2006-Jul-27
by JACK DANIELS

There are 2 classifications of Amenorrhea: 1. Primary amenorrhea is defined as the failure of menses to occur by age 16 years. 2. Secondary amenorrhea is defined as the cessation of menses once they have begun. Oligomenorrhea is defined as menses occurring at intervals longer than 35 days. No consensus has been reached regarding the point at which oligomenorrhea becomes amenorrhea. Some authors suggest the absence of menses for 6 months constitutes amenorrhea, but the basis for this recommendation is unclear. Practically speaking, a woman aged 20-40 years who experiences loss of an established regular menstrual pattern should have an evaluation to seek the cause.

This reading addresses the evaluation and treatment of women with amenorrhea who have no evidence of androgen excess. Women with amenorrhea who do have evidence of androgen excess, such as hirsutism, virilization, or sexual ambiguity, should be evaluated differently from women with amenorrhea alone.

Amenorrhea occurs if the hypothalamus and pituitary fail to provide appropriate gonadotropin stimulation to the ovary, resulting in inadequate production of estradiol or in failure of ovulation and progesterone production. Amenorrhea can also occur if the ovaries fail to produce adequate amounts of estradiol despite normal and appropriate gonadotropin stimulation by the hypothalamus and pituitary. In some cases, the hypothalamus, pituitary, and ovaries all may be functioning normally, yet amenorrhea occurs because of adhesions in the endometrial cavity or an obstruction to the cervicovaginal outflow tract.

1. Primary Amenorrhea Primary amenorrhea However, the main cause is a delay in the beginning of puberty either from natural reasons (such as heredity or poor nutrition) or because of a problem in the endocrine system, such as a pituitary tumor or hypothyroidism. An obstructed flow tract or inflammation in the uterus may be the presenting indications of an underlying metabolic, endocrine, congenital or gynecological disorder.

Typical causes of primary amenorrhea include:

• excessive physical activity
• drastic weight loss (such as occurs in anorexia or bulimia)
• extreme obesity
• drugs (antidepressants or tranquilizers)
• chronic illness
• turner's syndrome. (A chromosomal problem in place at birth, relevant only in cases of primary amenorrhea)
• the absence of a vagina or a uterus
• imperforate hymen (lack of an opening to allow the menstrual blood through)

2.Secondary amenorrhea Some of the causes of primary amenorrhea can also cause secondary amenorrhea -- strenuous physical activity, excessive weight loss, use of antidepressants or tranquilizers, in particular. In adolescents, pregnancy and stress are two major causes. Missed periods are usually caused in adolescents by stress and changes in environment. Adolescents are especially prone to irregular periods with fevers, weight loss, changes in environment, or increased physical or athletic activity. However, any cessation of periods for four months should be evaluated.

The most common cause of seconardy amenorrhea is pregnancy. Also, a woman's periods may halt temporarily after she stops taking birth control pills. This temporary halt usually lasts only for a month or two, though in some cases it can last for a year or more. Secondary amenorrhea may also be related to hormonal problems related to stress, depression, anorexia nervosa or drugs, or it may be caused by any condition affecting the ovaries, such as a tumor. The cessation of menstruation also occurs permanently after menopause or a hysterectomy.

Causes of Amenorrhea Amenorrhea can have many causes. Primary amenorrhea can be the result of hormonal imbalances, psychiatric disorders, eating disorders, malnutrition, excessive thinness or fatness, rapid weight loss, body fat content too low, and excessive physical conditioning. Intense physical training prior to puberty can delay menarche (the onset of menstruation). Every year of training can delay menarche for up to five months. Some medications such as anti-depressants, tranquilizers, steroids, and heroin can induce amenorrhea.

Amenorrhea can be due to pregnancy, anatomic defects of the outflow tract, ovarian disorders, and pituitary or hypothalamic disorders. In some cases, the cause is functional, meaning that the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator has shut down the reproductive system in its role as an integrator of metabolic and psychogenic stress. Attributing the loss of menstrual regularity to a recent stressful life event is tempting; however, this approach can delay the detection of significant pathology that can have long-term health consequences. One study has shown that one third of control women report a significant stressful life event in the preceding year.

Pregnancy is the most common cause of amenorrhea. Determining whether the patient is sexually active and whether she is using contraceptive methods is important. In some cases, the hormonal contraception itself may be the cause of the amenorrhea.

• Disorders of the outflow tract

A history of otherwise normal growth and pubertal development in association with primary amenorrhea suggests the possibility of a congenital outflow tract abnormality such as imperforate hymen or agenesis of the vagina, cervix, or uterus. These findings are also compatible with the complete androgen resistance syndrome. Prior history of a surgical procedure involving the endometrial cavity, especially if performed in the presence of infection, raises the possibility of uterine synechiae (Asherman syndrome).

