Salivary testosterone across the menstrual cycle.

Testosterone production in women is thought to systematically shift across the menstrual cycle, peaking during the mid-cycle ovulatory window, and potentially influencing women's behavior. Testosterone is a molecular intermediary to the production of estradiol, which is necessary for ovulation to occur, but the amount of testosterone escape and exposure to the peripheral tissues is not fully understood. Salivary testosterone is a common biomarker in behavioral neuroendocrinological studies and is thought to reflect the bioactive portions in serum. In N = 339 women with confirmed ovulation via luteinizing hormone tests, salivary testosterone, assayed with LC-MS/MS, was sampled four times across the mid-cycle ovulatory window the luteal phase. Within-subject analysis revealed a significant but small pattern of a mid-cycle peak and a luteal decrease at the aggregate level. However, at the individual level, there was substantial variability in the direction and magnitude of the testosterone-cycle pattern. We discuss the relevant underlying physiology, background research, issues with assay methodolody, and considerations for researchers studying testosterone levels in women.

Combined perceptual and chemical analyses show no compelling evidence for ovulatory cycle shifts in women's axillary odour.

Although men's attraction to women's body odour has been suggested to vary over the ovulatory cycle, peaking around the fertile window, we still lack methodologically robust evidence corroborating this effect. Further, the chemical underpinnings of male preference for the odour of ovulating women remain unknown. Here, we combined perceptual and chemical analyses to investigate the axillary odour of naturally cycling women over 10 days, covering the gradual change in fertility across the ovulatory cycle with a focus on fertile days. The fertile state was confirmed by urinary ovulation tests as well as salivary oestradiol and progesterone levels. Men rated the scent of unfamiliar women, resembling a first encounter. We used multivariate analyses to relate variation in both odour ratings and chemical composition to female conception probability, temporal distance to ovulation and ovarian hormone levels. Our results provide no evidence that males prefer the odour of fertile women. Furthermore, the volatile analysis indicated no link between axillary odour composition and current fertility status. Together, our results showed no convincing support for a chemical fertility cue in women's axillary odour, questioning the presence of olfactory fertility information that is recognizable during first encounters in modern humans.

Impact of etiology, sex, diabetes mellitus and remission status on erythrocytic profile in patients with cushing's syndrome: a large population database study.

PURPOSE: The study aimed to characterize the erythrocytic profile in patients with cushing's syndrome (CS) versus controls from the normal population according to etiology, sex, presence of diabetes mellitus (DM) and hypercortisolemia remission status. METHODS: This retrospective cohort analysis compared erythrocytic parameters between patients with CS of pituitary (CD) and adrenal (aCS) etiology and age, sex, body mass index (BMI) and socioeconomic status-matched controls in a 1:5 ratio. Laboratory values at baseline were calculated as mean values during the year preceding CS diagnosis, and over one year thereafter. RESULTS: The cohort included 397 CS patients (68.26% female; mean age 51.11 ± 16.85 years) and 1970 controls. Patients with CS had significantly higher baseline median levels of hemoglobin (Hgb) (13.70 g/dL vs. 13.12 g/dL [p < 0.0001]) and hematocrit (Hct) (41.64% vs. 39.80% [p < 0.0001]) compared to controls. These differences were observed for both CD and aCS and for both sexes. Patients who attained remission had Hgb and Hct levels comparable to controls (13.20 g/dL and 40.08% in patients with CD and aCS vs. 13.20 g/dL and 39.98% in controls). Meanwhile, those with persistent/recurrent disease maintained elevated levels. Patients with comorbid DM had similar Hgb but higher Hct (p = 0.0419), while patients without DM showed elevated erythrocytic values compared to controls (p < 0.0001). CONCLUSION: Our data illustrates that erythrocytic parameters are directly influenced by glucocorticoid excess as Hgb and Hct are higher in patients with CS, and normalize after remission. We have identified the influence of DM on erythrocytic parameters in patients with CS for the first time.

Ovulatory cycle shifts in human motivational prioritisation of sex and food.

