Background: A variety of biological and psychosocial factors are associated with women’s sexual health in midlife and older age. Evidence suggests a decline in sexual functioning in the context of aging and the menopausal transition, including changes in sexual desire, arousal, lubrication, orgasm, pain, and/or contentment. However, not all women in midlife and older age experience such a decline, and it remains unclear how the endocrine environment and psychosocial aspects contribute to the maintenance of healthy sexual functioning. Therefore, the aim of this study was to examine psychobiological predictors of sexual functioning in healthy middle-aged and elderly females.Methods: A total of 93 healthy, sexually active women aged 40–73 years completed a battery of validated psychosocial questionnaires, including measures of sexual functioning (Female Sexual Function Index) and of protective psychological traits and interpersonal variables. The steroid hormones estrogen, testosterone, progesterone and dehydroepiandrosterone sulfate were determined in saliva samples, while follicle-stimulating hormone, luteinizing hormone and sex hormone-binding globulin were determined in dried blood spots. The findings were statistically adjusted for multiple testing.Results: Age and postmenopausal status were negatively associated with overall sexual functioning, arousal, and lubrication. Regression analyses revealed that relationship satisfaction, emotional support, self-esteem, optimism, and life satisfaction each significantly predicted overall sexual functioning or specific aspects of sexual functioning, including arousal, contentment, orgasm, and pain (all p < 0.029). For desire and lubrication, no associations were found with the tested psychosocial factors. In terms of steroid hormones, testosterone was positively linked to orgasm (p = 0.012). In this sample, 79.6% reported to have healthy sexual functioning according to the questionnaires’ cutoff. Younger age (OR = 0.911, 95% CI 0.854–0.970, p = 0.004) and a higher level of emotional support (OR = 1.376, 95% CI 1.033–1.833, p = 0.029) were associated with the presence of healthy sexual functioning.Discussion: Although aging and menopause negatively affected aspects of sexual functioning, the accompanying endocrine correlates were not predictive for sexual functioning in this healthy sample of middle-aged and older females. Instead, our findings suggest that sexual functioning is highly dependent on psychosocial aspects related to well-being. Accordingly, personality traits such as optimism, and interpersonal aspects such as emotional support and relationship satisfaction were identified as important predictors of sexual functioning.

Background: Adversity in early development seems to increase the risk of stress-related somatic disorders later in life. Physiologically, functioning of the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes is often discussed as long-term mediators of risk. In particular, DNA methylation in the glucocorticoid receptor gene promoter (NR3C1) has been associated with type and strength of early life adversity and subsequent effects on HPA axis signaling in humans. Animal studies, moreover, suggest changes in DNA methylation in the estrogen receptor gene (ERα) upon early life adversity. We investigated the association of type and severity of childhood adversity with methylation in NR3C1 and ERα and additionally considered associations between methylation and steroid hormone secretion. Methods: The percentage of methylation within the NR3C1 promoter and the ERα shore was investigated using dried blood spot samples of 103 healthy women aged 40–73 years. Childhood adversity was examined with the Childhood Trauma Questionnaire. Linear regression analyses were performed with methylation as dependent variable and the experience of emotional abuse and neglect, physical abuse and neglect, and sexual abuse (compared to non-experience) as independent variables. All analyses were controlled for age, BMI, annual household income, and smoking status and were adjusted for multiple testing. Results: Overall, over 70% of the sample reported having experienced any kind of abuse or neglect of at least low intensity. There were no significant associations between childhood adversity and methylation in the NR3C1 promoter (all p > .10). Participants reporting emotional abuse showed significantly higher methylation in the ERα shore than those who did not (p = .001). Additionally, higher levels of adversity were associated with higher levels of ERα shore methylation (p = .001). Conclusion: In healthy women, early life adversity does not seem to result in NR3C1 promoter hypermethylation in midlife and older age. This is the first study in humans to suggest that childhood adversity might, however, epigenetically modify the ERα shore. Further studies are needed to gain a better understanding of why some individuals remain healthy and others develop psychopathologies in the face of childhood adversity.

