Amenorrhea

The most common causes of anovulatory amenorrhea Some Causes of Anovulatory Amenorrhea involve a disruption of the hypothalamic-pituitary-ovarian axis . Thus, causes include

Women with amenorrhea due to hypothalamic dysfunction have lower levels of serum leptin (an anorectic hormone produced by fat cells); lower levels may contribute to decreased gonadotropin production.

Anovulatory amenorrhea is usually secondary but may be primary if ovulation never begins—eg, because of a genetic disorder. If ovulation never begins, puberty and development of secondary sexual characteristics are abnormal. Genetic disorders that confer a Y chromosome increase the risk of ovarian germ cell cancer.

The most common causes of ovulatory amenorrhea Some Causes of Ovulatory Amenorrhea include

Obstructive abnormalities are usually accompanied by normal hormonal function. Such obstruction may result in

Because ovarian function is normal, external genital organs and other secondary sexual characteristics develop normally. Some congenital disorders (eg, those accompanied by vaginal aplasia or a vaginal septum) also cause urinary tract and skeletal abnormalities.

Some acquired anatomic abnormalities, such as endometrial scarring after instrumentation for postpartum hemorrhage or infection (Asherman syndrome), cause secondary ovulatory amenorrhea.

History of present illness includes the following:

Review of systems should cover symptoms suggesting possible causes, including the following:

Patients with primary amenorrhea are asked about symptoms of puberty (eg, breast development, growth spurt, presence of axillary and pubic hair) to help determine whether ovulation has occurred.

Past medical history should note risk factors for the following:

Drug history should include specific questions about use of drugs, such as the following:

Family history should include height of family members and any cases of delayed puberty or genetic disorders in family members, including Fragile X syndrome Fragile X Syndrome Fragile X syndrome is a genetic abnormality on the X chromosome that leads to intellectual disability and behavioral disorders. Diagnosis is with molecular DNA analysis. Treatment is supportive... read more .

Clinicians should note vital signs and body composition and build, including height and weight, and should calculate body mass index (BMI). Secondary sexual characteristics are evaluated; breast and pubic hair development are staged using the Tanner method. If axillary and pubic hair is present, adrenarche has occurred.

With the patient seated, clinicians should check for breast secretion by applying pressure to all sections of the breast, beginning at the base and moving toward the nipple. Galactorrhea Galactorrhea Galactorrhea is lactation in any men or in women who are not breastfeeding. It is generally due to a prolactin-secreting pituitary adenoma. Diagnosis is by measurement of prolactin levels and... read more (breast milk secretion not temporally associated with childbirth) may be observed; it can be distinguished from other types of nipple discharge by finding fat globules in the fluid using a low-power microscope.

Pelvic examination is done to detect anatomic genital abnormalities (eg, imperforate hymen, vaginal septum, vaginal, cervical, or uterine aplasia). A bulging hymen may be caused by hematocolpos, which suggests genital outflow obstruction. Pelvic examination findings also help determine whether estrogen has been deficient. In postpubertal females, thin, pale vaginal mucosa without rugae and pH > 6.0 indicate estrogen deficiency. The presence of cervical mucus with spinnbarkeit (a stringy, stretchy quality) usually indicates adequate estrogen. Clinicians should check for enlargement of the uterus, ovaries, and clitoris.

General examination focuses on evidence of virilization, including hirsutism Hirsutism and Hypertrichosis Hirsutism is the excessive growth of thick or dark hair in women in locations that are more typical of male hair growth patterns (eg, mustache, beard, central chest, shoulders, lower abdomen... read more , temporal balding, acne, voice deepening, increased muscle mass, clitoromegaly (clitoral enlargement), and defeminization (a decrease in previously normal secondary sexual characteristics, such as decreased breast size and vaginal atrophy). Virilization results from increased androgen production by the adrenal glands and ovaries. Hypertrichosis (excessive growth of hair on the extremities, head, and back), which is common in some families, is differentiated from true hirsutism, which is characterized by excess hair on the upper lip and chin and between the breasts.

