Definitions
Hypermenorrea or menorragia: More than 80ml or 7 days of menstrual bleeding
Polymenorrea: Cycles lasting less than 21 days
Metrorragia: Intercycle bleeding
Childhood
Bleeding prior to menarche should be investigated as an abnormal
finding. Initial
evaluation should focus on determining the location of the bleeding, because
vaginal, rectal, or urethral bleeding can present similarly. In this age
group, the vagina, rather than the uterus, is the most common source of
bleeding. Vulvovaginitis is the most frequent cause, but dermatologic
conditions, neoplastic growths, or trauma by accident, abuse, or foreign body
may also be reasons. In addition to vaginal sources, bleeding may also
originate from the urethra and may reflect urethral prolapse or infection
Abnormal uterine bleeding is a frequent clinical problem, accounting for
70 percent of all gynecologic visits by peri- and postmenopausal women. As with perimenarchal girls,
anovulatory uterine bleeding from dysfunction of the
hypothalamic-pituitary-ovarian axis becomes a more common finding in this group.
Alternatively, the incidence of bleeding related to pregnancy and sexually
transmitted disease decreases. With increasing age, there are greater risks of
benign and malignant neoplastic growth.
Bleeding after menopause
typically originates from benign disease. For example, Choo and colleagues
(1985) found that the majority of cases resulted from atrophy of the
endometrium. Benign endometrial polyps may also cause bleeding in this population.
The endometrium consists
of two distinct zones, the functionalis layer and the basalis layer (Fig.
8-2). The basalis layer stretches beneath the functionalis, lies in direct
contact with the myometrium, and is less hormonally responsive. The basalis serves as a
reservoir for the regeneration of the functionalis following menses. In
contrast, the functionalis layer lines the uterine cavity, undergoes dramatic
change throughout the menstrual cycle, and ultimately sloughs during
menstruation. Histologically, the functionalis has a surface epithelium
and underlying subepithelial capillary plexus. Beneath these are organized stroma and glands in which
leukocyte populations are interspersed
Blood reaches the uterus
via the uterine and ovarian arteries (Fig. 38-13). From these, the arcuate
arteries are formed and supply the myometrium. These in turn branch into the
radial arteries, which extend toward the endometrium at right angles from the
arcuate arteries (see Fig. 8-2). At the endometrium-myometrium junction, the radial
arteries bifurcate to create the basal and spiral arteries. The basal arteries
serve the basalis layer of the endometrium and are relatively insensitive to
hormonal changes (Abberton, 1999; Hickey, 2000b; Weston, 2000). The spiral arteries stretch to
supply the functionalis layer. Their arteriole branches are thought to
be critical in controlling menstruation. Prior to menses these arterioles display increased
coiling with stasis of blood flow. Subsequently, vasodilatation and bleeding
from the spiral arteriole and capillary walls ensues. As a result, most
menstrual blood is lost through these vessels. This is followed by vasoconstriction which leads to
endometrial ischemia and necrosis. This necrotic tissue is sloughed with
menstruation.
Bleeding following intercourse most commonly develops in women aged 20
to 40 years and in those who are multiparous. No underlying pathology is identified in up to two
thirds (Rosenthal, 2001; Selo-Ojeme, 2004). If an identifiable lesion is
found, however, it typically is benign (Shalini, 1998). In a review of 248
women with postcoital bleeding, Selo-Ojeme and co-workers (2004) found that a
fourth of cases were caused by cervical eversion (see Chap. 29, Cervix). Other
causes included endocervical polyps, cervicitis, and less commonly, endometrial
polyps.
In some women, postcoital bleeding may be from cervical or other genital
tract neoplasia. The epithelium associated with cervical intraepithelial
neoplasia (CIN) and invasive cancer is thin and friable and readily detaches
from the cervix. In women
with postcoital bleeding, CIN was found in 7 to 10 percent, invasive cancer in
about 5 percent, and vaginal or endometrial cancer in <1 percent.