Previous research on the endogenous effects of ovarian hormones on motivational states in women has focused on sexual motivation. The Motivational Priority Shifts Hypothesis has a broader scope. It predicts a shift from somatic to reproductive motivation when fertile. In a highly powered preregistered online diary study across 40 days, we tested whether 390 women report such an ovulatory shift in sexual and eating motivation and behaviour. We compared 209 naturally cycling women to 181 women taking hormonal contraceptives (HC) to rule out non-ovulatory changes across the cycle as confounders. We found robust ovulatory decreases in food intake and increases in general sexual desire, in-pair sexual desire and initiation of dyadic sexual behaviour. Extra-pair sexual desire increased mid-cycle, but the effect did not differ significantly in HC women, questioning an ovulatory effect. Descriptively, solitary sexual desire and behaviour, dyadic sexual behaviour, appetite, and satiety showed expected mid-cycle changes that were diminished in HC women, but these failed to reach our strict preregistered significance level. Our results provide insight into current theoretical debates about ovulatory cycle shifts while calling for future research to determine motivational mechanisms behind ovulatory changes in food intake and considering romantic partners' motivational states to explain the occurrence of dyadic sexual behaviour.

Investigating cycle shifts in women's clothing style and grooming.

In contrast to some non-human primate species, human females do not show overt cues to fertility. Previous research argued that women still show systematic changes in their appearance across their ovulatory cycle to enhance their mating success when fertile. We report five studies investigating whether women's clothing style and grooming behaviour change across the ovulatory cycle. All studies were large (with N = 157 in Study 1, N = 109 in Study 2, N = 257 in Studies 3-5), longitudinal studies with four testing sessions per participant. They involved salivary hormone samples and luteinizing hormone tests to validate conception risk estimates. Across all studies, our results suggest no compelling evidence for cycle shifts in clothing style and grooming. Rather, two studies suggest effects in the opposite direction as hypothesized, as women wore more skin-revealing clothes when non-fertile. One study suggests small effects of wearing necklaces more and eyeglasses less often when fertile. However, these effects were not robust across all studies. Our results are in line with other recent null replications and suggest that, if existent, cues to fertility might be even more subtle than previously assumed. We discuss the need for testing competing theories that explain the evolution of concealed ovulation.

Revisiting the Relation Between Steroid Hormones and Unethicality in an Exploratory, Longitudinal Study With Female Participants.

Research on the relation between hormones and unethical behaviors and tendencies has provided mixed results, hindering the understanding of the potential biological regulation of unethical behaviors and tendencies. We conducted an exploratory, longitudinal study (N = 257 women) allowing to estimate relations between, on the one hand, steroid hormones (testosterone, cortisol, estradiol, and progesterone) and conception probability and, on the other hand, a broad variety of measures related to unethicality (self-reported personality variables, cheating in committed relationships, self-serving economic dishonesty in a behavioral task, namely, the mind game). Contrary to theoretical assumptions of and results from some previous studies, we find no consistent relation between hormones and unethical behavior or tendencies in the majority of analyses. Yet, some small, exploratory associations emerged that call for (preregistered) replications, before more firm conclusions can be made.

Stability and Change of Individual Differences in Ideal Partner Preferences Over 13 Years.

Ideal partner preferences for traits in a partner are said to be stable cognitive constructs. However, longitudinal studies investigating the same participants' ideals repeatedly have so far been limited to relatively short retest intervals of a maximum of 3 years. Here, we investigate the stability and change of ideals across 13 years and participants' insight into how ideals have changed. A total of 204 participants (M = 46.2 years, SD = 7.4, 104 women) reported their ideals at two time points. We found a mean rank-order stability of r = .42 and an overall profile stability of r = .73 (distinctive r = .53). Some ideals changed over time, for example, increased for status-resources in relation to age and parenthood. We found some but varying insight into how ideals had changed (mean r = .20). Results support the idea of ideals being stable cognitive constructs but suggest some variability related to the demands of different life stages.

Not within spitting distance: Salivary immunoassays of estradiol have subpar validity for predicting cycle phase.

