What Is Amenorrhea – Causes, Symptoms, Treatment

Primary amenorrhea (failure of menses to occur by age 16) can result from two main causes:

• 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.^1,2
• Problems with the hypothalamus or pituitary gland in the brain can cause an imbalance of hormones that can prevent periods from starting. Conditions such as eating disorders, excessive exercise, and extreme physical or psychological stress or a combination of these factors can also disrupt the normal functioning of the hypothalamus or pituitary gland, delaying the onset of menstruation.

In rare cases, physical problems—such as missing reproductive organs or blockage of reproductive passageways—can also lead to primary amenorrhea. Missing portions of the reproductive tract can cause endocrine disruptions and may combine with hypothalamic or pituitary problems to prevent menstruation. Blockages may also prevent menstrual bleeding, making it seem like a girl has primary amenorrhea, even if her menstrual cycles are actually normal.³

Secondary amenorrhea (missing three menstrual periods in a row or not having periods for at least 6 months after menstruating normally) can result from various causes, such as:

• Natural causes.
  • Pregnancy is the most common natural cause of secondary amenorrhea.
  • Other physiologic causes include breastfeeding and menopause.
• Medications and therapies.
  • Certain birth control pills, injectable contraceptives, and hormonal intrauterine devices (IUDs) can cause amenorrhea. It can take a few months after stopping one of these types of 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.⁴
  • 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.⁵
  • 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,⁶ 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.⁷ Common characteristics of women with hypothalamic amenorrhea include:⁸
  • 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, specifically those that lead to or result from hormone imbalances, may also have secondary amenorrhea as a main symptom.
  • 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. FXPOI is fairly common among women who seek treatment for amenorrhea.⁵
• 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.⁹ A thyroid gland that is overactive (called hyperthyroidism) or underactive (hypothyroidism) can cause menstrual irregularities, including amenorrhea.¹⁰
• Pituitary tumors. The pituitary gland in the brain regulates the production of hormones that affect many body functions, including metabolism and the reproductive cycle. Tumors on the pituitary gland are usually noncancerous (benign) but can interfere with the body’s hormonal regulation of menstruation.¹⁰

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.

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.

• Thyroid function test.^1,2,3 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.^1,2,3,4 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).⁴ Low or undetectable amounts of AMH may be associated with menopause or primary ovarian insufficiency.
• Androgen test.^1,2,3 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.^1,2,3
• Hormone challenge test.^1,2,3 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.⁵ Changes in this gene can cause the ovaries to stop functioning properly, leading to amenorrhea.
• Chromosome evaluation.^1,2,3 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.^1,2,3 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).^1,2,3 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).^1,2,3 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.^1,2,3 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 amenorrhea can be found. This situation is called idiopathic (pronounced id-ee-uh-PATH-ik) amenorrhea.⁶

Common medical treatments for secondary amenorrhea include:³

• Birth control pills or other types of hormonal medication. Certain oral contraceptives may help restart the menstrual cycle.
• Medications to help relieve the symptoms of PCOS. Clomiphene citrate (CC) therapy is often prescribed to help trigger ovulation.⁴
• Estrogen replacement therapy (ERT). ERT may help balance hormonal levels and restart the menstrual cycle in women with primary ovarian insufficiency (POI) or Fragile X-associated primary ovarian insufficiency (FXPOI).⁵ Women with FXPOI often experience symptoms of menopause, such as hot flashes and night sweats. ERT replaces the estrogen a woman’s body should be making naturally for a normal menstrual cycle. In addition, ERT may help women with FXPOI lower their risk for the bone disease osteoporosis.⁶ ERT can increase the risk for uterine cancer, so your health care provider may also prescribe progestin or progesterone to reduce this risk.

In general, medications are safe, but they can have side effects, some of which may be serious. You should discuss side effects and risks with your health care provider before deciding on any specific medical treatment.

Surgical treatment for amenorrhea is not common, but may be recommended in certain conditions. These include:

• Uterine scarring. This scarring sometimes occurs after removal of uterine fibroids, a cesarean section, or 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.⁷ Removal of the scar tissue during a procedure called a hysteroscopic resection can help restore the menstrual cycle.⁸

Pituitary tumor. Medications may be recommended to shrink the tumor. If this does not work, surgery may be necessary to remove the tumor. Pituitary tumors are not cancerous, but they can cause problems as they grow. Pituitary tumors can put pressure on surrounding blood vessels and nerves such as the optic nerve and may result in loss of vision.

Most of the time, pituitary tumors are removed through the nose and sinuses. Radiation therapy may be used to shrink the tumor, either in combination with surgery or, for those who cannot have surgery, by itself.