simple (cystic stromal and glandular)
complex
-
- adenomatous
- atypical adenomatous
- endometrial carcinoma
- endometrial sarcoma
postmenopausal dysfunctional
- atrophic
estrogen replacement related
- tamoxifen therapy related
Background
Under 40 years of age, the incidence of uterine cancer is quite
low so that endometrial sampling by biopsy or D&C is not always
the first step in a workup. Over the age of 40 and for high risk
patients (polycystic ovarian disease, patients with obesity and
hypertension, and anovulation) over the age of 35, all patients
with abnormal bleeding should have endometrial sampling. Also
there is more common occurrence of mechanical bleeding causes
such as endometrial polyps or uterine fibroids in this age
category. Abnormal uterine bleeding would be defined as any
menstrual bleeding longer than 7 days of menses and any menses
less than 23 days apart. Volume of flow also may be abnormal but
it is very to measure. History alone is not always accurate.
When it has been measured, a blood flow of more than 120 mls
(about 4 oz) per menses is considered excessive and would be
classified as abnormal.
Goals
Any abnormal bleeding over the age of 40 or over the age of 35 in
high risk patients should be primarily investigated by evaluation
for mechanical causes or cancer. Usually an endometrial biopsy
is performed, although imaging techniques such as ultrasound or
hysterosongraphy can also be used. Once endometrial cancer is
ruled out by biopsy, the patient can be treated with hormonal
therapy under the presumption of endocrinological causes of the
abnormal bleeding. If there is no response to this however, a
direct evaluation of the endometrium such as hysteroscopy should
be performed because of the high incidence of polyps and fibroids
that disturb the endometrial cavity and may produce abnormal
bleeding.
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Abnormal uterine bleeding - menarche to menopause
Background - importance and magnitude of problem
Diagnostic goals - for overall category
ovulatory but dysfunctional uterine bleeding
- hypothyroidism
- hyperthyroidism
- drug induced/medication side effects (coumadin, ASA, steroids)
coagulation disorders
- thrombocytopenia
- thrombocytopenia from septicemia and chronic infection
- immunologic thrombocytopenia
- diminished platelet production or increased destruction
- hereditary clotting factor abnormalities
- factor VIII deficiency (von Willibrand's disease)
- factor XI deficiency (Rosenthal's syndrome)
- factor V deficiency (Owren's disease)
- factor VII deficiency
- factor X deficiency (Stuart factor deficiency)
- prothrombin deficiency and dysfibrinogenemia
multiple factor deficiencies
- liver cirrhosis
- hepatitis
- trauma/foreign bodies
infection
- severe vaginal infection (trichomonas, bacterial vaginitis, yeast)
- cervicitis
anovulatory with atrophic endometrium
contraceptive associated
- depomedroxyprogesterone associated
- combined oral contraceptive associated
- progestin only OCP
- progestin implant
- postpill anovulation/galactorrhea
increased prolactin
- pituitary prolactinoma
- hyperprolactinemia
- other pituitary tumors
- empty sella syndrome
- growth hormone excess - acromegally
- ACTH excess - Cushing's disease
- Nelson's syndrome
- pseudotumor cerebri
- chronic renal failure/hemodialysis
- persistant postpartum amenorrhea-galactorrhea
- spontaneous amenorrhea-galactorrhea
- liver cirrhosis
- hepatitis
- chronic systemic disease
anovulatory with proliferative/hyperplastic endometrium
Background
Most women will have at least one, possibly more, episodes of
abnormal uterine bleeding, unrelated to pregnancy, during their
reproductive years. Most events are isolated and infrequent and
menses usually revert to normal within one or two cycles.
Goals
If abnormal bleeding patterns persist beyond one or two cycles,
then investigation is warranted. Any endocrine abnormalities or
medications or general metabolic diseases that interfere with the
normal ovulation sequence can produce abnormal uterine bleeding.
