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Symptom Occurrence in Persons with Chronic Fatigue Syndrome

  [ 59 votes ]   [ Discuss This Article ]
www.ProHealth.com • February 14, 2002


L.A. Jason, S.R. Torres-Harding, A.W. Carrico and R.R. Taylor
DePaul University, Center for Community Research, 990 West Fullerton Road,
Chicago, IL 60614, USA. Corresponding author. Tel.: +1-773-325-2018; fax: +1-773-325-4923. email: Ljason@depaul.edu


Abstract

This investigation compared differences in the occurrence of symptoms in
participants with CFS, melancholic depression, and no fatigue (controls). The
following Fukuda et al. [Ann. Intern. Med. 121 (1994) 953] criteria symptoms
differentiated the CFS group from controls, but did not differentiate the
melancholic depression group from controls: headaches, lymph node pain, sore
throat, joint pain, and muscle pain. In addition, participants with CFS
uniquely differed from controls in the occurrence of muscle weakness at
multiple sites as well as in the occurrence of various cardiopulmonary,
neurological, and other symptoms not currently included in the current case
definition. Implications of these findings are discussed.


1. Introduction

Chronic fatigue syndrome (CFS) remains a poorly understood and controversial
disease, because the exact causal agents are unknown, physical signs and
symptoms are variant, and diagnostic laboratory tests have poor sensitivity
and specificity (Holmes and Jason). In the absence of laboratory tests or
other objective indicators, case identification of CFS relies upon the
clinical assessment of a constellation of symptoms that have been present for
6 or more months since the onset of the fatiguing illness (Fukuda et al.,
1994). Since its emergence as a new disease category in the 1980s, four
definitions of CFS have been proposed, but none have been empirically derived
(Jason et al., 1997).

The current US case definition of CFS (Fukuda et al., 1994) requires that the
following criteria be met for diagnosis: (a) 6 or more months of persistent or
relapsing chronic fatigue of a new or definite onset that is neither the
result of ongoing exertion nor alleviated by rest, which results in
substantial reductions in previous levels of occupational, educational,
social, or personal activities; and (b) the concurrent occurrence of at least
four of eight symptoms (postexertional malaise, unrefreshing sleep, memory and
concentration difficulties, new headaches, sore throat, lymph node pain,
muscle pain, and joint pain) that persist or reoccur during 6 or more months
of the illness and do not predate the fatigue.

Researchers have sought to validate the criteria for CFS established by the
CDC using factor analytic methods. Nisenbaum et al. (1998) found that three
correlated factors (fatigue-mood-cognition symptoms, flu-type symptoms, and
visual impairment symptoms) explained a set of additional correlations between
fatigue lasting for 6 or more months and 14 inter-related symptoms. No factor
explained observed correlations among fatigue lasting for 1-5 months and other
symptoms, indicating that only fatigue lasting 6 or more months (with selected
symptoms) overlaps with published criteria to define CFS. In another study,
Friedberg et al. (2000) examined symptoms of patients with CFS who had an
illness duration of 10 or more years and found three factors: cognitive
problems, flu-like symptoms, and neurologic symptoms.

Other research has focused on classifying persons with CFS based on symptom
profiles. Using latent class analysis, Hadzi-Pavlovic et al. (2000) determined
that patients with CFS could be grouped into three classes: those with
multiple severe symptoms, those with lower rates of cognitive symptoms and
higher rates of pain; and those with a less severe form of multiple symptoms.
Participants with a less severe form of multiple symptoms tended to be younger
and with shorter illness duration. Jason and Taylor (2002) performed a cluster
analysis of persons in a community-based sample of persons with chronic
fatigue (fatigue lasting 6 or more months) to define a typology of chronic
fatigue symptomatology. Among the participants with CFS, findings suggested
that a majority of individuals with moderate to severe symptoms could be
classified into two important subgroups: one distinguished by severe
postexertional malaise with fatigue that was partially alleviated by rest; and
one distinguished by severe overall symptomatology, severe postexertional
malaise, and fatigue that was not alleviated by rest.

