Early Menopause and Other Gynecologic Risk Indicators for Chronic Fatigue Syndrome in Women

Roumiana S. Boneva, MD, PhD; Jin-Mann S. Lin, PhD; Elizabeth R. Unger, PhD, MD


Menopause. 2015;22(8):826-834. 

In This Article

Abstract and Introduction


Objective. This study aims to examine whether gynecologic conditions are associated with chronic fatigue syndrome (CFS).

Methods. This study includes a subset of 157 women from a population-based case-control study in Georgia, United States, conducted in 2004-2009. Gynecologic history was collected using a self-administered questionnaire. Crude odds ratios (ORs) with 95% CIs and ORs adjusted for body mass index and other covariates, where relevant, were estimated for gynecologic conditions between 84 CFS cases and 73 healthy controls.

Results. Cases and controls were of similar age. Women with CFS reported significantly more gynecologic conditions and surgical operations than controls: menopause status (61.9% vs 37.0%; OR, 2.37; 95% CI, 1.21-4.66), earlier mean age at menopause onset (37.6 vs 48.6 y; adjusted OR, 1.22; 95% CI, 1.09-1.36), excessive menstrual bleeding (73.8% vs 42.5%; adjusted OR, 3.33; 95% CI, 1.66-6.70), bleeding between periods (48.8% vs 23.3%; adjusted OR, 3.31; 95% CI, 1.60-6.86), endometriosis (29.8% vs 12.3%; adjusted OR, 3.67; 95% CI, 1.53-8.84), use of noncontraceptive hormonal preparations (57.1% vs 26.0%; adjusted OR, 2.95; 95% CI, 1.36-6.38), nonmenstrual pelvic pain (26.2% vs 2.7%; adjusted OR, 11.98; 95% CI, 2.57-55.81), and gynecologic surgical operation (65.5% vs 31.5%; adjusted OR, 3.33; 95% CI, 1.66-6.67), especially hysterectomy (54.8% vs 19.2%; adjusted OR, 3.23; 95% CI, 1.46-7.17). Hysterectomy and oophorectomy occurred at a significantly younger mean age in the CFS group than in controls and occurred before CFS onset in 71% of women with records of date of surgical operation and date of CFS onset.

Conclusions. Menstrual abnormalities, endometriosis, pelvic pain, hysterectomy, and early/surgical menopause are all associated with CFS. Clinicians should be aware of the association between common gynecologic problems and CFS in women. Further work is warranted to determine whether these conditions contribute to the development and/or perpetuation of CFS in some women.


Chronic fatigue syndrome (CFS) is a debilitating and complex illness affecting more than 1 million US adults and accounting for sizable economic costs to the individual, healthcare system, and society as a whole.[1,2,3,4,5] CFS is characterized by profound fatigue that is accompanied by symptoms affecting multiple body systems, including, most characteristically, postexertional malaise, unrefreshing sleep, problems with memory and concentration, and pain.[1] The fatigue in CFS is not relieved by rest; medical or psychiatric conditions that could explain the fatigue and symptoms have been ruled out or fully managed.[1] The cause of CFS remains unknown. CFS affects women two to four times more frequently than men, with the highest prevalence found in women in their middle to late 40s.[3,4,5,6] Although CFS is more common in women, only few studies have examined sex-specific risk factors for CFS. A case-control study with a population-based sample of women with CFS (n = 22) identified hysterectomy as a risk factor for CFS.[7] Another case-control study of women with CFS (n = 150) from a tertiary referral center found endometriosis, ovarian cysts, polycystic ovaries, uterine fibroids, menstrual abnormalities, and galactorrhea to be risk factors for CFS.[8] Furthermore, Harlow et al [8] and Studd and Panay [9] hypothesized that a deficiency or imbalance in endogenous sex hormones may be a risk factor for CFS in some women. We recently reported that endometriosis, irregular periods, a history of gynecologic surgical operation, and pelvic pain unrelated to menstruation were all significantly associated with CFS in a population-based sample from Wichita, KS.[10] Using the conceptual framework that irregular periods, bleeding between periods, menopause, and oophorectomy could be indicators of gonadal hormone deficiency, we examined the association between gynecologic conditions and CFS in this study to replicate previous findings and to explore additional risk indicators.