Jan Wesström

Restless legs syndrome among women: prevalence, co-morbidity and possible relationship to menopause

Objectives Restless legs syndrome (RLS) is a common neurological movement disorder with a female preponderance and an increasing prevalence with age. During the menopausal transition, sleep is affected. Prior studies suggest that female hormones are associated with the clinical manifestation of RLS. Methods A random sample of 5000 women aged 18–64 years was selected from the general Swedish population. They were sent questions on RLS, general health, sleep problems, reproductive health and menopausal state. Results The response rate was 70.3%; 15.7% of the women were diagnosed with RLS. Prevalence increased with age. RLS subjects more often had symptoms of affected sleep and depressed mood. Co-morbidity with heart disease was more common among RLS subjects, whereas hypertension and diabetes mellitus were not. There was a strong association between vasomotor symptoms and RLS but no statistical relationship between use of hormone replacement therapy, postmenopausal state and RLS. Conclusion The prevalence of RLS among Swedish women is high. RLS sufferers more often suffered from depression and heart disease, whereas no such associations were noted for diabetes or hypertension. We found an increased prevalence of RLS among women with vasomotor symptoms (night sweats) during the menopausal transition but not among women using hormone replacement therapy.

When gender matters: Restless legs syndrome. Report of the “RLS and woman” workshop endorsed by the European RLS Study Group

Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekboms 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism.

Sleep apnea and hormone replacement therapy: a pilot study and a literature review

Background.  Sleep apnea syndrome (SAS) is a common condition and a risk factor of cardiovascular and cerebrovascular diseases. The purpose of this pilot study was to investigate the effect of a gestagen (trimegeston) and estradiol hormone combination on perimenopausal and postmenopausal women with SAS.

Health-related quality of life and restless legs syndrome among women in Sweden

Aim:  Restless legs syndrome (RLS) is a common neurological movement disorder with a female preponderance, an increasing prevalence with age and comorbidity. Previous studies on the relationship between health‐related quality of life (HRQOL) and RLS are still sparse but knowledge is increasing. The aim of this study was to evaluate the unique impact of RLS on HRQOL in a population‐based sample.

A nonsense mutation in CEP55 defines a new locus for a Meckel‐like syndrome, an autosomal recessive lethal fetal ciliopathy

Mutations in genes involved in the cilium‐centrosome complex are called ciliopathies. Meckel‐Gruber syndrome (MKS) is a ciliopathic lethal autosomal recessive syndrome characterized by genetically and clinically heterogeneous manifestations, including renal cystic dysplasia, occipital encephalocele and polydactyly. Several genes have previously been associated with MKS and MKS‐like phenotypes, but there are still genes remaining to be discovered. We have used whole‐exome sequencing (WES) to uncover the genetics of a suspected autosomal recessive Meckel syndrome phenotype in a family with 2 affected fetuses. RNA studies and histopathological analysis was performed for further delineation. WES lead to identification of a homozygous nonsense mutation c.256C>T (p.Arg86*) in CEP55 (centrosomal protein of 55 kDa) in the affected fetus. The variant has previously been identified in carriers in low frequencies, and segregated in the family. CEP55 is an important centrosomal protein required for the mid‐body formation at cytokinesis. Our results expand the list of centrosomal proteins implicated in human ciliopathies and provide evidence for an essential role of CEP55 during embryogenesis and development of disease.

Maternal and fetal characteristics affect discrepancies between pregnancy‐dating methods: a population‐based cross‐sectional register study

Gestational age is estimated by ultrasound using fetal size as a proxy for age, although variance in early growth affects reliability. The aim of this study was to identify characteristics associated with discrepancies between last menstrual period‐based (EDD‐LMP) and ultrasound‐based (EDD‐US) estimated delivery dates.

Risk for girls can be adversely affected post-term due to underestimation of gestational age by ultrasound in the second trimester.

Post‐term pregnancies are associated with greater risks for mother and child. Accurate determination of gestational age is necessary for safe care. Female fetuses have been shown to be smaller than males at the time of second‐trimester ultrasound (US) examination, leading to underestimation of their age and, potentially, greater impacts of perinatal complications in post‐term girls than in post‐term boys. The purpose of this study was to investigate the sex ratio of post‐term births and differences in perinatal complications (stillbirth, low Apgar score, low birthweight, meconium aspiration and low umbilical artery pH) between post‐term boys and girls according to dating method [second‐trimester US and last menstrual period (LMP)].

Periodic Limb Movements are Associated with Vasomotor Symptoms

STUDY OBJECTIVES Periodic limb movements (PLMs) are characterized by involuntary movements of the lower extremity during sleep. The etiology of PLM has been suggested to involve the dopaminergic system which, in turn, can be modulated by estrogen. It is currently unknown whether PLMs are associated with the menopausal transition and/or concomitant vasomotor symptoms. The aim of the present study was to examine if objectively diagnosed PLMs (with and without arousals) are more common in postmenopausal women or in women with vasomotor symptoms. A secondary aim was to analyze the influence of PLMs on self-reported HRQoL. METHODS A community-based sample of 348 women underwent full-night polysomnography. PLMs (index > 15) and associated arousals (PLM arousal index > 5) were evaluated according to AASM scoring rules. Health-related quality of life was measured using the SF-36 questionnaire. The occurrence of peri- and postmenopausal symptoms were evaluated by a questionnaire and plasma levels of follicle stimulating hormone (FSH) were measured. RESULTS After adjusting for confounding factors, vasomotor symptoms remained a significant explanatory factor for the occurrence of PLMs (adj. OR 1.86, 95% CI 1.03-3.37). In women with PLM arousals, adjusted OR for vasomotor symptoms was 1.61, 95% CI 0.76-3.42. PLMs did not seem to affect HRQoL. CONCLUSION We found that clinically significant PLMs, but not PLM with arousals, were more common among women with vasomotor symptoms, even after controlling for confounding factors. Menopausal status per se, as evidenced by FSH in the postmenopausal range, was not associated with PLMs.

Health-Related Quality of Life and Depression Symptom Measures for the Assessment of Treatment in Restless Legs Syndrome/Willis–Ekbom Disease

One way of defining the concept of health-related quality of life (HRQoL) is: “The extent to which one’s usual or expected physical, emotional and social well-being are affected by a medical condition or its treatment” (Cella in Semin Oncol 22:73–81, 1995 [1]). Individual patients with the same objective health status can report dissimilar HRQoL due to unique differences in expectations and coping abilities and it must be measured from the individual’s viewpoint. There is a growing interest in HRQoL and there are several reasons for this. An increasing share of interventions is aimed at improving the quality of patients’ lives rather than preventing premature deaths (e.g., hip replacement, hypnotics). As people live longer, they become more susceptible to disorders and conditions that decrease their quality of life. With a greater amount of shared decision-making in the health care, patients are also requesting treatments that can improve their HRQoL (Guyatt et al. in Ann Intern Med 118:622–29 [2]). However, although reporting of several important aspects of trial methods has improved, quality of reporting remains well below an acceptable level. Without complete and transparent reporting of how a trial was designed and conducted, it is difficult for readers to assess its conduct and validity.