Researchers have also examined the occurrence of specific symptoms reported by
persons with chronic fatigue and CFS (Hartz and Komaroff). Komaroff et al.
(1996) examined the occurrence of minor symptoms (Holmes et al., 1988), as
well as respiratory, gastrointestinal, neurologic, rheumatologic, cardiac, and
miscellaneous objective and subjective symptoms that were not included in the
1988 case definition. The occurrence of these symptoms were compared among
persons with severe, disabling fatigue lasting for 6 or more months, persons
with multiple sclerosis, persons with major depression, and healthy controls.
Komaroff et al. (1996) concluded that rheumatologic and gastrointestinal
symptoms were found more frequently in patients meeting the major criteria.
Based upon these findings, researchers recommended adding anorexia and nausea
as well as eliminating the symptoms of muscle weakness, arthralgias, and sleep
disturbance to strengthen the case definition. Finally, Hartz et al. (1998)
examined the association between the number and severity of symptoms of CFS in
persons with idiopathic chronic fatigue and determined that persons with
fatigue could be classified by the degree to which they match the case
definition of CFS (Fukuda et al., 1994). In addition, Hartz et al. (1998)
suggested including symptoms such as frequent fever and chills, muscle
weakness, and sensitivity to alcohol in the current US case definition.

The occurrence of neurally mediated hypotension (NMH) has also been
investigated in persons with CFS. NMH is defined as a 30 mmHg drop in systolic
(or a 15 mmHg drop in diastolic) blood pressure in response to an orthostatic
challenge such as standing upright (Rowe and Calkins, 1998). This precipitous
drop in blood pressure is thought to be due to low blood volume (Streeten and
Bell, 1998) or excessive venous pooling in the extremities (Stewart and
Stewart). Symptoms of NMH include but are not limited to: lightheadedness,
dizziness when standing, nausea, fatigue, tremors, breathing or swallowing
difficulties, headaches, visual disturbances, and pallor (Streeten et al.,
2000). While the frequency of NMH in persons with CFS has not been
consistently reported across investigations, cardiopulmonary and neurological
abnormalities are heterogeneous and common (Wilke et al., 1998).

The findings reviewed herein suggest that other symptoms in addition to the
eight symptoms listed as part of the definitional criteria may be important
and occur frequently in persons with CFS. The present investigation examined
the occurrence of symptoms in the Fukuda et al. (1994) case definition of CFS
to determine whether these symptoms uniquely differentiated those with CFS
from controls. In addition, other fatigue/weakness related, sleep related,
neuropsychiatric, infectious, rheumatological, cardiopulmonary,
gastrointestinal, neurological, and reproductive symptoms not specified in the
current US case definition were examined. The occurrence of these additional
symptoms was examined to determine whether other symptoms occur with greater
frequency in persons with CFS when compared to controls, as well as what
symptoms occurred with greater frequency in the melancholic depression group
compared to controls.


2. Methods

2.1. PROCEDURE

The data are derived from a larger community-based study of the prevalence of
chronic fatigue syndrome (for more details of this study see Jason et al.,
1999). This larger study was carried out in three stages. Stage 1 involved
administering an initial telephone screening questionnaire in order to
identify the symptoms of chronic fatigue syndrome. Stage 2 involved
administering a semi-structured psychiatric interview. In stage 3,
participants underwent a complete physical examination. Following the
completion of the medical evaluation, four physicians and a psychiatrist were
responsible for making a final diagnosis with two physicians independently
rating each case using the current US case definition of CFS (Fukuda et al.,
1994). Where disagreement occurred, a third physician rater was used.


2.2. SAMPLE

Procedures developed by Kish (1965) were used to select one adult from each
household. Birth dates for each adult were gathered, and the person with the
most recent birthday was selected for interview. A stratified random sample of
several neighborhoods in Chicago was utilized (see Jason et al., 1999 for more
details). In stage 1, 28,673 residential/working telephone numbers were
contacted, and 18,675 adults completed the initial screening interview (65.1%
completion rate).

The stage 1 screen revealed that of the 18,765 participants who were
interviewed, 780 (4.2%) had chronic fatigue. Of these, 408 had chronic fatigue
and the concurrent occurrence of four or more symptoms. These participants
were defined as CFS-like (the suffix `like' was used to clarify that
individuals in this group only met the Fukuda et al. (1994) criteria by
self-report, and did not necessarily qualify as having a final diagnosis of
CFS rendered by a physician).

