Healthy Premenopausal Women Research Articles

Effects of separate and combined estradiol and progesterone administration on fear extinction in healthy pre-menopausal women

Altered fear conditioning and extinction learning are discussed as key etiological features in anxiety disorders. Women have an increased risk for anxiety disorders and fear conditioning has been shown to be influenced by the menstrual cycle phase and circulating gonadal hormones. The objective of our study was to investigate the effects of separate and combined estradiol and progesterone administration on fear extinction in healthy women. We conducted a placebo-controlled, randomized study in healthy women, who completed a fear conditioning paradigm on three consecutive days: fear acquisition training on day 1, fear extinction training on day 2, and return of fear test on day 3. Skin conductance responses (SCRs) served as main outcome variable. Two hours before testing on day 2, participants received pills containing either placebo, estradiol (2 mg), progesterone (400 mg) or the combination of both. We examined 116 women (mean age 25.7 ± 6.0 years), who showed significantly stronger conditioned SCRs to the CS+ than CS- during fear acquisition training indicating successful fear learning. At the beginning of the fear extinction training, estradiol administration reduced the differentiation between the conditioned stimuli. In the return of fear test, the estradiol groups showed heightened SCR responses to the previously extinguished stimulus, i.e., impaired extinction recall. Administration of progesterone did not have any significant influence on SCRs. There were also no effects on fear potentiated startle response. In our interpretation, exogenous estradiol administration affected the extinction of the conditioned fear response which led subsequently to a stronger return of fear. From a clinical perspective our findings suggest that estradiol levels may have an influence on the success of exposure therapy and could be taken into consideration when planning exposure sessions.

HR-pQCT reveals marked trabecular and cortical structural deficits in women with pregnancy and lactation associated osteoporosis (PLO).

Pregnancy and lactation associated osteoporosis (PLO) is a rare presentation of early-onset osteoporosis characterized by low trauma, spontaneous fractures during late pregnancy/lactation. Herein, we report areal BMD (aBMD) by DXA and volumetric BMD (vBMD), microarchitecture and strength at the distal radius and tibia by HR-pQCT in 59 women with PLO - in comparison to both healthy premenopausal Controls (n= 28) and premenopausal women with idiopathic osteoporotic fractures not associated with pregnancy/lactation (Non-PLO IOP;n= 50). Women with PLO (aged 34 ± 6yrs) had a more severe clinical presentation than Non-PLO IOP: 80% had vertebral and 92% had multiple fractures (P<.001). They had lower DXA aBMD at all sites vs Controls (all P<.001) and non-PLO IOP (all P<.05). By HR-pQCT, PLO had deficits in all radial/tibial density and most microarchitecture parameters, and lower bone strength than Controls (all P<.001). Compared to non-PLO IOP, PLO had lower total and trabecular density at radius and tibia (all P≤.01) and significant deficits in trabecular microstructure and cortical thickness at the radius only. We studied PLO subgroups with clinical factors potentially related to bone physiology: Within PLO, women with vertebral fractures had lower spine aBMD and higher tibial cortical porosity but were otherwise structurally similar to the nonvertebral group. Those with prior heparin exposure had larger bone size and trabecular area, and those with renal stones had smaller bone size and lower 1/3radius aBMD. We also compared groups based on postpartum timing: Recent PLO (n= 25) evaluated ≤12M postpartum, before expected recovery of pregnancy/lactation bone loss, had significantly lower aBMD than Distant PLO (n= 34) evaluated >12M postpartum. However, radial/tibial HR-pQCT measures did not differ, suggesting pre-existing and/or persistent structural deficits. This structural study increases our mechanistic understanding of the severe bone fragility presentation that characterizes PLO and also highlights areas of potential mechanistic heterogeneity that require additional investigation.

Morning tiredness and insomnia symptoms are associated with increased blood pressure in midlife women