Painful intercourse and
noncyclic pain are less frequent in women with abnormal bleeding and usually
suggests a structural or infectious cause. For example,
Lippman and colleagues (2003) reported increased rates of dyspareunia and
noncyclic pelvic pain in women with uterine leiomyomas. Similarly, Sammour and co-workers
(2002) correlated increasing pelvic pain with deepening myometrial invasion
with adenomyosis
The incidence and risk of
endometrial carcinoma increases with age and three fourths of women with this
malignancy are postmenopausal. Thus, in postmenopausal patients, the need to exclude cancer
intensifies and endometrial biopsy is warranted. In the remaining 25 percent of premenopausal women with
endometrial cancer, only 5 percent are less than 40 years of age
(Peterson, 1968). Most of these premenopausal women are obese or have chronic
anovulation, or both (Rose, 1996). Thus, obese or anovulatory women with abnormal bleeding should also
have endometrial cancer excluded. The American College of Obstetricians
and Gynecologists (2000) recommends endometrial assessment in any woman older
than 35 years with abnormal bleeding and in those younger than 35 years who are
suspected of having anovulatory uterine bleeding refractory to medical
management.
Initially, the site of uterine bleeding must be confirmed because
bleeding may also come from the lower reproductive tract, gastrointestinal
system, or urinary tract. This is more difficult when there is no active
bleeding. In these situations, urinalysis or stool guaiac evaluation may be
helpful adjuncts to a thorough examination
Hematologic and B-HCG Testing
A hemogram is useful to evaluate anemia from chronic blood loss as well
as the degree of blood loss in women with menorrhagia. An abnormally low serum ferritin level is a
satisfactory predictor of blood loss >80 mL per menstrual cycle
(Warner, 2004).
Pregnancy complications are quickly excluded with determination of urine
or serum levels of human chorionic gonadotropin (-hCG). Miscarriages and
ectopic pregnancies may cause simple spotting or lead to life-threatening
hemorrhage.
Sampling and histologic
evaluation of the endometrium in women with abnormal bleeding may disclose
infection or neoplastic lesions such as endometrial hyperplasia, cancer,
polyps, or gestational trophoblastic neoplasia
For years, dilatation and
curettage (D&C) was used for endometrial tissue sampling (see Section
41-16, Sharp Dilatation and Curettage). But because of the associated surgical
risks, expense, postoperative pain, and need for operative anesthesia, other
suitable substitutes were evaluated. In addition,
several investigators have demonstrated high rates of incomplete sampling and
missed pathology with D&C (Goldstein, 1997; Grimes, 1982; Stock, 1975).
Of suitable substitutes
for D&C, office techniques using metal curettes were implemented to obtain
endometrial samples, and these showed significant positive correlations with
histologic results from hysterectomy specimens
(Ferenczy, 1979; Stovall, 1989). The main disadvantages, however, were patient
discomfort, cost, and procedural complications such as uterine perforation and
infection. To minimize
these, a variety of thin, flexible plastic samplers have been evaluated, with
comparable histologic findings from tissues obtained by D&C, hysterectomy,
or stiff metal curette (Stovall, 1991). In their meta-analysis of endometrial biopsy tools,
Dijkhuizen and co-workers (2000) found the Pipelle (CooperSurgical, Trumbull,
CT) to be superior
Despite its advantages, there are limitations to endometrial sampling
with the Pipelle device. First, a tissue sample that is inadequate for
histologic evaluation or an inability to pass the catheter into the endometrial
cavity is encountered in up to 28 percent of biopsy attempts (Smith-Bindman,
1998). Cervical stenosis is the most common cause of obstruction. An incomplete
evaluation necessitates further investigation with D&C, transvaginal
sonography, or diagnostic hysteroscopy (Emanuel, 1995). Second, endometrial biopsy has a
cancer-detection failure rate of 0.9 percent. Thus, a positive histologic result is accurate to
diagnose cancer, whereas a negative result does not necessarily exclude it.
