Amenorrhea

Amenorrhea (uh-men-o-REE-uh) is the absence of menstruation — one or more missed menstrual periods. Women who have missed at least three menstrual periods in a row have amenorrhea, as do girls who haven't begun menstruation by age 15.

The most common cause of amenorrhea is pregnancy. Other causes of amenorrhea include problems with the reproductive organs or with the glands that help regulate hormone levels. Treatment of the underlying condition often resolves amenorrhea.

Types

There are two types of amenorrhea:

Primary amenorrhea. This is when a young woman has not had her first period by the age of 16.

Secondary amenorrhea. This is when a woman who has had normal menstrual cycles stops getting her monthly period for 3 or more months.

Causes of primary amenorrhea

There are three main causes of primary amenorrhea:

• Chromosomal or genetic abnormalities can cause the ovaries to stop functioning normally. Turner syndrome, a condition caused by a partially or completely missing X chromosome, and androgen insensitivity syndrome, often characterized by high levels of testosterone, are two examples of genetic abnormalities that can delay or disrupt menstruation.1
• Hypothalamic (pronounced hahy-poh-thuh-LAM-ik) or pituitary (pronounced pi-TOO-i-ter-ee) problems in the brain and physical problems such as problems with reproductive organs can prevent periods from starting.
• Excessive exercise, eating disorders, extreme physical or psychological stress, or a combination of these factors can delay the onset of menstruation.

Causes of secondary amenorrhea

Secondary amenorrhea can result from various causes, such as:

• Natural causes.
  • Pregnancy is the most common cause.
  • Other natural causes include breastfeeding and menopause.
• Medications and therapies.
  • Certain birth control pills, injectable contraceptives, and intrauterine devices (IUDs) can cause amenorrhea. It can take a few months after stopping birth control for the menstrual cycle to restart and become regular.
  • Some medications, including certain antidepressants and blood pressure medications, can increase the levels of a hormone that prevents ovulation and the menstrual cycle.
  • Chemotherapy and radiation treatments for hematologic cancer (including blood, bone marrow, and lymph nodes) and breast or gynecologic cancer can destroy estrogen-producing cells and eggs in the ovaries, leading to amenorrhea. The resulting amenorrhea may be short-term, especially in younger women.
  • Sometimes scar tissue can build up in the lining of the uterus, preventing the normal shedding of the uterine lining in the menstrual cycle. This scarring sometimes occurs after a dilation and curettage (D&C), a procedure in which tissue is removed from the uterus to diagnose or treat heavy bleeding or to clear the uterine lining after a miscarriage, a cesarean section, or treatment for uterine fibroids.
• Hypothalamic amenorrhea. This condition occurs when the hypothalamus, a gland in the brain that regulates body processes, slows or stops releasing gonadotropin-releasing hormone (GnRH), the hormone that starts the menstrual cycle. Common characteristics of women with hypothalamic amenorrhea include:
  • Low body weight
  • Low percentage of body fat
  • Very low intake of calories or fat
  • Emotional stress
  • Strenuous exercise that burns more calories than are taken in through food
  • Deficiency of leptin, a protein hormone that regulates appetite and metabolism
  • Some medical conditions or illnesses
• Gynecological conditions. Unbalanced hormone levels are common features of certain conditions that have secondary amenorrhea as a main symptom. These can include:
  • Polycystic ovary syndrome (PCOS). PCOS occurs when a woman's body produces more androgens (a type of hormone) than normal. High levels of androgens can cause fluid-filled sacs or cysts to grow in the ovaries, interfering with the release of eggs (ovulation). Most women with PCOS either have amenorrhea or experience irregular periods, called oligomenorrhea (pronounced ol-i-goh-men-uh-REE-uh).
  • Fragile X-associated primary ovarian insufficiency (FXPOI). The term FXPOI describes a condition in which a woman's ovaries stop functioning before normal menopause, sometimes around age 40. FXPOI results from certain changes to a gene on the X chromosome. As many as 10% of women who seek treatment for amenorrhea have FXPOI.
• Thyroid problems. The thyroid is a small butterfly-shaped gland at the base of the neck, just below the Adam's apple. The thyroid produces hormones that control metabolism and play a role in puberty and menstruation. A thyroid gland that is overactive (called hyperthyroidism) or underactive (hypothyroidism) can cause menstrual irregularities, including amenorrhea.
• Pituitary tumor. Noncancerous tumors in the pituitary gland in the brain, which regulates the production of hormones that affect many body functions, including metabolism and the reproductive cycle, can interfere with the body's hormonal regulation of menstruation.