ObjectivesThe objective of this study was to investigate how blood pressure, sleep architecture, sleep-disordered breathing, body habitus, and levels of serum follicle-stimulating hormone are associated with symptoms of insomnia and sleep quality during menopausal transition. Methods64 healthy premenopausal women (aged 45–47 years) were recruited to the study. Data were collected at baseline and at 10-year follow-up during sleep laboratory and laboratory visits. A sleep questionnaire was used to evaluate sleep quality and insomnia symptoms. Data were analysed using multiple linear and logistic regression with a backward method. ResultsDuring the menopausal transition, a change in insomnia symptoms was associated with a change in morning systolic blood pressure (β = 0.114 (CI95% 0.023–0.205), p = 0.016). At follow-up, at the age of 56, a higher percentage of REM sleep was associated with a lower odds of restless sleep (OR = 0.842 (95 % CI 0.742–0.954), p = 0.007), while both higher systolic and diastolic evening blood pressure was associated with an increased odds of morning tiredness.OR = 1.047 (95 % CI 1.003–1.092), p = 0.034 and OR = 1.126 (95 % CI 1.018–1.245), p = 0.007, respectively. ConclusionsIn healthy midlife women, a change blood pressure is related to the development of insomnia symptoms during menopausal transition. In postmenopausal women, a high evening blood pressure may be associated with morning tiredness and a reduced amount of REM sleep may be perceived as restless sleep.

Capillary Blood Docosahexaenoic Acid Levels Predict Electrocardiographic Markers in a Sample Population of Premenopausal Women.

Introduction: The relationship between blood N-3 polyunsaturated fatty acid (PUFA) levels and cardiovascular health is known, but direct evidence that N-3 PUFA levels influence electrocardiographic (ECG) parameters is non-existent. In the study described herein, we investigated the relationship between anthropometric biomarkers and capillary blood PUFAs with ECG outputs in a sample population of healthy pre-menopausal women. Method: Twenty-three consenting females were recruited, with the study power analysis sufficiently demonstrated. Food intake, anthropometric and cardiovascular parameters were obtained. Capillary blood was collected for fatty acid chromatographic analysis. Results: Body mass index, haematocrit, heart rate (HR), mean arterial pressure (MAP) and ECG readings all fell within healthy ranges. Principal component analysis-mediated correlations were carried out controlling for combined Components 1 (age, body fat % and waist-to-hip ratio) and 2 (height, HR and MAP) as control variables. Docosahexaenoic acid (DHA) unequivocally decreased the QRS area under the curve (AUC-QRS) regardless of the impact of control variables, with each unit increase in DHA corresponding to a 2.3-unit decrease in AUC-QRS. Mediation analysis revealed a significant overall effect of DHA on AUC-QRS, with the impact of DHA on R wave amplitude accounting for 77% of the total observed effect. Discussion: Our new findings revealed an inverse relationship between AUC-QRS with capillary blood DHA, suggesting that the association between ventricular mass and its QRS depolarising voltage is mediated by DHA. Our findings bridge a knowledge gap on the relationship between ventricular mass and ventricular efficiency. Further research will confirm whether the relationship identified in our study also exists in diseased patients.

Inhibition of muscle sympathetic nerve activity in premenopausal women: responses to sudden sensory stimuli predict responses to mental stress.

Muscle sympathetic nerve responses to sudden sensory stimuli have been elucidated in several studies on young healthy men, showing reproducible interindividual differences ranging from varying degrees of inhibition to no significant change, with very few subjects showing significant excitation. These individual response patterns have been shown to predict the neural response to mental stress and coupled blood pressure responses. The aim of this study was to investigate whether premenopausal healthy women show similar neural and blood pressure responses. Muscle sympathetic nerve recordings from the peroneal nerve were performed in 34 healthy women (mean age 27 ± 8 yr) during sudden sensory stimuli (electrical stimuli to a finger) and 3 min of mental stress (forced arithmetics). After sensory stimuli, 18 women showed varying degrees of inhibition of muscle sympathetic nerve activity (burst amplitude mean reduction 60%, range 34-100%). The remaining 16 showed no inhibition (mean 5%, range -31 to 28%; one subject exhibiting excitation). During 3 min of mental stress, the normalized change in burst incidence for muscle sympathetic nerve activity correlated with the percentage change of muscle sympathetic nerve activity induced by the sensory stimulation protocol (r = 0.64, P = 0.0042). In contrast to men, the neural responses did not predict changes in blood pressure. Thus, premenopausal females show a similar range of individual differences in defense-related muscle sympathetic neural responses as men, but no associated differences in blood pressure responses. Whether these patterns are unchanged after menopause remains to be investigated.NEW & NOTEWORTHY Muscle sympathetic neural responses to sudden sensory stimuli in premenopausal women showed interindividual differences and the distribution of sympathetic responses was similar to that previously found in men. Despite this similarity, the associated differences in transient blood pressure responses seen in men were not found in women. The increased risk of developing hypertension in postmenopausal women warrants an investigation of whether these response patterns are altered after menopause.