One hundred and sixty-six of the 408 CFS-like participants agreed to complete
a structured psychiatric interview and a comprehensive physical examination.
There were no significant differences on sociodemographic (i.e. gender, ethnic
identification, age, occupation, education, and marital status) or fatigue
scores between these 166 screened positive (CFS-like) participants and the 242
screened positive (CFS-like) non-participants. The control group was composed
of 199 individuals selected randomly from the remaining 18,260 screened
negatives (seven cases were excluded due to missing data). Of these 199
individuals, 47 completed medical evaluations. There were no sociodemographic
differences (i.e. gender, ethnic identification, age, occupation, education,
and marital status) or fatigue scores between the 152 screened negative
non-participants and 47 screened negative participants. Participants were then
classified by independent physician consensus.


2.3. PARTICIPANTS

The present investigation examined the occurrence of symptoms in three groups
of participants. The first group consisted of 32 persons from the larger group
of 166 persons with CFS-like symptoms who were diagnosed with CFS by the
independent physician review panel (CFS group). The second group consisted of
19 individuals with melancholic depression, who were taken from a larger group
of 33 CFS-like persons with a psychiatric explanation for their chronic
fatigue illness (Melancholic Depression group). Melancholic Depression was
diagnosed using the Structured Clinical Interview for the DSM-IV (SCID)
(Spitzer et al., 1995), which is a valid and reliable semi-structured
interview guide that approximates a traditional psychiatric interview.

Melancholic Depression is defined by either the absence of pleasure in almost
all activities or lack of reactivity to usually pleasurable stimuli. In
addition, there would need to be three or more other symptoms, such as
excessive guilt, significant weight loss, and marked psychomotor retardation
or agitation. The control group consisted of 47 randomly selected individuals
who screened negative for having a CFS-like illness (control group). Three
participants who initially screened negative for a CFS-like illness were
excluded from the control group following examination by the study physicians
who determined that they had idiopathic chronic fatigue or chronic fatigue
explained by a psychiatric condition.


2.4. MEASURES

2.4.1. Medical questionnaire

As part of a detailed medical questionnaire, participants were asked if they
were experiencing or had experienced each of the eight Fukuda et al. (1994)
symptoms of CFS in the past 6 months. Additional symptoms examined included
other medical symptoms and neuropsychiatric symptoms that incorporated
questions from a measure used by Komaroff et al. (1996). The definitional
symptoms and the additional symptoms were then classified into the following
categories: weakness/fatigue, disturbed sleep, neuropsychiatric, infectious,
rheumatological, cardiopulmonary, neurological, and reproductive
abnormalities. We examined the occurrence of Fukuda et al. (1994) symptoms in
the past 6 months because it was most comparable to available data on the
occurrence of other symptoms examined in the medical questionnaire. Also,
examining the occurrence of Fukuda et al. (1994) defined symptoms in the past
6 months allows results of the present investigation to be compared to those
of Komaroff et al. (1996).


2.5. STATISTICAL ANALYSES

First, the sociodemographic variables of gender, age, ethnicity, marital
status, parental status, work status, and socioeconomic status were examined,
using chi-squares across the three groups: CFS, melancholic depression, and
controls. The occurrence of symptoms was compared between the CFS and control
groups, and between the melancholic depression and control groups. Using
binomial logistic regression, sociodemographic variables that were found to be
significant between the groups were entered as predictors in the logistic
regression model to control for the effects of these variables on the
occurrence of symptoms. We first made the CFS group the referent group, and
have compared it to the controls and the depression group. We next made the
control group as a referent group to compare it with the depressed group. Due
to the numerous comparisons made, the overall statistical significance was set
at P<0.01 for all analyses in order to minimize the likelihood of type I
error.


3. Results

3.1. SOCIODEMOGRAPHIC VARIABLES

Analyses indicated that there were significantly more men in the control group
than in the Melancholic Depression group [chi^2(2,95)=11.297, P<0.01].

Furthermore, participants with CFS were significantly more likely to have
children than controls [chi^2(2,95)=9.431, P<0.05]. Thus, gender and parental
status were entered as predictors in the subsequent binomial logistic regression
analyses of symptom occurrence.


3.2. SYMPTOMS

Table 1 presents symptoms of Fatigue/Weakness, Disturbed Sleep,
Neuropsychiatric, Infectious, and Rheumatological symptoms, and these are the
symptom categories in which are located the current Fukuda et al. (1994) CFS
symptom criteria. Table 2 lists other categories (Cardiopulmonary,
Gastrointestinal, Neurological, and Reproductive) that consist of symptoms
that are not found within the Fukuda et al. (1994) criteria.