Therefore, if an endometrial biopsy with normal tissue is obtained, but
abnormal bleeding continues despite conservative treatment or if the suspicion
of endometrial cancer is high, then further diagnostic efforts are warranted
(Clark, 2002; Hatasaka, 2005). Finally, endometrial sampling is associated with a greater percentage
of false-negative results if the pathology is focal, such as with endometrial
polyps. Guido and associates (1995) reported false-negative results in
11 of 65 patients—17 percent—undergoing Pipelle endometrial sampling for
abnormal bleeding. Five of these 11 had malignant tissue present only in
endometrial polyps, and another three patients had disease localized to less
than 5 percent of the endometrial surface. Because of these limitations with
endometrial sampling, investigators have evaluated the use of sonography,
hysteroscopy, or both to replace or complement endometrial sampling.
TVU
Although the thickness of the endometrium varies, ranges have been
established. Granberg and
co-workers (1991) found thickness measurements of 3.4 ± 1.2 mm in
postmenopausal women with an atrophic endometrium, 9.7 ± 2.5 mm in those with
endometrial hyperplasia, and 18.2 ± 6.2 mm in those with endometrial cancer.
Subsequently, a number of
investigations have focused on endometrial thickness as it relates to the risk
of hyperplasia and cancer in postmenopausal women. Sensitivities of 95 to 97
percent have been reported using a measurement of >4 mm for exclusion of
endometrial cancer. This
guideline can be employed whether or not a patient is taking hormone
replacement therapy (Bakour, 1999; Karlsson, 1995; Tsuda, 1997). Women
with endometrial thicknesses >5 mm warrant additional evaluation with
saline-infusion sonography (SIS), hysteroscopy, or endometrial biopsy.
Endometrial thickness
guidelines, however, have not been established for premenopausal women. Merz and colleagues (1996) found
that the normal endometrial thickness in premenopausal women did not exceed 4
mm on day 4 of the menstrual cycle, nor did it measure over 8 mm by day 8.
In their review, Farquar
and co-workers (1999) suggested that a persistent finding of endometrial
thickness, independent of cycle day, measuring >12 mm should prompt further
evaluation in these women, especially in those with risk factors for
endometrial carcinoma (see Chap. 33). Risks include extended abnormal uterine
bleeding, chronic anovulation, nulliparity, diabetes, obesity, hypertension,
and tamoxifen use (Hatasaka, 2005).
Qualities other than endometrial thickness are also considered, and
textural changes may indicate pathology. For example, punctate cystic areas within the endometrium
may indicate a polyp. Conversely,
hypoechoic masses that distort the endometrium and originate from the inner
layer of myometrium most commonly are submucosal fibroids. Although
there are no specific sonographic findings that are characteristic of
endometrial cancer, some findings have been linked with greater frequency. For
example, intermingled hypo- and hyperechoic areas within the endometrium may
indicate malignancy. Endometrial cavity fluid collections and an irregular
endometrial-myometrial junction have also been implicated. Thus, even with a normal
endometrial stripe width, endometrial biopsy or hysteroscopy with biopsy should
be performed to exclude malignancy when there is heterogeneous endometrial echogenicity
or fluid collection.
A major limitation of TVS
is the higher false-negative rate in diagnosing focal intrauterine pathology.
This results in part from the physical inability of TVS to clearly assess the
endometrium when there is concurrent uterine pathology such as leiomyomas or
polyps. These women warrant either saline-infusion sonography or hysteroscopy
for further evaluation.
To perform SIS, a small catheter is threaded through the cervical os
into the endometrial cavity. Through this catheter, sterile saline is infused,
and the uterus is distended. Sonography is then performed using a traditional
transvaginal technique. Saline-infusion sonography (SIS) has also been compared
with hysteroscopy to detect uterine cavitary focal lesions. De Kroon and
co-workers (2003) performed a meta-analysis of 24 studies and reported SIS to equal the
diagnostic accuracy of hysteroscopy.
