INTRODUCTION — Menstrual cycle disorders can cause a woman's periods to be absent or infrequent. Although some women do not mind missing their menstrual period, these changes should always be discussed with a healthcare provider because they can signal underlying medical conditions and have long-term health consequences. A woman who misses more than three menstrual periods (either consecutively or over the course of a year) should see a healthcare provider.
DEFINITIONS
Amenorrhea — Amenorrhea refers to the absence of menstrual periods, and is classified as primary (when menstrual periods have not started by age 16) or secondary (when menstrual periods are absent for more than three to six months in a woman who previously had periods).
Oligomenorrhea — Oligomenorrhea refers to infrequent menstrual periods (fewer than six to eight periods per year).
The causes, evaluation, and treatment of amenorrhea and oligomenorrhea are similar, and will be discussed together.
CAUSES — The brain (including the pituitary gland), ovaries, and uterus normally follow a sequence of events once per month; this sequence helps to prepare the body for pregnancy. Two hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH), are made by the pituitary gland. Two other hormones, progesterone and estrogen, are made by the ovaries.
During the first half of the cycle, small increases in FSH stimulate the ovary to develop a follicle (cyst) that contains an egg (oocyte). The follicle produces rising levels of estrogen, which cause the lining of the uterus to thicken and the pituitary to release a very large amount of LH. This midcycle "surge" of LH causes the egg to be released from the ovary (called ovulation, show figure 1).
Menstrual cycle disorders can result from conditions that affect the hypothalamus, pituitary gland, ovaries, uterus, cervix, or vagina.
Primary amenorrhea — Many of the conditions that cause primary amenorrhea are present at birth, but may not be noticed until puberty. These conditions include genetic or chromosomal abnormalities and structural abnormalities (eg, if the uterus is not present or developed abnormally) of the reproductive tract.
Functional hypothalamic amenorrhea can also cause primary amenorrhea. This occurs when the hypothalamus slows or stops releasing GnRH (gonadotropin releasing hormone), a hormone that influences when a woman has a menstrual period. The hypothalamus is sensitive to many factors, including low body weight (defined as weighing 10 percent below ideal body weight, show table 1A-1B), having very little body fat, a very low calorie or fat intake, emotional stress, strenuous exercise, and some medical conditions or illnesses. When GnRH production slows or stops, a woman may stop having regular menstrual periods. For example, a woman who is training to run a marathon may stop menstruating until she is no longer training intensively.
Other causes of primary amenorrhea, such as prolactin-secreting tumors of the pituitary gland, are less common. All of the conditions that lead to secondary amenorrhea can also cause primary amenorrhea.
Secondary amenorrhea — Pregnancy is the most common of secondary amenorrhea. Among nonpregnant women, ovarian conditions are the most common cause of secondary amenorrhea; these conditions include polycystic ovary syndrome and ovarian failure (early menopause).
Functional hypothalamic amenorrhea is also a common cause of secondary amenorrhea (see above).
Prolactin-secreting pituitary tumors are another common cause of secondary amenorrhea. (See "Patient information: Lactotroph adenomas (prolactinomas)").
Oligomenorrhea — Many of the conditions that cause primary or secondary amenorrhea can also cause oligomenorrhea. However, most women who develop infrequent periods have polycystic ovary syndrome (see "Polycystic ovary syndrome" below).
EVALUATION — The approach to evaluating amenorrhea/oligomenorrhea will depend upon a woman's medical history and the results of a physical examination.
History — There are often clues about the cause of amenorrhea in a woman's personal and family medical history. Factors to consider include health during infancy and childhood, sexual development during puberty, as well as the family's growth and puberty patterns. The menstrual history will also be reviewed, including when the first period started (if there was a first period) and how frequently periods have occurred since.
Other important points include the presence of discharge from the breasts, hot flashes, masculine features, and headaches or impaired vision. The clinician will also ask about any medications, herbs, and vitamins used, recent stress, recent gynecologic procedures and events, changes in weight, diet, or exercise patterns, and any illnesses.
