Download abnormal bleeding around puberty

MINISTRY OF PUBLIC HEALTH OF UKRAINE
NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSYA
CHAIR OF OBSTETRICS AND GYNECOLOGY №1
METHODICAL INSTRUCTIONS
for practical lesson
« Gynecological disorders of childhood and adolescence»
MODULE 4: Obstetrics and gynecology
TOPIC 12
I. Topic: Abnormalities of sexual development of girls. Classification, clinical picture,
diagnostics and principles of treatment
II. Class duration – 4 hours.
III. Educational objectives:
The student must know:
1.
Special methods of examination in girls with abnormalities of sexual development.
2.
Deontology of communication with patients with such pathology in juvenile age.
3.
Estimate data of general clinical, special, hormonal, roentgenological, medical and
genetic examination of girls with abnormalities of sexual development.
The student must be able to:

Examine of a patient with abnormalities of sexual development.

Make diagnostics and treatment.

Interpret data of clinical and laboratorial and instrumental examination.
IV. Advice to the student.
Disorders of Puberty

Delayed Puberty
o
Delay of puberty can be caused by anatomic abnormalities, chromosomal
disorders, neoplastic growths, or nutritional deficiencies.
o
Commonly presents as a physical delay in maturation combined with amenorrhea.
o
Causes of delayed puberty can be classified, based on the level of follicle
stimulating hormone (FSH) present, as outlined in Table 30.5.
o
Hypergonadotropic Hypogonadism (High FSH)
A sufficient amount of gonadotropins are present, but the end organs are not responsive and
therefore do not produce sex steroids.
Gonadal dysgenesis
Present as phenotypic female with persistent prepubertal development. Usually lack breast
development.
May have some secondary sex characteristics and spontaneous menstruation. Most often
associated with primary amenorrhea.
Table 30.5 An Overview of Causes of Delayed Puberty
FSH Level
Differential Diagnosis
gh >30 mIU/mL Gonadal dysgenesis syndromes: Turner's syndrome, Sweyer's syndrome
Primary ovarian failure
ow <10 mIU/mL Constitutional delay
Intracranial neoplasms
Isolated gonadotropin deficiencies
Hormone deficiencies
Kallmann syndrome
Prader-Labhart-Willi syndrome
Laurence-Moon-Biedl syndrome
Chronic disease and malnutrition
mal
omic deformities result in normal development with primary amenorrhea.
Imperforate hymen
Transverse vaginal septum
MГјllerian agenesis
Turner syndrome (45, X) is most commonly associated with gonadal dysgenesis. Occurs in 1 in
2,000 to 2,500 born girls and is present in approximately 6% of all spontaneous abortions (3).
Sweyer syndrome(46, XY) is also associated with gonadal dysgenesis, but patients often have a
normal-to-tall stature. Most often related to a mutation or structural abnormality of the Y
chromosome. Must remove gonads.
Primary ovarian failure
Ovaries develop but do not contain oocytes; may be associated with chemotherapy, radiation,
galactosemia, gonadotropin resistance, autoimmune ovarian failure, or ovarian failure secondary to
previous infection.
Treatment involves administration of exogenous estrogen and progesterone to avoid osteoporosis
and to facilitate development of secondary sexual characteristics.
Hypogonadotrophic Hypogonadism (Low FSH)
An insufficient level of gonadotropins is present to permit follicular development and therefore
sex steroids are not produced.
Chronic disease of malnutrition: Conditions including states of malnutrition, including starvation,
anorexia nervosa, cystic fibrosis, Crohn's disease, diabetes mellitus, inflammatory disease, and
hypothyroidism, are thought to lead to a disruption of gonadotropin-releasing hormone GnRH
production, therefore resulting in pubertal delay (4).
Constitutional delay: A delay in the (GnRH) pulse generator postpones the normal physiologic
events of puberty.
Intracranial neoplasms: Both craniopharyngiomas and pituitary adenomas may cause delayed
puberty. Visual symptoms are often associated with these tumors, as is short stature and diabetes
insipidus. Diagnosis is by CT or MRI of the head. Treatment includes either surgical excision or
radiotherapy.
Isolated gonadotropin deficiencies: often secondary to abnormalities in genes encoding proteins
related to GnRH, FSH, or leutinizing hormone (LH) (3).
Hormone deficiencies: Any aberration of growth hormone or thyroid hormone levels will affect
puberty. Therefore, these levels should be investigated and treated appropriately. In addition,
hyperprolactinemia can cause a decrease in levels of FSH and LH and thus delay puberty.
Kallmann syndrome: A sporadic or X-linked syndrome with a classic triad of anosmia,
hypogonadism, and color blindness. The hypothalamus cannot secrete GnRH due to dysfunction in
the arcuate nucleus. Few or no secondary sexual characteristics are present.
Prader-Labhart-Willi syndrome: an autosomal dominant condition associated with extreme obesity,
emotional instability, and delayed puberty secondary to hypothalamic dysfunction (4).
Laurence-Moon syndrome: a rare autosomal disorder associated with retinitis pigmentosa,
hypogonadism, and spastic paraplegia (4).
Bardet-Biedl syndrome: a rare autosomal recessive disorder associated with retinitis pigmentosa,
hypogonadism, and postaxial polydactyly (4).
Eugonadism (Normal FSH)
In cases of eugonadism, the hypothalamic-pituitary-gonadal axis remains intact, and delay of
puberty presents with primary amenorrhea related to anatomic abnormalities in the genitourinary
tract, androgen insensitivity, or inappropriate positive feedback mechanisms.
Anatomic abnormalities of the genitourinary tract resulting in primary amenorrhea:
Imperforate hymen: may be evident in a neonate and may regress as the girl enters childhood. After
menarche, the imperforate hymen may become evident when accumulating menstrual blood forms a
hematocolpos and may present as an abdominal mass. Surgical intervention is required to incise the
hymen and allow stored debris to escape.
Transverse vaginal septum: due to failure of canalization of mГјllerian tubules and the sinovaginal
bulb, leaving a membrane present. May be associated with urinary tract abnormalities as well. If the
membrane is thin, it can be incised and dilated. If it is thick, surgical excision with a split thickness
skin graft may be required.
MГјllerian agenesis: failure of the mГјllerian tract to develop results in a blind vaginal pouch
without uterus or fallopian tubes present. Ovaries are present and function normally and, therefore,
puberty progresses as usual with primary amenorrhea as a presenting complaint. This must be
distinguished from androgen insensitivity, as described later. One-third of these patients have
associated urinary tract anomalies, and 12% have skeletal anomalies. A neovagina can be created by
progressive dilation or surgery.
Vaginal atresia: The lower vagina is replaced by fibrous tissue; differentiated from mГјllerian
agenesis by the presence of normal uterus and fallopian tubes.
Androgen insensitivity: discussed later under male feminization. Karyotype XY males present as
phenotypic females with a blind vaginal pouch secondary to an insensitivity of circulating
androgens.
Other causes of primary amenorrhea with eugonadism include anovulation, androgen producing
adrenal disease, and polycystic ovarian syndrome.

Precocious Puberty
o
Precocious puberty is a rare condition that occurs in only 1 of 10,000 girls (5).
o
Defined as evidence of secondary sexual characteristics, including breast or pubic
hair development at an age more than 2.5 standard deviations below the mean (5).
o
According to a recent study, such findings should be investigated in African
American girls under age 6 and Caucasian girls under age 7 (6).
o
Characteristic accelerated growth velocity in combination with rapid bone growth
and maturation can result in short adult stature (7).
o
Common causes of precocious puberty can be divided into GnRH-dependent
disorders, or true or central precocious puberty, versus GnRH-independent disorders, or
pseudoprecocious puberty.
o

Central Precocious Puberty
Most commonly idiopathic; secondary sexual characteristics progress in
normal sequence but more rapidly than in normal puberty, and may fluctuate between
progression and regression.

Related to premature development of the hypothalamic-pituitary axis and
is therefore GnRH-dependent, but the initiating cause is unknown (5).

May be transmitted in an autosomal recessive fashion, so check family
history.

Often ovarian follicular cysts are present due to elevated levels of LH and
FSH (5).

Other causes of central precocious puberty involve central nervous system
disease:

Disease often involves areas surrounding the hypothalamus; mass
effect, radiation, or ectopic GnRH secreting cells are thought to cause premature activation of
pulsatile secretion of GnRH from the hypothalamus.

Diagnosis by CT or MRI of the head; history may be significant
for headache, mental status changes, mental retardation, dysmorphic syndromes, along with the
premature development of secondary sexual characteristics.

Treatment should be directed at the underlying cause; the location
of many of such tumors makes resection difficult, and, as a result, chemotherapy or radiation
may be involved.

GnRH agonist administration can result in a short burst of gonadotropin
release followed by down-regulation and desensitization resulting in an overall decrease in the
level of circulating gonadotropins. Follow estradiol levels to make appropriate dose adjustments
(8).
o
Pseudoprecocious Puberty

Premature development of secondary sexual characteristics occurs by a
GnRH-independent mechanism.

Differential
diagnosis
includes
estrogen-secreting
tumors,
benign
follicular ovarian cysts, McCune-Albright syndrome, Peutz-Jeghers syndrome, adrenal disorders,
and primary hypothyroidism.


Estrogen secreting ovarian tumors
Granulosa cell tumors (60%): usually >8 cm in size; 80% are
palpable on abdominal examination; others include arrhenoblastomas, thecomas, lipid cell
tumors, teratomas, or choriocarcinomas.

Diagnose by sonography, manage surgically with adjuvant
chemotherapy, if indicated, and follow by estradiol levels.

Benign follicular ovarian cysts

Most common form of estrogen-secreting masses in children

May require a diagnostic laparoscopy versus exploratory
laparotomy to differentiate from a malignant tumor. Removal of the cyst may be therapeutic.


McCune-Albright syndrome
Triad: cafГ© au lait spots, polyostotic fibrous dysplasia, and cysts
of skull and long bones; precocious puberty is present in 40% (9).

Sexual precocity results from recurrent follicular cyst. Removal of
cyst is not helpful.

Aromatase inhibitors (i.e., testolactone) may help symptoms.