3.2.1. Fatigue/weakness

Participants with CFS differed significantly from controls in the occurrence
of generalized muscle weakness, and more specific weakness in their legs,
arms, neck, and back. Weak legs was the most frequently reported form of
weakness for the CFS group. Also, participants with CFS and those with
melancholic depression both reported significantly more postexertional malaise
than controls.


3.2.2. Disturbed sleep

The occurrence of unrefreshing sleep was reported with significantly greater
frequency in both the CFS and melancholic depression groups compared to
controls. Those in the CFS group had significantly more insomnia than the
controls.


3.2.3. Neuropsychiatric

Participants with CFS reported the occurrence of new headaches with
significantly greater frequency than controls. Both the CFS and melancholic
depression groups reported the occurrence of memory and concentration
difficulties, depression, and irritability with significantly greater
frequency than controls.


3.2.4. Infectious

The occurrence of sore throats and lymph node pain was significantly greater
in the CFS group when compared to controls. There were no significant
differences between the melancholic depression and control groups in the
occurrence of other infectious symptoms.


3.2.5. Rheumatological

The CFS group reported muscle pain, joint pain, morning stiffness, and hay
fever with significantly greater frequency than controls. Participants with
melancholic depression only reported the occurrence of dry mouth with
significantly greater frequency than controls.


3.2.6. Cardiopulmonary

The CFS group reported the occurrence of chest pain and cough with
significantly greater frequency than controls. The CFS group and melancholic
depression group significantly differed on shortness of breath.


3.2.7. Gastrointestinal

Neither the CFS nor the melancholic depression groups reported
gastrointestinal symptoms with significantly greater frequency than controls.


3.2.8. Neurological

The CFS group reported dizziness after standing, skin sensations, general
dizziness, alcohol intolerance and dizzy moving head with significantly
greater frequency than controls.


3.2.9. Reproductive

Participants with CFS reported the occurrence of decreased sexual interest
with significantly greater frequency than controls and those with melancholic
depression. The occurrence of impairment of sexual functioning was reported
with significantly greater frequency in both the CFS and melancholic
depression groups when compared to controls.


4. Discussion

Results of this investigation lend support to the importance of the CFS
diagnostic criteria (Fukuda et al., 1994). Participants with CFS more
frequently experienced the Fukuda et al. (1994) CFS symptoms when compared to
other symptoms in their respective categories, with the exception of
postexertional malaise. These findings were anticipated, given the selection
criteria of four of eight symptoms to receive a diagnosis of CFS. In addition,
the CFS group in comparison to controls reported significantly higher
frequencies of all eight Fukuda et al. (1994) definitional symptoms.

Furthermore, the occurrence of postexertional malaise, cognitive and memory
difficulties and unrefreshing sleep did not uniquely discriminate between the
CFS and control groups, as individuals in the melancholic depression group
also experienced these symptoms with significantly greater frequency than
controls.

Interpreting these findings, it is important to note that the present
investigation examined only the occurrence of symptoms. The CFS group may also
uniquely differ from controls in symptom duration and severity. For example,
Jason et al. (2000) found that examining symptoms utilizing severity
criteria has proven useful in uniquely differentiating CFS from fatigue
explained by a psychiatric disorder (Jason et al., 2000). Also, the frequency
of the occurrence of the Fukuda et al. (1994) defined symptoms in the
melancholic depression group may have been elevated due to the screening
process. Only chronically fatigued participants initially reporting four or
more symptoms specified in the current US case definition of CFS were
classified as `CFS-like' and subsequently received a medical examination.

Cardiopulmonary and neurological abnormalities have been investigated as they
relate to neurally mediated hypotension (NMH) in persons with CFS (Rowe;
Streeten and Wilke). NMH occurs when the central nervous system
misinterprets the body's needs when it is in an upright position, then sends a
message to the heart to slow down and lower the blood pressure, responses that
are directly opposite to the responses the body`s needs. Several
cardiopulmonary and neurological symptoms in the present investigation
occurred with higher frequency and uniquely differentiated the CFS group from
controls. Shortness of breath, chest pain, dizziness after standing, skin
sensations, general dizziness, dizzy moving the head, and alcohol intolerance
uniquely differentiate those with CFS from controls. It is possible that
examining these cardiopulmonary and neurological abnormalities not currently
assessed by the current case definition (Fukuda et al., 1994) could provide
greater diagnostic reliability.

