Amenorrhea

Definition

The absence of menstrual periods is called amenorrhea. Primary amenorrhea is the failure to start having a period by the age of 16. Secondary amenorrhea is more common and refers to either the temporary or permanent ending of periods in a woman who has menstruated normally in the past. Many women miss a period occasionally. Amenorrhea occurs if a woman misses three or more periods in a row.

Description

The absence of menstrual periods is a symptom, not a disease. While the average age that menstruation begins is 12, the range varies. The incidence of primary amenorrhea in the United States is just 2.5%.

Some female athletes who participate in rowing, long distance running, and cycling, may notice a few missed periods. Women athletes at a particular risk for developing amenorrhea include ballerinas and gymnasts, who typically exercise strenuously and eat poorly.

— Carol A. Turkington

Dictionary: a·men·or·rhe·a  (ā-mĕn'ə-rē'ə)

Abnormal suppression or absence of menstruation.

[A–¹ + Greek mēn, month + –RRHEA.]

Key Terms: Alkylating agents, Aplastic anemia, Asherman's syndrome, Autoimmune dysfunction, Craniopharyngioma, Crohn's disease, Imperforate hymen, Intermenstrual, Luteinizing hormone, Menopause, Menses/Menstruation, Polycystic ovary disease, Postcoital, Progestins.

Definition

Amenorrhea is the absence of menstruation and is a symptom, not a diagnosis.

Primary amenorrhea refers to the absence of the onset of menstruation by age 16 whether or not normal growth and secondary sexual characteristics are present, or the absence of menses after age 14 when normal growth and signs of secondary sexual characteristics are present. Secondary amenorrhea is the absence of menses for three cycles or six months in women who have previously menstruated.

In terms of the relationship of amenorrhea to cancer, amenorrhea may be a symptom of a gynecologic tumor, or the pause or cessation in menstruation may develop as a side effect of cancer treatment.

Demographics

The prevalence of primary amenorrhea is 0.3% and secondary amenorrhea occurs in approximately 1%–3% of women. However, among college students and athletes the incidence can range from 3%–5% and 5%–60%, respectively.

For cancer-related amenorrhea, one clinician noted that nine out of ten women under his care reported secondary amenorrhea following bone marrow transplants. Chemotherapy and abdominal-pelvic radiation therapy likewise produce similar outcomes.

Causes

Normal menstrual bleeding occurs between menarche and menopause and has an average length of 28 days but varies from woman to woman. The normal menstrual cycle depends on cyclic changes in estrogen and progesterone levels, as well as the integrity of the clotting system and the ability of the spiral arterioles in the uterus to constrict. Abnormalities in any of these components may cause bleeding to stop or increase.

Primary Amenorrhea

There are multiple causes for primary amenorrhea once pregnancy, lactation and missed abortion are ruled out. These include:

• anorexia nervosa/bulimia/malnutrition
• extreme obesity
• hyperthyroidism/hypoglycemia
• congenital heart disease
• cystic fibrosis/Crohn's disease
• genetic abnormalities
• obstructions: imperforate hymen/vaginal or cervical absence
• ovarian, pituitary (craniopharyngioma) or adrenal tumors
• polycystic ovarian disease
• testicular feminization

It is rare for primary amenorrhea to be caused by tumors but it can be a cause and should always be a consideration if other factors are ruled out.

Gonadal failure (a nonfunctioning sex gland) is the most common cause of primary amenorrhea, accounting for almost half the patients with this syndrome. The second most common cause is uterovaginal agenesis (absence of a uterus and/or vagina) with an incidence of about 15% of individuals with this syndrome. One of the most important, and probably most common, causes of amenorrhea in adolescent girls is anorexia nervosa, which occurs in about 1 in 1,000 white women. It is uncommon in women older than 25 and rare in women of both African and Asian descent. When women lose weight 15% below ideal body weight, amenorrhea can occur due to central nervous system-hypothalamic dysfunction. When weight loss drops below 25% ideal body weight, pituitary gonadotrophin function (follicle stimulating hormone and luteinizing hormone) can also become abnormal.

