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Absence of Menstrual Periods

by JoAnn V. Pinkerton, MD

Having no menstrual periods is called amenorrhea. Amenorrhea is normal before puberty, during pregnancy, while breastfeeding, and after menopause. At other times, it may be the first symptom of a serious disorder.

Amenorrhea may be accompanied by other symptoms, depending on the cause. For example, women may develop masculine characteristics (virilization), such as excess body hair (hirsutism), a deepened voice, and increased muscle size. They may have headaches, vision problems, or a decreased sex drive. They may have difficulty becoming pregnant. In most women with amenorrhea, the ovaries do not release an egg. Such women cannot become pregnant.

If amenorrhea lasts a long time, problems similar to those associated with menopause may develop. They include hot flashes, vaginal dryness, decreased bone density (osteoporosis), and an increased risk of heart and blood vessel disorders. Such problems occur because in women who have amenorrhea, the estrogen level is low.

Types of amenorrhea

There are two main types of amenorrhea:

  • Primary: Menstrual periods never start.

  • Secondary: Periods start, then stop.

Usually if periods never start, girls do not go through puberty, and thus secondary sexual characteristics, such as breasts and pubic hair, do not develop normally.

If women have been having menstrual periods, which then stop, they may have secondary amenorrhea. Secondary amenorrhea is much more common than primary.

Hormones and menstruation

Menstrual periods are regulated by a complex hormonal system (see Overview of the Female Reproductive System). Each month, this system produces hormones in a certain sequence to prepare the body, particularly the uterus, for pregnancy. When this system works normally and there is no pregnancy, the sequence ends with the uterus shedding its lining, producing a menstrual period. The hormones are produced by the hypothalamus (part of the brain that helps control the pituitary gland), the pituitary gland (which produces luteinizing hormone and follicle-stimulating hormone), and the ovaries (which produce estrogen and progesterone ). Other hormones, such as thyroid hormones and prolactin (produced by the pituitary gland), can affect the menstrual cycle.

The most common reason for no menstrual periods is malfunction of any part of this hormonal system. Less commonly, the hormonal system is functioning normally, but another problem prevents periods from occurring. For example, menstrual bleeding may not occur because the uterus is scarred or because a birth defect, fibroid, or polyp blocks the flow of menstrual blood out of the vagina.

High levels of prolactin, which stimulates the breasts to produce milk, can result in no periods.

Causes

Amenorrhea can result from conditions that affect the hypothalamus, pituitary gland, ovaries, uterus, cervix, or vagina. These conditions include hormonal disorders, birth defects, genetic disorders, and drugs.

Which causes are most common depends on whether amenorrhea is primary or secondary.

Primary amenorrhea

The disorders that cause primary amenorrhea are relatively uncommon, but the most common are

  • A genetic disorder

  • A birth defect of the reproductive organs that blocks the flow of menstrual blood

Genetic disorders include Turner syndrome, Kallman syndrome, overproduction of male hormones by the adrenal glands (congenital adrenal hyperplasia), and disorders that result in ambiguous—neither male nor female—genitals (pseudohermaphroditism or true hermaphroditism). Genetic disorders and birth defects that cause primary amenorrhea may not be noticed until puberty. These disorders cause only primary amenorrhea, not secondary.

All disorders that cause secondary amenorrhea can cause primary amenorrhea.

Sometimes puberty is delayed in girls who do not have a disorder, and normal periods simply begin at a later age. Such delayed puberty may run in families.


Secondary amenorrhea

The most common causes are

  • Pregnancy

  • Breastfeeding

  • Malfunction of the hypothalamus

  • Polycystic ovary syndrome

  • Premature menopause (premature ovarian failure)

  • Malfunction of the pituitary gland

  • Use of certain drugs, such as birth control pills (oral contraceptives), antidepressants, or antipsychotic drugs

Pregnancy is the most common cause of amenorrhea among women of childbearing age.

