Amenorrhea

Amenorrhea due to ovulatory dysfunction is usually secondary but may be primary if ovulation never begins—eg, because of a genetic disorder. If ovulation never begins, delayed puberty Delayed Puberty Delayed puberty is absence of sexual maturation at the expected time. Diagnosis is by measurement of gonadal hormones (testosterone and/or estradiol), luteinizing hormone, and follicle-stimulating... read more usually results, and development of secondary sexual characteristics is abnormal. Genetic disorders that confer a Y chromosome increase the risk of ovarian germ cell cancer.

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

Hypothalamic dysfunction may result in decreased GnRH production, which in turn may cause decreased gonadotropin production. A common cause is insufficient energy intake due to dietary restriction or strenuous exercise. 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 (2 Etiology references Amenorrhea (the absence of menstruation) can be primary or secondary. Primary amenorrhea is failure of menses to occur by age 15 years in patients with normal growth and secondary sexual characteristics... read more ).

Amenorrhea may also occur if patients have abnormalities that affect menstrual function or obstruct menstrual flow. Many patients with these conditions have normal reproductive endocrine function and may have ovulatory menstrual cycles.

The most common causes of amenorrhea due to reproductive tract abnormalities Some Causes of Ovulatory Amenorrhea include

Obstructive abnormalities cause primary amenorrhea and 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 uterine instrumentation (Asherman syndrome), cause secondary ovulatory amenorrhea.

History of present illness includes questions about menstrual function (see table Normal Menstrual Parameters Normal Menstrual Parameters* [ 2 Evaluation references Amenorrhea (the absence of menstruation) can be primary or secondary. Primary amenorrhea is failure of menses to occur by age 15 years in patients with normal growth and secondary sexual characteristics... read more ]):

Questions about associated symptoms or factors include

For adolescents and some young patients, questions about pubertal development should be included:

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

Past medical history should note risk factors for the following:

Medication history should include specific questions about current or past medications, such as the following:

Family history should include any cases of delayed puberty or genetic disorders, 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 calculate body mass index (BMI).

If pubertal development may be abnormal, secondary sexual characteristics are evaluated; breast and pubic hair development are staged using the Tanner method (see Sexual Maturation Sexual Maturation During adolescence (usually considered age 10 to the late teens), boys and girls reach adult height and weight and undergo puberty. For boys, see Sexual Differentiation, Adrenarche, and Puberty... read more ). If axillary and pubic hair is present, adrenarche has occurred.

A breast examination should be done to check for 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); it can be distinguished from other types of nipple discharge Nipple Discharge Nipple discharge is a common complaint in women who are not pregnant or breastfeeding, especially during the reproductive years. Nipple discharge is not necessarily abnormal, even among postmenopausal... read more by finding fat globules in the fluid using a low-power microscope.

Pelvic examination is done to check for enlargement of the uterus (possibly due to pregnancy or a tumor), ovaries, and clitoris (clitoromegaly). Pelvic examination findings also help determine whether estrogen has been deficient. In women of reproductive age, the presence of cervical mucus with spinnbarkeit (a stringy, stretchy quality) usually indicates adequate estrogen; thin, pale vaginal mucosa without rugae and pH > 6.0 indicates estrogen deficiency. In girls or some young women, examination may 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.

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, 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 or ovaries. Hypertrichosis 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 (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.

Finding black patches on the skin due to acanthosis nigricans is a possible sign of polycystic ovary syndrome Polycystic Ovary Syndrome (PCOS) Polycystic ovary syndrome is a clinical syndrome typically characterized by anovulation or oligo-ovulation, signs of androgen excess (eg, hirsutism, acne), and multiple ovarian cysts in the... read more (PCOS) or diabetes.

Clinicians should check for hypothermia, bradycardia, hypotension, and reduced subcutaneous fat, which suggest anorexia nervosa Anorexia Nervosa Anorexia nervosa is characterized by a relentless pursuit of thinness, a morbid fear of obesity, a distorted body image, and restriction of intake relative to requirements, leading to a significantly... read more , 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 Bulimia Nervosa Bulimia nervosa is characterized by recurrent episodes of binge eating followed by some form of inappropriate compensatory behavior such as purging (self-induced vomiting, laxative or diuretic... read more .

The following findings are of particular concern in patients with amenorrhea:

History and physical examination findings may suggest an etiology of amenorrhea, even before laboratory testing (see table Findings Suggesting Possible Causes of Amenorrhea Findings Suggesting Possible Causes of Amenorrhea ).

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 caused by ovulatory dysfunction (eg, due to a genetic disorder).

In secondary amenorrhea, clinical findings sometimes suggest a mechanism:

History and physical examination help direct testing.

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.

A pregnancy test is required, even before menarche, if it is possible that ovulation has started. Pregnancy should not be excluded based on sexual or menstrual history. The beta subunit of human chorionic gonadotropin should be measured with high-sensitivity urine tests or serum tests. Results of urine tests 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.

Additional blood tests that are commonly done (to exclude specific etiologies) include

Amenorrhea with high follicle-stimulating hormone (FSH) levels (hypergonadotropic hypogonadism) suggests ovarian dysfunction. Amenorrhea with low FSH levels (hypogonadotropic hypogonadism) suggests hypothalamic or pituitary dysfunction.

Mildly elevated levels of testosterone or DHEAS suggest PCOS, but levels can be elevated in women with hypothalamic or pituitary dysfunction and are sometimes normal in hirsute women with PCOS. 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.

If symptoms or signs suggest an underlying disorder, specific tests may be indicated. 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.