Menstrual and Bleeding Disorders

In this section, we review the following conditions:

• Fibroids

• Menstrual and Bleeding Disorders

• Postmenopausal Bleeding

• Endometriosis

Fibroids

Fibroids (uterine leiomyomas) are common benign tumors of the uterus, made of smooth muscle cells and fibroblasts.

(Adapted from Uterine Fibroids. N Eng J Med 2015.)

• Risk factors include a family history of fibroids, early menarche, black or Asian race, and obesity.

• Timing: Fibroids are controlled by estrogen and progesterone. Therefore, they are almost never seen prior to menarche and typically regress with improvement of symptoms after menopause.

  • Submucosal and intramural fibroids are more likely to decrease pregnancy rates, although evidence is inconclusive.

• Clinical presentation: Fibroids vary in size and clinical presentation, with many being asymptomatic. Clinical presentation can include heavy menstrual bleeding, pelvic pain, and infertility.

• Diagnosis: Fibroids can be suspected clinically and on physical exam with confirmation by ultrasound; occasionally MRI is needed to further characterize inconclusive lesions.

• Referral: Red-flag symptoms that should prompt specialty referral include:

  • intermenstrual or postcoital bleeding

  • sudden onset of pain

  • increase in fibroid size in postmenopausal women

• Treatment: Symptomatic patients may desire treatment. Treatment options depend on the number, size, and location of fibroids; desired outcome; and desire for preservation of fertility. The evidence comparing these options is relatively limited. Treatment options include:

  • medical therapy:

    • to reduce active symptoms (bleeding and cramping): levonorgestrel intrauterine device, subdermal implant, or other hormonal contraceptives; in addition to reducing bleeding and fibroid size, the progesterone-receptor modulator ulipristal acetate also improved quality-of-life measures in a pooled analysis

    • to decrease fibroid size: ulipristal acetate, gonadotropin-releasing hormone agonists

  • surgery: hysterectomy, myomectomy

    • Preoperative medical therapy with gonadotropin-releasing hormone agonists or ulipristal acetate before surgery for fibroids has been found to improve surgical outcomes.

  • interventional therapy: uterine-artery embolization

(Source: Uterine Fibroids. N Engl J Med 2015.)

Menstrual and Bleeding Disorders

Common menstrual and bleeding abnormalities include the following:

• menorrhagia: excessively heavy menstrual flow

• metrorrhagia: uterine bleeding at irregular intervals

• oligomenorrhea: infrequent menstrual periods

• amenorrhea: absence of a menstrual period

Menorrhagia and Abnormal Uterine Bleeding in Premenopausal Women

The PALM-COEIN classification system categorizes etiologies of abnormal uterine bleeding as related to structural and nonstructural abnormalities.

(Source: Management of Acute Abnormal Uterine Bleeding in Nonpregnant Reproductive-Aged Women. Obstet Gynecol 2013. Reprinted with permission.)

Clinical classification of uterine bleeding categorizes uterine bleeding as ovulatory or anovulatory bleeding.

• Ovulatory bleeding: Differential diagnosis includes:

  • normal menses with longer cycles (causing increased estrogen exposure)

  • coagulopathy

  • structural causes (fibroids, malignancy)

  • thyroid disease

  • endometriosis

(Source: Abnormal Uterine Bleeding in Premenopausal Women. Am Fam Physician 2019.)

• Anovulatory bleeding: Differential diagnosis is the same for oligomenorrhea and amenorrhea, including pregnancy, thyroid disease, premature ovarian failure, perimenopause, and use of hormonal contraception.

  • Up to 13% of women with heavy menstrual bleeding have some variant of von Willebrand syndrome, and up to 20% have underlying coagulation disorder. Initial workup includes a thorough history, including heavy bleeding since menarche, postpartum hemorrhage, surgery-related bleeding, bleeding with dental work, easy bruising, and epistaxis.

  • All women older than 45 years, or women younger than 45 years with history of obesity or unopposed estrogen exposure, with abnormal uterine bleeding should be referred for endometrial tissue sampling.

  • Treatment depends on the etiology of the bleeding.

  • For acute bleeding, only one treatment (intravenous [IV]-conjugated estrogen) is approved by the FDA.

  • For chronic treatment for menorrhagia, medical options include combined hormonal contraceptive (pill, patch, or ring), oral or injectable (subcutaneous or intramuscular) progestins, a subdermal implant or levonorgestrel intrauterine device (IUD), and/or tranexamic acid.

  • See the American College of Obstetricians and Gynecologists (ACOG) guidelines for additional information on treatment options.

(Source: Evaluation and Management of Abnormal Uterine Bleeding in Premenopausal Women. Am Fam Physician 2012. Reprinted with permission.)

Postmenopausal Bleeding

Any woman with vaginal bleeding after menopause requires evaluation to exclude malignancy. All women should be referred to an obstetrician/gynecologist or clinician capable of performing endometrial biopsy.

ACOG recommendations for postmenopausal bleeding are as follows:

• Perform initial assessment with endometrial biopsy or transvaginal ultrasonography.

• Endometrial sampling is not recommended for endometrial thickness ≤4 mm.

• Further evaluation is required for endometrial thickness ≥4 mm.

Secondary Amenorrhea

• Secondary amenorrhea is defined as the cessation of regular menses for 3 months or irregular menses for 6 months.

• Pregnancy is the most common cause of secondary amenorrhea and should be excluded in all cases.

• Polycystic ovary syndrome and hypothalamic amenorrhea are other common causes.

• Workup may include serum levels of luteinizing hormone, follicle-stimulating hormone (FSH), prolactin, and thyroid-stimulating hormone (TSH).

(Source: Amenorrhea: A Systematic Approach to Diagnosis and Management. Am Fam Physician 2019.)

Endometriosis

Endometriosis is the presence of endometrial-like tissue outside the uterus. Endometrial implants appear almost anywhere, although they are primarily found in the peritoneum, on the ovaries, and occasionally on and above the diaphragm. The exact mechanisms underlying the development of endometriosis remain unclear but are likely to involve a number of processes.

Presentation: Common clinical presentation includes pelvic pain, dyspareunia, bladder and bowel symptoms, dysmenorrhea, and infertility.

Diagnosis and staging: Laparoscopic visualization and biopsy with histological confirmation are ideal. Transvaginal ultrasound and MRI can both detect ovarian endometriomas but are less sensitive at identifying peritoneal or ovarian implants.

Treatment:

• First-line treatment for endometriosis is traditionally medical management; oral contraceptive pill hormonal therapy is widely used. However, subdermal contraceptive implants and injectable contraceptives are also effective.

• Second-line treatments include systemic estrogen suppression with gonadotrophin-releasing hormone (GnRH) agonists; however, the hypoestrogenic adverse effects of bone loss make these less desirable.

• Elagolix, a GnRH antagonist, has been approved for treatment of endometriosis; studies suggest it is associated with reduced dysmenorrhea and nonmenstrual-related pelvic pain in women with endometriosis-associated pain.

• Ovarian suppression with lactation has recently been found to decrease the risk of incident endometriosis.

(Source: Endometriosis. N Engl J Med 2010.)