Differential brainstem connectivity according to sex and menopausal status in healthy men and women.

Brainstem nuclei play a critical role in both ascending monoaminergic modulation of cortical function and arousal, and in descending bulbospinal pain modulation. Even though sex-related differences in the function of both systems have been reported in animal models, a complete understanding of sex differences, as well as menopausal effects, in brainstem connectivity in humans is lacking. This study evaluated resting-state connectivity of the dorsal raphe nucleus (DRN), right and left locus coeruleus complex (LCC), and periaqueductal gray (PAG) according to sex and menopausal status in healthy individuals. In addition, relationships between systemic estrogen levels and brainstem-network connectivity were examined in a subset of participants. Resting-state fMRI was performed in 50 healthy men (age, 31.2 ± 8.0 years), 53 healthy premenopausal women (age, 24.7 ± 7.3 years; 22 in the follicular phase, 31 in the luteal phase), and 20 postmenopausal women (age, 54.6 ± 7.2 years). Permutation Analysis of Linear Models (5000 permutations) was used to evaluate differences in brainstem-network connectivity according to sex and menopausal status, controlling for age. In 10 men and 17 women (9 premenopausal; 8 postmenopausal), estrogen and estrogen metabolite levels in plasma and stool were determined by liquid chromatography-mass spectrometry/mass spectrometry. Relationships between estrogen levels and brainstem-network connectivity were evaluated by partial least squares analysis. Left LCC-executive control network (ECN) connectivity showed an overall sex difference (p = 0.02), with higher connectivity in women than in men; however, this was mainly due to differences between men and pre-menopausal women (p = 0.008). Additional sex differences were dependent on menopausal status: PAG-default mode network (DMN) connectivity was higher in postmenopausal women than in men (p = 0.04), and PAG-sensorimotor network (SMN) connectivity was higher in premenopausal women than in men (p = 0.03) and postmenopausal women (p = 0.007). Notably, higher free 2-hydroxyestrone levels in stool were associated with higher PAG-SMN and PAG-DMN connectivity in premenopausal women (p < 0.01). Healthy women show higher brainstem-network connectivity involved in cognitive control, sensorimotor function, and self-relevant processes than men, dependent on their menopausal status. Further, 2-hydroxyestrone, implicated in pain, may modulate PAG connectivity in premenopausal women. These findings may relate to differential vulnerabilities to chronic stress-sensitive disorders at different life stages.

Safety of topical sildenafil cream, 3.6% in a randomized, placebo-controlled trial for the treatment of female sexual arousal disorder.

There are currently no Food and Drug Administration-approved treatments for female sexual arousal disorder (FSAD), which is physiologically analogous to male erectile dysfunction. The study sought to test the systemic and local genital safety of topical sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD and their sexual partners over a 12-week treatment period. This was a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream among healthy premenopausal women with FSAD. Safety was assessed by the frequency and incidence of treatment-emergent adverse events (TEAEs) among participants and their sexual partners. Participants recorded the incidence of TEAEs in a daily eDiary (electronic diary). Sexual partners were contacted within 72hours of each sexual event in which investigational product was used. All participants used placebo cream for 1 month, during a single-blind run-in period, and then if eligible, were randomized 1:1 to sildenafil cream or placebo cream. Participants used their assigned investigational product over a 12-week double-blind dosing period. They attended monthly follow-up visits, in which their eDiary TEAE data were reviewed by the study staff and graded for severity and relationship to study product. The frequency and incidence of TEAEs among participants and their sexual partners. During the 12-week double-blind dosing period, there were 78 TEAEs reported by 29 of 99 sildenafil-assigned participants and 65 TEAEs reported by 28 of 94 placebo-assigned participants (P= .76). All TEAEs were mild or moderate in severity. The most common treatment-related TEAE among active and placebo-assigned participants was application site discomfort. There were no differences in the number of treatment-related TEAEs among sildenafil cream vs placebo cream users (P> .99). Four sildenafil cream participants and 3 placebo cream participants discontinued the study due to TEAEs involving application site discomfort (P> .99). There were 9 TEAEs reported by 7 of 91 sexual partners exposed to sildenafil cream vs 4 TEAEs reported by 4 of 84 sexual partners exposed to placebo cream (P= .54). These data support further clinical development of topical sildenafil cream for the treatment of FSAD. Safety was assessed among participants and their sexual partners after 1357 and 1160 sexual experiences in which sildenafil cream or placebo cream were used, respectively. The phase 2b study was powered for the primary objectives of efficacy, rather than safety. These data demonstrate that topically applied sildenafil cream was safe and well tolerated by exposed users and their sexual partners.

