Postmenopausal, Premenopausal
Conditions
Keywords
Oxytocin, Postmenopausal, Premenopausal, Neurophysin-I, cyclic hormonal condition, menstrual cyclic phase
Brief summary
The aim of the present study is to assess whether cumulative endogenous neurophysin I secretion over one month differs between premenopausal and postmenopausal women. Using repeated measurements of neurophysin-I (NP-I, equimolar surrogate marker of oxytocin) across defined physiological time points, this study investigates oxytocin system regulation under cyclic and non-cyclic hormonal conditions. The primary hypothesis is that cumulative NP-I release, expressed as the area under the curve (AUC) is lower in the postmenopausal group compared to the premenopausal group.
Detailed description
Oxytocin (OXT) plays a key role in pair-bonding behavior, social cognition, stress regulation and emotional processing, while peripherally it regulates parturition, lactation, and smooth muscle function. Beyond reproductive physiology, OXT has been implicated in numerous other metabolic functions. It has been suggested to exert cardioprotective effects, including attenuation of cardiac apoptosis and fibrosis, negative chronotropic and inotropic actions \[7\], and anti-inflammatory effects. Furthermore, it has been associated with the regulation of glucose homeostasis and pain perception. In women, elevated OXT levels have been suggested to enhance cognitive control over food cravings. While a clinical study including 55 women examined postprandial OXT levels across different menstrual phases, data on fasting OXT levels across an entire cycle in premenopausal women, as well as comparisons with postmenopausal women, remain scarce. In general, most research on the relation between OXT and food intake has been done outside the context of the menstrual cycle or in clinical populations (e.g. patients with bulimia nervosa). The synthesis, release and expression of OXT are modulated by sex steroids, particularly estrogen. Across the menstrual cycle, circulating OXT levels exhibit dynamic changes in women of reproductive age. Menopause, however, is characterized by complete cessation of ovarian function leading to sustained estrogen deficiency and loss of cyclical hormonal regulation. A longitudinal assessment of circulating OXT across a physiological menstrual cycle, compared with repeated measurements in postmenopausal women, may provide a more robust characterization of OXT secretion patterns. Quantifying NP-I release over time using the area under the curve (AUC) may overcome limitations of single time-point measurements and improve understanding of menopause-related alterations in OXT physiology. The aim of the present study is to assess whether cumulative endogenous NP-I secretion (equimolar OXT surrogate marker) over one month differs between premenopausal and postmenopausal women
Interventions
OTHERRepeated assessments
This study is an observational investigation involving repeated venous blood sampling and non-invasive clinical assessments ov four study visits.
Sponsors
University Hospital, Basel, Switzerland
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female sex at birth * Age ≥18 years Premenopausal group: • Premenopausal women aged 18-35 years with regular menstrual cycles (21-35 days) for ≥3 months prior to study entry Postmenopausal group: • Postmenopausal women ≥2 years of postmenopause (i.e. 3 years since last menstrual period (LMP), with menopause defined as ≥ 12 months of amenorrhea)
Exclusion criteria
* Pregnancy or breastfeeding * Use of hormonal contraception or hormone replacement therapy within the last 3 months * Known endocrine disorders affecting the hypothalamic-pituitary-gonadal axis * Use of medications * Severe depression (BDI score \> 28 points), any other severe psychiatric illness or acute medical disease * Inability to comply with study procedures * Participation in a trial with investigational drugs within the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve of Neurophysin-1 (NP-I) | 1 month | The primary endpoint is the Area under the curve (AUC) of circulating plasma NP-I assessed over four standardized study visits within one month, corresponding to mid-menstruation, mid-follicular phase, ovulation, and mid-luteal phase in premenopausal women, and four weekly visits in postmenopausal women. The primary comparison will be the NP-I AUC between premenopausal and postmenopausal participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Psychological and affective measures - anxiety | 1 month | Perceived anxiety symptoms assessed by validated questionnaires (State-Trait Anxiety Inventory). The State-Trait Anxiety Inventory score measures general trait anxiety using a 20-item subscale rated on a 1-to-4 scale. Total scores range from 20 to 80, with higher numbers showing greater general anxiety. |