Each year of athletic training before menarche (the beginning of menstrual function) delays menarche about four to five months. Amenorrhea associated with strenuous exercise is related to stress, not weight loss, and is most probably caused by an increase in central nervous system endorphins and other compounds which interfere with gonadotrophin-releasing hormone release.

Secondary Amenorrhea

Once pregnancy, lactation and menopause are ruled out, the causes for secondary amenorrhea include:

• extreme obesity
• prolonged or extreme exercise
• anxiety or emotional distress
• non-oral contraceptives (Norplant/Depo-Provera)
• D&C (dilatation and curettage)(Asherman's syndrome)
• early menopause
• autoimmune dysfunction
• pituitary tumors and central nervous system lesions

Cancer and Secondary Amenorrhea

As mentioned, not only does amenorrhea occur as a symptom of a tumor and/or lesion, but it often develops in women undergoing treatment for cancer.

Radiation

Radiation therapy is used in conjunction with chemotherapy in a number of clinical situations, including Hodgkin's disease and childhood leukemia and lymphomas. Ovarian damage occurs under these circumstances to varying degrees, depending upon the total dosage of radiation as well as the age of the patient at the time of exposure.

CHEMOTHERAPY Premenopausal women receiving single or multi-agent chemotherapy are at risk for short-term amenorrhea, as well as ovarian damage. Even young women who resume menstruation following chemotherapy are at risk for early menopause; therefore, those treated in childhood and adolescence should be counseled regarding the chance of early menopause in order to plan ahead for childbearing.

WEIGHT LOSS Side effects of cancer as well as treatments can cause a decrease in appetite and nausea and vomiting, which, in turn, can cause severe weight loss as associated with malnutrition. Thus, menstruation may cease for the same reasons as it does in young adolescents with anorexia nervosa—hypothalamic dysfunction.

Stress

Stress has always been noted to play a large role in the cause of amenorrhea, so the actual stress of having cancer and undergoing treatments may also cause amenorrhea to occur.

Return of Normal Ovarian Function Following Treatment

Research on the recovery of normal ovarian function with young girls and/or young women has not revealed any reliable data. There are individual success stories especially with new advances in assisted reproductive technologies (ARTs), but overall, the return of normal ovarian function seems to be age-dependent. One researcher recently reported on ovarian function in 65 women who underwent high-dose chemotherapy and bone marrow transplants for aplastic anemia. All women younger than 26 years at the time of chemotherapy recovered ovarian function, while 7 of the 18 women aged 26 to 38 years did not recover ovarian function. Thus, the risk of ovarian dysfunction appears to increase with advancing age when ovarian reserve decreases. Additionally, the risk of dysfunction increases with the dose of alkylating agents, notably cyclophosphamide.

Treatments

Even with the possibility of ovarian compromise, women previously treated for cancer have successfully achieved pregnancy via ART's. Advances in the area of ART's include the use of donor eggs, the possibility of freezing embryos, and eventual oocyte (immature ovum) pretreatment offer more options to young women facing cancer chemotherapy.

Special Concerns

The need for effective contraception during and after cancer treatment is imperative. Normal menstrual cycles do not imply normal fertility and likewise, irregular menses or even amenorrhea does not imply a lack of fertility. Women with dysfunctional bleeding or amenorrhea are still capable of spontaneous ovulation and conception.

The most reliable form of birth control for any population of women is injectable progestins, which suppress luteinizing hormone secretion. Depo-Provera, 150 mg injected intramuscularly, will effectively block ovulation for four months. Norplant (six rubber capsules placed under anesthesia in the upper arm) will effectively block ovulation for five years. If the treatment or the specific cancer diagnosis contraindicates the use of either of these contraceptives, other options should be considered, i.e., sterilization for the woman or her partner, an intrauterine device (IUD), or barrier methods (condoms, diaphragm or spermicides).

Resources

Books

Jarvis, Carolyn. Physical Examination and Health Assessment. Philadelphia: W. B. Saunders Company, 2000.

Trimble, E. Cancer Obstetrics and Gynecology. Philadelphia: Lippincott William & Wilkins, 1999.

—Linda K. Bennington, C.N.S., M.S.N.