The effect of hygienic material use during menstruation on the prevalence of RTIs symptoms among women in India

Background: Every month, healthy adolescent girls and pre-menopausal adult women are impacted by the crucial topic of menstrual hygiene. Menstrual hygiene management is essential to women’s reproductive health. Menstrual product consumption, poor cleaning techniques, and material reuse are examples of suboptimal menstrual health and hygiene. So, the current study was planned to assess the impact of hygienic material use during menstruation on the prevalence of RTIs among women in India. Methods: A cross-sectional, comparative community-based study was conducted in urban and rural areas of Bangalore, India. Study was conducted from December 2023 to March 2024. All female patients in reproductive age group attending RHTC and UHTC OPD were included. Interview method was used to collect data from consented participants on socio demographic details, products used for menstrual hygiene and symptoms suggestive of RTI in last 6 months were collected. Results: A community-based study was conducted in rural and urban field practice area of a medical college in Bangalore. A total of 258 participants attending UHTC and RHTC centres were included from each area. The proportion of participants with RTI symptoms were 62.2%. In current study 20.3% participants reported lower abdominal pain and 18.6% of participants had pain during micturition in past 6 months. Conclusions: Our study’s findings show a direct link between subpar MHM procedures and RTI symptoms. Our results confirm international recommendations for a dual focus on providing suitable absorbent materials and making sure that ambient conditions allow associated hygiene, such as washing, safety, and dignity for women.

Comparisons and correlations of 1-month recall vs 24-hour recall in patient-reported outcomes of an exploratory, phase 2b, randomized, double-blind, placebo-controlled clinical trial of sildenafil cream, 3.6% for the treatment of female sexual arousal disorder.

Efficacy assessments in clinical trials of treatments for female sexual arousal disorder (FSAD) and other female sexual dysfunction (FSD) diagnoses rely on various patient-reported outcomes (PROs). We sought to compare 1-month recall PRO measures among participants enrolled in a clinical trial who provided these data without (test population) vs with (control population) use of an at-home, 24-hour recall electronic diary (eDiary), capturing similar data. Preplanned subset analysis as performed during a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD. Preliminary product efficacy was assessed via 1-month recall and 24-hour recall questionnaires. A subset of the participants, the Evaluation of Recall Subset [ERS] provided PROs via the 1-month recall instruments but did not provide data via the 24-hour recall eDiary. Responses to the 1-month recall instruments were compared among ERS (test) vs non-ERS (control) participants. Among the non-ERS population, correlations between 1-month and 24-hour recall endpoints were calculated. There were no significant differences in the study co-primary 1-month recall efficacy endpoints, the Arousal Sensation (AS) domain of the 28-item Sexual Function Questionnaire (SFQ28) and the Female Sexual Distress Scale - Desire, Arousal, Orgasm question 14, among ERS vs non-ERS participants during the initial 1-month no-drug run-in period or the 1-month single-blind placebo run-in period (P values > .47). Scores on these 1-month recall PROs continued to be similar after randomization for sildenafil cream (P values > .30) and placebo cream (P values > .20) assigned ERS and non-ERS participants during the 3-month double-blind dosing period. There were strong correlations between the SFQ28 AS and eDiary AS scores during the no-drug run-in (R= 0.79, P< .01) and the single-blind run-in (R= 0.73 P< .001). During the double-blind dosing period, the SFQ28 AS score continued to be highly correlated with the eDiary AS score among sildenafil cream users (R= 0.83; P< .001) and placebo cream users (R= 0.8; 2 P< .001). There was no evidence that 1-month recall PRO instruments introduce recall bias; assessing arousal sensations with 24-hour vs 1-month PRO instruments is similar and either method could be used to assess efficacy depending on study objectives. This preplanned subset analysis compared efficacy of PROs based on recall duration. While the subset was preplanned, the study was powered to detect significant differences in the primary efficacy objectives, not among this subset analyses. These data will be used in planning future efficacy assessments of sildenafil cream for FSAD. This clinical trial was registered with ClinicalTrials.gov, NCT04948151.