Background Persistent infection with high-risk human papillomavirus (HR-HPV) is the most important risk factor for the development of cervical cancer, but factors contributing to HR-HPV persistence are incompletely understood. The objective of this study was to test for associations of chronic stress and two aspects of diurnal cortisol secretion (i.e., the cortisol awakening response [CAR] and total cortisol output over the day [AUCgday]) with HR-HPV status at baseline and 12 months later (follow-up). Methods We evaluated 188 women (25 ± 3 years) at baseline. Follow-up investigation was restricted to HR-HPV infected women at baseline. Of the initial 48 HR-HPV positive participants, 42 completed the follow-up (16 HR-HPV positive and 26 HR-HPV negative). At baseline and follow-up, we determined HR-HPV status in cervical smears, assessed chronic stress, and repeatedly measured salivary cortisol over the day. At baseline, we analyzed salivary cortisol only in a subgroup of 90 participants (45 HR-HPV negative and 45 HR-HPV positive). Results At baseline, higher chronic stress (excessive demands at work: p = .022, chronic worrying: p = .032), and a higher CAR (p = .014) were related to baseline HR-HPV positivity. At follow-up, there was a statistical trend for a positive association between the CAR and HR-HPV positivity (p = .062). Neither the CAR nor the AUCgday mediated the associations between chronic stress and HR-HPV status. Conclusions Our findings suggest that both chronic stress and diurnal cortisol are related to the presence of HR-HPV infection and may thus play a role in HPV-associated cervical carcinogenesis.

Background Estrogen receptor α (ERα) contributes to maintaining biological processes preserving health during aging. DNA methylation changes of ERα gene (ESR1) were established as playing a direct role in the regulation of ERα levels. In this study, we hypothesized decreased DNA methylation of ESR1 associated with postmenopause, lower estradiol (E2) levels, and increased age among healthy middle-aged and older women. Methods We assessed DNA methylation of ESR1 promoter region from dried blood spots (DBSs) and E2 from saliva samples in 130 healthy women aged 40–73 years. Results We found that postmenopause and lower E2 levels were associated with lower DNA methylation of a distal regulatory region, but not with DNA methylation of proximal promoters. Conclusion Our results indicate that decreased methylation of ESR1 cytosine-phosphate-guanine island (CpGI) shore may be associated with conditions of lower E2 in older healthy women.

Background Healthy aging is particularly important in women, as their life-span is generally longer than men’s, leaving women at higher risk for age-related diseases. Understanding determinants of women’s healthy aging is therefore a major public health interest. Clinical utility of previous research is limited, through its focus on either single psychosocial or biological predictors. The present study investigated psychobiological predictors of women’s healthy aging, for the first time including positive psychological traits and biomarkers of healthy aging. Methods Totally, 121 generally healthy women aged 40 to 75 were investigated cross-sectionally. Healthy aging was operationalized via self-rated health (SRH). To gain a nuanced view of the particularities at the upper end of the illness-wellness continuum, women with excellent SRH and those with good SRH were analyzed as distinct groups. Socioeconomic and sociodemographic variables, health behavior, resilience, optimism, and self-worth as well as menopausal symptoms, and levels of steroid hormones and gonadotropins were considered as predictors of SRH. Binary logistic regression analyses using the forward conditional method were performed with the two health status groups as dependent variable. Results Women with a lower body mass index (BMI; OR = .59, 95% CI = .33–1.03), higher intensive physical activity (OR = 2.27, 95% CI = 1.06–4.86), and higher resilience (OR = 2.37, 95% CI = 1.34–4.18) were more likely to rate their health as excellent compared to good. No clinically significant differences could be found regarding endocrine levels. Conclusion Psychobiological indicators (lower BMI, intensive physical activity, higher resilience) discriminated SRH at the top level of the health spectrum. In healthy women, the predictive value of endocrine markers seems to be secondary. Interventions targeting these indicators could promote women’s healthy aging.