The CFS and melancholic depression group only significantly differed for two
symptoms: decreased sexual interest and shortness of breath. Decreased sexual
interest might very well be a result of low levels of cortisol. A deficit of
cortisol has been found in patients with CFS, and is linked to lethargy and
fatigue, and this deficit might be contributing to an overactive immune system
(Scott and Dinan, 1999). Shortness of breath as well as other neurological
symptoms might reflect a finding that has been confirmed by other
investigators, who have not found neurally mediated hypotension to play a
major role in CFS (Poole et al., 2000).

Komaroff et al. (1996) have suggested that eliminating the symptoms of muscle
weakness, arthralgias, and sleep disturbance would provide greater sensitivity
and specificity in CFS diagnosis. In contrast, the present investigation found
that muscle weakness and arthralgias were reported in over half of
participants with CFS and uniquely differentiated this group from controls.

Regarding sleep disturbance, results of the present investigation did not
support the ability of any symptoms in this category to uniquely discriminate
between CFS and control groups. Komaroff et al. (1996) also suggested adding
anorexia and nausea as minor symptoms in the CFS case definition. However, in
the present study, both occurred with relatively low frequency and neither
uniquely differentiated those with CFS from controls.

Hartz et al. (1998) also investigated the occurrence of symptoms in persons
with fatigue, and recommended the inclusion of fever and chills, muscle
weakness, and sensitivity to alcohol as CFS case definition symptoms. Results
of the current investigation also indicated that muscle weakness and
sensitivity to alcohol uniquely differentiated the CFS group from controls,
but neither the CFS nor the melancholic depression groups significantly
differed from controls in the occurrence of fever and chills. Furthermore, it
appeared that muscle weakness in the CFS group occurred at multiple sites,
with weak legs being the most frequently reported form of weakness. These
findings concur with those of Hartz et al. (1998), and therefore provide
further support for the inclusion of muscle weakness in the case definition of
CFS.

Differences between the present investigation and previous work could be a
result of the sampling methods employed. Other research has relied on
predominantly clinic-based samples that may report greater occurrence and
severity of symptoms, especially those of a viral or infectious nature
(Wessely, 1998). Persons with CFS found in clinic-based samples may
represent a more severely ill population. Current findings should be
interpreted within the context of limitations on statistical power imposed by
a small sample size. Small sample sizes might have precluded the detection of
significant differences between groups, and this may be especially true for
all comparisons with the depressed group because they have the smallest sample
size and because they appear to be mid-way on most measures between the CFS
group and controls. Because some differences between groups may have not been
detected, more research with larger samples is necessary to replicate these
results.

In summary, results from this investigation in a community-based sample
support the use of the symptoms included in the current CFS case definition
(Fukuda, et al., 1994). Furthermore, this investigation found that weakness
and various neurological, cardiopulmonary, neuropsychiatric, and
rheumatological symptoms uniquely differentiated persons with CFS from the
control group. In contrast, relatively few of these symptoms significantly
differentiated the group of individuals with melancholic depression from the
control group.


Acknowledgements

Financial support for this study was provided by NIAID grant number AI36295.
Requests for reprints should be sent to Leonard Jason, Ph.D., Center for
Community Research, DePaul University, 990 W. Fullerton Ave. Chicago, IL
60614.


Tables

Table 1. Occurrence of symptoms in Fukuda Symptom Categories
------------------------------------------------------------------------
CFS Melancholic No Significance
Depression Fatigue
(N=32) (N=19) (N=44)
% % %
------------------------------------------------------------------------

