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Gynecological Concerns in
Women with Chronic Fatigue Syndrome
MB, BS, MRCOG, United
Women suffering from chronic fatigue syndrome (CFS) commonly
have a bewildering array of symptoms that can occur in every body system,
including the reproductive system. Diagnostic confusion sometimes occurs because
some symptoms are common to both CFS and gynecological conditions such as
premenstrual syndrome or menopause. These common gynecological conditions can
also cause an exacerbation of CFS symptoms. The female reproductive hormone
system might also play a part in the causation and persistence of CFS, since the
illness occurs twice as often in women as men.1
Although scientific studies are few, a number of gynecological
conditions have been found to occur more frequently in women with CFS. These
conditions are usually associated with abnormal reproductive hormone levels,
immune dysfunction and/or pain. Some of these conditions may even pre-date the
onset of the CFS.2,3 Why this should happen is open to conjecture.
Endocrine and/or immunological changes may possibly be present in some CFS
patients before the full-blown syndrome becomes manifest.
Gynecological symptoms in women with CFS should not be assumed
to be merely part of the CFS symptomatology. Their investigation and treatment
in patients with CFS should follow standard gynecological practice, and patients
will benefit from relief of symptoms.
Low estrogen states,
menopause and osteoporosis
Many pre-menopausal CFS patients have
scanty, irregular periods, inter-menstrual bleeding and sometimes periods of
amenorrhea. These symptoms can predate the onset of CFS, are typical of
anovulatory or oligoovulatory cycles and can be associated with a low estrogen
state. Hirsutism may be associated with oligomenorrhea. Researchers have found
that ovarian hormone (estradiol) levels were low in some 25 percent of a small
group of pre-menopausal women with CFS, in spite of normal follicle stimulating
hormone (FSH) levels.4 The researchers suggested that a chronic
estrogen deficiency state is present in a subgroup of women with
CFS.4 The normal FSH levels distinguish this condition from menopause
where FSH levels are raised. At menopause, heavy irregular periods, scanty
periods or amenorrhea can occur.
There are number of central nervous system symptoms associated
with the low estrogen state. They are tiredness, headaches, dizziness, lack of
concentration, insomnia, depression and anxiety. When FSH levels are also raised
at menopause, this can result in vasomotor instability, causing night sweats,
feeling hot often and flushing of the face. All of these symptoms may be due to
reproductive hormone changes, CFS or a combination of both. One point of
difference is that vaginal dryness is usually present if estrogen levels are low
and less likely to be present if symptoms are due to CFS. Many women find that
their CFS symptoms worsen at menopause.
In younger pre-menopausal women, the presence of a low estrogen
state can be confirmed by measuring blood estradiol levels (low) and FSH levels
(not raised). In peri-menopausal women between 40 and 50, FSH levels may
fluctuate, making serial measurements helpful. In women over 50, menopause is
more likely and blood FSH is high.
Women with CFS who have had a low estrogen state for some
are at risk for osteoporosis. A small study found that five of seven
hypo-estrogenic pre-menopausal women with CFS had a low bone density.4
Other factors contributing to osteoporosis in CFS patients are exercise
intolerance, because exercise exacerbates CFS symptoms, and lack of vitamin D,
due to inability to go outside in the sunlight, as a result of weakness and
photophobia. Calcium intake may also be low, if the patient avoids milk due to
lactose intolerance, which is common in CFS. The diagnosis can be confirmed by
bone density measurement.
patients, treatment to regularize periods is not necessary. But if estrogen
levels are low, the co-existing central nervous system symptoms can be much
improved by hormone replacement therapy (HRT), although it will not cure
symptoms due to CFS. In one uncontrolled trial, it was found that symptoms
improved in 80 percent of patients with low estrogen levels, following hormone
treatment of estradiol patches and cyclical progesterone therapy.4
HRT is also helpful in menopausal patients. For example, insomnia associated
with CFS is much improved if a menopausal patient is no longer woken several
times each night by hot sweats.