Ultrasonographic threshold of ovarian structure in premenopausal women of different ethnicity

The polycystic ovarian morphology (PCOM) is a generally accepted ultrasound marker for ovulatory dysfunction, is one of the criteria for polycystic ovary syndrome (PCOS) and is established based on the assessment of ovarian volume (OV) and the follicle number per ovary (FNPO), taking into account the upper normal values determined in healthy premenopausal women. However, there is a necessity for regular revision of the PCOM characteristics depending on ethnic and age characteristics.The aim. To develop differentiated standards for assessing the ultrasonographic ovary structure in premenopausal women of various ethnicity.Materials and methods. From March 2016 to December 2019, a multicenter cross-sectional prospective study was conducted in Eastern Siberia (Irkutsk region) and in the neighboring Republic of Buryatia. The study included 1134 participants: 715 women of Caucasian origin, 312 Asian women, 107 women of mixed ethnic subpopulation.Results. It has been established that for Caucasians, it is advisable to diagnose PCOM when the ovarian volume is 9 cm3 and/or FNPO ≥ 12; for women of the Asian population – when the ovarian volume is 7 cm3 and/or FNPO ≥ 11; for women of mixed ethnicity – when the ovarian volume is 8 cm3 and/or FNPO ≥ 9. An important advantage of our study is that all participants were recruited from a non-selective multi-ethnic population of women with comparable socio-demographic characteristics living in the same geographical conditions.Conclusion. Differentiated approach for identifying the polycystic ovarian morphology in premenopausal women of different ethnic groups requires using ethnically differentiated normative readings

Male Body Odor Affects Emotional State, LH, and Cortisol Secretion in Women of Different Age Groups.

Hormone changes across women's menstrual cycles may lead to changes in their perceptions of chemical signals and their hormonal responses to these cues. The aim of the present study was to determine the role of menstrual cycle phase in the response to extracts of male axillary secretions (EMAS) in women. We tested healthy reproductive age and premenopausal women (n = 29). An EMAS/control solution was applied once every two hours during either the follicular or luteal phase, at which point saliva samples for luteinizing hormone (LH) and cortisol monitoring were collected. LH and cortisol concentrations were analyzed using the enzyme immunoassay (EIA) technique. Positive and Negative Affect Schedule (PANAS) and Visual Analogue Scales (VAS) scores were used to assess the participants' moods. For the first time, we showed that EMAS may produce opposite effects on LH secretion depending on the menstrual cycle phase of the recipient. We observed a significant increase in the number of LH peaks (p = 0.0447) and their amplitudes (p = 0.0469) when EMAS was applied during the follicular phase, while the same application in the luteal phase lowered the amplitudes of LH peaks (p = 0.0382). For the first time, we showed that EMAS application increased salivary cortisol levels in reproductive age women relative to premenopausal women (p = 0.0032). PANAS scores revealed changes in positive and negative affect after EMAS application. Our data indicate the significance of the menstrual cycle phase for EMAS' effects on LH secretion and mood, but not on cortisol secretion in women.

Transcriptomic Profile of Breast Tissue of Premenopausal Women Following Treatment with Progesterone Receptor Modulator: Secondary Outcomes of a Randomized Controlled Trial.

Progesterone receptor antagonism is gaining attention due to progesterone's recognized role as a major mitogen in breast tissue. Limited but promising data suggest the potential efficacy of antiprogestins in breast cancer prevention. The present study presents secondary outcomes from a randomized controlled trial and examines changes in breast mRNA expression following mifepristone treatment in healthy premenopausal women. We analyzed 32 paired breast biopsies from 16 women at baseline and after two months of mifepristone treatment. In total, 27 differentially expressed genes were identified, with enriched biological functions related to extracellular matrix remodeling. Notably, the altered gene signature induced by mifepristone in vivo was rather similar to the in vitro signature. Furthermore, this gene expression signature was linked to breast carcinogenesis and notably linked with progesterone receptor expression status in breast cancer, as validated in The Cancer Genome Atlas dataset using the R2 platform. The present study is the first to explore the breast transcriptome following mifepristone treatment in normal breast tissue in vivo, enhancing the understanding of progesterone receptor antagonism and its potential protective effect against breast cancer.

Assessment of the Efficacy of a Novel Oral Supplement on Symptoms of Bloating Among Healthy Pre-Menopausal Women

Assessment of the Efficacy of a Novel Oral Supplement on Symptoms of Bloating Among Healthy Pre-Menopausal Women

Preliminary Efficacy of Topical Sildenafil Cream for the Treatment of Female Sexual Arousal Disorder: A Randomized Controlled Trial.