The hypothalamus may malfunction for several reasons.Stress or excessive exercise (as done by competitive athletes, particularly women who participate in sports that involve maintaining a low body weight) may affect the hypothalamus, causing periods to stop. Poor nutrition (as occurs in women with eating disorders) and mental disorders (such as depression or obsessive-compulsive disorder) may cause the hypothalamus to malfunction. Radiation therapy or an injury may also damage the hypothalamus or cause it to malfunction.

The pituitary gland may malfunction because it is damaged or because levels of prolactin are high. Antidepressants, antipsychotic drugs, or certain other drugs can cause prolactin levels to increase, as can pituitary tumors and some other disorders.

Less common causes of secondary amenorrhea include chronic disorders (particularly of the lungs, digestive tract, blood, kidneys, or liver), some autoimmune disorders, thyroid disorders, cancer, HIV infection, radiation therapy, head injuries, a hydatidiform mole (overgrowth of tissue from the placenta), Cushing syndrome, and malfunction of the adrenal glands. Scarring of the uterus (usually due to an infection or surgery), polyps, and fibroids can also cause secondary amenorrhea.


Evaluation

Doctors determine whether amenorrhea is primary or secondary. This information can help them identify the cause.

Warning signs

Certain symptoms are cause for concern:

  • Delayed puberty

  • Development of masculine characteristics, such as excess body hair, a deepened voice, and increased muscle size

  • New or unusual headaches

  • Vision problems


When to see a doctor

Girls should see a doctor within a few weeks if

  • They have no signs of puberty (such as breast development or a growth spurt) by age 13.

  • Pubic hair has not appeared by age 14.

  • Periods have not started by age 16 or by 2 years after girls develop secondary sexual characteristics.

Such girls may have primary amenorrhea.

If women of childbearing age have had menstrual periods that have stopped, they should do a home pregnancy test. If the test is negative and if they have headaches or changes in vision, they should see a doctor within a week. Otherwise, they should see a doctor within a few weeks if

  • They are not pregnant and have missed 3 menstrual periods.

  • They have fewer than 9 periods a year.

  • The pattern of periods suddenly changes.

Such women may have secondary amenorrhea.


What the doctor does

Doctors first ask about the medical history, including the menstrual history. Doctors then do a physical examination. What they find during the history and physical examination often suggests a cause of amenorrhea and the tests that may need to be done (see Table: Some Causes and Features of Amenorrhea).

For the menstrual history, doctors determine whether amenorrhea is primary or secondary by asking the girl or woman whether she has ever had a menstrual period. If she has, she is asked how old she was when the periods started and when the last period occurred. She is also asked to describe the periods:

  • How long they lasted

  • How often they occurred

  • Whether they were ever regular

  • How heavy they were

  • Whether her breasts were tender or she had mood changes related to periods

If a girl has never had a period, doctors ask whether breasts have started to develop, whether she has had a growth spurt, and whether pubic and underarm hair (signs of puberty) has appeared. This information enables doctors to rule out some causes. Information about delayed puberty and genetic disorders in family members can help doctors determine whether the cause is a genetic disorder.

Doctors ask about other symptoms that may suggest a cause and about use of drugs, exercise, eating habits, and other conditions that can cause amenorrhea.

During the physical examination, doctors determine whether secondary sexual characteristics have developed. A breast examination is done. A pelvic examination is done to determine whether genital organs are developing normally and to check for abnormalities in reproductive organs. Doctors also check for symptoms that may suggest a cause such as

  • A milky discharge from both nipples: Possible causes include pituitary disorders and drugs that increase levels of prolactin (a hormone that stimulates milk production).

  • Headaches and partial loss of vision or double vision: Possible causes include tumors of the pituitary gland or hypothalamus.

  • Development of masculine characteristics, such as excess body hair, a deepened voice, and increased muscle size: Possible causes include polycystic ovary syndrome, tumors that produce male hormones, and use of drugs such as synthetic male hormones (androgens), antidepressants, or high doses of synthetic female hormones called progestins.

