Tag: menopause

Sex- and menopause-related differences in immune and gastrointestinal symptom architecture in ME/CFS: evidence from factor analysis and structural equation modeling

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem disorder characterized by neuroimmune, autonomic, and gastrointestinal dysfunction. Previous studies identified coherent symptom domains involving Brain, Autonomic, Gut, and Immune manifestations and demonstrated pronounced sex-specific differences in neurocognitive-sensory and autonomic symptom organization. However, whether immune-related and gastrointestinal symptoms form distinct or integrated latent structures in women and men with ME/CFS remains unclear. In addition, the potential influence of menopausal status on these symptom domains has not been systematically investigated.

Methods: Data from 748 adults with a medical diagnosis of ME/CFS were included in this cross-sectional analysis (608 women, 137 men, and 3 non-binary participants). Sex-stratified analyses were restricted to women and men. Symptoms were coded dichotomously. Sex-stratified analyses included cross-tabulations, Cramér’s V, tetrachoric correlations, logistic and linear regression models, exploratory factor analysis, and structural equation modeling (SEM). Additional subgroup analyses compared pre- and postmenopausal women. Model robustness was evaluated using a stratified training dataset.

Results: In women, Immune (flu-like symptoms, susceptibility to infections) and Gut (gastrointestinal complaints, food intolerances) symptoms formed two distinct but related clusters, characterized by moderate within-cluster correlations (tetrachoric ρ = 0.47-0.60) and weaker cross-cluster associations (ρ = 0.30-0.35). Exploratory factor analysis (EFA) supported a two-factor solution. Consistent with this result, the alternative one-factor SEM showed comparatively poor fit (CFI = 0.913; RMSEA = 0.119), whereas the specified two-factor model was just-identified and therefore not suitable for global fit evaluation. In men, all four symptoms loaded onto a single integrated Gut/Immune factor, with within- and cross-domain tetrachoric correlations ranging from 0.43 to 0.68. SEM confirmed excellent fit for a one-factor model (CFI = 0.981; RMSEA = 0.074). Susceptibility to infections emerged as the dominant predictor in regression analyses. Among women, menopausal status selectively affected immune-related symptoms. Women classified as premenopausal reported flu-like symptoms more frequently than women classified as postmenopausal, whereas gastrointestinal symptoms and food intolerances remained stable across groups. These findings suggest differential hormonal sensitivity of immune versus gastrointestinal symptom trajectories.

Conclusions: Immune and gastrointestinal symptoms in ME/CFS exhibit sex-specific latent structures. Women demonstrate two partially separable but related symptom domains, whereas men show a more integrated immune-gastrointestinal architecture. Furthermore, menopausal status appears to selectively modulate immune-related symptom expression while leaving gastrointestinal symptom patterns comparatively stable. Taken together, these results provide an exploratory framework that supports the concept of sex-dependent neuroimmune-autonomic mechanisms in ME/CFS and aligns with a dynamic, hormonally modulated immune component as well as a more persistent, gut-related process. The results highlight the importance of sex- and hormone-sensitive approaches to phenotyping, mechanistic research, and therapeutic stratification in ME/CFS.

Source: Habermann-Horstmeier L, Horstmeier LM. Sex- and menopause-related differences in immune and gastrointestinal symptom architecture in ME/CFS: evidence from factor analysis and structural equation modeling. J Transl Med. 2026 Jul 27;24(1):970. doi: 10.1186/s12967-026-08699-6. PMID: 42522006. https://link.springer.com/article/10.1186/s12967-026-08699-6 (Full text)

Hormonal Fluctuations and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Women: The Role of Menstrual Cycle and Menopause

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystem disease, predominantly affecting women as compared to men and showing extreme symptom variability across reproductive life stages. The aim of this research was to determine the effects of hormonal changes, menopause status, and symptom severity in individuals with ME/CFS.

This was a prospective observational cohort study conducted at JPMC, Karachi from January 2024 to June 2025. Final recruitment was of 150 women with ME/CFS (90 were in the premenopausal, 30 in the perimenopausal and 30 in the postmenopausal strata). Baseline demographic and clinical profiling, laboratory hormonal assays (estradiol, progesterone, LH, FSH), symptom daily profiles and monthly activity data, and objective autonomic probe reflex testing (tilt-table studies) were obtained.

The findings revealed a clear hormonal gradient across the groups (ANOVA p < 0.001), with estradiol and progesterone levels becoming lower and gonadotropins higher with older reproductive age.

Symptom trajectories varied according to for premenopausal women: fatigue and pain peaked pre menstrually (CFQ p = 0.01, VAS p = 0.02) and cognitive impairment was lowest at ovulation (p = 0.04).

When comparing across menopause groups, symptom burden was greater in the perimenopausal and postmenopausal participants and the perimenopausal and postmenopausal participants had lower SF-36 quality-of-life component scores (physical functioning 0.01, mental health 0.04).

Tilt-table findings from the cohort suggest age-related differences in autonomic dysfunction with postmenopausal women more likely to exhibit orthostatic hypotension (36.7%) and premenopausal women more likely to express POTS (38.9%).

