Abnormal Premenopausal Bleeding

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General Considerations

Normal menstrual bleeding lasts an average of 4 days (range, 2-7 days), with a mean blood loss of 40 mL. Blood loss of over 80 mL per cycle is abnormal and frequently produces anemia. Excessive bleeding, often with the passage of clots, may occur at regular menstrual intervals (menorrhagia) or irregular intervals (dysfunctional uterine bleeding). When there are fewer than 21 days between the onset of bleeding episodes, the cycles are likely to be anovular. Ovulation bleeding, a single episode of spotting between regular menses, is quite common. Heavier or irregular intermenstrual bleeding warrants investigation.

Dysfunctional uterine bleeding is usually caused by overgrowth of endometrium due to estrogen stimulation without adequate progesterone to stabilize growth; this occurs in anovular cycles. Anovulation commonly occurs in teenagers, in women aged late 30s to late 40s, and in extremely obese women or those with polycystic ovary syndrome.

Essentials of Diagnosis

• Blood loss of over 80 mL per cycle.
  
• Excessive bleeding, often with the passage of clots, may occur at regular menstrual intervals (menorrhagia) or irregular intervals (dysfunctional uterine bleeding).
  
• Etiology most commonly dysfunctional uterine bleeding on a hormonal basis.

Clinical Findings

A. Symptoms and Signs

The diagnosis of the disorders underlying the bleeding usually depends on the following: (1) A careful description of the duration and amount of flow, related pain, and relationship to the last menstrual period (LMP). The presence of blood clots or the degree of inconvenience caused by the bleeding may be more useful indicators. (2) A history of pertinent illnesses or weight change. (3) A history of all medications the patient has taken in the past month. (4) A history of coagulation disorders in the patient or family members. (5) A careful pelvic examination to look for pregnancy, uterine myomas, adnexal masses, or infection.

B. Laboratory Studies

Cervical smears should be obtained as needed for cytologic and culture studies. Blood studies should include a complete blood count, sedimentation rate, and glucose levels to rule out diabetes. Diabetes may occasionally initially present with abnormal bleeding. A test for pregnancy and studies of thyroid function and coagulation disorders should be considered in the clinical evaluation. Tests for ovulation in cyclic menorrhagia include basal body temperature records, serum progesterone measured 1 week before the expected onset of menses, and analysis of an endometrial biopsy specimen for secretory activity shortly before the onset of menstruation.

C. Imaging

Ultrasound may be useful to evaluate endometrial thickness or to diagnose intrauterine or ectopic pregnancy or adnexal masses. Endovaginal ultrasound with saline infusion sonohysterography may be used to diagnose endometrial polyps or subserous myomas. MRI can definitively diagnose submucous myomas and adenomyosis.

D. Cervical Biopsy and Endometrial Curettage

Biopsy, curettage, or aspiration of the endometrium and curettage of the endocervix may be necessary to diagnose the cause of bleeding. Polyps, endometrial hyperplasia, and submucous myomas are commonly identified in this way. If cancer of the cervix is suspected, colposcopically directed biopsies and endocervical curettage are indicated as first steps.

E. Hysteroscopy

Hysteroscopy can visualize endometrial polyps, submucous myomas, and exophytic endometrial cancers. It is useful immediately before dilatation and curettage (D&C).

Treatment

Premenopausal patients with abnormal uterine bleeding include those with submucous myomas, infection, early abortion, or pelvic neoplasms. The history, physical examination, and laboratory findings should identify such patients, who require definitive therapy depending on the cause of the bleeding. A large group of patients remains, most of whom have dysfunctional uterine bleeding on a hormonal basis.

Dysfunctional uterine bleeding can usually be treated hormonally. Women over the age of 35 should have endometrial sampling to rule out endometrial hyperplasia or carcinoma prior to initiation of hormonal therapy. Progestins, which limit and stabilize endometrial growth, are generally effective. Medroxyprogesterone acetate, 10 mg/d, or norethindrone acetate, 5 mg/d, should be given for 10-14 days starting on day 15 of the cycle, following which withdrawal bleeding (so-called medical curettage) will occur. The treatment is repeated for several cycles; it can be reinstituted if amenorrhea or dysfunctional bleeding recurs. In women who are bleeding actively, any of the combination oral contraceptives can be given four times daily for 1 or 2 days followed by two pills daily through day 5 and then one pill daily through day 20; after withdrawal bleeding occurs, pills are taken in the usual dosage for three cycles. In cases of intractable heavy bleeding, danazol, 200 mg four times daily, is sometimes used to create an atrophic endometrium. Alternatively, a GnRH agonist such as depot leuprolide, 3.75 mg intramuscularly monthly, or nafarelin, 0.2-0.4 mg intranasally twice daily, can be used for up to 6 months to create a temporary cessation of menstruation by ovarian suppression.

In cases of heavy bleeding, intravenous conjugated estrogens, 25 mg every 4 hours for three or four doses, can be used, followed by oral conjugated estrogens, 2.5 mg daily, or ethinyl estradiol, 20 mcg daily, for 3 weeks, with the addition of medroxyprogesterone acetate, 10 mg daily for the last 10 days of treatment, or a combination oral contraceptive daily for 3 weeks. This will thicken the endometrium and control the bleeding. If the abnormal bleeding is not controlled by hormonal treatment, a D&C is necessary to check for incomplete abortion, polyps, submucous myomas, or endometrial cancer.

Endometrial ablation through the hysteroscope with laser photocoagulation or electrocautery - or blindly with hyperthermia or cryotherapy - is an option; these techniques are designed to reduce or prevent any future menstrual flow.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen or mefenamic acid in the usual anti-inflammatory doses will often reduce blood loss in menorrhagia - even that associated with a copper intrauterine device (IUD). The levonorgestrel-releasing IUD will markedly reduce menstrual blood loss and may be a good alternative to other medical or surgical therapies.

Prolonged use of a progestin, as in a minipill, in injectable contraceptives, or in the therapy of endometriosis, can also lead to intermittent bleeding, sometimes severe. In this instance, the endometrium is atrophic and fragile. If bleeding occurs, it should be treated with estrogen as follows: ethinyl estradiol, 20 mcg/d for 7 days, or conjugated estrogens, 1.25 mg/d for 7 days.

It is useful for the patient and the clinician to discuss stressful situations or lifestyles that may contribute to anovulation and dysfunctional bleeding, such as prolonged emotional turmoil or excessive use of drugs or alcohol.

Dubinsky TJ: Value of sonography in the diagnosis of abnormal vaginal bleeding. J Clin Ultrasound 2004;32:348. [PMID: 15293302]

Hurskainen R et al: Levonorgestrel-releasing intrauterine system in the treatment of heavy menstrual bleeding. Curr Opin Obstet Gynecol 2004;16:487. [PMID: 15534445]

RELATED STORIES:
Disorders of the Menstrual Cycle   Postmenopausal Vaginal Bleeding   Dysmenorrhea   Ovarian Failure   Abnormal Uterine Bleeding   Dysfunctional Uterine Bleeding (Functional Uterine Bleeding)   Primary Dysmenorrhea (Functional Dysmenorrhea)   Secondary Dysmenorrhea (Acquired Dysmenorrhea)   Amenorrhea   Premature Ovarian Failure (Premature Menopause)   Premenstrual Syndrome (Premenstrual Tension)   Menorrhagia

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