Evaluate with serial pelvic sonograms to detect the presence of
gonadal tumors.

Peutz-Jeghers syndrome

Commonly characterized by mucocutaneous pigmentation and GI
polyposis

Also associated with rare sex cord tumors, including epithelial
tumors of the ovary, dysgerminomas, or Sertoli-Leydig cell tumors, whose estrogen secretion
may result in feminization and incomplete sexual precocity

Girls with Peutz-Jeghers syndrome should be screened with serial
pelvic sonograms.

Adrenal disorders

Some adrenal adenomas have been noted to secrete estrogen alone
and may therefore give rise to sexual precocity.

Primary hypothyroidism

Characterized by premature breast development and galactorrhea
without an associated growth spurt

Key points in evaluation and management of precocious puberty

Perform a detailed evaluation with Tanner staging.

Laboratory data should include LH, FSH, estradiol, progesterone,
17-hydroxyprogesterone, DHEA, DHEAS, TSH, T4, hCG (5).

A GnRH stimulation test would provide a definitive diagnosis of
central precocious puberty (5).

Obtain an x-ray to determine bone age. Head CT or MRI can rule
out an intracranial mass. Abdominal/pelvic ultrasound can be used to evaluate the ovaries (5).

Goals for management include maximizing adult height and
delaying maturation until a normal age of puberty. Treat the intracranial, ovarian, or adrenal
pathology if present and attempt to reduce associated emotional problems (8).

Male Feminization
o
Genetic males (XY) undergo feminization related to androgen insensitivity.
o
Complete androgen insensitivity, or “testicular feminization” (10).

Transmitted in a maternal X-linked recessive fashion

Pathophysiology: Androgen presence is unable to induce the Wolffian
duct to mature and, as a result, seminal vesicles, vas deferens, and epididymis do not form.
AntimГјllerian hormone is present so mГјllerian duct formation remains inhibited such that
uterus, cervix, and fallopian tubes do not form either. The resulting phenotype is female, with a
vagina derived from the urogenital sinus that ends in a blind pouch, and testes that often descend
through the inguinal canal.

Clinical presentation: primary amenorrhea, Tanner stage V breast
development, scant axillary and pubic hair

Management: gonadectomy is recommended secondary to an increased
incidence of malignancy; exogenous estrogen therapy is also recommended.
o
Incomplete androgen insensitivity (10)

Less
common
with
presentation
ranging
from
near
complete
masculinization to near complete failure or virilization.

As minimal sensitivity to androgens is present, the Wolffian duct system
develops to some extent, although spermatogenesis usually remains absent.

Physical exam may include a range of clitoromegaly or ambiguous
genitalia.

Sex assignment depends on the degree of masculinization present; if a
male sex assignment is made, caution should be taken because gynecomastia may occur during
puberty, if androgen receptor presence is inadequate.
o
5-alpha reductase deficiency is a condition in genotypic males (XY) who are
phenotypically female in the prepubertal state and become phenotypic men at puberty. No breast
development is present, which distinguishes this condition from androgen insensitivity. Normal
testicular function is present.

Female Virilization
o
Genetic females (XX) are exposed to increased androgen levels that lead to
inappropriate virilization, most often an indicator of organic disease in girls.
o
Virilizing congenital adrenal hyperplasia (CAH): most commonly associated with
deficiency of 21-hydroxylase, an autosomal recessive disorder. Many present as the newborn girl
with ambiguous genitalia and possible associated salt-wasting due to mineralocorticoid
deficiency. Virilization may also be delayed until later childhood, related to androgen excess at
that time (11).
o
Cushing's disease: may result from an adrenal carcinoma and may manifest as
growth failure, with or without virilization, obesity, striae, or moon facies.
o
Ovarian tumors: arrhenoblastoma is the most common virilizing ovarian tumor.
Others include lipoid cell tumor and gonadoblastoma.
VIII. Premature Thelarche

Definition: bilateral breast development without other signs of sexual maturation in girls
before age 8 (12).

Commonly occurs by age 2 and is rare after age 4.

The etiology behind premature thelarche is unclear, but an exogenous estrogen source
must be excluded. Not known to be associated with central nervous system pathology and is not
known to be a familial condition. The mechanism is thought to be related to a temporary
activation of the hypothalamic-pituitary-gonadal axis with increased FSH secretion (12).

Upon finding during physical examination, precocious puberty must be ruled out:
o
Document the appearance of the vaginal mucosa, breast size, and presence or
absence of a pelvic mass on pelvic/rectal examination.
o
Determine bone age with radiographic imaging; should be within normal range in
premature thelarche and advanced in precocious puberty.
o
Pelvic sonography should demonstrate a normal prepubertal uterus.
o
Plasma estrogen levels may be mildly elevated, but dramatic elevations suggest
another etiology. Stimulated responses of LH and FSH may be obtained and are both generally
elevated in precocious puberty, whereas only stimulated FSH is elevated in premature thelarche
(12).

Also, review recently used medications and topical creams as application of topical
conjugated estrogens (Premarin) for longer than 2 to 3 weeks, which may result in breast
changes.