Symptoms

Primary or secondary amenorrhea (respectively) is considered to be present when a girl has:

• not developed menstrual periods by age 16; or
• a woman who has previously had a menstrual cycle stops having menstrual periods for three cycles in a row, or for a time period of six months or more and is not pregnant.

Other symptoms and signs may be present, which are highly variable and depend upon the underlying cause of the amenorrhea. For example, symptoms of hormonal imbalance or male hormone excess can include irregular menstrual periods, unwanted hair growth, deepening of the voice, and acne. Elevated prolactin levels as a cause of amenorrhea can result in galactorrhea (a milky discharge from the nipples that is not related to normal breastfeeding).

When should I seek medical care for amenorrhea?

It is always appropriate to seek medical attention for amenorrhea. Amenorrhea that is not related to pregnancy or the menopausal transition (time when there has been no menstrual periods for 12 consecutive months and no other biological or physiological cause can be identified, and the female is at the end of her biologically-determined child bearing years) should be further investigated to rule out serious conditions that may result in amenorrhea

Diagnoses

A health care provider will usually ask a series of questions to begin diagnosing amenorrhea, including:

• How old were you when you started your period?
• What are your menstrual cycles like? (What is the typical length of your cycle? How heavy or light are your periods?)
• Are you sexually active?
• Could you be pregnant?
• Have you gained or lost weight recently?
• How often and how much do you exercise?

Primary Amenorrhea

If you are older than 16 and have never had a period, your health care provider will do a thorough medical history and physical exam, including a pelvic exam, to see if you are experiencing other signs of puberty. Depending on the findings and on your answers to the questions above, other tests may be ordered to determine the cause of your amenorrhea.

Secondary Amenorrhea

If you are sexually active, your health care provider will likely order a pregnancy test. He or she will also perform a complete physical exam, including a pelvic exam.

You should contact your health care provider as soon as possible after you miss a period.

Other Tests You May Need:

• Thyroid function test. This test measures the amount of thyroid-stimulating hormone (TSH) in your blood, which can help determine if your thyroid is working properly. A thyroid gland that is overactive (hyperthyroidism) or underactive (hypothyroidism) can cause menstrual irregularities, including amenorrhea.
• Ovary function test. This test measures the amount of follicle-stimulating hormone (FSH) or luteinizing hormone (LH)—hormones made by the pituitary gland—in your blood to determine if your ovaries are working properly. Your health care provider may also evaluate the level of anti-Mullerian hormone (AMH), which is produced by the ovarian follicles. Higher levels of AMH may be associated with polycystic ovary syndrome (PCOS). Low or undetectable amounts of AMH may be associated with menopause or primary ovarian insufficiency.
• Androgen test. Androgens are sometimes called "male hormones" because men need higher levels of these hormones than woman do for overall health. However, both men and women need androgens to stay healthy. Your health care provider may want to check the level of androgens in your blood.
• High levels of androgens may indicate a woman has PCOS.
• Hormone challenge test. With this test, you will take a hormonal medication for seven to 10 days in an effort to trigger a menstrual cycle. Results from the test can tell your health care provider whether your periods have stopped because of a lack of estrogen.
• Screening for a premutation of the FMR1 gene. Changes in this gene can cause the ovaries to stop functioning properly, leading to amenorrhea.
• Chromosome evaluation. This test, also known as a karyotype, involves counting and evaluating the chromosomes from cells in the body to identify any missing, extra, or rearranged cells. Results from this evaluation can help determine the cause of the chromosomal abnormality causing primary or secondary amenorrhea.
• Ultrasound. This painless test uses sound waves to produce images of internal organs. This test can help determine if your reproductive organs are all present and shaped normally.
• Computed tomography (CT). CT scans combine many X-ray images taken from different directions to create cross-sectional views of internal structures. A CT scan can indicate whether your uterus, ovaries, and kidneys look normal.
• Magnetic resonance imaging (MRI). MRI uses radio waves with a strong magnetic field to produce detailed images of soft tissues within the body. Your health care provider may order an MRI to check for a pituitary tumor or to examine your reproductive organs.
• Hysteroscopy. In this procedure a thin, lighted camera is passed through your vagina and cervix to allow your health care provider to look at the inside of your uterus.