Another disadvantage to SIS is that it is best performed in the
proliferative phase of the cycle to minimize false-negative and false-positive
results. For example, focal lesions may be concealed in a thick, secretory
endometrium. Also, the amount of endometrial tissue that can develop during the
normal secretory phase can be mistaken for small polyps or focal hyperplasia
(Goldstein, 2004). For many, SIS has more patient discomfort than TVS, and
about 5 percent of examinations cannot be completed because of cervical
stenosis or patient discomfort. As expected, stenosis is more prevalent in
postmenopausal women (De Kroon, 2003). This rate of incompletion mirrors that
of diagnostic hysteroscopy. Although accurate for identifying focal lesions,
SIS may not add to the value of TVS alone to evaluate diffuse lesions such as
hyperplasia and cancer. Therefore,
in postmenopausal women with abnormal bleeding, and in whom the exclusion of
cancer is more relevant than evaluating focal intracavitary lesions, use of SIS
as an initial diagnostic tool may not have advantages over TVS alone.
Histeroscopy: This procedure involves inserting an optic endoscope,
usually 3 to 5 mm in diameter, into the endometrial cavity (see Section 41-35,
Hysteroscopy). The uterine cavity is then distended with saline or another
medium for visualization. In addition to inspection, biopsy of the endometrium
allows histologic diagnosis of visually abnormal areas and has been shown to be
a safe and accurate means to identify pathology (van Dongen, 2007). In fact,
for many studies done to investigate the accuracy of TVS or SIS for evaluation
of intracavitary uterine pathology, hysteroscopy is used as the gold standard for comparison.
The main advantage of hysteroscopy is to detect intracavitary lesions
such as leiomyomas and polyps that might be missed using transvaginal
sonography or endometrial sampling (Fig. 8-10) (Tahir, 1999). In fact, some have advocated
hysteroscopy as the primary tool for the diagnosis of abnormal uterine
bleeding. Although it is highly accurate for identifying endometrial cancer, it
is less accurate for endometrial hyperplasia. Thus, some recommend endometrial biopsy or
endometrial curettage in conjunction with hysteroscopy.
There are other limitations to hysteroscopy. Cervical stenosis sometimes
will block successful introduction of the endoscope, and heavy bleeding may
limit an adequate examination (Beukenholdt, 2003). The use of misoprostol, 100
mg orally the evening before and the morning of hysteroscopy, is useful for
cervical softening in patients with suspected cervical stenosis. Hysteroscopy
is more expensive and technically challenging than TVS or SIS. Many perform
hysteroscopy in their office, whereas others prefer a day-surgery setting to
provide increased patient analgesia. Obviously, greater cost and anesthetic
risks can attend completion in this latter setting. Although it can be painful,
use of a 3.5-mm minihysteroscope instead of the conventional 5-mm endoscope
significantly decreases patient discomfort during office hysteroscopy
(Cicinelli, 2003). Associated infection and uterine perforation have been
reported with hysteroscopy, but fortunately their incidence is low.
There is concern that peritoneal seeding with malignant cells may take
place during hysteroscopy in some women subsequently diagnosed with endometrial
cancer (Obermair, 2000; Zerbe, 2000). Caution is advised with hysteroscopy in
women at high risk for endometrial cancer, and some suggest a negative
endometrial biopsy result is necessary before hysteroscopy is done (Oehler,
2003). Although there may be a risk of peritoneal contamination by cancer cells
with hysteroscopy, there is no evidence that the prognosis for patients is
worsened.
There is no one clear sequence to use of endometrial biopsy, TVS, SIS,
and hysteroscopy when evaluating abnormal uterine bleeding. None of these will
distinguish all anatomic lesions with high sensitivity and specificity. That said, TVS for several
reasons is a logical first step. It is well-tolerated, cost-effective,
and requires relatively minimal technical skill. Additionally, it has the
advantage of reliably determining whether a lesion is diffuse or focal. Once
anatomic lesions have been identified, subsequent evaluation requires
individualization. If endometrial hyperplasia or cancer is suspected, then
endometrial biopsy may offer advantages. Alternatively, possible focal lesions
may be best investigated with either hysteroscopy or SIS. Ultimately, the
selection of appropriate tests depends on their accuracy to characterize the
most likely anatomic lesions.
