Irregular Bleeding

 

Normal menstrual bleeding is characterized by Duration between two and seven days, flow less than 80 mL,  occurring in cycles of 24 to 35 days.

 

Menorrhagia

Excessive menstrual blood flow is termed menorrhagia. Menorrhagia may be due to local disturbances in prostaglandins or may be related to any of the uterine etiologies described below.

  • Anovulation — In premenopausal nonpregnant women, anovulation is a common cause of abnormal uterine bleeding (AUB). Anovulatory bleeding is characterized by noncyclical bleeding of variable flow and duration.  Many women with chronic anovulation have an adequate amount of biologically active estrogen however, their anovulatory cycles lack the progesterone secretion normally present in the luteal phase. This puts them at risk of developing endometrial hyperplasia and endometrial cancer.

 

 Anovulation should be suspected in the following settings:

  • Adolescents — Anovulatory cycles are the most common cause of AUB in adolescent girls due to a slowly maturing hypothalamic-pituitary axis during the first two to three postmenarchal.
  • Menopausal transition — Anovulation is also a common cause of AUB in women in the menopausal transition. Ovulatory cycles and the normal cyclic production of estrogen and progesterone become disturbed as women approach menopause. Ovulation occurs intermittently, interspersed with anovulatory (estrogen only) cycles of varying length. As a result, menses become irregular. The duration and volume of blood loss can be short and light, but prolonged heavy bleeding can occur during longer periods of anovulation
  • Polycystic ovary syndrome — Chronic anovulation in reproductive-age women is most often attributable to an endogenous disorder, such as the polycystic ovary syndrome (PCOS), which is characterized by oligomenorrhea (irregular infrequent menstrual cycles) and hyperandrogenism (hirsutism, acne, and male pattern balding). Obesity and insulin resistance are common. Women with PCOS have an adequate amount of biologically active estrogen since androgens can be converted peripherally to estrogens even in the absence of normal ovarian function, but low levels of progesterone. Thus, constant mitogenic stimulation of the endometrium leads to endometrial hyperplasia, intermittent estrogen unscheduled (breakthrough) bleeding, and menorrhagia.
  • Endocrine disorders — Endocrine disorders may be associated with hormonal changes that affect ovulation. These disorders are uncommon causes of AUB, with the exception of polycystic ovary syndrome, which occurs in 6 percent of reproductive age women.
  • Both hypo- and hyper- thyroid activity are associated with AUB. Women with hypothyroidism, even when subclinical, may have heavy or prolonged uterine bleeding . Hypothyroidism can cause hyperprolactinemia; this usually results in amenorrhea and galactorrhea, but women may develop anovulatory bleeding prior to amenorrhea. Hyperthyroidism may cause anovulation due to alterations in sex hormone binding globulin.

Menstrual irregularities are common in women with Cushing's syndrome. Menstrual abnormalities correlate with increased serum cortisol and decreased serum estradiol concentrations, but not with serum androgen concentrations. The menstrual irregularities may be due to suppression of secretion of gonadotropin-releasing hormone by hypercortisolemia. High doses of corticosteroids have a similar effect.

 

Hormone secreting adrenal and ovarian tumors are rare causes of anovulation and menstrual irregularities.

Endocrine changes leading to anovulation may also be caused by strenuous exercise/activity (eg, running, ballet dancing), sudden weight change, or significant stress.

 

Anatomic abnormalities

 A significant number of women who complain of abnormal uterine bleeding have uterine abnormalities. When anatomic abnormalities are the cause of abnormal bleeding, cyclic menses with molimina typically occur. However, the duration and flow of the menstrual period may be altered or there may be bleeding between menstrual periods. Anatomic abnormalities can often be diagnosed by imaging studies.

Polyp — Uterine polyps are usually benign endometrial growths of unknown etiology that are a common cause of abnormal uterine bleeding in women in the menopausal transition and early postmenopausal women. Irregular bleeding is the most frequent symptom, occurring in about one-half of symptomatic cases. Bleeding after straining or heavy lifting is common. Less frequent symptoms include heavy or prolonged bleeding, postmenopausal bleeding, prolapse through the cervical os, and unscheduled (breakthrough) bleeding during hormonal therapy. Polyps can be stimulated by estrogen replacement or tamoxifen. The uterus is typically normal on bimanual examination.

  • Fibroids — Leiomyomas, also known as fibroids, are the most common pelvic tumors in women, occurring in approximately 25 percent of those who are of reproductive age. There are three uterine locations for fibroids: submucosal, intramural, and subserosal  Intramural and submucosal fibroids distort the endometrial cavity, resulting in heavy or prolonged menstrual periods. Intermenstrual bleeding can also occur, but this is less likely and other lesions of cervix or uterus must be considered. The uterus often feels enlarged and asymmetric on bimanual examination
  • Adenomyosis — Adenomyosis is a disorder in which endometrial glands and stroma are present within the uterine musculature. The ectopic endometrial tissue appears to induce hypertrophy and hyperplasia of the surrounding myometrium, which results in a diffusely enlarged uterus and heavy, prolonged, painful menstrual periods. The diagnosis may be suspected by ultrasound or magnetic resonance imaging, but can only be confirmed by pathologic examination following hysterectomy.
  • Hysterotomy scar — Endometrial abnormalities related to previous hysterotomy (particularly cesarean delivery) can lead to postmenstrual or intermenstrual bleeding.
  • Other structural abnormalities — Case reports have described sarcoidosis of the endometrium detected during the evaluation and treatment of AUB.

A rare cause of heavy uterine bleeding is a congenital or acquired uterine arteriovenous malformation. This lesion should be suspected when an invasive procedure (eg, endometrial biopsy, curettage) for unexplained uterine bleeding seems to aggravate the problem. Color Doppler studies can confirm the presence of abnormal blood flow, but pelvic arteriography is the standard for diagnosis. Uterine arteriovenous malformations have traditionally been treated with hysterectomy, but uterine artery embolization is often effective and may preserve fertility.