Salivary steroid immunoassays are widely used in psychoneuroendocrinological studies of menstrual cycle phase, puberty, and menopause. Though manufacturers advertise their assays as suitable, they have not been rigorously validated for these purposes. We collated data from eight menstrual cycle studies across > 1200 female participants and > 9500 time points. Seven studies collected saliva and one collected serum. All assayed estradiol and progesterone and had an independent measure of cycle phase (LH-surge, menstrual onset). In serum, cycle phase measures strongly predicted steroid concentrations. In saliva, cycle phase poorly predicted estradiol values, which showed an upward bias compared to expectations from serum. For salivary progesterone, predictability from cycle phase was mixed, low for enzyme-linked assays and moderate for tandem mass spectrometry. Imputing the population-average serum steroid changes from cycle phase may yield more valid values of hormonal changes for an independent person than directly assessing their hormone levels using salivary immunoassays.

Does emotion recognition change across phases of the ovulatory cycle?

Recognizing emotions is an essential ability for successful interpersonal interaction. Prior research indicates some links between the endocrine system and emotion recognition ability, but only a few studies focused on within-subject differences across distinct ovulatory cycle phases and this ability. These studies have demonstrated mixed results that might be potentially due to heterogeneity in experimental tasks, methodologies, and lacking ecological validity. In the current study, we investigated associations between within-subject differences in ovarian hormones levels and emotion recognition from auditory, visual, and audiovisual modalities in N = 131 naturally cycling participants across the late follicular and mid-luteal phase of the ovulatory cycle. We applied a within-subject design with sessions in the late follicular and mid-luteal cycle phase, and also assessed salivary progesterone and estradiol in these sessions. Our findings did not reveal any significant difference in emotion recognition ability across two cycle phases. Thus, they emphasize the necessity of employing large-scale replication studies with well-established study designs along with proper statistical analyses. Moreover, our findings indicate that the potential link between ovulatory cycle phases (late follicular and mid-luteal) and emotion recognition ability might have been overestimated in previous studies, and may contribute to theoretical and practical implications of socio-cognitive neuroendocrinology.

Men are not aware of and do not respond to their female partner's fertility status: Evidence from a dyadic diary study of 384 couples.

Understanding how human mating psychology is affected by changes in female cyclic fertility is informative for comprehending the evolution of human reproductive behavior. Based on differential selection pressures between the sexes, men are assumed to have evolved adaptations to notice women's within-cycle cues to fertility and show corresponding mate retention tactics to secure access to their female partners when fertile. However, previous studies suffered from methodological shortcomings and yielded inconsistent results. In a large, preregistered online dyadic diary study (384 heterosexual couples), we found no compelling evidence that men notice women's fertility status (as potentially reflected in women's attractiveness, sexual desire, or wish for contact with others) or display mid-cycle increases in mate retention tactics (jealousy, attention, wish for contact or sexual desire towards female partners). These results extend our current understanding of the evolution of women's concealed ovulation and oestrus, and suggest that both might have evolved independently.

Stability and validity of steroid hormones in hair and saliva across two ovulatory cycles.

Steroid hormones are often assessed via saliva samples, as they are noninvasive and easy to collect. However, hormone levels in saliva can fluctuate from moment-to-moment, are influenced by factors such as momentary emotional states and food intake, and some vary strongly across women's ovulatory cycle. In contrast, hormone levels in hair seem to be more robust against these influences and were previously suggested to be a good alternative to obtain women's baseline hormone levels. In the current study, we investigated whether hormone levels are stable across multiple assays and whether hormone levels from saliva and hair samples correlate. We collected saliva and hair samples from N = 155 naturally cycling women across two ovulatory cycles. All samples were analyzed for progesterone, testosterone and cortisol levels via mass spectrometry (LC-MS/MS). Results showed that both averaged saliva and hair hormone levels were moderately stable across cycles. Hair progesterone levels showed higher stability than the respective levels from saliva. Saliva and hair levels for progesterone and testosterone were moderately correlated, whereas cortisol levels from saliva and hair were only weakly correlated. Results suggest that the type of sample from which baseline hormone levels are assessed and the cycle phase in which saliva samples are collected may have a high impact on the obtained results. Implications for future studies are suggested.