Copper-Containing Intrauterine Device
These intrauterine devices (IUDs) have long been associated with
menorrhagia and metrorrhagia (see Chap. 5, Menorrhagia) (Milsom, 1995; Bilian,
2002). Several explanations for this bleeding have been suggested. At the cellular level,
unbalanced ratios of prostaglandins and thromboxane have been proposed as a
potential source of IUD-induced menorrhagia
Initially, patients with
IUD-related bleeding may be managed with empiric trials of NSAIDs (Table
8-3). Persistent abnormal bleeding, however, may result from other gynecologic
pathology and not from the IUD. These patients should be managed similarly to
other women with the complaint of abnormal uterine bleeding. Although
sonographic evaluation may be limited by IUD shadowing, endometrial biopsy with
small catheters can be performed without removal of the device.
This system, marketed as Mirena (Berlex, Wayne, NJ) (see Fig. 5-5), can
lead to abnormal uterine bleeding in some users.
Combination Hormonal Contraception
Bleeding associated with combination oral contraceptive pills (COCs) is
common (see Chap. 5, Estrogen Plus Progestin Contraceptives). As many as 30 to
50 percent of women experience abnormal uterine bleeding in the first month
that they use combination COCs (Hatcher, 2004). The presumed source of this bleeding stems from
endometrial atrophy, which is induced by the progestin component of COCs.
During this process,
spiral arterioles do not characteristically coil, and they become thinner and
more sinusoidal. In addition, venules become dilatated and prone to
thrombosis. This often leads to local tissue infarction and is thought to be
the cause of breakthrough bleeding
This selective estrogen receptor modulator (SERM) is used as an adjunct
for treatment of estrogen-receptor–positive breast cancer. Although it
diminishes estrogen action in breast tissue, its effects on the endometrium stimulate proliferation
(see Chap. 12, Breast Cancer Prevention). Tamoxifen use has been linked to endometrial hyperplasia,
polyps, and carcinoma as well as uterine sarcomas (Cohen, 2004).
Screening women who use tamoxifen and do not have abnormal bleeding has
not proved effective. Protocols using sonography or endometrial biopsy failed
to effectively identify endometrial cancer in asymptomatic users (Barakat,
2000; Love, 1999). As a result, women using tamoxifen should undergo evaluation
for endometrial cancer only when bleeding develops
Dysfunctional Uterine Bleeding
Once organic causes of
abnormal uterine bleeding have been excluded, the term dysfunctional uterine
bleeding (DUB) is used. Up to one-half of women with abnormal
bleeding will have DUB (Hickey, 2000b). In 80 to 90 percent of these, bleeding results from dysfunction of
the hypothalamic-pituitary-ovarian axis, which leads to anovulation (see
Chap. 16). Because
anovulatory cycles produce no progesterone to stabilize cyclic withdrawal of
the estrogen-prepared endometrium, bleeding episodes become irregular and
amenorrhea, metrorrhagia, and menorrhagia are common. For example, many
women with anovulation may have amenorrhea for weeks to months followed by
irregular, prolonged, and heavy bleeding.
In the other 10 to 20
percent of women with DUB, ovulation occurs cyclically, and menorrhagia is
thought to originate from defects in the control mechanisms of menstruation.
No progesterone is produced when ovulation does not occur, and thus
proliferative endometrium persists. At the tissue level, presistent proliferative endometrium is often
associated with stromal breakdown, decreased spiral arteriole density, and
increased dilated and unstable venous capillaries (Singh, 2005). At the
cellular level, the availability of arachidonic acid is reduced, and
prostaglandin production is impaired. For these reasons, bleeding associated with anovulation
is thought to result from changes in endometrial vascular structure and in
prostaglandin concentration, and from an increased endometrial responsiveness
to vasodilating prostaglandins
Whereas anovulatory DUB results from alterations in vascular
architecture and tone, ovulatory
DUB is thought to stem predominantly from vascular dilatation alone. For
example, women with ovulatory bleeding lose blood at rates three times faster
than women with normal menses, but the number of spiral arterioles is not
increased (Abberton, 1999).