Cessation of menstruation, normally occurring between the ages of 40 and 55 (the menopause), but sometimes at an early age, especially as a result of severe under-nutrition (as in anorexia nervosa) when body weight falls below about 45 kg.

Absence of periods or menses (the flow of blood from the genital tract of women during menstruation). There are many causes of amenorrhoea including pregnancy, stress, weight loss and extreme thinness (amenorrhoea is one of the symptoms of anorexia), and high levels of exercise. The latter condition is sometimes called athletic amenorrhoea. It is relatively common among middle- and long-distance runners, gymnasts, and dancers who tend to have low body weights and a low percentage body fat. There is good evidence that menstruation ceases when the percentage of body fat falls below a critical level, but the relationship between fat levels and menstruation is not simple. Some extremely thin female athletes menstruate normally while others with a higher body fat content are amenorrhoeic. Athletic amenorrhoea is probably due to a number of factors, including the stress associated with regular, intense exercise.

Until recently, athletic amenorrhoea has been regarded as a harmless variation of the female rhythm since it does not affect long-term fertility. However, failure to menstruate over a long period of time is linked with reduced secretions of female hormones, such as oestrogens. These hormones are made in adipose tissue as well as the ovaries; therefore when the levels of body fat are very low, oestrogen production is reduced. Oestrogens are required for normal mineralization of bone. Low levels of female hormones in young women are associated with a weakening of bones, an increased risk of stress fractures, and osteoporosis. The situation is further exacerbated if the dietary intake of calcium is low. Nevertheless, people of all ages (except young amenorrheic women with low blood oestrogen levels) benefit from exercise, particularly when it is combined with a high calcium diet. It increases bone mineralization and reduces the risk of osteoporosis. See also menstruation.

The absence or abnormal cessation of the menstrual cycle.

Definition

Amenorrhea is the medical term for the absence of menstruation. There are two types of amenorrhea, primary and secondary. Primary amenorrhea refers to delayed menarche (the first menstrual period) and is defined as any one of three conditions:

• the absence of menarche by age 16 in a girl with otherwise normal pubertal development (development of breasts and/or pubic hair)
• the absence of menarche by age 14 combined with delayed pubertal development
• the absence of menarche two years after puberty is otherwise completed

Secondary amenorrhea is defined as the absence of menstruation after menarche has taken place. Although it is not uncommon for a girl's menstrual periods to be irregular during early adolescence, most girls' periods usually become regular within 18 months after the first one. After that time, it is considered abnormal for an adolescent to miss three consecutive periods.

Description

Normal menstrual periods are the result of proper functioning and synchronization of the hypothalamus, pituitary gland, and ovaries. The hypothalamus is the part of the brain that controls body temperature, cellular metabolism, and such basic functions as appetite for food, the sleep/wake cycle, and reproduction. The hypothalamus also secretes hormones that regulate the pituitary gland. The pituitary gland in turn produces hormones that stimulate the ovaries to secrete two hormones known as estradiol and progesterone. These ovarian hormones encourage the growth of the endometrium, which is the tissue that lines the uterus. If pregnancy does not occur, the endometrium breaks down and the uterus sheds the extra tissue during the next menstrual period.

Amenorrhea can result from an interruption at any of several points in the normal cycle:

• The hypothalamus and pituitary may fail to produce enough hormone to stimulate the ovaries to produce their hormones.
• The ovaries may fail to produce enough estradiol to stimulate the growth of the endometrium.
• There may be structural abnormalities in the uterus, cervix, or vagina that prevent the shed tissue from leaving the body.

Demographics

Secondary amenorrhea is more common in females in North America than primary amenorrhea. One study estimates that about 5 percent of menstruating women have an episode of secondary amenorrhea each year.

The average age for the onset of the menses in girls in the United States and Canada is 12.77 years. There is no evidence as of the early 2000s that the incidence of either primary or secondary amenorrhea is related to race or ethnic background.