Prognosis: In idiopathic cases, a regression in breast enlargement often occurs after a few
months but may persist for several years. In approximately 50% of patients, breast development
can last 3 to 5 years.
V. Self-assessment tasks:
1.
What is premature development?
2.
Methods of diagnostics of premature sexual development.
3.
Make a plan to treat the patient with premature sexual development.
4.
What is sexual development delay? Clinical picture.
5.
Methods of diagnostics and treatment of syndrome of sexual development delay.
AMENORRHOEA
Amenorrhoea is the absence of menstruation; it is a symptom, not a disease and is often
physiological, as in pregnancy.
The term primary amenorrhoea refers to a patient of any age who has never menstruated.
Secondary amenorrhoea refers to cessation of the periods after menstruation has been
established.
Amenorrhoea may be classified as:
Physiological
• before puberty
• during pregnancy
• during lactation
• after the menopause
Pathological
uterine lesions
ovarian lesions
pituitary disorders
disorders of other endocrine glands
psychiatric illness and emotional stress
severe general illness
drugs
following surgical operations or radiotherapy.
PHYSIOLOGICAL AMENORRHOEA BEFORE PUBERTY
Menstruation normally begins between the ages of 11 and 14, but this will be affected by
heredity and the nutritional state of the patient. Oestrogenic activity of the ovary begins some
years before the menarche, but at first the oestrogen levels are not usually sufficient to promote
adequate endometrial development to cause bleeding when oestrogen levels are reduced.
DURING PREGNANCY
Amenorrhoea lasts through pregnancy and beyond during lactation. Until the 12th week
of pregnancy there is a decidual space between the decidua capsularis (the decidual layer that
covers the ovary after fertilization), the decidua vera (the decidual layer that lines the uterus after
fertilization) and the fetal sac. Although in theory bleeding may occur from the decidual space,
such bleeding should be regarded as being potentially pathological, with partial separation of
embryonic attachments.
DURING LACTATION
The average time between delivery and the first subsequent period is 10—12 weeks in
those patients who do not breast-feed their infants, whereas in those who do, it depends on the
duration of the breast-feeding. Ovulation may start again at about the same time.
During lactation prolactin is secreted in large amounts by the anterior lobe of the pituitary
gland and there is partial, but not complete, suppression of secretion of luteinizing hormone, so
that ovarian follicles may mature but fail to rupture.
AFTER THE MENOPAUSE
Examination of the ovaries of a woman who is well past the menopause shows no active
Graafian follicles. Cessation of oestrogen production from the ovary is temporarily associated
with overproduction of gonadotrophic hormone from the pituitary gland.
PATHOLOGICAL AMENORRHOEA UTERINE LESIONS
In general uterine causes of amenorrhoea are rare. Amenorrhoea occurs when the uterus
is rudimentary and only represented by a nodule of fibromuscular tissue at the top of the vagina.
In such cases the vagina may also be absent, but the ovaries and the secondary sexual
characteristics are usually normal. Failure of canalization of the cervix or vagina can lead to
haematomeira and haematocolpos respectively.
Except with these severe congenital defects of the uterus it is rare for amenorrhoea to be
due to uterine hypoplasia. If there is any endometrium present it will respond to stimulation by
oes-trogens. Removal of the endometrium by excessive curettage or endometrial ablation may
result in obliteration of the uterine cavity.
Destruction of the endometrium by advanced pelvic tuberculosis is not now seen in the
UK, although such cases still occur in some developing countries.
OVARIAN LESIONS
Primary amenorrhoea occurs with ovarian dysgenesis.
Secondary amenorrhoea may be caused by failure of the ovarian enzyme systems
necessary for the production of oestrogens.
There is a spectrum of such disorders, of which the polycystic ovary (Stein—Lev enthal)
syndrome is the one most commonly recognized. In this disorder, secondary amenorrhoea is
associated with bilateral enlargement of the ovaries, which contain multiple small follicular cysts
in a dense stroma. Many of these patients are obese, and have an excessive growth of facial and
body hair. The secretion of FSH is within the normal range but the LH level may be raised
producing a reversed FSH/LH ratio of 1:3. The serum testosterone may also be raised. Some
oestrogen is produced, but not enough to cause uterine bleeding. Because of the enzyme block
increasing levels of one of the precursors of oestrogen, androstenedione, a weak androgen, is
found in the follicular fluid and in the blood plasma; this may explain the hirsuties. A surprising
thing about this condition is that a fairly extensive wedge-resection of both ovaries is often
followed by a return of normal menstruation and even pregnancy. However, such surgical
treatment is not now usually employed, because ovulation and menstruation can usually be
induced with clomiphene.
Secondary amenorrhoea from ovarian failure may occur without evident cause. The
serum level of oestrogens is low, while the level of gonado-trophins is raised, hence the disorder
is sometimes called hypergonadotrophic amenorrhoea.
If ovarian laparoscopic biopsy shows that follicles are present the term resistant ovary
syndrome is used, and in such cases ovulation may sometimes be induced with clomiphene, or
with LH-RH (GnRH).
Absence of ovarian follicles leads to premature ovarian failure (premature menopause).
However, ovarian biopsy is not always conclusive, as only a small part of the ovary is examined,
and both spontaneous and induced ovulation may unexpectedly occur. Hormone replacement
therapy will be required to avoid immediate and long-term menopausal symptoms and sequelae.
Inflammatory disease or neoplasms of the ovaries do not cause amenorrhoea.
PITUITARY DISORDERS
Pituitary infantilism
Rare cases of pituitary infantilism (Levi-Lorain syndrome) occur; the cause is unknown.
The patients are of child-like stature and proportions, with primary amenorrhoea. Secretion of
FSH is absent or low, and no oestrogens are found in the urine.
Ischaemic necrosis of the pituitary gland
This was originally described by Simmonds, but is often known as Sheehan's disease. It is
the result of thrombosis of the pituitary blood vessels after profound hypotension and
hypovolaemia, most commonly caused by severe postpartum haemorrhage. The production of
gonadotrophic, thyro-trophic and adrenotrophic hormones ceases, or is very inadequate. The
patients are lethargic, gain weight and have a low metabolic rate, hypotension and amenorrhoea.
Treatment with hormones is disappointing. Thyroxine and cortisone are usually given.
Oestrogens may produce cyclical bleeding, but this can only be of psychological benefit.
Methyltestosterone has also been given for its anabolic effect.
Adenoma of the anterior lobe of the pituitary gland (prolactinoma)
This may cause an excessive secretion of prolactin and consequent amenorrhoea. The
tumour may be very small and difficult to demonstrate by computerized tomography or even
magnetic resonance imaging. Hyperprolactinaemia may be diagnosed if the prolactin level
exceeds 1000 mIU/L. Stress can cause a temporary increase in secretion of prolactin.
Galactorrhoea can occur.
If the tumour is large enough it may press on the optic nerves causing diminished vision
at the edges of the visual fields. The other cells of the pituitary are usually unaffected.
If a specific tumour is found it is treated by radiotherapy or surgery, but if no tumour is
evident bromocriptine will inhibit the output of prolactin.
DISORDERS OF OTHER ENDOCRINE GLANDS
Adrenal gland
The adrenogenital syndrome is caused by either a tumour or hyperplasia of the adrenal
cortex. There is excessive production of androgens and the urinary excretion of oxosteroids is
increased. The symptoms and signs are those of virilism, with
deepening of the voice, hirsuties, acne, amenorrhoea and enlargement of the clitoris.
In Cushing's syndrome, hyperplasia (or less commonly a tumour) of the adrenal cortex
produces an excess of glucocorticoids which stimulate the conversion of protein into
carbohydrate. These patients have amenorrhoea, hypertension, poly-cythaemia, osteoporosis and
diabetes; the abdomen often shows striae like those of pregnancy.
Amenorrhoea occurs in advanced cases of Addi-son's disease when adrenal tissue is
deficient.
Thyroid gland
Amenorrhoea may occur in either myxoedema or hyperthyroidism, if they are severe.
Pancreas
Amenorrhoea may occur in severe or badly controlled diabetes.
PSYCHIATRIC ILLNESS AND EMOTIONAL STRESS
The hypothalamus controls the output of gonado-trophins from the pituitary gland, and
higher centres in the brain affect the function of the hypothalamus. Starting a new job, being
away from home for the first time or emigration are examples of stressful conditions which may
cause amenorrhoea until social readjustment has been made. Sudden bad news or severe
emotional distress may have the same effect. The periods are likely to return spontaneously and
reassurance is all that is required, but the possibility of some other coincidental cause such as
pregnancy must not be forgotten.
Amenorrhoea accompanies anorexia nervosa. The girl is often rejecting the imagined
burdens of maturity, and the refusal of food is intended to stop progress from childhood to
womanhood. Psychiatric help is necessary, and restoration of a diet with adequate proteins and
vitamins.
GENERAL ILLNESS AND WEIGHT-LOSS
Menstrual function may be temporarily suppressed during or after any severe illness, or
during a chronic illness such as chronic renal disease.
Secondary amenorrhoea occurs with starvation. This was seen in the inmates of
concentration camps during World War II, although other severe psychological stresses were
also present. A less severe example is found in ballet dancers and other young women who strive
to maintain a slight, slim figure by strict dieting. Amenorrhoea is common and periods return
when a more reasonable body mass is restored. Strenuous and continued exercise with diet
restriction, such as in preparation for a major athletic season, may often lead to amenorrhoea.
This is usually reversed when body mass is allowed to return to a normal level.
DRUGS
Amenorrhoea sometimes occurs after stopping oral contraception; it can continue for
some months. Spontaneous return of menstruation is to be expected within 6 months, but in a
few cases treatment by induction of ovulation with clo-miphene or gonadotrophins is required.
This type of amenorrhoea is more common in women who had irregular periods before starting
oral contraception, and some of them are merely reverting to their previous menstrual pattern.
The possibility that the amenorrhoea is due to pregnancy must not be forgotten.
Prostaglandin inhibitors occasionally cause amenorrhoea.
SURGICAL OPERATIONS OR RADIOTHERAPY
Obviously, amenorrhoea will follow hysterectomy or removal of both ovaries. The
ovaries may also be suppressed by pelvic irradiation for malignant disease.
Amenorrhoea can also be obtained by laser ablation of the endometrium, by cryosurgery
or by removal of the endometrium with a resecto-scope.
INVESTIGATION AND TREATMENT
PRIMARY AMENORRHOEA
If a girl has not begun to menstruate by the age of 17, investigation is advised. The
management of these cases calls for some discretion; to subject an embarrassed young woman to
a barrage of investigations is not always helpful. Some or all of the following may be required,
but the more invasive, such as examination under anaesthesia or laparos-copy, should not be
made until the other tests show that they are essential.
Stature and body form
Dwarfism may be the result of some long-standing metabolic disorder; for example, renal
disease, a malabsorption syndrome or lack of growth hormone, as in pituitary infantilism. In such
cases amenorrhoea is a small part of a wider problem.
In some cases of gonadal dysgenesis (Turner's syndrome) the patients are of short stature,
but in others (simple gonadal dysgenesis) the patients tend to be tall. Webbing of the neck or
wide carrying angles at the elbows suggest Turner's syndrome. Patients with the adrenogenital
syndrome may be short and muscular with hirsuties.
Breast and pelvic examination
If breast development has taken place there must have been some oestrogenic activity,
and in such cases it is possible that there is some abnormality of the lower genital tract such as
haematocolpos causing cryptomenorrhoea, or a rudimentary uterus.
A special problem is testicular feminization. In these cases the breasts are well formed,
but the vagina may be short and the uterus is absent. There may be a family history of the
disease. The diagnosis rests on the discovery that the patient is chro-matin negative, XY.
Patients without breast development are likely to have gonadal dysgenesis, and for such
cases chromosomal analysis is essential. There will also be absence of breast development in
cases of pituitary infantilism.
Hormone assays
The essential distinction to be made is between cases of hypothalamic or pituitary failure,
in which the levels of FSH, LH and oestrogens will be low. When the ovary fails to respond, the
level of both gonadotrophins will be high and that of oestrogens low.
Chromosomal studies
In all cases of primary amenorrhoea in which the diagnosis is not clinically certain a full
chromosomal analysis should be carried out to exclude a
congenital abnormality such as 46 XY in a female.
Radiological examination and CT scan
An intravenous urogram is carried out in all cases of uterine or vaginal malformation, as
there are often associated abnormalities of the ureters and kidneys in these cases.
A lateral X-ray tomogram or a computed tomography (CT) scan of the sella turcica may
show it to be expanded by a pituitary tumour; this examination should be made in all cases in
which there is a raised prolactin level, or clinical reason to suspect such a tumour.
Ultrasound
An ultrasound scan of the pelvis is useful for determining the size of ovaries, the presence
of follicles and their size. The importance of this non-invasive investigation is increased when
following ovarian problems longitudinally for the usefulness of treatments can be measured by
observations on follicular development.
Laparoscopy
Laparoscopy and biopsy of the gonads is not indicated if the diagnosis can be made by
less invasive methods. If the diagnosis is certain after clinical examination, perhaps with the
addition of chromosomal or hormonal studies, little purpose is served by proving, in Turner's
syndrome for example, that the ovaries are mere streaks. However, laparoscopy is useful in cases
which there is doubt about the nature of the gonads, or if it is uncertain whether there are any
primordial oocytes in the ovary, when ovarian biopsy is performed. Laparoscopy is also
occasionally useful in cases of vaginal atresia to determine whether the uterus is present,
although an ultrasound scan will usually give the answer.
In cases of testicular feminization, laparotomy is usually required to remove the testes
after the secondary sexual characteristics have been established, to prevent the danger of
