.88-1.23; interaction, p = 0.42). CONCLUSIONS: CEE reduces the risk of fracture and increases BMD in hysterectomized postmenopausal women. Even among the women with the highest risk for fractures, when considering the effects of estrogen on other important health outcomes, a summary of the burden of monitored effects does not indicate a significant net benefit.

Time for primary review 31 days. On average, women develop heart disease some 10–15 years later than men. This raises the question of whether there is some aspect of ‘femaleness’ which reduces risk, or whether there is some aspect of ‘maleness’ that raises risk. To date, most attention has been focused on the hypothesis that endogenous estrogen is cardioprotective in women [1]. Rising rates of coronary heart disease (CHD) after the menopause, and after oophorectomy, are among the strands of evidence in humans that endogenous estrogen may prevent CHD [2]. However, upon closer examination this evidence is not persuasive, and in fact the evidence is amenable to alternative explanations. During the first 3 decades of adult life, low-density lipoprotein (LDL) cholesterol levels are lower in women than men, and this may contribute to the delayed onset of CHD in women. A more widely held explanation for the later onset of CHD in women is their higher high-density lipoprotein (HDL) cholesterol levels, attributed to higher endogenous estrogen levels in women. However, the difference in HDL cholesterol between women and men is an androgen effect, not an estrogen effect. Up to puberty, young men and women have similar HDL cholesterol levels. At puberty, concurrent with the rise in endogenous testosterone levels, the HDL cholesterol levels in young men decline to the adult level [3,4]. A 20% difference in HDL cholesterol levels predicts at least a 20% difference in CHD rates in the short term, and may predict even larger differences in CHD rates over a lifetime [5]. Thus, the entire gender difference in CHD risk may indeed be due to the lifelong difference in HDL cholesterol levels; however, this difference is a consequence of having the Y chromosome. During fetal development, the Y chromosome directs the formation of … * Tel.: +1-301-435-6669; fax: +1-301-480-5158 rossouwj{at}nih.gov