For a regular menstrual cycle, the median age of menarche is 12.77 years. The average interval between thelarche and menarche is about 2 years, and 90% of females menstruate by the time they have Tanner IV breast and pubic hair development. Most cycles occur between 21-35 days with 3-10 days of bleeding and 30-40 mL of blood loss. Anovulatory cycles and irregular menstrual patterns are common within 24 months of menarche.

Classification of menstrual disorders

Amenorrhea and oligomenorrhea (lack of bleeding or too little bleeding)

Dysmenorrhea (painful menstruation)

Menorrhagia (excessive bleeding)

Amenorrhea

Amenorrhea may be primary (ie, never menstruated) or secondary (ie, menarche, but no periods for 3 consecutive months). Primary amenorrhea is the absence of menstruation by age 16 years in the presence of normal pubertal development or by age 14 years in the absence of normal pubertal development. Evaluating for breast and uterine development in patients with a menstruation disorder is important. Secondary amenorrhea is more common than primary amenorrhea. The most common etiology is dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis.

Dysmenorrhea

Dysmenorrhea is a very common complaint and may be primary or secondary, though primary dysmenorrhea is more prevalent. Symptoms include crampy lower abdominal and pelvic pain radiating to the thighs and back without associated pelvic pathology. Dysmenorrhea is caused by prostaglandins during ovulatory cycles. Endometrial prostaglandin levels increase during the luteal and menstrual phases of the cycle, causing uterine contractions. Secondary dysmenorrhea is rare, and pain is associated with pelvic pathology (eg, bicornuate uterus, endometriosis, pelvic inflammatory disease, uterine fibroids).

Menorrhagia

Menstrual bleeding lasting more than 8-10 days and with blood loss of over 80 mL is considered excessive.

Pathophysiology:
Hormonal changes in the normal menstrual cycle

In the ovulatory cycle, the hypothalamus secretes gonadotrophin-releasing hormone (GnRH), which stimulates the pituitary to release follicle-stimulating hormone (FSH). This, in turn, causes an ovarian follicle to grow and mature. In mid cycle, a surge of luteinizing hormone (LH) occurs with a FSH surge resulting in ovulation. The developing follicle produces estrogen, which stimulates the endometrium to proliferate. After the ovum is released, FSH and LH levels fall, corpus luteum develops at the site of the ruptured follicle, and progesterone is secreted from the ovary. Progesterone causes the proliferating endometrium to differentiate and stabilize. Fourteen days after ovulation, menstruation results from endometrial shedding secondary to the rapid decline in the levels of estrogen and progesterone from the involuting corpus luteum.

Hormonal changes during anovulatory cycles

Anovulatory cycles are common in the first 2 years after menarche because of the immaturity of the HPO axis. They also can occur in a variety of pathological conditions.

In anovulatory cycles, the follicular growth occurs with the stimulation from FSH; however, due to lack of LH surge, ovulation fails to occur. Consequently, no corpus luteum is formed and no progesterone is secreted. The endometrium continues its proliferative phase excessively. When the follicle involutes, estrogen levels drop and estrogen withdrawal bleeding occurs. Most anovulatory cycles are regular with normal bleeding; however, the unstable proliferative endometrium can shed irregularly, resulting in prolonged heavy bleeding.

History:

• Amenorrhea

• Detailed history of pubertal development

• Family history of menarche, pubertal development

• History of weight loss, stress, exercise

• Detailed dietary history

• History of contraception, medications

• History suggestive of CNS disease (eg, headaches, visual changes)

• History of chronic illnesses (eg, Crohn disease)

• Dysmenorrhea

• Evaluation should include a detailed menstrual history and the relationship of the pain to the menstrual cycle.

• Ask about a family history of endometriosis.

• Ascertain the degree of incapacitation. If pain is mild and physical examination is normal, a pelvic examination is not indicated. If pain is severe and interferes with daily living, a pelvic examination is warranted. If a patient is sexually active, a pelvic examination is mandatory. Be suspicious of secondary dysmenorrhea if onset of dysmenorrhea occurs at menarche.

• Menorrhagia

• Date of menarche

• Menstrual calendar (invaluable)

   

• Sexual activity

• Use of hormones, such as oral contraceptive pills or depo-medroxyprogesterone acetate, and use of other medications such as coumadin, aspirin

• Chronic illnesses

• Bleeding disorders, including family and personal history

• CNS symptoms

• Acne, hirsutism

Physical:

• Amenorrhea

• Height, weight, and growth charts

• Breast development, pubic hair

• Syndromic appearance (eg, short stature, webbed neck)

• Visual fields, thorough neurologic examination, optic fundi

• Evidence of hyperandrogenism (eg, acne, hirsutism, clitoromegaly)

• Evidence of thyroid disease

• Evidence of chronic illnesses

• Evidence of pregnancy

• Menorrhagia

• Growth percentiles

• Palpation of thyroid

• Breast examination for galactorrhea

• Evidence of bleeding elsewhere

• Pelvic examination, if sexually active

Causes:

• Primary amenorrhea with absent breast development and present uterus

• Constitutional delay of puberty
• Hypothalamic dysfunction (eg, stress, anorexia, chronic illness, exercise)
• Pituitary failure
• Gonadal failure
• Gonadal dysgenesis (eg, Turner syndrome, Swyer syndrome)
• Gonadotrophin deficiency (eg, Kallmann syndrome)

• Primary amenorrhea with breast development and present uterus

• Hyperandrogenic amenorrhea
• Hypothalamic amenorrhea
• Hypothyroidism
• Hyperprolactinemia
• Outflow tract obstructions (eg, imperforate hymen, vaginal atresia)