dysgerminoma arising.
Ovarian dysgenesis and absence of the uterus cannot be altered, but in some girls morale
can be improved by intermittent oestrogen therapy. This will cause breast enlargement and
monthly withdrawal bleeding if the uterus is present. A low dose combined oral contraceptive
pill can be used. After an interval of 7 days the cycle is repeated.
For delayed puberty in girls whose ovaries are shown to contain oocytes, ovulation may
be induced with human gonadotrophin. GnRH and synthetic analogues are a better alternative,
admin-stered intravenously or subcutaneously in pulses by a portable pump.
SECONDARY AMENORRHOEA
A patient who has previously menstruated must have a patent lower genital tract, an
endometrium which has responded to ovarian hormones and ovaries which have responded to
gonadotrophins. In every case pregnancy must be excluded, even if the patient thinks it to be
unlikely. This done, a systematic management is:
Previous menstrual history
Enquiry about the patient's previous menstrual history is made. If she has had irregular
cycles for many years there is little point in investigating or treating a minor abnormality unless
infertility is her problem.
Change in the patient's environment
Enquiry should be made about any recent change in her social and emotional
environment, any stress that she has undergone, or any attempt at severe dieting.
General medical examination
After a history of recent or long-standing illness is sought, a general examination is made
(including observation of the body build, weight and hair distribution) to exclude any general
illness. The breasts and pelvic organs are examined. Any appropriate investigations, such as triiodo-thyronine binding capacity and free thyroxine indices for suspected disorder of the thyroid,
are performed. Serum prolactin, FSH, LH, oestradiol, testosterone, SHBG are measured.
If pregnancy is not desired, and if the patient has no evidence of any underlying disease
which has caused the amenorrhoea, at this point the doctor must decide whether there is any
useful purpose in further investigation. In some cases the further steps will be as follows:
Hormone assays
Generally, LH levels correspond with those for FSH, although the latter may be a more
sensitive index of pituitary function and show earlier change. By assessment of the tests relating
to the various levels of the hypothalamic-pituitary-ovarian axis, the patient's problems can be
placed at the appropriate level. With hypothalamic or pituitary failure the levels of both
gonadotrophins and ovarian hormones will be low; with failure of ovarian response, because of
lack of negative feedback the gonadotrophin levels may be raised. Reversal of the FSH/LH ratio
with a raised LH level (to 1:3) with a raised serum testosterone may indicate a polycystic ovary
syndrome.
Ultrasound scan
This identifies ovarian follicles and, if done serially, can be used to guide dosage of
ovarian stimulants.
Radiographic tomography or CT scan
Visualization of the pituitary fossa may be required.
If amenorrhoea is judged to be caused by stress or an emotional problem, spontaneous
recovery is to be expected if the problem can be removed or alleviated by the passage of time.
If it is caused by some underlying disease or nutritional deficiency this must be treated or
removed.
If no cause is obvious and the patient wants periods and contraception, the combined OC
pill may be given. If she wishes to conceive, induction of ovulation can be produced by clomid,
gonadotrophins or pulsatile GnRH. A polycystic ovary syndrome may be treated by laser drilling
or wedge resection of the ovaries.
Those found to have high levels of prolactin (above 1000 mIU/L) must have the assay
repeated, as temporary rises may occur from stress. Hypo-thyroidism or the effect of drugs such
as phe-nothiazines must also be excluded. If radiological examination or CT scan of the sella
turcica does not reveal a pituitary adenoma then microadeno-mata are assumed to be present and
the prolactin level can be reduced with the dopamine agonist, bromocriptine. The dose has to be
varied according to the prolactin level and this treatment should be employed only in units that
have the facilities for hormone assays. The dose is increased very cautiously, starting at 2.5 mg
daily.
In summary, provided the uterus is present, primary amenorrhoea can be treated with
hormones to induce menstruation. With secondary amenorrhoea, the ability to induce
menstruation will depend on the state of the endometrium and the hypothalamic-pituitary-ovary
axis. The latter can be influenced by drug therapy.
Conception in both cases can only occur if there is ovarian tissue with primary ovarian
follicles.
Prepubertal Bleeding without Secondary Signs of Puberty
Puberty in the female is the process of biologic change and physical development after which
sexual reproduction becomes possible. This is a time of accelerated linear skeletal growth and
development of secondary sexual characteristics, such as breast development and the appearance
of axillary and pubic hair. The usual sequence of the physiologic events of puberty begins with
breast development, the subsequent appearance of pubic and axillary hair, followed by the period
of maximal growth velocity, and lastly, menarche. Menarche may occur before the appearance of
axillary or pubic hair in 10% of normal females. Normal puberty occurs over a wide range of
ages (see Chapters 4 and 38 [Reproductive Endocrinology and Primary and Secondary
Amenorrhea and Precocious Puberty]). Precocious puberty is arbitrarily defined as the
appearance of any signs of secondary sexual maturation at an early specific age more than 2.5
standard deviations below the mean. Precocious puberty is covered in detail in Chapter 38 . A
common clinical problem that is sometimes mistaken for precocious puberty is prepubertal
bleeding in children without any other signs of puberty such as breast development
Table -- Differential Diagnosis of Prepubertal Bleeding Without Any Breast Development
Foreign
object
Genital
trauma
Genital
abuse
Lichen
sclerosus
Infectious
vaginitis
(especially
from
Shigella)
Urethral
prolapse
Breakdown
Friable
of
genital
labial
warts
or
adhesions
vulvar
Vaginal
lesions
tumor
Rare presentation of McCune–Albright syndrome (typically have breast development)
Isolated menarche (controversial)
Vaginal Bleeding
The normal sequence of puberty is that thelarche precedes menarche. In children with
prepubertal bleeding without breast budding there is almost never an endocrinologic cause, with
the exception being a very rare presentation of McCune–Albright syndrome.
The differential diagnosis of vaginal bleeding without pu-bertal development includes foreign
body, vulvar excoriation, lichen sclerosus, shigella vaginitis, separation of labial adhesions,
trauma (abuse and accidental), urethral prolapse, and friable genital warts. Rare causes include
malignant tumors (sarcoma botryoides and endodermal sinus tumors of the vagina) and an
unusual presentation of McCune–Albright syndrome. Lists of the differential diagnosis of
prepubertal bleeding often also include accidental estrogen exposure (for example from ingestion
of a mother's birth control pills). However, in reality such exposure would rarely provide enough
endometrial stimulation to produce a withdrawal bleed without breast budding. Neonates may
develop a white mucoid vaginal discharge or a small amount of vaginal spotting. Both conditions
are secondary to exposure during pregnancy to the high levels of estrogen and are self-limited.
In a 20-year review of vaginal bleeding, 52 cases were identified in girls 10 years and younger
from the Chelsea Hospital for Women in London. Genital tumors, precocious puberty, vulvar
lesions, and urethral prolapse were the four leading causes in this series. This report was from a
referral center and therefore may not truly represent the cases seen in the practitioner's office.
The absence of sexual abuse in this study likely reflects referral patterns. However, it should be
remembered that although the differential diagnosis of prepubertal bleeding includes sexual
abuse, the vast majority of sexually abused children do not have prepubertal bleeding. In some
settings, such as emergency departments, it is more likely that the cause of prepubertal bleeding
is sexual abuse than in tertiary referral practice where the cause of the bleeding is often unclear
to the referring physician.
ABNORMALLY INCREASED AND IRREGULAR UTERINE BLEEDING
(DURING MENSTRUAL LIFE)
Excessive menstrual bleeding is called menorrhapa. Strictly, this term should be used
only to describe heavy menstrual loss with a normal cycle, but it is often used more loosely.
Straightforward descriptions such as excessive or prolonged bleeding, or frequent cycles, are
preferable. For clarity, the period should be described as a fraction with the numerator referring
to the number of days of bleeding and the denominator, the length of cycle e.g. 4-7/22-31.
It is important to realize that abnormalities of menstruation are only symptoms and do not
describe pathological entities. Before treatment is given the cause must be determined and any
endocrine treatment without previous investigation is to be condemned.
Excessive or irregular vaginal bleeding may be caused by the following:
LOCAL LESIONS
Causing regular excessive periods:
uterine fibroids adenomyosis pelvic endometriosis salpingo-oophoritis intrauterine
contraceptive device
Causing irregular bleeding;
urethral caruncle
polyps—cervical, endometrial and fibroid carcinoma of the cervix carcinoma of the
uterine body oestrogen-secreting ovarian tumour, granulosa or theca cell tumour.
The diagnosis and treatment of all these conditions have been described in previous
chapters. In this chapter the conditions in which these local lesions have been excluded will be
considered.
GENERAL DISEASES
In some cases of myxoedema menorrhagia occurs;
this will respond to treatment with thyroxine. In advanced cases there is usually
amenorrhoea. It is probable that the thyroid deficiency affects the pituitary gland.
Blood diseases are very rare causes of menorrhagia. However, it may occur in acute
leukaemia, thrombocytopenic purpura and hereditary capillary fragility (von Willebrand's
disease), but in all these diseases the diagnosis is evident on other grounds. Anaemia is almost
invariably the effect and not the cause of menorrhagia.
Change of country with climatic change and stress can cause menorrhagia.
EMOTIONAL CAUSES
Women suffering from a psychosomatic disturbance may temporarily develop heavy or
frequent periods which resolve when the cause has subsided, just as other individuals may
present with peptic ulcers, for example. The menstrual irregularity in these cases is due to
disturbance of pituitary function, which arises in turn from hypothalamic response to activity of
higher centres. Some, but not all, cases of dysfunctional bleeding which are described in the next
section have an emotional cause, and this possibility must always be considered.
DYSFUNCTIONAL UTERINE BLEEDING
The term dysfunctional uterine bleeding refers to those cases in which the bleeding is not
due to some diagnosed local disorder, such as new growth or pelvic infection, or to some
complication of pregnancy. It may occur at any age between the menarche and the menopause.
Heavy or irregular bleeding without abnormal physical signs on ordinary examination
will always suggest this diagnosis, but this must never be taken for granted because curettage
may reveal that there is a local cause for the bleeding after all. An endometrial polyp may be
discovered, unsuspected retained products of conception, or even early malignant disease of the
endometrium or cervix may be found.
CAUSES
Dysfunctional bleeding may be caused by alters-1 tion in the output, or balance, of
gonadotrophic or ovarian hormones, and probably also of endomet- j rial prostaglandins.
Under the influence of prostaglandins, bleeding from the endometrium is controlled by
vasocon-striction, myometrial contraction and local aggregation of platelets with deposition of
fibrin around them. The endometrium and myometrium are able to synthesize prostaglandins
from arachi-donic acid by the action of the enzyme cyclo-oxygenase. The endometrium
manufactures:
PGF^oi, which causes myometrial contraction and vasoconstriction PGE2, which causes
myometrial contraction but is a vasodilator Prostacyclin (PGLi), which causes myometrial
relaxation and vasodilatation and also inhibits platelet activity.
It is believed that PGF^ normally plays the chief part in preventing excessive menstrual
bleeding. In theory abnormal bleeding may occur if there is a decrease in production of PGFza,
or an increase in production of PGEa or of prostacyclin. In support of this suggestion, a relative
decrease in PGF^n against PGEa has been reported in the endometrium in some cases of
menorrhagia. Drugs which block the action of cyclo-oxygenase, such as mefe-namic acid, are
sometimes effective in checking menorrhagia.
In some cases of dysfunctional bleeding the cycles are ovulatory but in others, perhaps
the majority, ovulation is not occurring.
Ovulatory cycles
In ovulatory cycles excessive bleeding may be caused by corpus luteum insufficiency,
with decreased secretion of oestrogen and progesterone in the second half of the cycle. The luteal
phase is abnormally short, but at the same time the en-dometrium shows irregular ripening, with
patchy response to the hormones and consequent prolongation of menstrual bleeding. On the
other hand, the corpus luteum persists longer than is normal, sometimes with the formulation of a
luteal cyst. The luteal phase of the cycle is then prolonged, but there is eventual irregular
shedding of the endometrium, with prolonged and heavy bleeding.
Anovular cycles
In women with dysfunctional bleeding with anovular cycles the oestrogen secretion rises
to high levels, and then the output of FSH is reduced by feedback, so that the oestrogen level
falls and endometrial shedding takes place. In many women with anovular cycles the loss is not
excessive, and unless they are complaining of infertility nothing abnormal may be noticed. But
in a few cases the endometrial shedding is irregular and incomplete, and is associated with
excessive blood loss.
Cystic glandular hyperplasia
In cystic glandular hyperplasia, oestrogen production rises to high levels, but there is no
feedback inhibition of the pituitary gland, so FSH secretion and high oestrogen levels continue,
perhaps for 6-8 weeks. There is amenorrhoea during this time but the prolonged action of the
abnormally high level of oestrogen, in the absence of progesterone, causes endometrial
hyperplasia.
On macroscopical examination the endometrium is very thick, and in places almost
polypoid. Microscopical examination shows hypertrophy of the columnar epithelium of the
endometrial glands, and many of the glands show cystic dilatation so that the tissue has many
large, round holes. There are areas of necrosis in the stroma, with small haemorrhages and
leucocytic infiltration.
The myometrium may also show some hyperplasia. After a time the oestrogen level
begins to fluctuate and when it falls excessive endometrial bleeding ensues. Bleeding may also
occur because parts of the grossly hypertrophied endometrium have outgrown their blood supply.