Osteoporosis can be prevented and treated by use of HRT,
calcium, magnesium, vitamin D supplementation, and weight-bearing exercise, if
tolerated. Several pharmacological agents, which can reduce the incidence of
fractures, have been approved for treatment of severe osteoporosis. With the
exception of HRT, their effect on CFS patients has not been
syndrome (PMS) occurs widely in the general population but is more common in CFS
patients, occurring in more than 50 percent of them. PMS can pre-date the onset
of CFS, although it is less common before the onset of the CFS than in
Symptoms start in the luteal phase of the menstrual cycle
improve within a day or two of the period. The most common symptoms include mood
swings, irritability, depression, headache, insomnia, carbohydrate cravings,
breast pain and tenderness, and abdominal bloating. Fluid retention may cause a
weight gain of two or more pounds. In addition, CFS symptoms frequently worsen
The cause of PMS is disputed. It is thought to be hormonal
that it usually occurs in association with ovulatory cycles. Some recent
research has found that it is linked to a deficiency in serotoninergic activity
in the brain.5
used in the past have been found to be no better than placebo. These include the
use of progestogens, estrogens, vitamin B6 and evening primroseoil.6
Recently, in several placebo controlled trials, serotoninergic antidepressants
(SSRIs) such as fluoxetine 20 mg daily, or use on days 14–28 of the menstrual
cycle, were found to be successful, relieving PMS symptoms in up to 90 percent
of patients,7 but there are no specific studies in CFS patients. Side
effects of treatment tended to improve with time.
15 percent of
normal women suffer from dysmenorrhea, but at least 30 percent of CFS patients
may suffer from it.8 Severe dysmenorrhea may occur on its own, or it
can be a symptom of several gynecological conditions which are more common in
CFS patients. These include endometriosis, fibroids, pelvic inflammatory disease
and ovarian cysts. In all these conditions, menses may be heavy. If there is any
abnormality found on examination, such as a pelvic mass, further gynecological
investigation is indicated. Mild dysmenorrhea usually responds to analgesics
such as aspirin or Tylenol, but NSAIDS may work better. Severe pain can be
treated by suppressing ovulation with oral contraceptives.
reported to occur in up to 20 percent of women with CFS. It can predate its
onset.2 Dysmenorrhea is the most frequent problem. It can be very
severe even in apparently mild cases of the condition. Pain before the period,
dyspareunia, pelvic pain and pain related to the bladder or bowel may also
occur. There may be no symptoms, and the condition is only discovered during
surgery for another condition, such as infertility, which is often associated
In endometriosis, endometrial cells which line the uterus
also found in the pelvic cavity and sometimes elsewhere. Retrograde transport of
endometrial fragments along the fallopian tubes occurs in many normal
menstruating women, without signs of endometriosis. These endometrial cells are
normally removed by immune system scavenger cells. In women with immune
abnormalities such as CFS, the scavenging cells may be overwhelmed. With each
menstrual cycle, the ectopic endometrial cells are shed, resulting in localized
bleeding. This is painful and may lead to inflammation and scarring in the
A physical exam may be normal, but scarring may cause lack
mobility of the uterus and cystic enlargement of the ovaries may be present.
This can be seen on an ultrasound scan. If symptoms are severe, the diagnosis
can be confirmed and other conditions excluded by laparoscopy and biopsy. No
abnormality may be seen on laparoscopy. The cause of pelvic pain can sometimes
be difficult to find.
Women with endometriosis who do become pregnant are often
improved following delivery of the child. If severe pain caused by endometriosis
does not respond to medication, surgery may be required as a last resort. It is
very important to distinguish endometriosis pain from pain due to other problems
before embarking on surgery.
Treatment considerations: The treatment
symptomatic endometriosis is by analgesics, such as NSAIDS, oral contraceptive
pills or progestational agents. Also used are anti-estrogens with immune
modulating effects, such as Danocrine, or the GnRH agonist Leuprolide acetate.
These anti-estrogens all have side effects which may not be tolerated in CFS
patients. For the treatment of infertility, there is no proof that the treatment
of mild endometriosis by hormones is helpful.
percent of CFS patients have dysuria.9 Symptoms of pain, frequency
and urgency of urination both by day and night may be present. Urine culture may
show a bacterial infection which can be treated with antibiotics. However,
sometimes the urine is sterile and symptoms may be due to interstitial cystitis,
detruser instability, urethral syndrome or endometriosis. The patient should be
referred for further investigation.
