Why Males ≠ Corvettes, Females ≠ Volvos, and Scientific Criticism ≠ Ideology: A Response to “Equal ≠ The Same: Sex Differences in the Human Brain” by Larry Cahill in Cerebrum

A recent Cerebrum article by Larry Cahill about sex differences in the human brain has prompted a group of women academicians to respond and for the author to reply to their response. We encourage you to evaluate both points of view, as well as the original article, and form your own opinion.

Sex Differences in Semantic Processing: Event-Related Brain Potentials Distinguish between Lower and Higher Order Semantic Analysis during Word Reading

Behavioral studies suggest that women and men differ in the strategic elaboration of verbally encoded information especially in the absence of external task demand. However, measuring such covert processing requires other than behavioral data. The present study used event-related potentials to compare sexes in lower and higher order semantic processing during the passive reading of semantically related and unrelated word pairs. Women and men showed the same early context effect in the P1-N1 transition period. This finding indicates that the initial lexical-semantic access is similar in men and women. In contrast, sexes differed in higher order semantic processing. Women showed an earlier and longer lasting context effect in the N400 accompanied by larger signal strength in temporal networks similarly recruited by men and women. The results suggest that women spontaneously conduct a deeper semantic analysis. This leads to faster processing of related words in the active neural networks as reflected in a shorter stability of the N400 map in women. Taken together, the findings demonstrate that there is a selective sex difference in the controlled semantic analysis during passive word reading that is not reflected in different functional organization but in the depth of processing.

Biologically relevant sex differences for fitness-related parameters in active octogenarians

The number of elderly people is growing in western populations, but only few maximal performance data exist for people >75 years, in particular for European octogenarians. This study was performed to characterize maximal performance of 55 independently living subjects (32 women, 81.1 +/- 3.4 years; 23 men, 81.7 +/- 2.9 years) with a focus on sex differences. Maximal performance was determined in a ramp test to exhaustion on a bicycle ergometer with ergospirometry, electrocardiogram and blood lactate measurements. Maximal isometric extension strength of the legs (MEL) was measured on a force platform in a seated position. Body composition was quantified by X-ray absorptiometry. In >25% of the subjects, serious cardiac abnormalities were detected during the ramp test with men more frequently being affected than women. Maximal oxygen consumption and power output were 18.2 +/- 3.2 versus 25.9 +/- 5.9 ml min(-1) kg(-1) and 66 +/- 12 versus 138 +/- 40 W for women versus men, with a significant sex difference for both parameters. Men outperformed women for MEL with 19.0 +/- 3.8 versus 13.6 +/- 3.3 N kg(-1). Concomitantly, we found a higher proportion of whole body fat in women (32.1 +/- 6.2%) compared to men (20.5 +/- 4.4%). Our study extends previously available maximal performance data for endurance and strength to independently living European octogenarians. As all sex-related differences were still apparent after normalization to lean body mass, it is concluded that it is essential to differentiate between female and male subjects when considering maximal performance parameters in the oldest segment of our population.

Sex differences in cryptogenic stroke with patent foramen ovale

BACKGROUND: Sex differences in patients with patent foramen ovale (PFO) and cryptogenic stroke have not been systematically analyzed. We aimed to determine sex influences on demographics, vascular risk factors, clinical manifestations, stroke location, and clinical outcome. METHODS: One thousand two hundred eighty-eight consecutive patients with ischemic stroke or transient ischemic attack (TIA) were admitted to a single stroke center. All patients underwent a complete stroke workup including clinical examination, standard blood tests, cerebral and vascular imaging, transesophageal echocardiography, and 24-hour electrocardiography. In 500 patients, no definite etiology could be established (cryptogenic stroke/TIA). Of them, 167 patients (107 men and 60 women, mean age 52 +/- 13 years) had an PFO. RESULTS: The prevalence of PFO in patients with cryptogenic stroke or TIA was higher in men than in women (38% vs 28%, P = .014). Stroke severity and the prevalence of risk factors did not differ between the 2 sexes. There was an independent association between male sex and stroke location in the posterior cerebral circulation (OR 3.0, 95% CI 1.4-6.5, P = .006). Men and women did not differ in respect to PFO grade, prevalence of right-to-left shunt at rest, or coexistence of atrial septal aneurysm. Clinical outcome at 3 months was similar in both sexes. CONCLUSION: Patent foramen ovale was more prevalent in men than in women with cryptogenic stroke. There were no sex influences on age, risk factors, echocardiographic characteristics of PFO, or clinical outcome. Male sex was independently associated with stroke in the posterior cerebral circulation.

Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study

The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle-brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P = 0.44), but a higher prevalence of ABI 0.9-1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0.9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9-1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53-15.31) and men (3.49, 1.39-8.72). However, ABI 0.9-1.0 was significantly associated with incident clinical PAD (3.33, 1.44-7.70) and incident stroke (2.45, 1.38-4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD.

Sex differences in acute coronary syndrome symptom presentation in young patients

IMPORTANCE Little is known about whether sex differences in acute coronary syndrome (ACS) presentation exist in young patients and what factors determine absence of chest pain in ACS presentation. OBJECTIVES To evaluate sex differences in ACS presentation and to estimate associations between sex, sociodemographic, gender identity, psychosocial and clinical factors, markers of coronary disease severity, and absence of chest pain in young patients with ACS. DESIGN, SETTING, PARTICIPANTS We conducted a prospective cohort study of 1015 patients (30% women) 55 years or younger, hospitalized for ACS and enrolled in the GENESIS PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome) study (January 2009-September 2012). MAIN OUTCOMES AND MEASURES The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered during hospitalization. RESULTS The median age for both sexes was 49 years. Women were more likely to have non-ST-segment elevation myocardial infarction (37.5 vs 30.7; P = .03) and present without chest pain compared with men (19.0% vs 13.7%; P = .03). Patients without chest pain reported fewer symptoms overall and no discernable pattern of non-chest pain symptoms was found. In the multivariate model, being a woman (odds ratio [OR], 1.95 [95% CI, 1.23-3.11]; P = .005) and tachycardia (OR, 2.07 [95% CI, 1.20-3.56]; P = .009) were independently associated with ACS presentation without chest pain. Patients without chest pain did not differ significantly from those with chest pain in terms of ACS type, troponin level elevation, or coronary stenosis. CONCLUSIONS AND RELEVANCE Chest pain was the most common ACS symptom in both sexes. Although women were more likely to present without chest pain than men, absence of chest pain was not associated with markers of coronary disease severity. Strategies that explicitly incorporate assessment of common non-chest pain symptoms need to be evaluated.

Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity

Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. We demonstrate that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D). Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D. Transfer of gut microbiota from adult males to immature females altered the recipient's microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity. Thus, the commensal microbial community alters sex hormone levels and regulates autoimmune disease fate in individuals with high genetic risk.

Sex differences in heart rate variability: a longitudinal study in international elite cross-country skiers

PURPOSE: Exercise-related sudden cardiac deaths (SCD) occur with a striking male predominance. A higher sympathetic tone in men has been suggested as risk factor for SCD. Elite athletes have the highest risk for exercise-related SCD. We aimed to analyze the autonomic nervous system of elite cross-country skiers from Norway, Russia and Switzerland in supine position and after orthostatic challenge in various training periods (TP). METHOD: Measurements of heart rate variability (HRV) were performed on a weekly basis over 1 year using an orthostatic challenge test with controlled breathing. Main outcome parameters were the high-frequency power in supine position (HFsupine) as marker of cardiac parasympathetic activity and the low-frequency/high-frequency power ratio after orthostatic challenge (LF/HFstand) as marker of cardiac sympathetic activation. Training intensity and duration were recorded daily and expressed as training strain. The training year was divided into three TPs. An average of weekly HRV measurements was calculated for each TP. RESULT: Female (n = 19, VO2max 62.0 +/- 4.6 ml kg(-1) min(-1), age 25.8 +/- 4.3 years) and male (n = 16, VO2max 74.3 +/- 6.3 ml kg(-1) min(-1), age 24.4 +/- 4.2 years) athletes were included. Training strain was comparable between sexes (all p > 0.05) and changed between TPs (all p < 0.05) while no HRV parameters changed over time. There were no sex differences in HFsupine while the LF/HFstand was significantly higher in male athletes in all TPs. CONCLUSION: For a comparable amount of training, male athletes showed constantly higher markers of sympathetic activity after a provocation maneuver. This may explain part of the male predominance in sports-related SCD.