Bleeding tends to be heavy, prolonged and irregular.
In cases of dysfunctional bleeding successive episodes may vary in pattern. It is clear that
an emotional upset, presumably acting through the hypothalamus, can sometimes precipitate an
episode of dysfunctional bleeding, but in most cases no such trigger is evident.
It has been suggested that in dysfunctional bleeding of puberty the output of
gonadotrophins is erratic, whereas near the menopause the ovary may be failing to respond. It is
worth repeating that in about half of the cases of dysfunctional uterine bleeding no histological
abnormality of the endometrium is found on curettage, and in some of these cases the cause of
the bleeding remains obscure. Hormone assays are equally unhelpful.
Cases can be grouped roughly by the ages of the patients into those occurring at puberty,
during the childbearing period and near the menopause. Although this classification has little
basis in pathology it is useful when considering management.
ABNORMAL BLEEDING AROUND PUBERTY
Menorrhagia for a few periods after the menarche is not uncommon. This cyclical
bleeding is anovular in type. Less commonly there may be severe and continuous bleeding with a
diminishing haemoglobin level—such cases are similar to those described as cystic glandular
hyperplasia, and show endometrial hyperplasia from the effect of oestrogen in the absence of
progesterone. Nearly all cases recover spontaneously in a few months.
An ultrasound examination should be made to exclude an ovarian tumour, but there is no
indication for curettage unless the medical history strongly suggests the possibility of
tuberculosis. In a few cases with heavy bleeding norethisterone 5 mg three times daily is given
by mouth, gradually reducing the dose over the succeeding 10 days. Iron is prescribed if the girl
is anaemic.
ABNORMAL BLEEDING IN THE CHILDBEARING YEARS
Abnormal bleeding without obvious local cause is not uncommon in women of this age
group. The bleeding may be cyclical or irregular. The uterus may be slightly and symmetrically
enlarged, particularly in parous women.
It is not uncommon for abnormal bleeding of endocrine origin to undergo spontaneous
remission; in young women without abnormal physical signs it is worth waiting for a short time
to see if normal menstruation returns. When abnormal bleeding persists the following options
may be tried:
Under 40 years of age, one can use the combined oral contraceptive pill for non-smoking
and non-obese women. Otherwise non-steroidal anti-inflammatory drugs (NSAID) which inhibit
pros-taglandin synthesis in the endometrium will relieve both menorrhagia and sysmenorrhoea
(e.g. mefe-namic acid 500 mg tds given during ther period). Alternatively, anti-fibrinolysins will
reduce bleeding by inhibiting plasminogen activity that may cause nausea and vomiting in a third
of cases (tranexamic acid is given at a dose of 1.5gtds during the period). In a woman over 40
years of age, heavy bleeding of recent onset should be managed by hyseroscopy and diagnostic
D & C, to exclude endometrial pathology such as endomet-rial hyperplasia.
If nothing sinister is found at D & C, other measures include danazol which competitively
binds sex hormones to their receptors and inhibits their production by direct enzymatic action. It
is given orally as a dose of 200-800 mg daily in divided doses. It sometimes causes unpleasant
masculinizing side effects.
GnRH analogues may be used to inhibit gona-dotrophin secretion but they are expensive
and cause menopausal side effects and osteoporosis. If these measures fail, endometrial resection
or ablation can be considered. About one third of patients will have amenorrhoea, one third will
be improved and one third will be unchanged.
Finally, hysterectomy may be offered when menorrhagia cannot be controlled by any of
these methods and there are still some 7 years before the menopause is expected. The ovaries are
not removed unless involved by pathology or over the age of 50. Between the ages of 45 and 50
the case for their removal is more controversial and needs to be discussed on an individual case
with each patient.
INTERMENSTRUAL BLEEDING
Slight bleeding may occur at mid-cycle at the time of ovulation—it only lasts for a few
hours. Breakthrough bleeding may occur with oral contraception.
Irregular bleeding between the periods may be associated with a local lesion in the genital
tract. A urethral caruncle occasionally bleeds. Intercourse may cause bleeding from carcinoma of
the cervix, from an adenomatous (mucous) polyp of the cervix, or from a vascular cervical
erosion, especially during pregnancy or if the patient is taking the oral contraceptive pill.
Endometrial adenomatous polypi may cause intermenstrual bleeding, and sometimes carcinoma
of the body of the uterus may occur coincidentally before the menopause.
It must be strongly emphasized that in every case of intermenstrual bleeding at any age
the diagnosis must be established before treatment is given, otherwise an occasional carcinoma
may be missed, with fatal results. Diagnostic curettage must be performed in all cases in which a
local cause is not found on ordinary examination with a speculum, and in all cases where local
treatment is followed by persistence of the intermenstrual bleeding.
DYSMENORRHOEA AND PREMENSTRUAL TENSION
Although menstruation is often painless, many women suffer from discomfort or pain in
association with periods at some time during their reproductive life.
It has been customary to classify cases of dysmenorrhoea into two main groups:
• primary or spasmodic dysmenorrhoea
• secondary or congestive dysmenorrhoea.
These terms are unsatisfactory because they have been used in two senses; to indicate the
time of origin of the complaint (at puberty or later) and, alternatively, to express an opinion
about the cause of the pain and whetherjtji secondary to evident pelvic disease. It may be more
useful to classify the cases into:
• those due to evident pelvic disease
• those without evident pelvic disease.
DYSMENORRHOEA CAUSED BY PELVIC DISEASE
The type of pain experienced is very variable. It may precede the onset of a period for
about a week. The pain is often a dull ache felt equally on both sides of the lower abdomen and
back, sometimes extending down the thighs.
Apart from the discovery of abnormal physical signs of endometriosis or pelvic
inflammatory disease on examination, two features suggest that there may be underlying pelvic
disease. First, the symptoms may appear after some years of painless menstruation, and
secondly, there may be other symptoms of pelvic disease such as menorrhagia, dyspareunia or
infertility.
An acute colicky pain may occur if a fibro-myomatous polyp is being extruded through
the cervix, and in some women an intrauterine contraceptive device will cause colicky
dysmenorrhoea.
Dysmenorrhoea caused by pelvic disease is best treated according to the cause.
DYSMENORRHOEA WITHOUT EVIDENT PELVIC DISEASE
This is the commoner type of dysmenorrhoea and it usually occurs in girls or young
women. It is difficult to state its frequency, as most women have occasionally experienced some
degree of pain. Severe pain only occurs in a minority, but there is no doubt that it can be
incapacitating and often leads to absence from work.
The pain is spasmodic or colicky in nature, usually starting on the first day of the period.
It may last for several hours or continue throughout the first and second day. Not infrequently the
menstrual flow is scanty at first, and the pain often becomes easier when the flow is properly
established. The acute colicky pain may be followed by a dull ache. Nausea and vomiting, and
occasionally diarrhoea may occur, and sometimes headache and fainting.
Most women present for advice between 16 and 25 years old. They may say that they
have had pain ever since their periods started, but closer questioning will usually show that the
periods were painless at first, and only became painful after a few months or even years,
sometimes becoming progressively worse.
Examination usually reveals no general local abnormality. The patient is physically
healthy, although she may be somewhat tense. A vaginal examination, or if the hymen is intact a
rectal examination, must always be made to exclude unexpected pelvic pathology. In nearly
every case the genital tract is normal.
THE CAUSE OF THE PAIN IN WOMEN WITHOUT EVIDENT PELVIC
DISEASE
The pain is usually due to the spasm of the uterine muscle, which is sufficiently intense to
cause ischaemia. The cause of the muscle spasm is not certain, and several factors have been
discussed.
Cervical obstruction
Although organic stricture of the cervix can cause menstrual pain this is exceedingly rare,
and there is no evidence of obstruction in the ordinary cases. Dilatation of the cervix is still
sometimes practised but seldom effects a permanent cure.
Dysmenorrhoea occurs only when ovulation has occurred; anovular cycles are painless,
as is seen in women using oral contraception. It is probable that necrosis of the endometrium is
caused by prostaglandins, especially PGFzo,, and this also causes spasm of the myometrium. The
endometrial content of PGF2n increases under the influence of progesterone in the second half of
the cycle. Administration of prostaglandins to normal women can produce many of the
symptoms associated with dysmenorrhoea, and prostaglandin inhibitors will relieve these
symptoms.
Psychological factors
Although spasmodic dysmenorrhoea is often described as psychosomatic, because of the
lack of any recognizable pelvic pathology, it is wrong to state that all these patients are neurotic.
Upbringing can have some effect; a girl may have come to expect that menstruation must be
painful, while adolescence may bring fears of sex or child-bearing. However, the majority of
patients areentirely free from any fear or phobia. It is true that they may have an increased
sensitivity to painful stimuli, but this may sometimes be the effect of recurrent pain rather than
the cause.
Nerve pathways
Division of the sympathetic superior hypogastric plexus (wrongly called the presacral
nerve) may abolish pain during menstruation by interrupting the sensory pathway.
Treatment
Attention should be paid to the woman's general health, and it is advisable to enquire
about her family and social life so as to discover, and if possible to correct, any cause of
emotional stress. It will help to tell her, after examination, that she is normal and to explain that
menstruation is a healthy normal function.
During an attack of severe pain many patients take a hot bath and then relax in bed with a
hot water bottle. Analgesic drugs such as aspirin, codeine or dihydrocodeine should be
prescribed. Antispasmodic drugs such as atropine are usually
ineffective, although many proprietary preparations containing such drugs are sold.
Drugs which inhibit the production of prostaglandins in the endometrium may diminish
myometrial contractions and therefore relieve dysmenorrhoea. These drugs, which are given
orally 3 times daily during the period, include mefenamic acid (Ponstan) 500 mg, flufenamic
acid 200 mg and indomethacin 50 mg.
The most effective medical treatment is to suppress ovulation with the combined oral
contraceptive pill containing 20 to 30 micrograms of oestrogen. The fact that this is a
contraceptive should be mentioned. Alternatively, an oral progestogen such as dydrogesterone
(Duphaston) is often used in doses of 10 mg daily by mouth from days 5 to 25 of each cycle.
Obviously, hormonal treatment is unsuitable for a patient who wishes to become pregnant.
In patients aged over 30 whose symptoms are unrelieved by other measures laparoscopy
should always be considered, as small endometriomatous lesions may otherwise be missed.
Presacral sympathectomy is usually reserved for patients who have not obtained relief by
other methods; the operation is seldom performed now. The superior hypogastric plexus conveys
afferent fibres from the uterus. It lies immediately behind the parietal peritoneum in front of the
fifth lumbar vertebra and between the diverging iliac arteries. After opening the abdomen the
posterior parietal peritoneum just below the aortic bifurcation is incised to expose the plexus, a
segment of which is then removed.
PREMENSTRUAL TENSION
The premenstrual tension syndrome is a separate entity from painful periods. It mostly
occurs in women over 30 years of age. It is characterized by premenstrual discomfort in the
lower abdomen and back, and in the breasts. It is often described as a bloated feeling of
distension or pelvic engorge-ment, which precedes the period by a week or 10 days. Sometimes
the onset of the menstrual flow brings relief. It is accompanied by varying degrees of irritability,
depression and other emotional disturbances, and not infrequently by headache. Some women
may notice a deterioration in their concentration, and it is said that there is a relationship between
violent and antisocial behaviour and this conditipn. Examination performance may be affected at
this time.
Patients may show a gain of weight of 1 kg or more in the latter part of the menstrual
cycle due to salt and water retention. The retention of fluid is partly due to ovarian steroids, but
there is also an increased output of antidiuretic hormone from the posterior pituitary gland. It
may also be caused by a relative lack of progesterone.
Emotional stress often contributes to the symptoms, and the social relationships of the
patient must be reviewed. A pelvic examination to exclude unexpected pelvic pathology is also
essential.
Treatment
The exploration of emotional and work-related stress often allows the woman to reveal
her problems and to compensate accordingly.
Reassurance and simple psychotherapy will help, but it also may be necessary to treat the
symptoms with various drugs.
Some women obtain relief with diuretics such as chlorothiazide 500 mg three times daily
in the premenstrual week.
Progestogens help some women taken ether orally (norethisterone 5 mg bd or
dydrogesterone lOmgbd from day 15-25) or rectally (cyclogest 200 mg supositories) for the
same period of time. Oestrogens have been used to suppress ovulation on the basis that cyclical
ovarian activity is necessary for the symptoms of premenstrual tension. They can be given as
oestradiol implants (25-100 mg) which last for three to six months. A disadvantage is the
prolonged action of the implants and a more flexible approach is to use transdermal oestradiol
patches in a strength that can vary from 50-200 /Ag every 3 days. Both of these have to have
concomitant cyclical norethisterone (5 mg daily for the last 12 days of the cycle) to prevent
endometrial hyperplasia.
Combined oral contraceptive pills may also be of benefit because they suppress
ovulation. Evening primrose oil (gamma linolenic acid) has been widely used: it may have some
benefit. Prostaglan-din synthetase inhibitors may improve fatigue, headaches, general aches and
pains and general mood symptoms. The dose is mefenamic acid 250 mg three times a day
starting 12 days before the anticipated onset of menstruation and increasing to 500 mg three
times daily during menstruation. Danazol which suppresses gonadotrophin secretion and
abolishes cyclical ovarian function may be of help. The dose varies between 200— 400 mg a day
but unwanted androgenic effects such as weight gain, hirsutism and acne have been a problem