Causes and Symptoms

Causes

There are a number of possible causes of amenorrhea:

• Pregnancy: An adolescent with amenorrhea most likely does not have a serious underlying medical problem. All teenagers with amenorrhea should seek medical care, and an adolescent who has had sexual intercourse even once and then missed a period should assume she is pregnant until a reliable pregnancy test proves otherwise. It should be noted that spotting or even bleeding is not unusual during early pregnancy. In addition, it is possible for a girl to conceive before she has had even one period.
• Disorders of the hypothalamus or the pituitary gland: These problems may be associated with brain tumors.
• Ovarian disorders: These disorders may include premature ovarian failure or may be the side effects of chemotherapy or radiation therapy for cancer. Premature ovarian failure accounts for about 10 percent of cases of secondary amenorrhea.
• Hyperandrogenism: The overproduction of male hormones (androgens) by the girl's body can interrupt menstruation. Male hormones are produced in small quantities by all women, but some individuals produce excessive amounts, leading to such conditions as polycystic ovarian syndrome (PCOS), hirsutism (excessive growth of body hair), or abnormalities of the external genitalia. PCOS in adolescents is often triggered by obesity.
• Genetic disorders: Some genetic disorders that affect the X chromosome, such as Turner's syndrome, prevent normal sexual maturation in girls.
• Psychiatric disorders: Depression, obsessive-compulsive disorder, eating disorders, and schizophrenia can all cause disturbances of the menstrual cycle.
• Abuse of alcohol or other drugs: Excessive alcohol intake can lead to malnutrition, while cocaine and opioids (narcotics) can affect the menstrual cycle directly.
• Immunodeficiency disorders or conditions.
• Emotional stress: This disturbance can interfere with the brain's hormonal signals to the ovaries. It is not uncommon for a girl's period to be delayed when she is having problems with school, work, or relationships. A change in environment (the first year of college or taking a new job, for example) can also cause a young woman's period to be late.
• Female athlete triad: Female athletes at the high school or college level are at increased risk for a triad of disorders: excessive dieting or disordered eating, amenorrhea, and loss of bone minerals leading to osteoporosis. The triad was first formally named in 1993 but had been known to doctors for decades before. Girls who are involved in sports that emphasize weight control or a slender body build (gymnastics, track and field, cheerleading) are at greater risk than those who play field hockey, basketball, softball, or other sports that emphasize strength.

Symptoms

Amenorrhea may be associated with the symptoms of other disorders; for example, girls with an eating disorder will often have eroded tooth enamel, tiny pinpoint hemorrhages around the eyes, an abnormal heart rhythm, low blood pressure, and other signs of frequent vomiting. Girls whose amenorrhea is part of the female athlete triad may have a record of bone fractures or other evidence of bone mineral loss. Hot flashes and night sweats may indicate premature ovarian failure. Headaches or visual disturbances may suggest a brain tumor.

When to Call the Doctor

Girls who have not had a menstrual period by age 16 or who have not shown any signs of breast development or other indications of puberty by age 14 should be examined for causes of primary dysmenorrhea. Girls who have begun to menstruate and have missed three periods should be evaluated for secondary amenorrhea. If they are sexually active, they should have a pregnancy test after missing even one period.

Diagnosis

History and Physical Examination

The first part of diagnosing amenorrhea is a careful history, including a record of medications and any surgical procedures involving the abdomen or genitals. The doctor will ask detailed questions about stress, dieting, sexual activity, and athletic participation, as well as questions about chronic diseases or disorders of the central nervous system. Family history should be taken into consideration in any adolescent with primary amenorrhea, as mothers who started to menstruate late will often have daughters who also menstruate late.

In the case of female athletes, the doctor may need to establish a relationship of trust with the patient before asking about such matters as diet, practice and workout schedules, and the use of such drugs as steroids or ephedrine. The presence of stress fractures in young women should be investigated. In some cases, the doctor may give the patient the Eating Disorder Inventory (EDI) or a similar screening questionnaire to help determine whether the patient is at risk for developing anorexia or bulimia.

The doctor will then perform a physical examination to evaluate the patient's weight in proportion to her height as well as her general nutritional status; to check for breast development, pubic hair, and other signs of normal female sexual development; to make sure the heart rhythm, blood pressure, and other vital signs are normal; and to palpate (feel) the thyroid gland for evidence of swelling. The physical examination may include a pelvic examination to check for abnormalities in the structure of the vagina or cervix.