Your health care provider might use several of these tests to attempt to diagnose the cause of amenorrhea. In some cases, no specific cause for the amenorrhea can be found. This situation is called idiopathic amenorrhea.

Treatments

• In some women, nutritional deficiencies induced by dieting can cause amenorrhea. Such women should eat a properly balanced diet.
• In some women, excessive body weight can be the cause of amenorrhea. These women should restrict the amount of fat in their diet, and they should exercise moderately to maintain an ideal body weight.
• More than 8 hours of vigorous exercise a week may cause amenorrhea. A moderate exercise program may restore normal menstruation.
• In women with anorexia nervosa or excessive weight loss, normal menstrual cycles can often be restored by undergoing treatment to restore and maintain a healthy body weight.
• If amenorrhea is caused by emotional stress, finding ways to deal with stress and conflicts may help.
• Maintaining a healthy lifestyle by avoiding alcohol consumption and cigarette smoking is also helpful.

Medical Treatment

Treatment depends on the cause of amenorrhea. Once the cause is determined, treatment is directed at correcting the underlying disease, which should restore menstruation. In case of anatomical abnormalities of the genital tract, surgery may be indicated.

Some causes of amenorrhea can be managed by medical (drug) therapy. Examples include the following:

• Dopamine agonists such as bromocriptine (Parlodel) or pergolide (Permax), are effective in treating hyperprolactinemia. In most women, treatment with dopamine agonists medications restores normal ovarian endocrine function and ovulation.
• Hormone replacement therapy consisting of an estrogen and a progestin can be used for women in whom estrogen deficiency remains because ovarian function cannot be restored.
• Metformin (Glucophage) is a drug that has been successfully used in women with polycystic ovary syndrome to induce ovulation.
• In some cases, oral contraceptives may be prescribed to restore the menstrual cycle and to provide estrogen replacement to women with amenorrhea who do not wish to become pregnant. Before administering oral contraceptives, withdrawal bleeding is induced with an injection of progesterone or oral administration of 5-10 mg of medroxyprogesterone (Provera) for 10 days.

 Amenorrhea Surgery Options

Patient Comments Share Your Story

• Some pituitary and hypothalamic tumors may require surgery and, in some cases, radiation therapy.
• Women with intrauterine adhesions require dissolution of the scar tissue.
• Surgical procedures required for other genital tract abnormalities depend on the specific clinical situation

Emotional health concerns

Primary amenorrhea and the potential for impaired fertility affect the emotional health of the adolescent and her family. Adolescence encompasses a broad spectrum of emotional maturity, which needs to be considered in assessment and treatment. For the adolescent girl, a reproductive disorder impacts her developing sense of self, body-image, and sexuality, which, in turn, can affect her self-esteem and relationships with others.

Because of the sexual nature of a reproductive disorder, feelings of embarrassment, inadequacy, or protectiveness can make it difficult for families. Families should be encouraged to be open and honest regarding the condition and discouraged from keeping the diagnosis a secret.

The family is an emotional unit and a family systems approach to deal with health issues is most appropriate. Parents must first deal with their own feelings about the condition before they can help their child. They must also be provided with tools to build an ongoing conversation with their child. Physicians need to be culturally sensitive because in some cultures a woman's identity in adulthood as a mother could play a crucial role in her life. The objective is to help the adolescent girl formulate positive self-esteem and body image, despite impaired fertility.

References

• emedicine.medscape.com/article/252928-treatment
• emedicinehealth.com/amenorrhea/page4_em.htm
• chd.nih.gov/health/topics/amenorrhea/conditioninfo/Pages/diagnosed.aspx

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• Hormone Health Network: "Amenorrhea."
• National Institute of Child Health & Human Development: "Amenorrhea."