particularly with the higher dosage.
Gonadotrophin-releasing hormone analogues (GnRH) have been used for premenstrual
tension but, because of their unwanted menopausal side effects and long-term risk of
osteoporosis, they are not warranted. Some respond to a mild tranquillizer (e.g. diazepam 2.5 mg
bd) or an antidepressant (e.g. amytriptyline 50 mg a day). Bromocriptine (2.5—5.0 a day) may
be tried if mastalgia is a problem.
V. Self-assessment tasks:
1. What classifications of abnormalities of menstrual cycle do you know?
2. What is bleeding of juvenile period?
3. Clinical picture of certain forms of abnormalities of menstrual cycle.
4. Methods of non-hormonal hemostasis by bleedings.
5. When can hormonal hemostasis be prescribed?
6. What are the indications for surgical treatment of bleedings?
7. What is primary amenorrhea?
8. What is secondary amenorrhea?
9. Make up a plan of examination of a patient with primary amenorrhea.
10. Make up a plan of examination of a patient with secondary amenorrhea.
ENDOMETRITIS
During reproductive life endometritis is uncommon, except after delivery or abortion.
The cavity of the uterus is protected against bacterial invasion by the acid barrier of the vagina
and the cervical mucus, and in addition the shedding of the en-dometrium at each menstrual
period prevents organisms from gaining a foothold for long. However, after delivery or abortion
lochial discharge forms an excellent culture medium and organisms may enter the tissues at the
site from which the placenta has separated.
Endometritis may follow operations such as curettage, or the insertion of an intrauterine
device. When an intrauterine device is in place the subjacent endometrium shows infiltration
with polymorphonuclear leucocytes. This may merely be a response to the foreign body, but in a
few cases actinomyces-like organisms have been noticed in smears or cultured from the uterus.
Gonococcal infection may spread upwards from the cervix to the endometrium and tubes,
while tuberculosis endometritis often follows tuberculous salpingitis.
With advanced carcinoma of the endometrium or of the cervix, especially if the cervical
canal is obstructed, infection occurs.
After the menopause there may be ascending infection which causes what was formerly
called senile endometritis, now called atrophic endometritis.
PELVIC INFLAMMATORY DISEASE
Pelvic inflammatory disease (PID) is a clinical syndrome attributed to the ascending
spread of micro-organisms (unrelated to pregnancy or surgery) from the vagina and cervix to the
endometrium, fallopian tubes and or contiguous structures.
The clinical syndrome usually begins with an acute episode which can be followed either
by complete resolution or gradual subsidence into a more chronic process which may also
exhibit further acute or subacute resurgences. At the other extreme, however, it may be a
clinically benign condition which goes unrecognized and is only diagnosed when the damage has
been done and the woman is under investigation for infertility or has an ectopic pregnancy. It is
suggested that only a minority of women whose infertility is due to tubal damage give a history
of previous overt disease.
Diagnosis of pelvic inflammatory disease
Even experienced gynaecologists have difficulty in correctly diagnosing PID; the
symptoms are often unreliable. Hare (1986) produced an algorithm for pelvic inflammatory
disease. He advised that unless three or more of his listed symptoms were present, in addition to
abdominal pain and dyspareunia, the diagnosis must remain uncertain. He felt that signs were
more usual than symptoms, but at least three signs should be elicited. Obviously if doubt remains
laparoscopy should be performed—both for the immediate safety of the patient, in making the
correct diagnosis, and for planning treatment.
ACUTE SALPINGITIS
Pathology
In acute salpingitis both tubes are congested, red and oedematous and there is usually a
seropurulent exudate. The plicae of the tubal mucosa are swollen, and the epithelium covering
them is shed in places. It is possible for this type of inflammation to subside without leaving any
gross changes, but in most cases damage is done to the ciliated epithelium of the tube, causing
infertility or a delay in the transport of the fertilized ovum and therefore an ectopic pregnancy.
The infected tube frequently becomes occluded. The lumen of the interstitial part is so
fine that the slightest inflammatory reaction blocks it. The fimbriae adhere at the other end of the
tube and are drawn into the tube, and the abdominal ostium is sealed. Once the ends are closed,
inflammatory exudate collects and distends the tube. When the collection of fluid is more or less
clear it is called a hydrosalpinx, when it is purulent, a pyosalpinx. Because the ampullary end of
the tube distends more easily than the isthmus the tube becomes retort-shaped If the infecting
organisms are virulent they can pass deep into the wall of the tube, which becomes thickened,
and as the covering peritoneum becomes involved in the inflammation peritoneal adhesions
occur.
The ovaries are also affected by the inflammation. They become enlarged by oedema and
adhere to the fallopian tubes by filmy adhesions. If the infection is severe the ovary develops
small abscesses, or may form part of the wall of an abscess cavity with the tube and adjacent
structures. A distended tube may communicate with a cyst of the ovary, forming a tubo-ovarian
abscess.
In some cases the inflammation does not result in the collection of pus within the lumen
of the tube. Inflammatory changes within the muscle wall produce areas of variable thickening
and fibrosis, often with kinking. This condition is called interstitial salpingitis, and is often
found as a residual lesion in patients whose symptoms have resolved.
Symptoms and signs
The patient feels ill and complains of lower abdominal pain, which is worse on
movement. Vomiting may occur at the onset and the bowels are constipated. The pulse rate is
increased and the temperature is raised, often above 39.5°C. The tongue is dry but not usually
furred. Because there is pelvic hyperaemia there may be a mucous discharge from the uterus
which may be purulent if there is cervicitis or infection by Trichomonas vaginalis. Because there
is oophoritis the menstrual cycle is often upset. In many cases in which the infection is of low
virulence all symptoms disappear in a few days, and the true nature of the illness is never
discovered.
Examination shows tenderness and rebound tenderness over the pelvis and both iliac
fossae. If peritonitis is present there may be rigidity and abdominal distension over the lower
abdomen. Pelvic examination causes pain, especially on movement of the uterus. In many cases
the tenderness in the fornices is such that no other physical signs can be made out. In less acute
cases a sense of fullness is noticed in the lateral fornices on bi-manual examination. The
converse is perhaps more useful; if bimanual pressure to the side of the uterus is not painful, the
patient is certainly not suffering from acute salpingitis.
If there is a peritubal abscess, the encysted serous peritonitis around it forms a mass,
which may become palpable above the symphysis pubis.
It is irregular in outline and partly resonant on percussion because of adhering coils of
intestine. In order to relax the abdominal muscles over this tender mass the patient often lies in
bed with both knees flexed.
Abscess formation, inside or outside the tube, is accompanied by deterioration of the
patient's condition. She looks and feels ill, and complains of increasing pain. Her appetite
deteriorates and she sleeps badly. Temperature and pulse rate increase and rigors may occur;
there is increasing leuco-cytosis. The pelvic mass increases in size, and if left alone the abscess
usually points and drains into the rectum; this event is often preceded by mucous diarrhoea.
With modern antibiotic treatment the formation of a large pelvic mass is seen less often
than it used to be, and, left alone, it tends to absorb after one or two weeks. The tender fallopian
tubes may then be felt as oblong, tender, fixed masses behind the uterus. The patient may be left
with blocked tubes and more or less dense pelvic adhesions.
Diagnosis
At its onset acute salpingitis must be distinguished from acute appendicitis. If the
appendix is pelvic, the signs may be similar.
The history will often be helpful, for in salpingitis there will generally be history and
signs of recent abortion or delivery or of gonococcal infection.
In appendicitis the pain usually starts near the umbilicus and later becomes localized to
the right iliac fossa; in salpingitis the pain starts in the lower abdomen and is bilateral. The
temperature with salpingitis is usually higher, often reaching 39.5°C, whereas in appendicitis it
seldom exceeds 38.5°C;the pulse rate, however, is not as high in salpingitis as in appendicitis.
Vomiting may occur with either condition but is more constant with appendicitis. A furred
tongue suggests appendicitis. In cases of salpingitis, vaginal examination shows tenderness in
both lateral fornices; in appendicitis the signs will be more marked on the right side. If a
pyosalpinx has formed, the history will usually make the nature of the swelling obvious.
However, if the patient is first seen at this stage, the swelling will have to be differentiated from
an ectopic gestation with a tubal mole or from a small ovarian cyst.
Treatment
Bed rest, adequate fluid intake and analgesics are the basic necessities in the treatment of
acute salpingitis, but the selection of suitable antibiotics, in adequate dosage, is also essential.
Should an intrauterine contraceptive device be in place it should be removed after antibiotic
cover is achieved.
Bacterial swabs are taken from the cervix and urethra and should be tested for Chlamydia
and, although gonococcal salpingitis is now less common in the UK, this must also be excluded.
However, treatment should be carried out without waiting for a bacteriological report, so as to
avoid permanent damage to the tubes.
There is no ideal antibiotic regime for the treatment of salpingitis. Treatment should
begin with a single (antigonococcal) dose of spectinomycin (2 g intramuscularly) or cefuroxime
(1.5 g intramuscu-larly), followed by a tetracycline (e.g. oxytetracy-cline 500 mg four times
daily by mouth, or doxy-cycline 100 mg twice daily by mouth), plus oral metronidazole 400 mg
daily for 14 days. Initial parenteral therapy (tetracycline hydrochloride 500 mg 12 hourly
intravenously plus metronidazole 500 mg intravenously or per rectum) may be required in severe
cases. Pregnant patients, or those who are intolerant of tetracyclines, should be given
erythromycin stearate 500 mg four times daily by mouth, plus metronidazole as above for 14
days. However, this latter regimen will not be effective against Mycoplasma hominis, and is
unreliable for N. gonorrhoeae.
Recurrent PID is not uncommon and the risk of infertility or ectopic pregnancy increases
with further episodes of infection. It is therefore important to trace the patient's contacts, and her
partners should be referred to a genitourinary medicine clinic for investigation and treatment.
Surgical treatment of acute salpingitis is seldom called for and if laparotomy (performed
when the diagnosis is doubtful and appendicitis may be a possibility) shows that the tubes are
acutely inflamed, they should not be removed if there is any hope of restoration of function.
Bacterial swabs should be taken from any pus and from the lumen of the tubes before closing the
abdomen.
Surgery may be contemplated in the very rare cases of deterioration in spite of active
medical forms of treatment. When there is definite evidence of a pelvic abscess, this must be
drained. Where the patient suffers from repeated recurrent attacks of acute salpingitis the tubes
become irretrievably blocked and their removal during a quiescent phase is advised.
CHRONIC SALPINGITIS
An abscess often does not form after an attack of acute salpingitis, yet the disease
obviously fails to resolve completely. A patient with chronic salpingitis may be ambulant and
even follow her regular employment. However, she does not feel well and many ordinary daily
tasks become a burden. The menstrual loss is often heavy and is preceded by congestive
dysmenorrhoea with pain which precedes, and lasts throughout, each period.
The inflammation of the ovaries may upset the menstrual cycle and produce irregular
bleeding. In addition to menstrual pain there is often continuing dull pain or aching in the lower
abdomen or back. There is dyspareunia and there may be an excessive cervical discharge. On
pelvic examination there is tenderness and residual thickening of one or both tubes, or a fixed
tender mass in the rectouterine pouch of Douglas due to bilateral pyosalpinges. Ovarian
endometriomatous cysts may cause pelvic pain and menorrhagia, and the physical signs closely
resemble those of chronic salpingitis with bilateral tubal swellings. The absence of a history of
infection after abortion or delivery, gonorrhoea, any suggestion of tuberculosis and the absence
of pyrexia, help in reaching the correct diagnosis.
Treatment
Only prolonged antibiotic therapy and convalescence have any prospect of resolving this
condition. It may be necessary to continue treatment for 3-6 months, changing between the
various broad spectrum antibiotics.
Often these measures fail and surgical treatment is indicated. While healthy tissue should
obviously be conserved, the patient should not be left with infected tissues which will need
further surgical treatment. This means that both tubes may have to be removed, and in such
cases, especially if there is menorrhagia and discharge, total hysterectomy is often wise. An
effort should be made to find and conserve any healthy ovarian tissue.
Tuberculous infection of the genital tract is becoming uncommon in the UK; it is seen
more often in developing countries. The infection is a chronic one, and is almost invariably
secondary to a tuberculous infection in the lung, although by the time the genital infection
becomes manifest the primary lesion may be quiescent or healed. Although it is theoretically
possible for a patient to be infected directly from a male with tuberculous epididymitis, this
event is almost unknown.
The fallopian tube is the most common site of initial infection in the pelvic organs.
Diagnosis
Since, in nearly every case of active tuberculous salpingitis, the endometrium is involved,
histolo-gical examination of curettings will show the presence of tubercles. Part of the material
removed by currettage is sent for bacterial culture or guinea-pig Fig. 5.6 Bilateral tuberculous
pyosalpinges. The walls of both tubes are thickened and they contain caseous material. Tubercles
are seen on the peritoneal surface inoculation. In every case a radiological examination of the
chest must be made.
Treatment
It is recommended that extrapulmonary tuberculosis should be treated in the same way as
pulmonary tuberculosis. Several drugs are given in combination to prevent the emergence of
resistant strains. Use of an intensive four-drug regimen (for example, rifampicin, isoniazid,
ethambutol and pyrazinamide) for 8 weeks allows the total treatment to be reduced to 6 months.
Infections of the Upper Genital Tract

