Amenorrhea (pronounced ey-men-uh-REE-uh or uh-men-uh-REE-uh) is the medical term for the lack of a menstrual period. Amenorrhea is not a disease, but it can be a symptom of another condition.
Primary amenorrhea occurs when a girl has not had her first period by age 16. Secondary amenorrhea describes women who experience an absence of more than three menstrual cycles after having regular periods.
Primary amenorrhea. This describes a young woman who has not had a period by age 16.
Secondary amenorrhea. This occurs when a woman who once had regular periods experiences an absence of more than three cycles. Causes of secondary amenorrhea include pregnancy.
Having regular periods is an important sign of overall health. Missing a period, when not caused by pregnancy, breastfeeding, or menopause, is generally a sign of another health problem. If you miss your period, talk to your health care provider about possible causes, including pregnancy.
What are the symptoms of amenorrhea?
Missing a period is the main sign of amenorrhea.
Depending on the cause, a woman might have other signs or symptoms as well, such as:
Excess facial hair
Hair loss
Headache
Lack of breast development
Milky discharge from the breasts
Vision changes
Who is at risk of amenorrhea?
According to the American Society for Reproductive Medicine, amenorrhea that is not caused by pregnancy, breastfeeding, or menopause occurs in a small percentage (less than 5%) of women during their lifetime.
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
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
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.
Lin, K. & Barnhart, K. (2007). The clinical rationale for menses-free contraception. Journal of Women's Health, 16(8), 1171–1180.
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.
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/
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
How is amenorrhea diagnosed?
A health care provider will usually ask a series of questions to begin diagnosing amenorrhea, including:1
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?
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 the amenorrhea can be found. This situation is called idiopathic (pronounced id-ee-uh-PATH-ik) amenorrhea.6
Citations
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
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.
Warren, M. P., & Fried, J. L. (2001). Hypothalamic amenorrhea. The effects of environmental stresses on the reproductive system: A central effect of the central nervous system. Endocrinology & Metabolism Clinics of North America, 30, 611−629. Retrieved May 31, 2016, from http://www.ncbi.nlm.nih.gov/pubmed/11571933
What are the treatments for amenorrhea?
The treatment for amenorrhea depends on the underlying cause, as well as the health status and goals of the individual.
If primary or secondary amenorrhea is caused by lifestyle factors, your health care provider may suggest changes in the areas below:
Weight. Being overweight or severely underweight can affect your menstrual cycle. Attaining and maintaining a healthy weight often helps balance hormone levels and restore your menstrual cycle.
Stress. Assess the areas of stress in your life and reduce the things that are causing stress. If you can't decrease stress on your own, ask for help from family, friends, your health care provider, or a professional listener such as a counselor.
Level of physical activity. You may need to change or adjust your physical activity level to help restart your menstrual cycle. Talk to your health care provider and your coach or trainer about how to train in a way that maintains your health and menstrual cycles.
Be aware of changes in your menstrual cycle and check with your health care provider if you have concerns. Keep a record of when your periods occur. Note the date your period starts, how long it lasts, and any problems you experience. The first day of bleeding is considered the first day of your menstrual cycle.
For primary amenorrhea, depending on your age and the results of the ovary function test, health care providers may recommend watchful waiting. If an ovary function test shows low follicle-stimulating hormone (FSH) or luteinizing hormone (LH) levels, menstruation may just be delayed. In females with a family history of delayed menstruation, this kind of delay is common.1
Primary amenorrhea caused by chromosomal or genetic problems may require surgery. Women with a genetic condition called 46, XY gonadal dysgenesis have one X and one Y chromosome, but their ovaries do not develop normally. This condition increases the risk for cancer developing in the ovaries. The gonads (ovaries) are often removed through laparoscopic surgery to prevent or reduce the risk of cancer.2
Treatment for secondary amenorrhea, depending on the cause, may include medical or surgical treatments or a combination of the two.
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.
Citations
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
Verkauskas, G., Macianskyte, D., Janciauskas, D., Preiksa, R. T., Verkauskiene, R., & Jaubert, F. (2009). Diagnosis and management of 46,XY mixed gonadal dysgenesis and disorder of sexual differentiation. Medicina,45(5), 357–364. Retrieved May 31, 2016, from http://www.ncbi.nlm.nih.gov/pubmed/19535881
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.