Hormones, ovulatory cycle phase and pathogen disgust: A longitudinal investigation of the Compensatory Prophylaxis Hypothesis.

Multiple studies have argued that disgust, especially pathogen disgust and contamination sensitivity, change across women's ovulatory cycle, with higher levels in the luteal phase due to an increase in progesterone levels. According to the Compensatory Prophylaxis Hypothesis (CPH), women have a higher disgust sensitivity to pathogen cues when in the luteal phase (or when progesterone levels are higher), because progesterone is associated with suppressed immune responses. Evidence for this hypothesis is rather mixed and uncertain, as the largest study conducted so far reported no compelling evidence for an association between progesterone levels and pathogen disgust. Further, ovulatory cycle research has been criticized for methodological shortcomings, such as invalid cycle phase estimates, no direct hormone assessments, small sample sizes or between-subjects studies. To address these issues and to contribute to the literature, we employed a large, within-subjects design (N = 257 with four sessions each), assessments of salivary hormone levels and cycle phase estimates based on luteinizing hormone tests. A variety of multilevel models suggest no compelling evidence that self-reported pathogen disgust or contamination sensitivity is upregulated in the luteal phase or tracks changes in women's hormone levels. We further found no compelling evidence for between-subjects associations of pathogen disgust or contamination sensitivity and hormone levels. Results remain robust across different analytical decisions (e.g. in a subsample of women reporting feeling sick). We discuss explanations for our results, limitations of the current study and provide directions for future research.

The evidence for good genes ovulatory shifts in Arslan et al. (2018) is mixed and uncertain.

In Arslan et al. (2018), we reported ovulatory increases in extra-pair sexual desire, in-pair sexual desire, and self-perceived desirability, as well as several moderator analyses related to the good genes ovulatory shift hypothesis, which predicts attenuated ovulatory increases in extra-pair desire for women with attractive partners. Gangestad and Dinh (2021) identified errors in how we aggregated two of the four main moderator variables. We are grateful that their scrutiny uncovered these errors. After corrections, our moderation results are more mixed than we previously reported and depend on the moderator specification. However, we disagree that the evidence for moderation is robust and compelling, as Gangestad and Dinh (2021) claim. Our data are consistent with some previously reported effect sizes, but also with negligible moderator effects. We also show that what Gangestad and Dinh (2021) call an "a priori[…]more comprehensive and valid composite" is poorly justifiable on a priori grounds, and follow-up analyses they report are not robust to a composite specification that we consider at least as reasonable. Psychologists have to become acquainted with techniques such as cross-validation or training and test sets to manage the risks of data-dependent analyses. In doing so, we might learn that we need new data more often than we intuit and should remain uncertain far more often. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A longitudinal evaluation of ovulatory cycle shifts in women's mate attraction and preferences.

Are ovulatory cycle shifts in women's mate attraction and preferences robust? What are underlying mechanisms of potential cycle shifts? These questions are the subject of a current scientific debate surrounding the good genes ovulatory shift hypothesis. Here, we report a large, preregistered, within-subjects study, including salivary hormone measures and conception risk estimates based on luteinizing hormone tests. In four sessions across one ovulatory cycle, N = 257 women (= 1028 sessions) rated the attractiveness of 40 natural male bodies, 40 natural female bodies and 40 objects. Multilevel analyses yielded weak evidence for ovulatory increases in women's general attraction, specifically to male bodies, though they are not systematically related to changes in steroid hormone levels. Further, we found no compelling robust evidence for mate preference shifts across the cycle, as only one out of many different tests showed some weak evidence for such effects. Mechanisms regulating cycle shifts, the impact of our results on developing and revising cycle shift theories, and influences of different methodologies on results are discussed.

Are Sexual Desire and Sociosexual Orientation Related to Men's Salivary Steroid Hormones?