Pelvic inflammatory disease (PID) is an infection of the upper genital tract. The
disease process may include the endometrium, fallopian tubes, ovaries, myometrium,
parametrium, and pelvic peritoneum.
o
Pathophysiology and Microbiology. PID is caused by the spread of infection via
the cervix. Although PID is associated with sexually transmitted infections of the lower tract, its
process is polymicrobial. N. gonorrhoeae or C. trachomatis are implicated in many cases, but
numerous micro-organisms may be involved. A positive endocervical culture result for a
particular pathogen does not necessarily correlate with positive intra-abdominal culture findings.
o
Prevention. Emphasis must be placed on aggressive treatment of lower genital
tract infection and early aggressive treatment of upper genital tract infection. This helps reduce
the incidence of long-term sequelae. Treatment of sexual partners and education is important in
reducing the rate of recurrent infections.
Table 24.10 Centers for Disease Control and Prevention Treatment
Recommendations for Neisseria Gonorrhoeae
Durat
Medication
Recommended
Dosage ion
Use
pregnancy
in
Cefixime
400
mg
1 dose
—
125
mg
1 dose
Recommended
500
mg
1 dose
Contraindicated
400
mg
1 dose
Contraindicated
250
mg
1 dose
Contraindicated
PO
Ceftriaxone
IM
Ciprofloxacin
PO
Ofloxacin
PO
Levofloxacin
PO
PLUS treatment for Chlamydia if not ruled out
Azithromycin
1 g PO
1 dose
Recommended
Doxycycline
100
mg
7 days
Contraindicated
500
mg
7days
Recommended
PO bid
Erythromycin
base
PO qid
From Centers for Disease Control and Prevention. Sexually transmitted
diseases treatment guidelines 2006. MMWR 2006;55(No. RR-11), with
permission.
o
P.299
o
o
Risk factors include a previous history of PID, multiple sex partners, defined as
more than two partners in 30 days, and infection by a sexually transmitted organism. Use of an
IUD can increase the risk of PID by up to six times but only within the first 3 weeks after
placement. Thereafter, the risk is relatively low (10). Use of nonbarrier contraception is also a
developing risk factor.
o
Signs and Symptoms. The most common presenting symptom is abdominopelvic
pain. Other complaints are variable, including vaginal discharge or bleeding, fever and chills,
nausea, and dysuria.
o
Diagnosis of PID is difficult because the presenting signs and symptoms vary
widely. Because of the sequelae of PID, especially infertility, ectopic pregnancy, and chronic
pelvic pain, health care providers should maintain a low threshold for diagnosis PID (4).