 

Malignancy

 Uterus — Adenocarcinoma of the endometrium is the most common gynecologic cancer in women over 45 years of age; it is rarely seen before age 35. All women who experience postmenopausal uterine bleeding in the absence of estrogen therapy must be evaluated for endometrial cancer since age is a significant risk factor for this disorder.

Sarcomas of the uterus constitute only 3 to 5 percent of all uterine tumors. These cancers arise from the stroma of the endometrium (endometrial stromal sarcomas) or the myometrium. They may look and feel like benign leiomyomas; diagnosis requires a hysterectomy. Women with leiomyosarcomas usually present with heavy prolonged bleeding or postmenopausal bleeding and a uterine mass

 Other — Bleeding from fallopian tube cancer can track through the uterus, but this is a rare cause of uterine bleeding.

Abnormal uterine bleeding can also be a symptom of ovarian cancer or gestational trophoblastic disease.

Rarely, the endometrium is the site of metastatic disease from nongynecologic malignancy (eg, melanoma).

Endometritis and pelvic inflammatory disease — Endometritis (infection of the endometrium)  may be acute or chronic. Premenopausal women with chronic endometritis usually present with abnormal uterine bleeding, which may consist of intermenstrual bleeding, spotting, postcoital bleeding, or heavy prolonged periods. Vague, crampy lower abdominal pain may accompany the bleeding.   Women with acute endometritis frequently have fever, while it is less common in women with the chronic process.

Acute endometritis occurs postpartum in women with recent complications of pregnancy: spontaneous or induced abortion, premature rupture of membranes, intrauterine procedures, retained products of conception, or cesarean delivery. Symptoms include fever, uterine tenderness, foul lochia, and leukocytosis.

Endometritis may also occur after placement of an intrauterine contraception or with pelvic inflammatory disease. Lower abdominal pain is the cardinal presenting symptom of pelvic inflammatory disease. The onset of pain during or shortly after menses is particularly suggestive of this disorder. The abdominal pain is usually bilateral and rarely of more than two weeks' duration.

Bleeding diatheses (coagulation disorders)

 von Willebrand's disease is a relatively common inherited bleeding disorder that is characterized by a deficiency of a plasma protein that stabilizes factor VIII. It should be suspected in young women who present with menorrhagia from the onset of menarche, particularly if there is a family history of coagulopathy.

 Thrombocytopenia due to immune thrombocytopenia (ITP), hypersplenism, or systemic diseases, such as chronic renal failure, may cause menorrhagia. Uremia also causes anovulatory menstrual bleeding.

 Women with acute leukemia or who are undergoing chemotherapy for malignancy may develop a bleeding diathesis and heavy, prolonged uterine bleeding

 Advanced liver disease may cause reduced synthesis of vitamin K-dependent clotting factors, fibrinogen, and antithrombins.

 Anticoagulants enhance the volume of blood loss from menstruation or AUB. Menorrhagia has been reported in women taking SSRIs, presumably related to the effect of these agents on platelets .

Drugs

 

Contraception

 Contraceptive techniques that can cause abnormal vaginal bleeding include combination hormonal contraceptives, intrauterine contraception, and progestin-only contraceptives.

 Combination hormonal contraceptives — Intermenstrual (breakthrough) bleeding is the most common side effect of combination hormonal contraceptives. Its occurrence does not indicate a decrease in efficacy (unless the patient has been noncompliant), but reflects tissue breakdown as the endometrium adjusts to a new thin state in which it is fragile and atrophic. Unscheduled (breakthrough) bleeding is related to a relatively high progesterone-to-estrogen ratio and was less of a problem when high doses of estrogen were used because estrogen stabilizes the endometrium. The frequency of bleeding is independent of the type of progestin [16,17], and is increased in women who smoke cigarettes, probably due to the accelerated metabolism of estrogen caused by smoking [18]. Women should be cautioned that missing pills results in an increase in unscheduled bleeding, as well as a decrease in contraceptive efficacy

 Progestin-only contraceptives — Prolonged bleeding and spotting are common complications of progestin-only contraceptives, such as depo tmedroxyprogesterone acetate (Depo-Provera), the levonorgestrel-releasing intrauterine contraceptive, implantable progestin rods (eg, Implanon), and progestin-only pills. Bleeding tends to be an early complication of these methods; many women develop amenorrhea with continued use. The mechanism of progesterone-breakthrough bleeding is endometrial atrophy and ulceration due to insufficient estrogen.

Copper IUC — Copper IUCs cause a foreign body reaction in the uterus that creates an inflammatory response. The endometrium may hypertrophy at the site of inflammation with normal cyclic estrogen stimulation, resulting in intermenstrual bleeding.

Postmenopausal hormone therapy — Postmenopausal women who take postmenopausal hormone therapy may develop uterine bleeding; the frequency depends upon the regimen used .

Other — Drugs that can cause hyperprolactinemia may also cause abnormal uterine bleeding. Although severe hyperprolactinemia results in amenorrhea, mild degrees of hyperprolactinemia may cause oligomenorrhea and menstrual abnormalities.

Chemotherapy-induced thrombocytopenia can cause menorrhagia, while antipsychotic drugs may lead to anovulation and irregular bleeding.

Ruptured ovarian cyst — Symptoms include pain and light uterine bleeding (due to a drop in ovarian hormone levels).

 

 

 

Dr. Pinky Ronen, M.D.

950 Threadneedle, Suite 282

Houston, Texas 77079

713-464-4444 phone

713-465-9718 fax

 

 

 

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