  • Hot flashes, vaginal dryness, and night sweats: Possible causes include premature menopause, a disorder that causes the ovaries to malfunction, radiation therapy, and use of a chemotherapy drug.

Some Causes and Features of Amenorrhea

Cause*

Common Features

Tests

Hormonal disorders

Hyperthyroidism (an overactive thyroid gland)

Warm, moist skin, difficulty tolerating heat, excessive sweating, an increased appetite, weight loss, bulging eyes, double vision, shakiness (tremor), and frequent bowel movements

Sometimes an enlarged thyroid gland (goiter)

Blood tests to measure thyroid hormone levels

Hypothyroidism (an underactive thyroid gland)

Difficulty tolerating cold, a decreased appetite, weight gain, coarse and thick skin, loss of eyebrow hair, a puffy face, drooping eyelids, fatigue, sluggishness, slow speech, and constipation

Blood tests to measure thyroid hormone levels

Pituitary disorders, including tumors that produce prolactin and injuries

Vision problems and headaches, particularly at night

Sometimes production of breast milk in men or in women who are not breastfeeding (galactorrhea)

Blood test to measure prolactin levels

MRI of the brain

Polycystic ovary syndrome

Development of masculine characteristics (such as excess body hair, a deepened voice, and increased muscle size)

Irregular or no menstrual periods, acne, excess fat in the torso, and dark, thick skin in the underarm, on the nape of the neck, and in skinfolds

Blood tests to measure hormone levels

Ultrasonography of the pelvis

Premature menopause

Symptoms of menopause, including hot flashes, night sweats, and vaginal dryness and thinning (atrophic vaginitis)

Risk factors such as removal of the ovaries, chemotherapy, or radiation therapy directed at the pelvis (the lowest part of the torso)

Blood tests to measure levels of estrogen and other hormones

For women under 35, examination of chromosomes in a sample of tissue (such as blood)

Tumors that produce male hormones (androgens), usually in the ovaries or adrenal glands

Development of masculine characteristics, acne, and genitals that are not clearly male or female (ambiguous genitals)

CT, MRI, or ultrasonography

Structural disorders

Birth defects:

  • Cervical stenosis (narrowing of the passageway through the cervix)

  • Imperforate hymen (an abnormal hymen that completely blocks the vagina's opening)

  • Transverse vaginal septum (a wall of tissue across the vagina, which prevents menstrual blood from flowing out)

  • Absence of reproductive organs

Primary amenorrhea

Normal development of breasts and secondary sexual characteristics

Abdominal pain that occurs in cycles and bulging of the vagina or uterus (because menstrual blood is blocked and accumulates)

A doctor's examination

Hysterosalpingography (x-rays taken after a dye is injected into the uterus and fallopian tubes) or hysteroscopy (insertion of a viewing tube through the vagina to view the uterus)

Asherman syndrome (scarring of the lining of the uterus due to an infection or surgery)

Secondary amenorrhea

Often repeated miscarriages and infertility

Ultrasonography, sonohysterography (ultrasonography after fluid is infused into uterus), or hysterosalpingography

Sometimes if results are unclear, MRI

Fibroids

Secondary amenorrhea

Pain, vaginal bleeding, constipation, repeated miscarriages, and an urge to urinate frequently or urgently

Ultrasonography

Polyps

Secondary amenorrhea

Vaginal bleeding

Ultrasonography

Conditions that cause the hypothalamus to malfunction

Excessive exercise

Often a low body weight and body fat

A doctor's examination

Mental disorders (such as depression or obsessive-compulsive disorder)

Withdrawl from usual activities

Sluggishness or sadness

Sometimes weight gain or weight loss, difficulty sleeping or too much sleep

A doctor's examination

Poor nutrition (as may result from poverty, eating disorders, or excessive dieting)

Often low body weight and body fat

A doctor's examination

Stress

A stressful life event, difficulty concentrating, worry, and sleep problems (too much or too little)

A doctor's examination

*Drugs can also cause amenorrhea (see Table below).

