What causes amenorrhea?

 

Amenorrhea is often a sign of another health problem rather than a disease itself, and it can happen for many reasons. It can occur as a natural part of life, such as during pregnancy or breastfeeding. It can also be a sign of a health problem, such as polycystic ovary syndrome (PCOS). Because amenorrhea is associated with health conditions that are also linked to infertility, understanding amenorrhea is an important part of NICHD's research on infertility and fertility.

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

Citations

  1. Pascal, P., Leprieur, E., Zenaty, D., Thibaud, E., Polak, M., Frances, A. M., et al. (2010). Steroidogenic factor-1 (SF-1) gene mutation as a frequent cause of primary amenorrhea in 46,XY female adolescents with low testosterone concentration. Reproductive Biology and Endocrinology, 8, 28.
  2. Lin, K. & Barnhart, K. (2007). The clinical rationale for menses-free contraception. Journal of Women's Health, 16(8), 1171–1180.
  3. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Gynecology. (2013). Practice bulletin no. 136: Management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstetrics and Gynecology, 122(1), 176–185.
  4. La Torre, D., & Falorni, A. (2007). Pharmacological causes of hyperprolactinemia. Therapeutic and Clinical Risk Management, 3, 929–951. Retrieved May 31, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376090/
  5. ACOG. (2014). ACOG Committee Opinion: Primary ovarian insufficiency in the adolescent. Retrieved May 31, 2016, from https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/07/primary-ovarian-insufficiency-in-adolescents-and-young-women external link
  6. ACOG. (2016). Dilation and curettage. Retrieved May 31, 2016, from https://www.acog.org/patient-resources/faqs/special-procedures/dilation-and-curettage external link (PDF 69 KB)
  7. Gordon, C. M. (2010). Functional hypothalamic amenorrhea. New England Journal of Medicine,363, 365–371.
  8. Hormone Health Network. (2011). Amenorrhea. Retrieved May 31, 2016, from https://www.hormone.org/diseases-and-conditions/womens-health/amenorrhea external link
  9. U.S. Department of Health and Human Services Office of Women's Health. (2015). Thyroid disease fact sheet. Retrieved May 31, 2016, from http://womenshealth.gov/publications/our-publications/fact-sheet/thyroid-disease.html
  10. Master-Hunter, T., & Heiman, D. L. (2006). Amenorrhea: Evaluation and treatment. American Family Physician,73, 1374–1382. Retrieved May 31, 2016, from http://www.aafp.org/afp/2006/0415/p1374.html external link
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