Thus in women with ovulatory DUB, it is thought that the vessels supplying the
endometrium have decreased vascular tone and therefore increased rates of blood
loss resulting from vasodilatation (Rogers, 2003). A number of causes
that provoke this change in vascular tone have been suggested, and
prostaglandins have been strongly implicated
Nonsteroidal Anti-Inflammatory Drugs
These medicines are effective and well-tolerated oral agents commonly
used for the treatment of DUB (see Table 8-3). The rationale for their use
stems from the suspected role of prostaglandins in the pathogenesis of DUB. A
number of investigators have documented the effectiveness of NSAIDs in
decreasing DUB-related menorrhagia (Makarainen, 1986b; Marchini, 1995). Among
NSAIDs, there are no differences in clinical efficacy,
Women lose 90 percent of menstrual blood volume during the first 3 days
of menses (Haynes, 1977). Accordingly, NSAIDs are most effective if used with
the onset of menses or just prior to its onset and continued throughout its
duration. Therefore, one
advantage to NSAIDs is that they are required only during menstruation.
Another advantage is that commonly associated dysmenorrhea also improves with
NSAIDs.
The so-called "conventional" NSAIDs nonspecifically inhibit both
cyclooxygenase-1 (COX-1), an enzyme critical to normal platelet function, and
COX-2, which mediates inflammatory response mechanisms. They are effective
analgesics, but their use with bleeding may not be ideal considering their
inhibitory effects on platelet function. The other class of NSAIDs inhibits
only COX-2 and does not interfere with platelet aggregation and hemostasis
(Leese, 2000). Some have proposed that COX-2 inhibitors might be more effective
to treat menorrhagia, however, there have been no randomized trials that
validate this idea (Hayes, 2002). Additionally, there are now concerns that
long-term use of COX-2 inhibitors is associated with increased myocardial
infarction, stroke, and heart failure (Solomon, 2005). As a result, further
investigation is needed before routine use of COX-2 inhibitors is recommended
for menorragia.
This is an
antifibrinolytic drug that exerts its effects by reversibly blocking lysine
binding sites on plasminogen. The resulting decreased plasmin levels
diminish fibrinolytic activity within endometrial vessels to prevent bleeding. The drug has no effect on
other blood coagulation parameters such as platelet count, activated partial
thromboplastin time, and prothrombin time (Wellington, 2003).
In women with DUB, there is increased fibrinolytic activity within the
endometrium compared with women with normal menses (Gleeson, 1994). Clinically,
the drug has been shown effective to reduce bleeding in up to half of women
with DUB-related menorrhagia (Coulter, 1995; Lethaby, 2000). In addition, tranexamic acid
requires administration only during menstruation and has few minor reported
side effects. These are predominantly gastrointestinal and
dose-dependent.
As discussed earlier, unopposed estrogen stimulation, resulting from anovulatory cycles,
causes proliferation of the endometrium and erratic bleeding. Progestins halt endometrial
growth and allow for an organized sloughing with their withdrawal
(Saarikoski, 1990). Thus, progestin treatment of women with anovulatory DUB is
usually successful. Of the oral progestins, either norethindrone—also known as
norethisterone—or medroxyprogesterone acetate may be used. For immediate
control of bleeding, norethindrone, 5 mg, is given two or three times daily, or
medroxyprogesterone acetate 10 mg is taken once daily for 10 days. This is
followed by withdrawal bleeding 3 to 5 days after completion of the either
course. For long-term management, similar dosages of these drugs are given
during days 16 through 25 following commencement of the most recent menstrual
flow (Fraser, 1990). Again, withdrawal bleeding will follow cessation each
month
In contrast, ovulatory
menorrhagia is not due to a progestin deficiency but may result from altered
prostaglandin synthesis or disruption of hemostasis. As expected, ovulatory
menorrhagia is relatively unresponsive to cyclic administration of oral
progestins (Cameron, 1987, 1990; Preston, 1995; Singh, 2005).