Fatigue/weakness
General muscle 75.0 a 47.4 18.2 **
weakness

Postexertional 68.8 a 47.4 13.6 **
malaise

Legs weak 62.5 a 26.3 9.1 **

Arms weak 53.1 a 26.3 11.4 **

Neck weak 40.6 a 21.1 4.5 **

Shoulders weak 40.6 21.1 6.8

Back weak 40.6 a 15.8 9.1 **

Head weak 25.0 5.3 2.3

Abdomen weak 9.4 5.3 0.0

Buttocks weak 3.1 0.0 0.0

Other weak muscles 3.1 15.8 0.0

Disturbed sleep
Unrefreshing sleep 90.6 a 84.2 25.0 **

Insomnia 59.4 a 36.8 15.9 **

Early morning 59.4 47.4 25.0
awakening

Trouble staying 43.8 21.1 11.4
asleep

Hypersomnia 31.3 42.1 22.7

Neuropsychiatric
Memory and 87.5 a 63.2 b 20.5 **
concentration

New headaches 75.0 a 68.4 31.8 **

Depression 56.3 a 73.7 b 13.6 **

Irritability 50.0 a 42.1 b 11.4 **

Disturbances in 46.9 26.3 11.4
eyesight

Infectious

Sore throat 62.5 a 42.1 29.5 **

Lymph pain 40.6 a 21.1 9.1 **

Fever/chills 21.9 15.8 9.1

Oral herpes 6.3 21.1 9.1

Shingles 3.1 0.0 4.5

Oral thrush 3.1 5.3 0.0

Genital herpes 0.0 15.8 0.0

Rheumatological
Muscle pain 84.4 a 52.2 22.7 **

Joint pain 56.3 a 26.3 20.5 **

Morning stiffness 56.3 a 36.8 15.9 **

Stiff after sitting 56.3 a 31.6 25.0

Hay fever 46.9 a 42.1 13.6 **

Puffy face 40.6 21.1 11.4

Dry mouth 37.5 57.9 b 11.4 **

Night sweats 34.4 15.8 0.0

Sinus infection 31.3 21.1 9.1

Earaches 25.0 31.6 6.8

Dry eyes 21.9 15.8 9.1

Eye pain 21.9 5.3 9.1

Jaw pain 18.8 10.5 0.0

------------------------------------------------------------------------

Italics indicate symptoms that are part of the current CFS case definition
(Fukuda et al., 1994).

a Statistically significant difference between CFS and No Fatigue groups.

b Statistically significant difference between Melancholic Depression and
No Fatigue groups.

** Using binomial logistic regression analyses, difference is statistically
significant at the P<0.01 level.


Table 2. Occurrence of symptoms in Non-Fukuda Symptom Categories

------------------------------------------------------------------------

CFS Melancholic No Significance

Depression Fatigue

(N=32) (N=19) (N=44)
% % %

------------------------------------------------------------------------

Cardiopulmonary

Shortness of breath 65.6 a 26.3 c 22.7 **

Chest pains 40.6 a 10.5 6.8 **

Rapid heartbeat 34.4 15.8 9.1

Cough 28.1 a 26.3 2.3 **

Heartbeat in ears 18.8 21.1 2.3

Raynaud' phenomenon 9.4 10.5 2.3


Gastrointestinal
Bloating 40.6 26.3 9.1

Lower abdominal 37.5 21.1 9.1
pain

Upper abdominal 31.3 21.1 9.1
pain

Anorexia 28.1 15.8 9.1

Nausea 25.0 21.1 0.0

Diarrhea 12.5 5.3 6.8

Black bowel movement 9.4 5.3 0.0

Blood in bowel 9.4 15.8 2.3
movement

Neurological

Dizzy after 46.9 a 21.1 9.1 **
standing

Skin sensations 46.9 a 21.1 9.1 **

General dizziness 43.8 a 36.8 2.3 **

Alcohol intolerance 43.8 a 15.8 6.8 **

Dizzy moving head 37.5 a 15.8 6.8 **

Unsteady upright 28.1 21.1 6.8

Ringing in ears 21.9 31.6 11.4

Tingling sensations 15.6 5.3 0.0

Paralysis 3.1 0.0 0.0

Temporary blindness 6.3 0.0 0.0

Reproductive

Decreased sexual 50.0 a 15.8 c 6.8 **
interest

Impairment of 50.0 a 36.8 b 2.3 **
sexual functioning

Nocturia 43.8 31.6 13.6

Irregular periods d 37.5 52.9 61.9

Incontinence 21.9 10.5 6.8

Menopause d 20.8 11.8 23.8

Vaginal discharge d 20.8 35.3 19.0

Excessive menstrual 16.7 17.6 0.0
bleeding d

Recurrent urinary 12.5 5.3 2.3
infections

Recurrent vaginal 6.3 10.5 2.3
infections d

Dysuria 6.3 0.0 0.0

Nipple discharge d 4.2 5.9 0.0

Positive pap smear d 0.0 0.0 4.8

Blood in urine 0.0 0.0 0.0

------------------------------------------------------------------------

a Statistically significant difference between CFS and No Fatigue groups.

b Statistically significant difference between Melancholic Depression and
No Fatigue groups.

c Statistically significant difference between the CFS and Melancholic
depression groups.

d Women only.

** Using binomial logistic regression analyses, difference is statistically
significant at the P<0.01 level.


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