OBJECTIVE: Although it is widely assumed that men's sexual desire and interest in casual sex (i.e., sociosexual orientation) are linked to steroid hormone levels, evidence for such associations is mixed. METHODS: We tested for both longitudinal and cross-sectional relationships between salivary testosterone, cortisol, reported sexual desire and sociosexuality in a sample of 61 young adult men, each of whom was tested weekly on up to five occasions. RESULTS: Longitudinal analyses showed no clear relationships between steroid hormones and self-reported sexual desire or sociosexual orientation. Cross-sectional analyses showed no significant associations between average hormone levels and self-reported sexual desire. However, some aspects of sociosexuality, most notably desire for casual sex, were related to men's average hormone levels. Men with higher average testosterone reported greater desire for casual sex, but only if they also had relatively low average cortisol levels. CONCLUSIONS: Our results support a Dual Hormone account of men's sociosexuality, in which the combined effects of testosterone and cortisol predict the extent of men's interest in casual sex. However, we did not detect compelling evidence for an association of within-subject hormone shifts and sexual desire or sociosexual orientation.

Probing Ovulatory-Cycle Shifts in Women's Preferences for Men's Behaviors.

The existence of ovulatory-cycle shifts in women's mate preferences has been a point of controversy. There is evidence that naturally cycling women in their fertile phase, compared with their luteal phase, evaluate specific behavioral cues in men as more attractive for sexual relationships. However, recent research has cast doubt on these findings. We addressed this debate in a large, preregistered, within-participants study using salivary-hormone measures and luteinizing-hormone tests. One hundred fifty-seven female participants rated the sexual and long-term attractiveness of 70 men in dyadic intersexual interactions in natural videos. Multilevel comparisons across two ovulatory cycles indicated that women's mate preferences for men's behaviors did not shift across the cycle for either competitive or courtship behavior. Within-women hormone levels and relationship status did not affect these results. Hormonal mechanisms and implications for estrus theories are discussed.

No evidence for an association between facial fluctuating asymmetry and vocal attractiveness in men or women.

Facial fluctuating asymmetry (FA), presumably a proxy measure of developmental instability, has been proposed to inversely relate to vocal attractiveness, which may convey information on heritable fitness benefits. Using an improved method of measuring facial FA, we sought to replicate two recent studies that showed an inverse correlation of facial FA with vocal attractiveness. In two samples of men (N = 165) and women (N = 157), we investigated the association of automatically measured facial FA based on 3D face scans with male and female observer-rated attractiveness of voice recordings. No significant associations were found for men or women, also when controlling for facial attractiveness, age, and body mass index. Equivalence tests show that effect sizes were significantly smaller than previous meta-analytic effects, providing robust evidence against a link of facial FA with vocal attractiveness. Thus, our study contradicts earlier findings that vocal attractiveness may signal genetic quality in humans via an association with FA.

Natural history of children with mild Crohn's disease.

BACKGROUND: There is a small and poorly studied population of patients with mild and limited Crohn's disease (CD), who either spontaneously enter remission and can discontinue therapy, or be maintained on milder anti-inflammatory treatment. AIM: To identify a group of children with mild CD who were not escalated to immunomodulators (azathioprine, mercaptopurine, or methotrexate) or biologics (infliximab or adalimumab) within the first two years after their Crohn's diagnosis and outline the natural history and phenotypic features of these patients. METHODS: In a retrospective chart review of the inflammatory bowel disease database at Boston Children's Hospital we reviewed all the mild CD patient's clinic visits, laboratory studies, and procedures for the duration of time they were followed at the center. Patients were included if they had clear diagnosis of Crohn's disease, and they were not escalated to immunosuppressive therapies for at least 2 years after the date of diagnosis. These mild CD patients were compared to controls diagnosed at a similar time, that were treated with immunomodulators or biologics. Data that was abstracted included: Age at diagnosis, sex, disease location utilizing the Paris classification, medical treatment, surgical treatment, endoscopic findings, histology, and hospitalizations. We also analyzed differences in the phenotypic features between those with mild CD and those with moderate to severe disease. RESULTS: Out of 1205 patients with CD diagnosed between 1990 and 2013, we identified 29 patients that met the inclusion criteria, and they were matched with 58 controls. There were no significant differences between the disease behaviors at presentation, with approximately 90% of patients in each group having inflammatory disease. However, patients with mild disease were more likely to have disease limited to the colon (31% vs 12%, P = 0.03). In contrast, patients with moderate to severe disease (aka control group) were more likely to have ileocolonic disease (70% vs 45% in the mild group, P = 0.02). Of the 29 patients, only 8 required medication escalation to immunomodulators during the period of follow-up. The primary indication for escalation to immune suppressive therapies was corticosteroid dependence. We also found that patients treated without immunomodulators or biologics for mild CD continue to exhibit histologic intestinal inflammation. Of the 29 patients, three developed significant complications of ileal disease, though only one required surgical intervention during the period of follow-up. CONCLUSION: We identified a cohort of children with mild CD, who were able to avoid the institution of immune suppressive therapies for several years, and generally had good outcomes during the period of follow-up. While a subset of these patients will eventually require either immunosuppression or surgery, the majority of them have a good quality of life despite having low-grade intestinal inflammation. Importantly, this subset of patients has managed to avoid the potential toxicities of immune suppression for several years. The majority of these patients have either colonic disease with minimal small bowel involvement or limited ileal disease.