Laboratory Tests

To rule out specific causes of amenorrhea, the doctor may order a pregnancy test in sexually active young women as well as blood tests to check the level of thyroid hormone. Based on the initial test results, the doctor may want to perform additional tests to determine the level of other hormones that play a role in reproduction. A special type of blood test called a karyotype may be done to analyze the girl's chromosomes if the doctor suspects Turner's syndrome or another genetic disorder.

One way to determine whether a teenager's ovaries and uterus are functioning is a progesterone challenge test. In this test, an amenorrheic teenager is given a dose of progesterone either orally or as an injection. If her ovaries are producing estrogen and her uterus is responding normally, she should have a menstrual period within a few days of the progesterone dose. This challenge indicates that the ovaries and uterus are functioning normally, and the cause of the amenorrhea is probably in the brain.

Imaging Studies

In some cases the doctor may order an ultrasound study of the pelvic region to check for anatomical abnormalities or x rays or a bone scan to check for bone fractures. In some cases the doctor may order an MRI to rule out tumors affecting the hypothalamus or pituitary gland.

Psychiatric Interview

Teenagers whose amenorrhea may be related to depression, family stress, eating disorders, or other mental health issues may be referred to a psychiatrist for further evaluation.

Treatment

The most frequent risk associated with amenorrhea is osteoporosis (thinning of the bone) caused by low estrogen levels. Because osteoporosis can begin as early as adolescence, hormone replacement therapy is sometimes recommended for teenagers with chronic amenorrhea.

Amenorrhea associated with hormonal, genetic, psychiatric, or immunodeficiency disorders may require a variety of different medications and other treatments administered by specialists. Tumors of the hypothalamus and the pituitary gland or abnormalities of the reproductive organs usually require surgery.

Alternative Treatment

As with conventional medical treatments, alternative treatments are based on the cause of the condition. If a hormonal imbalance is revealed by laboratory testing, hormone replacements that are more natural for the body (including tri-estrogen and natural progesterone) are recommended. Glandular therapy can assist in bringing about a balance in the glands involved in the reproductive cycle, including the hypothalmus, pituitary, thyroid, ovarian, and adrenal glands.

Since homeopathy and acupuncture work on deep energetic levels to rebalance the body, these two forms of therapy may be helpful in treating amenorrhea. Western and Chinese herbal medicines also can be very effective. Herbs used to treat amenorrhea include dong quai (Angelica sinensis), black cohosh (Cimicifuga racemosa), and chaste tree (Vitex agnus-castus). Herbal preparations used to bring on the menstrual period are known as emmenagogues. For some adolescents, meditation, guided imagery, and visualization can play a key role in the treatment of amenorrhea by relieving emotional stress.

Nutritional Concerns

Diet and adequate nutrition, including adequate protein, essential fatty acids, whole grains, and fresh fruits and vegetables are important for every female past puberty, especially if deficiencies are present or if she regularly exercises very strenuously. Girls who are abusing alcohol or other drugs should be evaluated for possible malnutrition as part of treatment for substance abuse.

Female athletes at the high school or college level should consult a nutritionist to make sure that they are eating a well-balanced diet that is adequate to maintain a healthy weight for their height. Girls participating in dance or in sports that emphasize weight control or a slender body type (gymnastics, track and field, swimming, and cheerleading) are at higher risk of developing eating disorders than those that are involved in such sports as softball, weight lifting, or basketball. In some cases the athlete may be given calcium or vitamin D supplements to lower the risk of osteoporosis.

Prognosis

The prognosis of either primary or secondary amenorrhea depends on the underlying cause.

Prevention

Amenorrhea related to pregnancy, the female athletic triad, drug or alcohol abuse, or eating disorders is preventable insofar as these are lifestyle choices. Primary or secondary amenorrhea associated with genetic mutations or other systemic diseases or disorders is not preventable.