Skin discoloration (eg, yellow due to jaundice or carotenemia, black patches due to acanthosis nigricans) should be noted.

Clinicians should check for hypothermia, bradycardia, hypotension, and reduced subcutaneous fat, which suggest anorexia nervosa, and for dental erosion, palatal lesions, reduced gag reflex, subconjunctival hemorrhage, and subtle hand changes with calluses on the dorsum of the hand (due to frequent vomiting), which suggest bulimia.

The following findings are of particular concern:

In primary amenorrhea, the presence of normal secondary sexual characteristics usually reflects normal hormonal function; amenorrhea is usually ovulatory and typically due to a congenital anatomic genital tract obstruction. Primary amenorrhea accompanied by abnormal secondary sexual characteristics is usually anovulatory (eg, due to a genetic disorder).

In secondary amenorrhea, clinical findings sometimes suggest a mechanism (see table Findings Suggesting Possible Causes of Amenorrhea Findings Suggesting Possible Causes of Amenorrhea ):

History and physical examination help direct testing.

Pregnancy should not be excluded based on history; a pregnancy test is required. High-sensitivity urine tests should be done, and occasionally, a blood test may be required. Results are usually accurate several days before a missed menstrual period and often as early as several days after conception. Some over-the-counter (OTC) tests are less sensitive and accurate.

If girls have secondary sexual characteristics, a pregnancy test should be done to exclude pregnancy and gestational trophoblastic disease as a cause of amenorrhea. Women of reproductive age should have a pregnancy test after missing one menses.

The approach to primary amenorrhea (see algorithm Evaluation of primary amenorrhea Evaluation of primary amenorrhea [a] ) differs from that to secondary amenorrhea (see algorithm Evaluation of secondary amenorrhea Evaluation of secondary amenorrhea* ), although no specific general approaches or algorithms are universally accepted.

If patients have primary amenorrhea and normal secondary sexual characteristics, testing should begin with pelvic ultrasonography to check for congenital anatomic genital tract obstruction. MRI may be needed if abnormalities are identified.

If symptoms or signs suggest a specific disorder, specific tests may be indicated regardless of what an algorithm recommends. For example, patients with abdominal striae, moon facies, a buffalo hump, truncal obesity, and thin extremities should be tested for Cushing syndrome Cushing Syndrome Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more . Patients with headaches and visual field defects or evidence of pituitary dysfunction require brain MRI.

If clinical evaluation suggests a chronic disease, liver and kidney function tests are done, and erythrocyte sedimentation rate (ESR) is determined.

Often, testing includes measurement of hormone levels; total serum testosterone or dehydroepiandrosterone sulfate (DHEAS) levels are measured only if signs of virilization are present. Certain hormone levels should be remeasured to confirm the results. For example, if serum prolactin is high, it should be remeasured; if serum follicle-stimulating hormone (FSH) is high, it should be remeasured monthly at least twice. Amenorrhea with high FSH levels (hypergonadotropic hypogonadism) suggests ovarian dysfunction; amenorrhea with low FSH levels (hypogonadotropic hypogonadism) suggests hypothalamic or pituitary dysfunction.

If patients have secondary amenorrhea without virilization and have normal prolactin and FSH levels and normal thyroid function, a trial of estrogen and a progestogen to try to stimulate withdrawal bleeding can be done (progesterone challenge test).

The progesterone challenge test begins by giving medroxyprogesterone 5 to 10 mg orally once a day or another progestogen for 7 to 10 days.

However, because this trial takes weeks and results can be inaccurate, diagnosis of some serious disorders may be delayed significantly; thus, brain MRI should be considered before or during the trial.

Mildly elevated levels of testosterone or DHEAS suggest polycystic ovary syndrome, but levels can be elevated in women with hypothalamic or pituitary dysfunction and are sometimes normal in hirsute women with polycystic ovary syndrome. The cause of elevated levels can sometimes be determined by measuring serum luteinizing hormone (LH). In polycystic ovary syndrome, circulating LH levels are often increased, increasing the ratio of LH to FSH.