Physical examination — A physical examination can provide information about growth and sexual development, hormonal status, reproductive tract anatomy, and the presence of other medical conditions, such as thyroid disease or diabetes (both of which can cause menstrual cycle problems).
During a physical examination, the clinician will note the woman's height, weight, and arm span (measurement of length, when arms are extended, from one side to the other). The clinician will examine the thyroid gland, evaluate breast development, and perform a pelvic examination.
Testing — Depending upon the history and physical examination, the clinician may order laboratory test. Because pregnancy is the most common cause of secondary amenorrhea, a pregnancy test is usually recommended for women whose menstrual periods have stopped, even if the results of a home pregnancy test are negative. Blood tests to measure hormone levels may also be ordered.
In selected cases, magnetic resonance imaging (MRI) may be done to determine if there are hypothalamic or pituitary gland abnormalities. In women with a suspected chromosomal abnormality, a chromosome analysis may be recommended. A pelvic ultrasound is recommended to identify potential structural abnormalities of the uterus, cervix, and vagina.
TREATMENT — The goal of treatment is to correct the underlying condition. For a woman who is trying to become pregnant, returning fertility may be another goal.
The type and result of treatment depends upon the underlying cause of amenorrhea. In some cases, the results of the evaluation are unexpected (such as early menopause) and can be distressing; in these situations, counseling with a social worker or psychotherapist may be of benefit.
Anatomic problems — Surgery is often an effective treatment if amenorrhea is caused by an obstruction of the reproductive tract. Examples of obstructions that cause amenorrhea or oligomenorrhea include an imperforate hymen or vaginal septum. In both cases, corrective surgery is needed.
Imperforate hymen — The hymen is the tissue that surrounds the vaginal opening; some young girls lack an opening in the hymen, which causes menstrual blood to collect in the vagina.
Vaginal septum — A vaginal septum is a band of tissue that divides the vagina, either longitudinally or transversely. A transverse vaginal septum is similar to an imperforate hymen because it blocks the flow of menstrual blood, causing it to collect in the vagina.
In rare cases, evaluation may reveal underdeveloped or completely absent structures of the female reproductive tract (such as the vagina or uterus). These anatomic problems are usually caused by chromosomal abnormalities, and treatment options are limited.
Ovarian failure — Normally, a woman's ovaries stop releasing eggs around the age of 50; this is called menopause. If a woman's ovaries stop releasing eggs before age 40, this is called premature ovarian failure. When the ovaries fail, estrogen production stops, leading to amenorrhea and the symptoms and health risks associated with menopause.
Although the ovarian production of eggs cannot be restored , hormone replacement therapy (HRT) with estrogen and progesterone (or a hormonal contraceptive such as a birth control pill) can help prevent or treat many of the symptoms and long-term health consequences, such as hot flashes, vaginal dryness, and osteoporosis. HRT has risks of its own. However, a young (20 to 50 year old) woman who takes HRT does not have the same risks as a woman who is greater than 50 years old and takes HRT. Women considering this option should discuss the pros and cons with their healthcare provider. (See "Patient information: Postmenopausal hormone therapy and breast cancer").
Turner's syndrome — Women with Turner's syndrome have a chromosomal abnormality that causes ovarian failure at an extremely young age (before puberty). However, hormone replacement that begins at puberty can lead to normal breast development and menstrual cycles (induced by the hormones). Women with Turner's syndrome have a normal uterus.
With most types of ovarian failure, pregnancy can be achieved using donor eggs.