Interstitial cystitis is thought to be associated with some
immune system abnormalities. An informal survey of patients with it found that
13.8 percent of them also suffered from CFS.10
percent of a series of CFS patients complained of vaginal
discharge.11 In all cases a swab should be obtained for diagnosis.
There are many causes of vaginal discharge. A thick, creamy, irritating
discharge may denote a vaginal infection with Candida albicans. The yeast
organism is present in the vagina of many asymptomatic women, but overgrowth
leading to symptoms may occur in patients who have had repeated courses of
antibiotics, are pregnant, have diabetes or have abnormal immune function. There
is disagreement as to whether vaginal candidiasis is more common than normal in
women with CFS.
Some people believe that women with CFS suffer from a chronic
multi-system yeast infection which exacerbates CFS symptoms. This has not been
proven by culture and oral swabs are rarely positive for yeast. Vaginal yeast
infection is normally a localized condition and only local treatment is
indicated. There are several effective vaginal anti-fungal preparations. A short
course of treatment may be adequate, but a longer two-week course may be
necessary and may have to be repeated to clear symptoms.
is present in up to 20 percent of CFS patients.9 Decreased libido is
common and dyspareunia may also occur. Loss of libido can be associated with low
reproductive hormone levels, or due to the severe fatigue, malaise and pain
which are prominent in CFS. Dyspareunia may be caused by vaginal dryness from
low estrogen levels, or the presence of a pelvic condition such as
endometriosis, interstitial cystitis, pelvic congestion syndrome or vulvodynia.
For low estrogen syndromes, a vaginal estrogen cream or hormone replacement
therapy may be helpful. Sexual problems put a severe strain on both patient and
her partner. They may need counseling to help them save their relationship.
For contraception, an oral contraceptive pill or a hormonal
implant can be used, if tolerated, but the intra-uterine contraceptive device
(IUD) is not recommended because of an increased possibility of pelvic
infection.12 The diaphragm, cervical cap or condom, while less
effective as contraceptives, can be used. Surgical sterilization carries
anesthetic risks in CFS patients and can cause a relapse.
Fibroids, ovarian cysts and
A history of ovarian cysts, including polycystic ovaries, and uterine
fibroids was found in one study to be more common in CFS patients than in
controls.2 They often predated the onset of the CFS. There are no
reports of any increase in ovarian cancer. If a pelvic mass is present, referral
to a gynecologist is indicated. Patients with CFS are significantly more likely
than controls to have had a hysterectomy.3 This may be associated
with the increased numbers of patients with fibroids, ovarian cysts or
Rosemary Underhill, MB, BS, is a physician who specializes
obstetrics and gynecology. Dr. Underhill served as a medical consultant for the
New Jersey consensus
manual for the primary care of CFS.
- Jason LA,
et al. A community-based Study of chronic fatigue syndrome. Arch Intern
et al. Reproductive correlates of chronic fatigue syndrome. AJM. 1998; 105(3A):
- Reyes M, et
al. Risk factors for CFS. J Chronic Fatigue Syndrome. 1996;
- Studd J and
Panay N. Chronic fatigue syndrome. Lancet (letter). 1996;
- Ashby CR,
et al. Alteration of platelet serotonergic mechanisms and mono-amine oxidase
activity in premenstrual syndrome. Biol Psych. 1988; 24(2): 225-233.
- Manu P. The
pharmacotherapy of common functional syndromes. The Haworth Press Inc. 2000;
- Stone AB,
et al. Fluoxetine in the treatment of late luteal phase dysphoric disorder.
J. Clin Psych. 1991; 52(7):290-293.
Clinical Features & Possible Etiology of
CFIDS Chronicle. Spring 1991; 71.
- Bell D.
“The Doctor’s Guide to Chronic Fatigue Syndrome.” Addison-Wesley 1995;
- Chalker L.
Interstitial cystitis. CFIDS
Chronicle. Summer 1996; 72.
encephalomyelitis. Croom Helm. 1986; 21.
- Shepherd C.
with M.E. Cedar. 1993; 241.