Despite this, women with
ovulatory DUB may respond to longer treatment schedules. Norethindrone 5 mg or
medroxyprogesterone acetate 10 mg, each given three times orally daily for days
5 to 26 of each menstrual cycle have been shown effective (Fraser,
1990; Irvine, 1998). Unfortunately, prolonged use of high-dose progestins is
often associated with side effects such as mood changes, weight gain, bloating,
headaches, and atherogenic changes in the lipid profile (Lethaby, 1998b). For
these reasons, they are considered unacceptable by many women for long-term use
Combination Oral Contraceptive Pills
Evidence suggests that these hormonal contraceptives are effective in
the treatment of DUB, and when used long term, reduce flow by 40 to 70 percent
(Agarwal, 2001; Fraser, 1991). Advantages to COC use include the additional
benefits of reducing dysmenorrhea and providing contraception (see Chap. 5,
Estrogen Plus Progestin Contraceptives). Their presumed method of action is endometrial atrophy.
There may also be diminished prostaglandin synthesis and decreased endometrial
fibrinolysis (Irvine, 1999).
In addition to chronic use
for the treatment of dysfunctional uterine bleeding, COCs can be used acutely
to manage menorrhagia. Pills containing at least 30 ug of ethinyl estradiol
should be prescribed. If there is active bleeding, the regimen begins with four
pills every 6 hours until the bleeding has stopped for at least 24 hours. An antiemetic may be needed to
control nausea. For most women, bleeding will cease within 48 hours. After the bleeding has stopped,
the dosage of COC is decreased to three pills per day for the next 3 days,
followed by two pills per day for 3 days. A once-a-day regimen is then
continued for 21 days to be followed by withdrawal menses. At this
point, COCs may be stopped or continued for cycle control (Rimsza, 2002).
Alternatively, less frequent dosing or smaller doses may also be effective in
the acute management of menorrhagia
Androgens (Danazol and Gestrinone)
Danazol is an isoxazole derivative of the synthetic steroid 17-ethinyl
testosterone (see Chap, 10, Androgens). The net effect of danazol creates a hypoestrogenic and
hyperandrogenic environment, which induces endometrial atrophy. As a
result, menstrual loss is reduced by approximately half, and it may even induce
amenorrhea in some women (Beaumont, 2002; Chimbira, 1980a; Higham, 1993).
For heavy menstrual
bleeding, suggested dosing is 100 to 200 mg taken orally every day
(Chimbira, 1980b). Unfortunately,
this agent has significant androgenic side effects that include weight
gain, oily skin, and acne.
It is thus usually reserved as a second-line drug for short-term use prior to
surgery
Estrogens, GNH agonists
Levonorgestrel-Containing Intrauterine System
Intrauterine devices were developed for contraceptive purposes, but the
levonorgestrel-containing intrauterine system (LNG-IUS) also provides relief of
menorrhagia for some women (see Chap. 5, Levonorgestrel-Containing Intrauterine
Device
The LNG-IUS can be used in all women as a first line of treatment of
menorrhagia in place of oral medications. It is particularly useful for
reproductive-aged women who also desire contraception
Dilatation and Curettage (D&C)
Curettage is rarely used for long-term treatment because its effects are
only temporary. In the
occasional woman, D&C is performed to arrest severe bleeding refractory to
high-dose estrogen administration
Endometrial Destructive Procedures
Although medical therapy is generally used first, over half of women
with menorrhagia undergo hysterectomy within 5 years of referral to a
gynecologist. In at least a third of these, an anatomically normal uterus is
removed (Coulter, 1991; Roy, 2004). As alternatives to hysterectomy, less
invasive procedures have been devised that either destroy or resect the
endometrium and lead to amenorrhea in a manner similar to Asherman syndrome
It is problematic that endometrial tissue has tremendous regenerative
capabilities. For this reason, to be successful, destructive procedures must
remove the endometrial functionalis and basalis as well as 3 mm of myometrial
depth. However, the persistence or regeneration of endometrium is possible.
Therefore, premenopausal women should be counseled before surgery about the
need for adequate postoperative contraception.
In addition, the American College of Obstetricians and Gynecologists
(2007) recommends endometrial sampling prior to surgery. Women with endometrial
hyperplasia or cancer should not undergo ablation
Both first- and second-generation procedures require dilation of the
cervix to admit the ablative device. They are typically performed using general
anesthesia or conduction analgesia. However, some have described the use of
paracervical block and/or intravenous sedation for second-generation procedures
(Fernandez, 1997; Soysal, 2001; Wallage, 2003). Recently, Marsh and co-workers
(2005) described the use of thermal balloon ablation using only preoperative
ibuprofen.