Drug suicide: a sex-equal cause of death in 16 European countries

Background There is a lack of international research on suicide by drug overdose as a preventable suicide method. Sex- and age-specific rates of suicide by drug self-poisoning (ICD-10, X60-64) and the distribution of drug types used in 16 European countries were studied, and compared with other self-poisoning methods (X65-69) and intentional self-injury (X70-84). Methods Data for 2000-04/05 were collected from national statistical offices. Age-adjusted suicide rates, and age and sex distributions, were calculated. Results No pronounced sex differences in drug self-poisoning rates were found, either in the aggregate data (males 1.6 and females 1.5 per 100,000) or within individual countries. Among the 16 countries, the range (from some 0.3 in Portugal to 5.0 in Finland) was wide. 'Other and unspecified drugs' (X64) were recorded most frequently, with a range of 0.2-1.9, and accounted for more than 70% of deaths by drug overdose in France, Luxembourg, Portugal and Spain. Psychotropic drugs (X61) ranked second. The X63 category ('other drugs acting on the autonomic nervous system') was least frequently used. Finland showed low X64 and high X61 figures, Scotland had high levels of X62 ('narcotics and hallucinogens, not elsewhere classified') for both sexes, while England exceeded other countries in category X60. Risk was highest among the middle-aged everywhere except in Switzerland, where the elderly were most at risk. Conclusions Suicide by drug overdose is preventable. Intentional self-poisoning with drugs kills as many males as females. The considerable differences in patterns of self-poisoning found in the various European countries are relevant to national efforts to improve diagnostics of suicide and appropriate specific prevention. The fact that vast majority of drug-overdose suicides came under the category X64 refers to the need of more detailed ICD coding system for overdose suicides is needed to permit better design of suicide-prevention strategies at national level.

Gender differences in spontaneous cervical artery dissection

We analyzed sex differences in 696 patients with spontaneous cervical artery dissection. There were more men (n = 399; p < 0.0001), and men showed a higher frequency of hypertension (31% vs 15%; p < 0.0001). Women were younger (42.5 +/- 9.9 vs 47.5 +/- 9.3 years; p < 0.0001), had more often multiple dissections (18 vs 10%; p = 0.001), migraine (47 vs 20%; p < 0.0001), and tinnitus (16 vs 8%; p = 0.001). Outcome and mortality were similar in both sexes.

Recanalization and outcome after intra-arterial thrombolysis in middle cerebral artery and internal carotid artery occlusion: does sex matter?

BACKGROUND AND PURPOSE: Recent studies have reported sex differences in recanalization and outcome after intravenous thrombolysis (IVT) in acute ischemic stroke. METHODS: We analyzed sex differences in outcome in consecutive patients with middle cerebral artery (MCA) M1 or M2 and internal carotid artery (ICA) occlusion treated with intra-arterial thrombolysis (IAT). Recanalization immediately after thrombolysis and outcome after 3 months were assessed. RESULTS: Two hundred five patients (111 men) with MCA and 43 (22 men) with ICA occlusion were identified. Baseline variables did not differ between the sexes except for a higher prevalence of smokers among men in the MCA group (31% vs 12%; P=0.001). Partial or complete recanalization (TIMI flow 2 or 3) of the MCA was observed in 71 (75%) women and 80 (72%) men (P=0.488). In the ICA group, 14 (67%) women and 11 men (50%) showed TIMI 2 or 3 recanalization (P=0.425). Favorable outcome (modified Rankin Scale score 0 to 2) was seen in 57 women (61%) and 63 men (57%) with MCA occlusion (P=0.512) and in 6 women (28%) and 4 men (18%) with ICA occlusion (P=0.656). After multiple-regression analyses, there was still no association between sex and outcome (P=0.763 for MCA and P=0.813 for ICA occlusion) or recanalization (P=0.488 for MCA and P=0.104 for ICA occlusion). CONCLUSIONS: There was no association between sex and recanalization or outcome after IAT. These findings are in contrast to previous studies reporting better recanalization and outcome after IVT in women and might have implications in the selection of patients for IAT or IVT.