To assess the efficacy of topical sildenafil cream, 3.6% among healthy premenopausal women with female sexual arousal disorder. We conducted a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream. Coprimary efficacy endpoints were the change from baseline to week 12 in the Arousal Sensation domain of the SFQ28 (Sexual Function Questionnaire) and question 14 of the FSDS-DAO (Female Sexual Distress Scale-Desire, Arousal, Orgasm). Two hundred women with female sexual arousal disorder were randomized to sildenafil cream (n=101) or placebo cream (n=99). A total of 174 participants completed the study (sildenafil 90, placebo 84). Among the intention-to-treat (ITT) population, which included women with only female sexual arousal disorder and those with female sexual arousal disorder with concomitant sexual dysfunction diagnoses or genital pain, although the sildenafil cream group demonstrated greater improvement in the SFQ28 Arousal Sensation domain scores, there were no statistically significant differences between sildenafil and placebo cream users in the coprimary and secondary efficacy endpoints. An exploratory post hoc subset of the ITT population with an enrollment diagnosis of female sexual arousal disorder with or without concomitant decreased desire randomized to sildenafil cream reported significant increases in their SFQ28 Arousal Sensation domain score (least squares mean 2.03 [SE 0.62]) compared with placebo cream (least squares mean 0.08 [SE 0.71], P =.04). This subset achieved a larger mean improvement in the SFQ28 Desire and Orgasm domain scores. This subset population also had significantly reduced sexual distress and interpersonal difficulties with sildenafil cream use as measured by FSDS-DAO questions 3, 5, and 10 (all P ≤.04). Topical sildenafil cream improved outcomes among women with female sexual arousal disorder, most significantly in those who did not have concomitant orgasmic dysfunction. In particular, in an exploratory analysis of a subset of women with female sexual arousal disorder with or without concomitant decreased desire, topical sildenafil cream increased sexual arousal sensation, desire, and orgasm and reduced sexual distress. ClinicalTrials.gov , NCT04948151.

(094) MEASURES OF FEMALE SEXUAL DISTRESS IN AN EXPLORATORY, PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL OF SILDENAFIL CREAM, 3.6% FOR THE TREATMENT OF FEMALE SEXUAL AROUSAL DISORDER

Abstract Introduction The diagnosis of female sexual arousal disorder (FSAD) requires that individuals experience clinically significant distress from their symptoms. Pre-trial content validity investigations were conducted by the sponsor to understand how women with FSAD best described their distress associated with this female sexual dysfunction (FSD) diagnosis. Objective Responses to the Female Sexual Distress Scale – Desire, Arousal, Orgasm (FSDS-DAO) survey among healthy premenopausal women enrolled in a Phase 2b, exploratory, randomized, placebo-controlled, double-blind study of Sildenafil Cream, 3.6% for FSAD treatment (NCT04948151). Methods After informed consent, enrollment diagnoses for each participant were established during a one-on-one clinical interview with independent experts. Baseline assessments were measured after a one-month, single-blind, placebo, run-in period. Participants were then randomized to Sildenafil Cream, 3.6% (n=101) versus Placebo (n=99) and used the investigational product (IP) as needed at home for 12 weeks, with monthly in-clinic assessments. The change from baseline at week 12 in question 14 (Q14) of the FSDS-DAO was a co-primary efficacy endpoint. All 15 FSDS-DAO questions begin with “How often did you feel, in the past 30 days” with a Likert score of 0 (Never) to 4 (Always). Results Although changes from baseline at week 12 in FSDS-DAO Q14 responses were not different among active versus placebo users in the intent-to-treat population (p=0.84) or the future target population (women with FSAD only or primary FSAD with secondary hypoactive sexual desire disorder (HSDD)) (p=0.95), responses to several FSDS-DAO questions, showed reduced sexual distress among Sildenafil Cream, 3.6% users (Table 1). While Q14 asked specifically about concerns with sexual arousal, the other 5 questions asked about generalized sexual distress, using verbiage more congruent with pre-trial content validity investigations. Post-trial psychometric validation studies selected question 5 as the most appropriate for measuring sexual distress among this population. Conclusions Data from this exploratory trial support that women with a diagnosis of FSAD only or primary FSAD with secondary HSDD experienced reduced sexual distress after receiving Sildenafil Cream, 3.6%. Disclosure Yes, this is sponsored by industry/sponsor: Dare Bioscience and Strategic Science and Technologies. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Dare Bioscience and Strategic Science and Technologies.