Features include symptoms and results of the doctor's examination. Features mentioned are typical but not always present.

High levels of prolactin (a hormone that stimulates the breasts to produce milk) can result in no periods.

CT = computed tomography; MRI = magnetic resonance imaging.

Drugs That Can Cause Menstrual Periods to Stop

Type

Examples

Symptoms

Drugs that can increase the production of prolactin

Antihypertensive drugs

Methyldopa

Reserpine

Verapamil

Production of breast milk in men or in women who are not breastfeeding

Antipsychotic drugs

Haloperidol

Molindone

Olanzapine

Phenothiazines

Pimozide

Risperidone

Illegal or recreational drugs

Cocaine

Hallucinogens

Estrogen

Drugs used to treat digestive disorders

Cimetidine

Metoclopramide

Opioids

Codeine

Morphine

Tricyclic antidepressants

Clomipramine

Desipramine

Drugs that affect the balance of female and male hormones

Synthetic androgens

Danazol

Development of masculine characteristics (such as excess body hair, a deepened voice, and increased muscle size)

Antidepressants (infrequently)

Paroxetine

Selegiline

Sertraline

Irregular bleeding


Testing

In girls or women of childbearing age, the first test is a pregnancy test. If pregnancy is ruled out, other tests are done based on results of the examination and the suspected cause.

Tests are usually done in a certain order, and causes are identified or eliminated in the process. Whether additional tests are needed and which tests are done depend on results of the previous tests. Typical tests include

  • Blood tests to measure levels of prolactin (to check for conditions that cause high levels), thyroid hormones (to check for thyroid disorders), follicle-stimulating hormone (to check for pituitary or hypothalamus malfunction), and male hormones (to check for disorders that cause masculine characteristics to develop)

  • Imaging tests of the abdomen and pelvis using computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography to look for a tumor in the ovaries or adrenal glands

  • Examination of chromosomes in a sample of tissue (such as blood) to check for genetic disorders

  • Imaging of the uterus and usually fallopian tubes (hysteroscopy or hysterosalpingography—see Diagnostic Procedures : Hysterosalpingography) to check for blockages in these organs

  • Use of hormones (estrogen and a progestin) to try and trigger menstrual bleeding

If hormones trigger menstrual bleeding, the cause is not a disorder of the uterus or a structural abnormality preventing menstrual blood from flowing out.

If symptoms suggest a specific disorder, tests for that disorder may be done first. For example, if women have headaches and vision problems, MRI of the brain is done to check for a pituitary tumor.


Treatment

When amenorrhea results from another disorder, that disorder is treated if possible. With such treatment, menstrual periods sometimes resume. For example, if an abnormality is blocking the flow of menstrual blood, it is usually surgically repaired, and periods resume. Some disorders, such as Turner syndrome and other genetic disorders, cannot be cured.

If a girl's periods never started and all test results are normal, she is examined every 3 to 6 months to check on the progression of puberty. She may be given a progestin and sometimes estrogen to start her periods and to stimulate the development of secondary sexual characteristics, such as breasts.

Problems associated with amenorrhea may require treatment, such as

Key Points

  • Various conditions can disrupt the complex hormonal system that regulates the menstrual cycle, causing menstrual periods to stop.

  • Doctors distinguish between primary amenorrhea (periods have never started) and secondary amenorrhea (periods started, then stopped).

  • The first test is a pregnancy test.

  • Unless a woman is pregnant, other testing is usually required to determine the cause of amenorrhea.

  • Problems related to amenorrhea (such as a low estrogen level) may also require treatment.

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • CRINONE
  • PAXIL
  • No US brand name
  • NORPRAMIN
  • ANAFRANIL
  • ZOLOFT
  • ORAP
  • CALAN
  • No brand name
  • HALDOL
  • RISPERDAL
  • ELDEPRYL
  • ZYPREXA
  • DURAMORPH PF, MS CONTIN
  • REGLAN
  • TAGAMET