Association between menstrual cycle phase and metabolites in healthy, regularly menstruating women in UK Biobank, and effect modification by inflammatory markers and risk factors for metabolic disease.

BACKGROUND: Preliminary evidence demonstrates some parameters of metabolic control, including glycaemic control, lipid control and insulin resistance, vary across the menstrual cycle. However, the literature is inconsistent, and the underlying mechanisms remain uncertain. This study aimed to investigate the association between the menstrual cycle phase and metabolites and to explore potential mediators and moderators of these associations. METHODS: We undertook a cross-sectional cohort study using UK Biobank. The outcome variables were glucose; triglyceride; triglyceride to glucose index (TyG index); total, HDL and LDL cholesterol; and total to HDL cholesterol ratio. Generalised additive models (GAM) were used to investigate non-linear associations between the menstrual cycle phase and outcome variables. Anthropometric, lifestyle, fitness and inflammatory markers were explored as potential mediators and moderators of the associations between the menstrual cycle phase and outcome variables. RESULTS: Data from 8694 regularly menstruating women in UK Biobank were analysed. Non-linear associations were observed between the menstrual cycle phase and total (p < 0.001), HDL (p < 0.001), LDL (p = 0.012) and total to HDL cholesterol (p < 0.001), but not glucose (p = 0.072), triglyceride (p = 0.066) or TyG index (p = 0.100). Neither anthropometric, physical fitness, physical activity, nor inflammatory markers mediated the associations between the menstrual cycle phase and metabolites. Moderator analysis demonstrated a greater magnitude of variation for all metabolites across the menstrual cycle in the highest and lowest two quartiles of fat mass and physical activity, respectively. CONCLUSIONS: Cholesterol profiles exhibit a non-linear relationship with the menstrual cycle phase. Physical activity, anthropometric and fitness variables moderate the associations between the menstrual cycle phase and metabolite concentration. These findings indicate the potential importance of physical activity and fat mass as modifiable risk factors of the intra-individual variation in metabolic control across the menstrual cycle in pre-menopausal women.

Changes in adipose tissue microRNA expression across the menstrual cycle in regularly menstruating females: a pilot study.

Cyclical changes in hormone profiles across the menstrual cycle are associated with alterations in metabolic control. MicroRNAs (miRNAs) contribute to regulating metabolic control, including adipose tissue metabolism. How fluctuations in hormonal profiles across the menstrual cycle affect adipose tissue miRNA expression remains unknown. Eleven healthy, regularly menstruating females underwent four sampling visits across their menstrual cycle. Subcutaneous abdominal adipose tissue and venous blood samples were collected at each sampling visit. Luteinizing hormone (LH) tests, calendar counting, and serum hormone concentrations were used to determine menstrual cycle phases: early-follicular (EF), late-follicular (LF), postovulatory (PO), and midluteal (ML). Serum follicle-stimulating hormone, LH, estrogen, progesterone, and testosterone were determined using multiplex magnetic bead panels and enzyme-linked immunosorbent assays. Global adipose tissue miRNA expression levels were determined via microarray in a subset of participants (n = 8) and 17 candidate miRNAs were validated by RT-qPCR in the whole cohort (n = 11). Global analysis of adipose tissue miRNA expression identified 33 miRNAs significantly altered across the menstrual cycle; however, no significant differences remained after correcting for multiple testing (P > 0.05). RT-qPCR analysis of candidate miRNAs revealed miR-497-5p expression was significantly altered across the menstrual cycle ([Formula: see text] = 0.18, P = 0.03); however, post hoc tests did not reveal any significant differences between menstrual cycle phases (P > 0.05). miR-30c-5p was associated with testosterone concentration (R2 = 0.13, P = 0.033). These pilot data indicate differences in adipose tissue miRNAs in healthy women across the menstrual cycle and a weak association with ovarian hormones. Further research in larger sample sizes is required to confirm regulation of miRNA expression across the menstrual cycle.

Relationship Between Insulin Sensitivity and Menstrual Cycle Is Modified by BMI, Fitness, and Physical Activity in NHANES.

CONTEXT: There is evidence demonstrating variation in insulin sensitivity across the menstrual cycle. However, to date, research has yielded inconsistent results. OBJECTIVE: This study investigated variation in insulin sensitivity across the menstrual cycle and associations with body mass index (BMI), physical activity, and cardiorespiratory fitness (CRF). METHODS: Data from 1906 premenopausal women in NHANES cycles 1999 to 2006 were analyzed. Menstrual cycle day was assessed using questionnaire responses recording days since last period. Rhythmic variation of plasma glucose, triglycerides, and insulin, homeostatic model of insulin resistance (HOMA-IR), and adipose tissue insulin resistance index (ADIPO-IR) across the menstrual cycle were analyzed using cosinor rhythmometry. Participants were assigned low or high categories of BMI, physical activity, and CRF, and category membership included in cosinor models as covariates. RESULTS: Rhythmicity was demonstrated by a significant cosine fit for glucose (P = .014) but not triglycerides (P = .369), insulin (P = .470), HOMA-IR (P = .461), and ADIPO-IR (P = .335). When covariates were included, rhythmicity was observed when adjusting for: 1) BMI: glucose (P < .001), triglycerides (P < .001), insulin (P < .001), HOMA-IR (P < .001), and ADIPO-IR (P < .001); 2) physical activity: glucose (P < .001), triglycerides (P = .006), and ADIPO-IR (P = .038); and 3) CRF: triglycerides (P = .041), insulin (P = .002), HOMA-IR (P = .004), and ADIPO-IR (P = .004). Triglyceride amplitude, but not acrophase, was greater in the high physical activity category compared to low (P = .018). CONCLUSION: Rhythmicity in insulin sensitivity and associated metabolites across the menstrual cycle are modified by BMI, physical activity, and CRF.

Human Subcutaneous Adipose Tissue Sampling using a Mini-liposuction Technique.

Studies on adipose tissue are useful in understanding metabolic and other conditions. Human subcutaneous adipose tissue is accessible. With appropriate training and strict adherence to aseptic technique, subcutaneous adipose samples can be safely and efficiently obtained in a non-clinical setting by researchers. Following the administration of local anesthetic lateral to the umbilicus, a 14 G needle attached to a 5 or 10 mL syringe is inserted through the skin into the subcutaneous tissue. Under suction, the syringe is moved in a reciprocating, slicing motion to isolate fragments of adipose tissue. Withdrawing the plunger is enough to ensure that adipose tissue fragments are aspirated through the needle into the syringe. A single biopsy can collect about 200 mg of tissue. This biopsy technique is very safe for both participants and research staff. Following the biopsy, participants can resume most everyday activities, although they should avoid swimming and overly strenuous activities for 48 h to avoid excessive bleeding. Participants can safely undergo 2 biopsies within a single day, meaning that the technique can be applied in before-after acute intervention studies.