Minimal Criteria. Empiric treatment should be initiated in young women
at risk for STDs if they are experiencing pelvic or lower abdominal pain, if no other cause can be
identified, and if one or more of the following are present on pelvic examination:

Cervical motion tenderness

Uterine tenderness

Adnexal tenderness

Additional Criteria for Diagnosis

Oral temperature >101В°F (>38.3В°C)

Abnormal cervical or vaginal mucopurulent discharge

Presence of white blood cells on saline microscopy of vaginal
secretions

Elevated erythrocyte sedimentation rate

Elevated C-reactive protein

Laboratory
documentation
of
cervical
infection
with
N.
gonorrhoeae or C. trachomatis

Specific Criteria for PID

Endometrial biopsy with histopathologic evidence of endometritis

Transvaginal
sonography
or
magnetic
resonance
imaging
techniques showing thickened, fluid-filled tubes with or without free pelvic fluid or tubo-ovarian
complex

o
Laparoscopic abnormalities consistent with PID
Treatment for PID should have as its goals the prevention of tubal damage that
leads to infertility and ectopic pregnancy and prevention of chronic infection. Many patients can
be successfully treated as outpatients, and early ambulatory
P.300
treatment should be the initial therapeutic approach. Antibiotic choice should target the major
etiologic organisms (N. gonorrhoeae and C. trachomatis) but should also address the
polymicrobial nature of the disease (Tables 24.11 and 24.12).

Criteria for Hospitalization

Surgical emergencies (e.g., appendicitis) should not be excluded.

The patient is pregnant.

The patient does not respond clinically to oral antimicrobial
therapy.

The patient is unable to follow or tolerate an outpatient oral
regimen.

The patient has severe illness, nausea and vomiting, or high fever.

The patient has a tubo-ovarian abscess.
o
Sequelae. Approximately 25% of PID patients experience long-term sequelae.
Infertility due to tubal occlusion affects anywhere from 6% to 60% of women following an
episode of PID, depending on severity, whereas the risk of ectopic pregnancy is approximately 6
to 10 times normal. Chronic pelvic pain and dyspareunia have also been reported. Fitz-HughCurtis syndrome is the development of fibrous perihepatic adhesions resulting from the
inflammatory process of PID. This can cause acute right upper quadrant pain and tenderness.
Table
24.11
Centers
for
Disease
Control
and
Prevention
Recommendations for Inpatient Management of Pelvic Inflammatory
Disease
Regimen
Cefotetan
A
2
g
IV
every
12
hours
2
g
IV
every
6
hours
or
Cefoxitin
PLUS
Doxycycline
*
100
mg
orally
or
IV
every
12
hours
Treatment with doxycycline (100 mg PO BID) should continue to complete 14
days. If TOA, add clindamycin or metronidazole for more effective anaerobic
coverage.
Regimen
B
Clindamycin
900
mg
IV
every
8
hours
PLUS
Gentamicin loading dose IV or IM (2 mg/kg) w/maintenance dose (1.5 mg/kg) q
8
*
hours.
Single
daily
dosing
may
be
substituted.
Treatment with doxycycline 100 mg PO BID or clindamycin 450 mg PO QID
should continue to complete a total of 14 days. If TOA, use clindamycin rather
than
doxycycline
for
more
effective
anaerobic
Alternative
Ofloxacin
coverage.
Regimens
400
mg
IV
every
12
hours
or
Levofloxacin
WITH
500
mg
or
IV
once
daily
WITHOUT
Metronidazole
500
mg
IV
every
8
hours
6
hours
12
hours
or
Ampicillin/sulbactam
3
g
IV
every
PLUS
Doxycycline
100
mg
PO
or
IV
every
Parenteral therapy can be discontinued 24 hours after patient improves clinically.
From Centers for Disease Control and Prevention. Sexually transmitted
diseases treatment guidelines 2006. MMWR 2006;55(No. RR-11), with
permission.
Table
24.12
Centers
for
Disease
Control
and
Prevention
Recommended Treatment Schedules for Outpatient Treatment of Pelvic
Inflammatory Disease
Regimen
Ofloxacin
A
400
mg
PO
twice
a
PO
daily
Г—
day
14
days
or
Levofloxacin
500
mg
WITH
Г—
14
or
Metronidazole
500
mg
PO
days
WITHOUT
twice
a
day
<
14
Regimen
days
B
Ceftriaxone
250
mg
IM
single
dose
or
Cefoxitin 2 g IM in a single dose and Probenecid, 1 g PO administered
concurrently
in
a
single
dose
or
Other parenteral third-generation cephalosporin (e.g., ceftizoxime, cefotaxime)
PLUS
Doxycycline
100
mg
PO
WITH
twice
a
day
Г—
or
Metronidazole
Alternative
500
mg
PO
14
days
WITHOUT
twice
a
day
Г—
14
days
Regimen
Amoxicillin/clavulanic acid + doxycycline (GI symptoms might limit
compliance)
From Centers for Disease Control and Prevention. Sexually transmitted
diseases treatment guidelines 2006. MMWR 2006;55(No. RR-11), with
permission.

Endometritis (Nonpuerperal)
o
Pathophysiology. Endometritis is caused by the ascension of pathogens from the
cervix to the endometrium. Pathogens include C. trachomatis, N. gonorrhoeae, Streptococcus
agalactiae, cytomegalovirus, HSV, and Mycoplasma hominis. Organisms that produce bacterial
vaginosis may also produce histologic endometritis, even in women without symptoms.
Endometritis is also an important component of PID and may be an intermediate stage in the
spread of infection to the fallopian tubes.
o
Signs and Symptoms

Chronic Endometritis. Many women are asymptomatic. The classic
symptom of chronic endometritis is intermenstrual vaginal bleeding. Postcoital bleeding,
menorrhagia, and a dull, constant lower abdominal pain are other complaints.

o
Acute Endometritis. Uterine tenderness is common.
Diagnosis. The diagnosis of chronic endometritis is established by endometrial
biopsy and culture. The classic histologic findings of chronic endometritis are an inflammatory
reaction of monocytes and plasma cells in the endometrial stroma (five plasma cells per highpower field). A diffuse pattern of inflammatory infiltrates of lymphocytes and plasma cells
throughout the endometrial stroma or even stromal necrosis is associated with severe cases of
endometritis.
o
Treatment. The treatment of choice for chronic endometritis is doxycycline, 100
mg PO bid for 10 days. Broader coverage of anaerobic organisms may also be considered,
especially in the presence of bacterial vaginosis. When endometritis is associated with acute PID,
treatment should focus on the major etiologic organisms, including N. gonorrhoeae and C.
trachomatis, and should also include broader polymicrobial coverage.
V. Self-assessment tasks:
1.
Classification of inflammatory gynaecological diseases in girls and juvenile.
2.
Clinical picture, diagnostics of inflammatory diseases of internal genitals in girls
and juvenile.
3.
Methods of diagnostics of clamidiosis.
4.
Prescribe the treatment of clamidiosis in accordance to age.
5.
What is ureaplasmatic vulvovaginitis? Clinical picture, diagnostics of treatment.
6.
What is gardnerelosis? Methods of its diagnostics in girls and juvenile and its
treatment.
7.
Bacterial vaginosis. Methods of its diagnostics and treatment in juvenile.
VI. Literature.
1. American Academy of Pediatrics Committee on Quality Improvement, Subcommittee on
Urinary Tract Infection. Practice Parameter: The diagnosis, treatment and evaluation of the
initial urinary tract infection in febrile infants and young children. Pediatrics
1999;103;4:843–852.
2. Sanfilippo JS. Pediatric and Adolescent Gynecology, 2nd Ed. Philadelphia: WB Saunders,
2001:227–231.
3. Reiter EO, Lee PA. Adolescent endocrinology: delayed puberty. Adolesc Med 2002;13
(1):101–118.
4. Larsen PR. Williams Textbook of Endocrinology, 10th Ed. Elsevier, 2003:1171–1202.
5. Stenchever MA. Comprehensive Gynecology, 4th Ed. Mosby, 2001:280–288.
6. Kaplowitz PB. Reexamination of the age limit for defining when puberty is precocious in girls
in the United States: implication for evaluation and treatment. Drug and Therapeutics and
Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics 1999;104
(4 Pt 1):936–941.
7. Antoniazzi F, Zamboni G. Central precocious puberty: current treatment options. Paediatr
Drugs 2004;6 (4):211–231.
8. Speroff L, Glass RH, Kase NG. Clinical Gynecologic Endocrinology and Infertility, 5th Ed.
Baltimore: Williams & Wilkins, 1994:380–382.
9. Eugster EA, Rubin SD, Reiter EO, et al. Tamoxifen treatment for precocious puberty in
McCune-Albright syndrome: a multicenter trial. J Pediatr 2003;143 (1):60–66.
10. Speroff L, Glass RH, Kase NG. Clinical Gynecologic Endocrinology and Infertility, 5th Ed.
Baltimore: Williams & Wilkins, 1994:340–342.
11. Sanfilippo JS. Pediatric and Adolescent Gynecology, 2nd Ed. Philadelphia: WB Saunders,
2001:277–287.
12. Sanfilippo JS. Pediatric and Adolescent Gynecology, 2nd Ed. Philadelphia: WB Saunders,
2001:605–608.