| Psychological and affective measures - depression | 1 month | Perceived depressive symptoms assessed by validated questionnaires (Becks Depression Inventory-II). The Beck Depression Inventory-II total score ranges from 0 to 63. Standard severity thresholds are minimal depression (0-13), mild depression (14-19), moderate depression (20-28), and severe depression (29-63). |
| Psychological and affective measure - sleep quality | 1 month | Sleep quality over one month assessed by a validated questionnaire (Pittsburgh Sleep Quality Index) after a sleep counselling session (session at baseline visit). The Pittsburgh Sleep Quality Index ranges from 0 to 21, with higher scores indicating greater sleep difficulties. |
| Climacteric symptoms | 1 month | Climacteric symptoms, assessed by a validated questionnaire (Menopause rating scale (MRS)). MRS is an 11-item self-assessment tool designed to measure symptom severity and quality of life in aging women. The total MRS score ranges from 0 to 44 points, with higher scores indicating more severe symptoms and a poorer outcome. |
| Emotion recognition performance | 1 month | Emotion recognition performance (accuracy and reaction time), assessed by a computerized facial emotion recognition task (Facial Emotion Recognition Test) |
| Empathy | 1 month | Empathy, assessed by validated questionnaire-based measures (Empathy Quotient). The Empathy Quotient (EQ) test is a 60-item questionnaire intended to measure levels of empathy in adults. The total EQ score ranges from 0 to 80 points, with higher scores indicating greater empathy and a better outcome. |
| Cycle-phase-specific OXT/NP-I concentrations | 1 month | Phase-specific plasma OXT/NP-I concentrations at each study visit |
| Socio-affective processing | 1 month | Socio-affective processing, assessed by validated questionnaire-based measures (Toronto Alexithymia Scale-20). The scale was designed to assess the three factors: (a) difficulty identifying feelings (DIF), (b) difficulty describing feelings (DDF), and (c) external-oriented thinking (EOT). The TAS-20 score measures alexithymia on a scale from 20 to 100 with higher scores indicating greater levels of alexithymia and a poorer outcome. |
| Stress reactivity - subjective stress rating | 1 month | Subjective stress ratings, assessed using a Numerical Rating Scale (NRS). Subjective stress reflects an individual's self-reported psychological and emotional distress. Fear will be assessed on an NRS ranging from 0 (no fear) to 10 (extreme fear/panic), with higher scores indicating greater perceived fear. |
| Stress reactivity - autonomic measures | 1 month | Stress reactivity is assessed using a standardized social stress test, including autonomic measures (heart rate and blood pressure) |
| Stress reactivity - endocrine stress markers | 1 month | Assessed using a standardized social stress test, including endocrine stress markers (e.g. salivary or plasma cortisol) |
| Cardiometabolic parameter | 1 month | Body mass index |
| Cardiometabolic parameters | 1 month | Fasting glucose (± insulin/Homeostatic Model Assessment for Insulin Resistance) |
| Body composition measure | 1 month | Fat mass |
| Bone health parameter | 1 month | Bone turnover markers (e.g., N-terminal propeptide of type I collagen) |
| Food intake and eating behavior | 1 month | Subjective craving, quantified by ratings (Numerical Rating scale 0-10) on two days during the menstrual and ovulation phase |
| Gonadal hormone concentrations | 1 month | Progesterone for confirmation of cycle phase and assessment of hormonal correlates |
| Gonodal Hormone concentrations | 1 month | Luteinizing Hormone for confirmation of cycle phase and assessment of hormonal correlates |
| Gonodal Hormone concentration | 1 month | Follicle Stimulating hormone for confirmation of cycle phase and assessment of hormonal correlates. |
| Gonadal Hormone concentrations | 1 month | Estradiol for confirmation of cycle phase and assessment of hormonal correlates |
| Oxytocin over Neurophysin-I secretion profile | 1 month | Temporal Oxytocin over Neurophysin-1 secretion profile including group and time interaction and intra-individual variability across four visits. |
Countries
Switzerland
Contacts
CONTACTMirjam Christ-Crain, Prof. Dr. med.
PRINCIPAL_INVESTIGATORMirjam Christ-Crain, Prof. Dr. med.
University Hospital Basel Endocrinology, Diabetes and Metabolism
Outcome results
None listed