• Ovarian disorders

Symptoms of vaginal dryness, hot flashes, night sweats, or disordered sleep may be a sign of ovarian insufficiency or premature ovarian failure. The presence of these symptoms in young women demands timely further evaluation. Prior history of chemotherapy or radiation therapy may be associated with ovarian failure. A distinguishing factor in the case of isolated ovarian insufficiency or failure and primary amenorrhea is that adrenarche occurs normally while estrogen-dependent breast development and the pubertal growth spurt are absent or delayed.

• Hypothalamic/pituitary disorders

Associated galactorrhea, headaches, or reduced peripheral vision could be a sign of intracranial tumor. These symptoms require immediate further evaluation. A history of hemorrhage after childbirth can lead to failure of regular menses to return. This may be an indication of postpartum pituitary necrosis. Failure of lactation is an even earlier sign. Detecting this condition early is important because of the possible development of associated central adrenal insufficiency, a potentially fatal condition.

• *An impaired sense of smell in association with primary amenorrhea and failure of normal pubertal development may be related to isolated gonadotropin deficiency, as is observed in persons with Kallmann syndrome.

• *Sarcoidosis can manifest insidiously, with development of mild fatigue, malaise, anorexia, weight loss, and fever. Because 90% of patients with sarcoidosis have pulmonary involvement at some stage of the disorder, cough and dyspnea may be present.
• *Hemachromatosis may manifest as weakness, lassitude, weight loss, and a change in skin color.

• Functional impairment of the hypothalamic GnRH pulse generator

Dieting with excessive restriction of energy intake, especially fat restriction, may lead to loss of menstrual regularity and associated bone loss. In extreme cases, the process may advance to anorexia nervosa, a potentially fatal condition. Associated symptoms are an intense fear of fatness and a body image that is heavier than observed. Eating disorders can be restrictive in nature or can be of a binge-eating/purging type.

• *Major psychiatric disorders such as depression, obsessive-compulsive disorder, or schizophrenia may disrupt the menstrual cycle. Symptoms associated with these conditions may be detected upon review of systems.

• *Autoimmune adrenal insufficiency, a potentially fatal condition, often manifests as vague and nonspecific symptoms. Loss of menstrual regularity may be the first clear symptom indicating a need for further evaluation to detect this condition.

• *Loss of menstrual regularity may herald the onset of other autoimmune endocrine disorders such as hyperthyroidism, hypothyroidism, or autoimmune lymphocytic hypophysitis. The same is true for other endocrine disorders such as Cushing syndrome or pheochromocytoma. A careful review of symptoms may help uncover these disorders.

• *Strenuous exercise related to a wide variety of athletic activities can be associated with the development of amenorrhea. Elicit a history regarding the type of exercise activity and its duration per week.

• *Abuse of drugs such as cocaine and opioids have central effects that may disrupt the menstrual cycle.

• *Malnutrition and cirrhosis associated with alcoholism may cause loss of menstrual regularity.

• *AIDS, HIV disease, or other types of immune-deficiency states may induce systemic infection leading to chronic disease and loss of menstrual regularity.

• *Occult malignancy with progressive weight loss and a catabolic state may lead to loss of menstrual regularity. A careful review of systems may help uncover such a disorder.

Treatment Treatment of amenorrhea depends on the cause. Primary amenorrhea often requires no treatment, but it's always important to discover the cause of the problem in any case. Not all conditions can be treated, but any underlying condition that is treatable should be treated.

If a hormonal imbalance is the problem, progesterone for one to two weeks every month or two may correct the problem. With polycystic ovary syndrome, birth control pills are often prescribed. A pituitary tumor is treated with bromocriptine, a drug that reduces certain hormone (prolactin) secretions. Weight loss may bring on a period in an obese woman. Easing up on excessive exercise and eating a proper diet may bring on periods in teen athletes. In very rare cases, surgery may be needed for women with ovarian or uterine cysts.

Prognosis Prolonged amenorrhea can lead to infertility and other medical problems such as osteoporosis (thinning of the bones). If the halt in the normal period is caused by stress or illness, periods should begin again when the stress passes or the illness is treated. Amenorrhea that occurs with discontinuing birth control pills usually go away within six to eight weeks, although it may take up to a year.

The prognosis for polycystic ovary disease depends on the severity of the symptoms and the treatment plan. Spironolactone, a drug that blocks the production of male hormones, can help in reducing body hair. If a woman wishes to become pregnant, treatment with clomiphene may be required or, on rare occasions, surgery on the ovaries.

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