Search for the multiple possible causes of this "dysfunctional"
bleeding is primarily by history and physical exam along with
targeted laboratory studies. Often a trial of hormonal therapy
is given.
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Background - importance and magnitude of problem
Diagnostic goals - for overall category
Hypogonadotropic hypogonadism (low FSH and low LH)
CNS lesions
- congenital CNS defects
- prolactinoma
- other pituitary adenomas
- malignant pituitary tumor
- craniopharyngioma
- hypothalamic hypogonadism with anosmia (Kallmann's syndrome)
- deficiency of GnRH
- hypopituitarism
- postsurgical hypopituitarism
- Laurence-Moon-Biedl syndrome
- Prader-Willi syndrome
- primary hypothyroidism
- congenital adrenal hyperplasia
- Cushing's syndrome
- gastrointestinal malabsorption
- physiologic delay
- exercise amenorrhea
- weight loss/anorexia
- (see also hypothalamic amenorrhea)
Hypergonadotropic hypogonadism (high FSH, low estradiol)
- gonadal dysgenesis 45 XO (Turner's syndrome)
- gonadal dysgenesis 46 XY (Swyer syndrome)
gonadal dysgenesis 46 XX
- familial gonadal dysgenesis
- 17-ą-hydroxylase deficiency
- galactosemia
- ataxia telangiectasia
- myotonia dystrophica
- autoimmune disorders
- chemotherapy/radiation therapy (ovarian cytotoxicity)
- resistant ovary syndrome
Background
This category of problems is relatively rare and indicates a
major abnormality of the normal developmental process. In this
case the problem is not so much the absence of menses but the
delayed progress of sexual development. Something has gone wrong
at the brain level in failing to initiate the normal sequence of
sexual development.
Goals
Multiple medical diseases and endocrinologic abnormalities can be
associated with this problem; many having to do with the brain or
central nervous system Thorough history and physical evaluation
along with quite a few endocrinological and other laboratory
studies is usually indicated. Imaging studies such as MRI, are
used to search for tumor or vascular lesions.
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Background - importance and magnitude of problem
Diagnostic goals - for overall category
- mullerian agenesis
- imperforate hymen
- transverse vaginal septum
- vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser Syndrome)
- testicular feminization
- intersexuality
- mosaicism
- polycystic ovarian syndrome
- adrenal hyperplasia or tumor (androgen producing)
- hypothyroidism
- exercise amenorrhea
- any other anovulation cause occuring just before menarche
Background
This category of problems also occurs very infrequently. A
major issue that arises is at what age should the first menstrual
period have occurred. A rule of thumb is that if menses has not
occurred within 2 years of breast development, that is abnormal.
Thus a woman at 16 years of age who began breast development at
13 years old would be classified as having primary amenorrhea
whereas a woman who is 17 years of age who began breast
development later at the age of 16 would still not fall into this
category.
Goals
Many of the problems in this category are based on anatomical
congenital anomalies. Therefore a good physical and pelvic exam
are important in the diagnostic workup as well as imaging
studies. This is differentiated from the category of amenorrhea
with delayed sexual development in which multiple hormonal
studies, are needed because of the lack of development.