Polycystic ovary syndrome — Polycystic ovary syndrome (PCOS) is a chronic condition that causes infrequent periods and an excess of androgens (male hormones); this often leads to acne and excessive facial hair. Women with PCOS can also have problems with high cholesterol levels and obesity. Most healthcare providers recommend medical treatment to alleviate the symptoms of androgen excess, reestablish normal menstrual cycles, and prevent the long-term complications of this disorder (an increased risk of type 2 diabetes and possibly coronary heart disease). (See "Patient information: Polycystic ovary syndrome (PCOS)").
Functional hypothalamic amenorrhea — Women who have functional hypothalamic amenorrhea may resume having normal menstrual periods with certain lifestyle changes, including increasing caloric and/or fat intake, gaining weight, reducing the intensity or frequency of exercise, and resolving emotional stress. Low body weight and/or nutritional deficiencies — Women with eating disorders such as anorexia nervosa or bulimia often need specialized care. This usually includes nutrition counseling and work with eating disorder specialists. Strenuous exercise — Although exercise offers wonderful health benefits, exercising frequently or excessively can lead to amenorrhea and infertility. Studies suggest that amenorrhea develops when a woman's caloric intake is less than she burns with exercise and other daily activities, or when a woman's percentage of body fat drops below a critical level. Most women with amenorrhea associated with exercise have also lost weight (resulting in a weight less than 10 percent of the ideal body weight, show table 1A-1B).
For women with exercise-associated amenorrhea, the primary treatments include increasing calorie intake and reducing the frequency and/or intensity of exercise. These measures are particularly important if a woman is trying to become pregnant. All exercising women with amenorrhea should be sure they eat 1200 to 1500 mg of calcium daily (or take a calcium supplement) and should take a vitamin D supplement (400 IU daily). (See "Patient information: Calcium for bone health").
Some clinicians recommend estrogen and progestin hormone replacement (or a hormonal contraceptive such as a birth control pill) for women with amenorrhea who do not wish to cut back on exercise or increase caloric intake. Nonhormonal medications may be recommended to minimize potential bone loss. (See "Patient information: Osteoporosis prevention and treatment").
Hypothalamic or pituitary conditions — Some hypothalamic and pituitary gland conditions that cause amenorrhea, such as a congenital deficiency of gonadotropin-releasing hormone (GnRH), are irreversible. However, women with these conditions can have menstrual periods and become pregnant when treated with gonadotropins or gonadotropin-releasing hormone (GnRH). These hormones require a daily injection, and function to induce ovulation.
Hyperprolactinemia — Women with amenorrhea and hyperprolactinemia can usually regain normal menstrual periods and become pregnant when treated with medications called dopamine agonists (bromocriptine and cabergoline are examples).
Endometrial adhesions (Asherman syndrome) — Some gynecologic procedures, such as a dilatation and curettage (D&C), can result in formation of adhesions (a type of scar tissue) which damage the uterine lining. If adhesion formation is so extensive that most or all of the normal endometrium is replaced by adhesions, then menstrual blood loss will be reduced or stop. A clinician may recommend surgery to remove the scarred tissue, which is followed by estrogen treatment to stimulate regrowth of the lining. (See "Patient information: Dilation and curettage (D&C)").
Other medical conditions — Treatment of medical conditions, such as hypothyroidism and diabetes mellitus, may restore normal menstrual periods in women with amenorrhea.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Academy of Family Physicians
(www.familydoctor.org)
The Nemours Foundation
(www.kidshealth.org, search for menstrual)
The Hormone Foundation
(www.hormone.org)
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Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Laufer, MR, Floor, AE, Parsons, KE, et al. Hormone testing in women with adult-onset amenorrhea. Gynecol Obstet Invest 1995; 40:200.
2. Laughlin, GA, Dominguez, CE, Yen, SS. Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1998; 83:25.
3. Loucks, AB, Vaitukaitis, J, Cameron, JL, et al. The reproductive system and exercise in women. Med Sci Sports Exerc 1992; 24:S288.
4. Warren, MP, Voussoughian, F, Geer, EB, et al. Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating. J Clin Endocrinol Metab 1999; 84:873.
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