The correlation analysis revealed that low levels of estradiol and progesterone were significantly correlated with higher levels of fatigue and pain, whereas the opposite association was found for LH and FSH, the latter two being positively correlated with fatigue and orthostatic symptoms.

These findings provide the first quantifiable evidence for reproductive hormonal dynamics substantially modulating the clinical expression of ME/CFS in women and the need for hormone-sensitive management approaches.

Source: Mehak Khan, Sidra Anees, Muhammad Muthar Anees, Komal Khalid Chaudhry, Syeda Marium Rashid Zaidi, Vishan Das, Rimal Rashid. Hormonal Fluctuations and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Women: The Role of Menstrual Cycle and Menopause. The Research of Medical Science Review; Volume 3, Issue 8, 2025. ISSN: 3007-1208 & 3007-1216. https://medscireview.net/index.php/Journal/article/view/2032 (Full text available as PDF file)

Endometriosis as a Comorbid Condition in Chronic Fatigue Syndrome (CFS): Secondary Analysis of Data From a CFS Case-Control Study

Abstract:

Background: Endometriosis (EM) is a recognized co-morbid condition in women with chronic fatigue syndrome (CFS). This analysis evaluates the impact of EM on the health of women with CFS by comparing selected health characteristics and laboratory parameters in women with CFS with and without EM (CFS+EM and CFS-only).

Methods: This secondary analysis included all 36 women with CFS from a cross-sectional study of CFS in Wichita, KS, conducted between 2002 and 2003. The health characteristics and laboratory parameters of interest included functioning, fatigue, CFS-related symptoms, gynecologic history, routine laboratory parameters, inflammatory markers, cortisol levels, allostatic load, and sleep parameters (overnight polysomnography). We used parametric or non-parametric tests to compare group differences in the selected health characteristics and laboratory parameters. For examining the association between EM and variables of interest, logistic regression models were performed and odds ratios (OR) with 95% confidence intervals (CI) were reported for the magnitude of associations. Statistical significance was set at 0.05 (two-sided).

Results: The mean age of this study sample was 50.9 years. Of women with CFS, 36.1% reported having EM. Age and body mass index (BMI) did not differ between CFS+EM and CFS-only groups. When examining the impact of EM, compared to women with CFS-only, women with both CFS and EM were more likely to report chronic pelvic pain [OR = 9.00 (95% CI, 1.47-55.25)] and hysterectomy [OR = 10.3 (1.82-58.39)], had more CFS symptoms (6.8 ± 0.3 vs. 5.5 ± 0.3, p = 0.02), younger mean age at menopause onset (36.4 ± 3.0 vs. 47.0 ± 2.7 years, p = 0.03), higher mean number of obstructive apnea episodes per hour (20.3 vs. 4.4, p = 0.05) and reported more negative life events (15.8 vs. 4.4, p = 0.05). Other parameters did not differ significantly between the two groups.

Conclusions: We found more than a third of women with CFS reported endometriosis as a comorbid condition. The endometriosis comorbidity was associated with chronic pelvic pain, earlier menopause, hysterectomy, and more CFS-related symptoms. However, endometriosis in women with CFS did not appear to further impact functioning, fatigue, inflammatory markers, or other laboratory parameters. Further investigations including younger women are warranted.

Source: Boneva RS, Lin JS, Wieser F, Nater UM, Ditzen B, Taylor RN, Unger ER. Endometriosis as a Comorbid Condition in Chronic Fatigue Syndrome (CFS): Secondary Analysis of Data From a CFS Case-Control Study. Front Pediatr. 2019 May 21;7:195. doi: 10.3389/fped.2019.00195. eCollection 2019. https://www.ncbi.nlm.nih.gov/pubmed/31179251

Menopausal transition symptoms in midlife women living with fibromyalgia and chronic fatigue

Abstract:

We aimed to determine how menopausal transition symptoms cluster across 216 midlife women with fibromyalgia, chronic fatigue syndromes (FMS/CFS), or both and subsequently to compare symptom factor severity scores by menopausal status among these women and compare symptom reporting with prior community-based samples of women without obvious illness.

We designed a cross-sectional telephone survey of 216 women aged 35 to 55, diagnosed with FMS/CFS, symptomatic in the prior 6 months, and without hysterectomy. Thirty-six of 61 symptoms loaded on five factors: aroused/anxious mood, depressed mood/withdrawal, musculoskeletal, gastrointestinal (GI), and vasomotor. Peri- and postmenopausal women had higher symptom severity scores for musculoskeletal, GI, and vasomotor factors but not mood factors.

Symptoms for the women we studied who had FMS/CFS clustered similar to those in previous community-based samples of midlife women without major illness; however, the number of women experiencing symptoms was much higher among our sample.

 

Source: Wilbur J, Shaver J, Kogan J, Buntin M, Wang E. Menopausal transition symptoms in midlife women living with fibromyalgia and chronic fatigue. Health Care Women Int. 2006 Aug;27(7):600-14. https://www.ncbi.nlm.nih.gov/pubmed/16844673