• Primary amenorrhea with breast development and absent uterus

• Müllerian agenesis

   

• Androgen insensitivity

• Menorrhagia

• Anovulatory dysfunctional uterine bleeding (DUB)

• Immature HPO axis, adolescent DUB

• Hyperandrogenic chronic anovulation (eg, polycystic ovarian syndrome, adrenal hyperplasia)

• Pregnancy-related complications

• Sexually transmitted diseases

• Chronic illnesses

• Blood dyscrasia

• Trauma

• Drugs

• Endocrine disorders

• Neoplasms

Other Problems to be Considered:

Secondary amenorrhea and oligomenorrhea

Pregnancy
Hormonal contraception
Hypothalamic causes (eg, stress, exercise, eating disorder, chronic illness, drugs, tumor, obesity syndromes)
Pituitary causes (eg, hypopituitarism, tumor, infiltration, infarction)
Ovarian causes (eg, premature ovarian failure)
Androgen excess (eg, polycystic ovarian disease, adrenal hyperplasia, adrenal or ovarian tumor)
Other endocrine causes (eg, thyroid disease, Cushing disease)

Lab Studies:

• Amenorrhea

• Workup depends on patient history and physical findings.

• No studies are necessary for constitutional growth delay.

• Obtain a karyotype if the patient is syndromic or has evidence of ovarian failure.

• Obtain serum FSH levels. Differentiating central from peripheral causes is important. High levels of FSH indicate ovarian failure or gonadal dysgenesis; low levels indicate hypothalamic or pituitary causes.

• Obtain a bone age in primary amenorrhea.

• Obtain a serum prolactin level.

• Obtain thyroid function tests.

• Obtain urine beta-human chorionic gonadotropin levels. This is mandatory for secondary amenorrhea.

• For secondary amenorrhea, consider testing serum LH, serum testosterone, dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and serum cortisol.

• Menorrhagia

• Test for gonorrhea and chlamydia if patient is sexually active.

• Obtain a urine pregnancy test.

• Obtain a CBC with reticulocyte count.

• Obtain coagulation studies.

• Obtain a blood type and cross-match in very severe cases.

• Also consider testing for thyroid-stimulating hormone (TSH) level, FSH level, serum prolactin, and serum androgens if clinical evidence of hyperandrogenism is present.

Imaging Studies:

• Amenorrhea

• Consider MRI of the head if CNS symptoms or hyperprolactinemia are present.

• Consider pelvic ultrasound if absent uterus or structural anomalies are suspected.

• Dysmenorrhea: Ultrasonography and MRI may be helpful if secondary cause of dysmenorrhea is suspected.

• Menorrhagia: Consider a pelvic ultrasound if a mass or structural anomaly is suspected.

Medical Care:

• Amenorrhea

• Treatment depends on etiology. Direct therapy to the underlying cause.
• If the patient has a completely normal physical examination with secondary amenorrhea, consider administering medroxyprogesterone 10 mg daily for 5-10 days to see if withdrawal bleeding occurs. If this occurs, it indicates adequate levels of endogenous estrogen and normal anatomy.

• Dysmenorrhea

• Provide symptomatic relief with nonsteroidal anti-inflammatory drugs (eg, naproxen, ibuprofen) at the first sign of cramps.
• If nonsteroidal anti-inflammatory therapy fails, consider oral contraceptive pills for 3-6 months.

• Menorrhagia

• Most cases of menorrhagia fall under the category of DUB. In situations where a specific etiology is identified, treatment of the underlying cause is necessary.
• For patients with mild DUB, provide reassurance and observation. Instruct the patient to keep a menstrual calendar. Consider iron supplementation and antiprostaglandin medications during bleeding episodes.
• For patients with moderate DUB, prescribe combination oral contraceptive pills beginning with 4 monophasic 45-microgram pills a day and tapering down. Oral contraceptive pills usually are continued for 6 months. Medroxyprogesterone alone also may be used. Also administer oral iron and folic acid supplements.
• For patients with severe DUB, consider hospitalization and coagulation studies. Administer intravenous Premarin every 4 hours until the bleeding stops, up to 4 doses. Simultaneously administer a monophasic 35-microgram oral contraceptive pill q6h for 24-48 hours and then bid to complete a 28-day course. If Premarin does not stop bleeding after 4 doses, consider pelvic pathology. Examination under anesthesia and dilatation and curettage may be necessary.

Medications used in the management of menstrual disorders depend on the type of disorder and the etiology of the disorder.
Drug Category: Hormones -- In patients with secondary amenorrhea who have a completely normal physical examination, medroxyprogesterone can be used to diagnose anovulation as the cause of amenorrhea (progesterone challenge test). Estrogens are effective in controlling acute, profuse bleeding. Estrogen also induces formation of progesterone receptors, making subsequent treatment with progestins more effective.

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs) -- Blocks formation of prostacyclin, an antagonist of thromboxane, which is a substance that accelerates platelet aggregation and initiates coagulation.

Drug Category: Mineral supplementation -- Used to provide adequate iron for hemoglobin synthesis and replenish body stores.

Complications:

• Excessive or prolonged bleeding can result in anemia.

• Excessive stimulation of the endometrium by estrogens with chronic anovulation increases the risk of endometrial cancer. Treating patients intermittently with combination oral contraceptives or progestins is important.

Patient Education:

• Educate patients about proper maintenance of a menstrual calendar. This is an invaluable tool in the evaluation of menstrual disorders.