HIsterectomy
Congenital structural lesions of the reproductive tract may at times
cause chronic intermenstrual bleeding superimposed upon normal menstrual cycles
(see Chap. 18, Description and Patient Presentation). In such cases, an anomalous partial vaginal septum
may collect blood behind it. Although sequestered, a small patent outflow from
the collection typically allows chronic release. Patients thus describe
cyclic menses with light but persistent intermenstrual flow
These soft, fleshy
intrauterine overgrowths are comprised of endometrial glands and fibrotic
stroma and are covered by a surface epithelium (Fig.
8-10 and 8-11). Polyps are common, and their prevalence ranges from 10 to 30
percent in women with abnormal bleeding (Bakour, 2000; Goldstein, 1997). As
shown in Figure 8-11, intact polyps may be single or multiple, may measure from
a few millimeters to several centimeters, and may be sessile or pedunculated
with a long and slender stalk (Kim, 2004). Most polyps are benign, but hyperplasia develops frequently.
Moreover, malignant transformation develops in 1 to 2 percent of polyps
More than 70 percent of
women with endometrial polyps will complain of menorrhagia or metrorrhagia (Preutthipan, 2005;
Reslova, 1999). It is thought that stromal congestion within the polyp leads to
venous stasis with apical necrosis and bleeding (Jakab, 2005). Although
bleeding is common, with the introduction of transvaginal sonography, a large
number of women with asymptomatic polyps have been identified during imaging for
other indications
The few risk factors associated with development of endometrial polyps
include hypertension and obesity as well as tamoxifen use (Reslova, 1999). Most
evidence does not support a link between hormone replacement therapy and polyp
formation.
Once a polyp has been
identified, operative hysteroscopy is often the treatment of choice. The technique is
detailed in Section 41-38, Polypectomy. Hysteroscopy and polypectomy is recommended for
symptomatic women or for those with risk factors for malignant transformation
(Savelli, 2003; Machtinger, 2005). Conversely, asymptomatic premenopausal women with polyps <1.5 cm
can be observed. There is only a small associated risk of malignant
transformation and high rates of spontaneous resolution.
These lesions represent overgrowths of benign endocervical stroma
covered by epithelium. They appear as single, red, smooth elongated masses
extending from the external os (see Fig. 4-13). Polyps vary in size and range
from several millimeters to 2 or 3 cm. These common growths are found more
frequently in multiparas and rarely in prepubertal females. Endocervical polyps
are typically asymptomatic, but they can cause metrorrhagia, postcoital
bleeding, and symptomatic vaginal discharge.
Endocervical polyps are usually identified by visual inspection during
pelvic examination. In some instances, Pap smear findings of atypical glandular
cells have been associated with endocervical polyps (Burja, 1999; Obenson,
2000). Although typically benign, malignant transformation may develop in 1
percent. Importantly,
cervical cancer can present as polypoid masses and can mimic these benign
lesions. For this reason, removal and histologic evaluation are recommended for
an endocervical polyp.
Endocervical polyps are removed by grasping the polyp with a ring or
polyp forceps. The polyp is twisted repeatedly about the base of its stalk to
strangulate its feeding vessels. With repeated twisting the base will avulse.
Monsel solution (ferric subsulfate) can be applied with direct pressure to the
resulting stalk stub to complete hemostasis
VWD: Treatments for women with menorrhagia and vWD include desmopressin, plasma
concentrates, hormonal contraception, antifibrinolytics, and surgery.
Combination oral contraceptive pills have been noted to arrest uterine
hemorrhage in 88 percent of women (Foster, 1995). Also, Kingman and co-workers
(2004) reported that the LNG-IUS effectively decreased blood loss and induced
amenorrhea in 56 percent of women with inherited bleeding disorders.
Preliminary success has been found with endometrial ablation for women with
vWD-related menorrhagia (El-Nashar, 2007; Rubin, 2004). Hysterectomy, of
course, is curative and preoperative consultation with a hematologist is
recommended