3D anthropometric assessment and perception of male body morphology in relation to physical strength.

OBJECTIVES: The assessment of men's physical strength is an important part of human social perception, for which observers rely on different kinds of cues. However, besides previous studies being limited in considerable ways, as yet there is no comprehensive investigation of a range of somatometric measures in relation to both objectively measured and observer-perceived physical strength using valid stimuli. METHODS: We examined observer-perceptions of physical strength from 3D body scans of n = 165 men, the usage and validity of somatometric measures as cues to strength, differences between strength ratings from stimuli presented on computer monitors vs in real-life size using a projector, and between male and female observers. RESULTS: A medium-sized correlation between measured and perceived strength was found, partly mediated by target men's chest-to-hip ratio, body density, ankle girth, height, upper arm, and forearm girth. No significant differences between men's and women's strength perceptions or the method of stimuli presentation (computer monitor vs projector) emerged. CONCLUSIONS: Our findings suggest that men's physical strength can be assessed with moderate accuracy from 3D body models and that some somatometric measures represent valid cues, which were used by observers, positively predicting both measured and perceived physical strength.

The Impact of Combination Therapy on Infliximab Levels and Antibodies in Children and Young Adults With Inflammatory Bowel Disease.

Goal: The aim of this study was to evaluate the effect of combination therapy with methotrexate or 6-mercaptopurine on infliximab levels (IFXL) and antibodies to infliximab (ATI). Background: Infliximab (IFX) is a highly effective therapy for inflammatory bowel disease (IBD). Unfortunately, 25%-50% of patients will lose response to IFX. Loss of response is correlated with low IFXL and ATI formation which accelerates drug clearance. Combination therapy is thought to decrease ATI formation. Methods: We performed a cross-sectional analysis of 223 pediatric and young adult patients with IBD on IFX. IFXL and ATI were measured and compared between subjects on current combination therapy, prior combination therapy, and IFX monotherapy. Results: Eighty-four (37.7%) patients were on combination therapy and 139 (62.3%) were on IFX monotherapy. Within the current monotherapy group, 112 (80.6%) had previously been on combination therapy, while 27 (19.4%) had never been on a concomitant immunomodulator. Patients currently on combination therapy had a higher IFXL (17.00 ± 1.33 µg/mL) than those currently on IFX monotherapy (13.18 ± 1.26 µg/mL), P < 0.01. IFXL was lowest in patients who had never been on combination therapy (11.53 ± 2.05 µg/mL) and highest in patients currently on combination therapy (17.00 ± 1.33 µg/mL). Patients currently on combination therapy had a lower rate of detectable ATI (9.5%) compared with those on monotherapy (20.0%) in multivariate analysis (odds ratio [OR]: 0.3; 95% confidence interval (CI), 0.1-0.7, P < 0.01). Conclusions: Current or prior combination therapy is associated with higher IFXL and lower rates of ATI formation.