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Background - importance and magnitude of problem
Diagnostic goals - for overall category
Hypothalamic anovulation - low, low/normal FSH and LH, low estrogen
CNS lesions
- craniopharyngioma
- metastatic tumors
- sarcoidosis
- Wegner's granulomatosis
- histiocytosis
- syphylitic gumma
- tuberculoma
- carotid artery aneurysm
- hydrocephalus
- empty sella syndrome
- pituitary stalk section
- postpartum pituitary necrosis (Sheehan's syndrome)
- stress-induced, psychogenic amenorrhea
- anorexia nervosa
- buleimia
- exercise amenorrhea
- pseudocyesis
- drug-induced
- idiopathic
Hypergonadotrophic anovulation - high FSH and LH, low estrogen
Ovarian
premature ovarian failure
- autoimmune disease
- chemotherapy
- hypoadrenalism
- ovarian dysgenesis
- resistant ovary syndrome
- pseudo-ovulation
- ovarian destruction
- ovarian tumors
- endometriosis
- post surgical
Ectopic gonadotropin production
- ovarian choriocarcinoma
- ovarian dysgerminoma
- liver hepatoblastoma
Eugonadotrophic anovulation -normal gonadotropins, low normal/normal/high estrogens
increased prolactin
- pituitary prolactinoma (micro or macroadenoma)
- hyperprolactinemia - medication induced
- amitriptyline (Elavil®)
- androgens (testosterone)
- anesthetics (usually post surgical)
- chlorpromazine (Thorazine®)
- cimetadine (Tagamet®)
- estrogens
- fluphenazine
- haloperidol (Haldol®)
- metoclopramide (Reglan®)
- monoamine oxidase inhibitors (Nardil®, Parmate®)
- opiates (codiene, pain pills, morphine)
- other pituitary tumors
- empty sella syndrome
- growth hormone excess - acromegally
- ACTH excess - Cushing's disease
- Nelson's syndrome
- pseudotumor cerebri
- hypothyroidism
- chronic renal failure
- persistant postpartum amenorrhea-galactorrhea
- spontaneous amenorrhea-galactorrhea
- postpill anovulation/galactorrhea
- polycystic ovarian syndrome
- acanthosis nigricans/hyperandrogenism/insulin resistance
- adrenogenital syndrome
- Cushing's syndrome
- hypothyroidism
- obesity
- chronic systemic disease
- intrauterine scarring (Asherman's syndrome)
Background
Pregnancy is the most common cause of cessation of menses and
therefore should be ruled out before placing a problem in this
category. Unfortunately there are other problems that can
frequently delay menses or cause infrequent menses in women and
this category of problems still presents frequently. Of the many
other causes listed above. stress-induced amenorrhea and
polycystic ovarian disease are the most common. The others tend
to be more infrequent.
Goals
This category is best divided into those associated with low
gonadatropins (FSH and LH), normal gonadatropins or high
gonadatropin levels. If the gonadatropins levels are in normal
ranges diagnoses should be directed toward whether estrogen
levels are low or not. Normal to high estrogen levels often can
be determined clinically. Copious, clear cervical mucous, ferning
of cervical mucous, vaginal stripe on endometrial ultrasound of
6mm or greater, or withdrawal bleeding to a progestin challenge
indicate estrogens are being produced. The different
gonadatropins levels give an indication of possible etiology of
the problem while the estrogen levels are helpful in determining
treatment for the problem. Patients with low estrogen levels
will probably need estrogen supplementation in order to
straighten out any bleeding while patients with normal or high
estrogen levels will periodically need some form of progestin
induced withdrawal bleed in order not to have more severe
abnormal uterine bleeding in the future.
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Background - importance and magnitude of problem
Diagnostic goals - for overall category
- menstrual distress
- anxiety/stress reaction with cyclic exacerbation
- depression with cyclic exacerbation
- premenstrual syndrome
Background
Some degree of mood affectation can occur in most women just
before their menses. Usually this does not become a severe
disturbance,but in approximately 5% of women, those disturbances
are severe enough to seek medical attention.
Goals
Many underlying psychologic states with mood problems can be
worsened premenstrually. It is critical to differentiate ongoing
psychologic problems such as depression and anxiety/stress
reactions that are worsened premenstrually, versus a "pure"
premenstrual syndrome. In the former instance treatment must be
directed toward the underlying mood disturbance whereas in the
later instance hormonal therapy may be more effective.
Psychologic mood evaluation questionaires are usually
administered in the first week after menses and also about 4-7
days prior to the next menses. These should show a 50% or
greater worsening in the premenstrual phase. A prospective
symptom calendar over one or more months should show definitely
lower symptom intensity in the first part of the menstrual cycle.
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