Evaluation of oral health, taste perception, nutritional status and emotional well-being in post-menopausal women.

In postmenopausal women (PMW), vasomotor symptoms, emotional oscillations and sleep disturbances can affect physiological and psychological functioning. However, the effect of menopause on oral health-related parameters is not been thoroughly studied. To evaluate oral health, taste perception, eating habits, nutritional status and emotional well-being in PMW compared with a group of young and healthy pre-menopausal women (PrMW). Two groups (Group I: PMW and Group II: PrMW) with 30 participants each, participated in the cross-sectional study. The study proforma contained measures of oral health, taste perception, nutritional status and anxiety levels of the women in both groups using validated and previously used tools were designed and implemented. The data were analysed with student t, Mann-Whitney U, and chi-squared tests to evaluate the differences between the two groups. The cross-sectional study indicates no major differences in oral health, taste perception, nutritional and emotional status between PMW and PrMW. Nonetheless, there was a significant difference in perception of 'front teeth lengthening in size' and change in hot and cold sensations between the groups. Furthermore, the study group with PMW tends to have fewer natural teeth than the reference group. Overall, menopause does not appear to affect oral health, taste perception, nutrition or emotional health. It is suggested that oral health and taste perception, as well as nutritional and emotional status, are associated with gradual aging processes that may or may not be affected by menopause.

Targeted Analysis of Plasma Polar Metabolites in Postmenopausal Depression.

Depression will be the disease with the highest incidence worldwide by 2030. Data indicate that postmenopausal women have a higher incidence of mood disorders, and this high vulnerability seems to be related to hormonal changes and weight gain. Although research evaluating the profile of metabolites in mood disorders is advancing, further research, maintaining consistent methodology, is necessary to reach a consensus. Therefore, the objective of the present study was to carry out an exploratory analysis of the plasma polar metabolites of pre- and postmenopausal women to explore whether the profile is affected by depression. The plasma analysis of 50 polar metabolites was carried out in a total of 67 postmenopausal women, aged between 50 and 65 years, either without depression (n = 25) or with depression symptoms (n = 42), which had spontaneous onset of menopause and were not in use of hormone replacement therapy, insulin, or antidepressants; and in 42 healthy premenopausal women (21 without depression and 21 with depression symptoms), aged between 40 and 50 years and who were not in use of contraceptives, insulin, or antidepressants. Ten metabolites were significantly affected by depression symptoms postmenopause, including adenosine (FDR = 3.778 × 10-14), guanosine (FDR = 3.001 × 10-14), proline (FDR = 1.430 × 10-6), citrulline (FDR = 0.0001), lysine (FDR = 0.0004), and carnitine (FDR = 0.0331), which were down-regulated, and dimethylglycine (FDR = 0.0022), glutathione (FDR = 0.0048), creatine (FDR = 0.0286), and methionine (FDR = 0.0484) that were up-regulated. In premenopausal women with depression, oxidized glutathione (FDR = 0.0137) was down-regulated, and dimethylglycine (FDR = 0.0406) and 4-hydroxyproline (FDR = 0.0433) were up-regulated. The present study provided new data concerning the consequences of depression on plasma polar metabolites before and after the establishment of menopause. The results demonstrated that the postmenopausal condition presented more alterations than the premenopausal period and may indicate future measures to treat the disturbances involved in both menopause and depression.

Age Comparisons of Cardiac Work During Exercise in Women: Insight from Acute β1 Adrenergic Blockade