Parental Concerns

Amenorrhea is a fairly dramatic symptom of menstrual dysfunction that often causes parents to consult a doctor about a girl's health. Parental concerns about amenorrhea, however, should be directed to the underlying cause. Amenorrhea related to emotional stress, dieting, or excessive exercise usually goes away when the stress is relieved or when the girl makes appropriate lifestyle adjustments. On the other hand, amenorrhea associated with glandular disturbances, tumors, genetic or anatomical abnormalities, diabetes, or other systemic disorders is part of a larger and more worrisome picture. Parents should discuss their concerns about the long-term effects of amenorrhea on the girl's health, whether she will be able to have children in adult life, and how they can help her manage her condition with the doctors, nutritionists, and other healthcare professionals who are treating her.

See also Anorexia nervosa; Bulimia nervosa; Menstruation; Oligomenorrhea; Sports.

Resources

Books

Diagnostic and Statistical Manual of Mental Disorders,4th edition, Text Revision. Washington, DC: American Psychiatric Association, 2000.

"Menstrual Abnormalities and Abnormal Uterine Bleeding." Section 18, Chapter 235 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers and Robert Berkow. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Pelletier, Kenneth R. "CAM Therapies for Specific Conditions: Menstrual Symptoms, Menopause, and PMS." In The Best Alternative Medicine, Part II. New York: Simon and Schuster, 2002.

Periodicals

Gordon, C. M., and L. M. Nelson. "Amenorrhea and Bone Health in Adolescents and Young Women." Current Opinion in Obstetrics and Gynecology 15 (October 2003): 377–84.

Khalid, A. "Irregular or Absent Periods: What Can an Ultrasound Scan Tell You?" Best Practice and Research: Clinical Obstetrics and Gynaecology 18 (February 2004): 311.

Seidenfeld, Marjorie E. K., and Vaughn J. Rickert. "Impact of Anorexia, Bulimia and Obesity on the Gynecologic Health of Adolescents." American Family Physician 64 (August 1, 2001): 445–50.

Warren, M. P., and L. R. Goodman. "Exercise-Induced Endocrine Pathologies." Journal of Endocrinological Investigation 26 (September 2003): 873–78.

Organizations

American Academy of Child and Adolescent Psychiatry. 3615 Wisconsin Avenue, NW, Washington, DC 20016–3007. Web site: www.aacap.org.

American College of Obstetricians and Gynecologists (ACOG). 409 12th Street, SW, PO Box 96920, Washington, DC 20090–6920. Web site: www.acog.org.

American College of Sports Medicine (ACSM). 401 West Michigan Street, Indianapolis, IN 46202–3233. Web site: www.acsm.org.

Web Sites

Barrow, Boone. "Female Athlete Triad." eMedicine, June 17, 2004. Available online at www.emedicine.com/sports/topic163.htm (accessed November 8, 2004).

Chandran, Latha. "Menstruation Disorders." eMedicine, August 9, 2004. Available online at www.emedicine.com/ped/topic2781.htm (accessed November 8, 2004).

Nelson, Lawrence M., et al. "Amenorrhea." eMedicine, August 9, 2004. Available online at www.emedicine.com/med/topic117.htm (accessed November 8, 2004).

[Article by: Gail Slap, MD]

For more information on amenorrhea, visit Britannica.com.

Absence of menses (blood flow during the menstrual cycle) for at least 3 months or less than 2 menstrual cycles in a year. Women over 18 years of age who have never started to menstruate are said to have primary amenorrhoea; those whose normal menstrual function has been lost for months or even years are said to have secondary amenorrhoea. Although its exact cause is not known, secondary amenorrhoea has been linked to stress and low body fat. It is common in middle- and long-distance runners who train intensively, and in athletes of appearance and weight-classification sports who restrict their diet. It was once regarded as a harmless variation of the gonadal rhythm, since its effects appear to be reversed when training is reduced and food intake increased, and it does not affect long-term fertility (in fact, even amenorrhoeic athletes can become pregnant). However, failure to menstruate for long periods may lead to hormonal alterations, decreasing oestradiol secretions, and increasing the risk to stress fractures and osteoporosis. Many questions still remain to be answered about the long-term effects of amenorrhoea on the skeletal integrity of female athletes.

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