Postmenopausal women exhibit exaggerated increases in blood pressure during activities of daily living and exercise. The decreased size and increased stiffening of postmenopausal women's hearts elevate myocardial oxygen demand when compared to age-matched men and younger cohorts. Together, this poses a risk to the safety of, and capacity for, exercise in postmenopausal women. We recently studied the effects of esmolol, a fast-acting, cardio-selective β1 antagonist, on oxygen transport variables during dynamic exercise in healthy young (Y) and older (O) women to better understand differences in cardiovascular responses to exercise. Objective: Determine the effects of acute cardiac specific blockade on myocardial oxygen demand (rate pressure product, RPP) and cardiac work (CW) in healthy young premenopausal and older postmenopausal women. Methods: Thirteen healthy young (20-32 yr) and older postmenopausal (58-70 yr) women performed moderate (85% of lactate threshold) and heavy (50% between lactate threshold and the respiratory compensation point) recumbent leg cycling exercise during IV infusion of saline or esmolol in randomized order. Whole body oxygen consumption (VO2, indirect calorimetry), brachial systolic blood pressure (SBP, automated cuff), heart rate (HR, ECG), and cardiac output (CO, bioimpedance) were measured continuously. RPP (HR×SBP), CW (CO×SBP), and cardiac effciency (CE, CW/VO2) were calculated. Mixed model repeated measures ANOVAs were used to determine the effect of treatment and age group. Results: Power outputs were lower in O vs. Y at both moderate (45±9W and 72±15W, p&lt;0.001) and heavy (81±21W vs. 117±32W, p&lt;0.001) intensities. During the saline trial CO was lower (p&lt;0.001), and RPP was higher (p&lt;0.001) in the O vs. Y group during both intensities. There was a main effect of treatment on RPP, CW, and CE. Esmolol reduced RPP (4638±775 SD, p&lt;0.001), CW (547±89, p&lt;0.001) and CE (1682±62, p&lt;0.001) in both O and Y. There was a main effect of age group on CE, pairwise comparisons showed CE was lower in O than Y (441±112, p&lt;0.001). Conclusions: Older postmenopausal women experience higher myocardial oxygen demand and perform more cardiac work for a given whole body liter oxygen consumed during dynamic leg exercise compared to younger premenopausal women. Acute β1 adrenergic blockade narrows the gap between central cardiovascular function in young and old women and provides a powerful tool to investigate age-related cardiovascular differences. NIH R21 AG054940. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Phase 1 study of safety and tolerability of an oral contraceptive containing low-dose ethinyl oestradiol combined with glecaprevir/pibrentasvir treatment in healthy premenopausal women.

Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline-recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 μg/250 μg EE/norgestimate. No Grade ≥2 elevation was observed with low-dose (20 μg) EE (n = 14). This Phase 1 study examined safety/tolerability of GLE/PIB coadministered with an OC containing low-dose EE using a larger sample size and longer treatment duration. Healthy premenopausal women were treated with EE/levonorgestrel alone (20/100 μg, Cycles 1-2), followed by coadministration with GLE/PIB (300/120 mg; Cycles 3-4). A safety criterion of special interest was a confirmed Grade ≥2 ALT elevation (>3× upper normal limit). Adverse events (AEs) and study drugs concentrations were examined. Of 85 enrolled women, 72 initiated combined GLE/PIB + EE/levonorgestrel treatment, 66 completed the study and 19 discontinued prematurely (non-safety reason, n = 16; AE [deemed unelated to GLE/PIB], n = 3). No participant met the safety criterion of special interest of confirmed Grade ≥2 ALT elevation. No serious/Grade ≥3 AEs were reported. Study drug concentrations were within the expected ranges. GLE/PIB in combination with an OC containing low-dose EE was generally well tolerated with no confirmed Grade ≥2 ALT elevation and no evidence of drug-induced liver injury. No pattern to the reported AEs and no new safety issues were identified. This was a Phase 1 study of healthy volunteers, not a registered clinical trial.

Higher number of steps is related to lower endogenous progesterone but not estradiol levels in women.

Sex steroid hormones are important not only for reproduction but also for many aspects of women's health, including the risk of breast cancer. Physical activity has been shown to influence sex hormone levels in women. This study aimed to investigate a relationship between the average daily number of steps and the sex hormone (estradiol and progesterone) levels in premenopausal women. Data were collected from 85 healthy, urban women of reproductive age who performed at least 180 minutes/week of moderate physical activity for two complete menstrual cycles. Physical activity was measured using wrist bands. Estradiol and progesterone concentrations were measured in daily-collected saliva samples in the second menstrual cycle. There was a significant negative association between the average number of steps taken daily and salivary progesterone levels after adjusting for potential confounding factors (age, BMI). Women who took more than 10,000 steps a day had significantly lower progesterone levels compared to women who took less than 10,000 steps. The association between physical activity and estradiol levels was statistically insignificant. Our results indicate that taking at least 10,000 steps a day reduces progesterone levels, but this intensity of physical activity may not be high enough to affect estradiol levels. Daily step tracking is a valuable element of health promotion, but currently recommended levels of physical activity may not be high enough for healthy premenopausal women to significantly reduce both sex hormone levels and thus their risk of postmenopausal breast cancer.