Gambadauro, P., Gudmundsson, J., & Torrejon, R. (2012). Intrauterine adhesions following conservative treatment of uterine fibroids. Obstetrics and Gynecology International,2012, 1–6. Retrieved May 31, 2016, from http://www.hindawi.com/journals/ogi/2012/853269/
NICHD Amenorrhea Research Goals
NICHD's research efforts related to amenorrhea address its underlying causes and recognize it as an important indicator of women's health. NICHD-supported research focuses on amenorrhea within the context of investigating ovarian function in conditions such as Fragile X-associated primary ovarian insufficiency (FXPOI) and polycystic ovary syndrome (PCOS), as well as infertility.
NICHD research on amenorrhea includes (but is not limited to):
Genetics of puberty. NICHD-supported studies on genetic mutations examine how mutations disrupt puberty and affect fertility.1
Role of gonadotropin-releasing hormone (GnRH) deficiency in amenorrhea. Researchers are studying the genetic basis of functional hypothalamic amenorrhea to understand if this reversible deficiency, commonly triggered by excessive exercise, nutritional deficits, or stress, is genetically induced.2
Impact of, treatment therapies for, and role of FMR1 premutation in FXPOI and ovarian function.3 Research goals related to amenorrhea and ovarian function include:
Understanding the role of the FMR1 repeat expansion in ovarian function and reproductive aging
Establishing longitudinal studies examining the course of FXPOI from menstrual irregularities to associated symptoms such as estrogen deficiency and consequent osteoporosis, and cardiovascular risk
Determining the symptoms that may trigger an FMR1diagnostic test
Raising awareness of amenorrhea as an important symptom for conditions such as FXPOI, PCOS, and infertility
Effects of gynecologic disorders such as PCOS on fertility rates and the prevention of infertility from these disorders. NICHD research is seeking to understand how these disorders may affect the choice of infertility treatments.3
Citations
Caronia, L. M., Martin, C., Welt, C. K., Sykiotis, G. P., Quinton, R., Thambundit, A., et al. (2011). A genetic basis for functional hypothalamic amenorrhea. New England Journal of Medicine, 364, 215−225. Retrieved May 31, 2016, from http://www.nejm.org/doi/full/10.1056/NEJMoa0911064#t=articleTop
Through its intramural and extramural organizational units, NICHD supports and conducts a broad range of research projects on amenorrhea and conditions for which amenorrhea is a symptom. Short descriptions of this research are included below.
Several NICHD organizational units support and conduct research on amenorrhea and the conditions for which it is a symptom.
The NICHD Unit on Reproductive and Regenerative Medicine, part of the Program in Reproductive and Adult Endocrinology (PRAE) within the NICHD Division of Intramural Research (DIR), leads numerous studies to advance understanding of primary ovarian insufficiency (POI) and Fragile X-associated ovarian insufficiency (FXPOI). In one study, researchers were able to slow an immune system attack on the ovaries of mice by "teaching" the animals' immune systems to recognize the ovarian protein MATER (a maternal antigen that embryos require) as part of its own tissues. Researchers hope to one day be able to screen and explore fertility-sparing options in women who are at risk for autoimmune FXPOI. Other studies focus on the increased risk for osteoporosis in women with FXPOI as compared to normally menstruating women. A late diagnosis of FXPOI contributes to reduced bone density by delaying proper therapy. Additional studies by this NICHD research group focus on the menstrual cycle as an indicator of overall health.
The Unit on Reproductive Endocrinology and Infertility, also within the NICHD DIR, is studying loss of ovarian function and secondary amenorrhea among women who receive chemotherapy for cancer. Recent studies indicate that mice pretreated with gonadotropin-releasing hormone (GnRH) therapy prior to chemotherapy had their ovarian function preserved and restored after chemotherapy ended. A clinical trial is under way to determine whether giving GnRH therapy to women prior to chemotherapy also restores ovarian function after the therapy ends.
The Fertility and Infertility (FI) Branch supports the Reproductive Medicine Network (RMN), which studies PCOS and other conditions that may include secondary amenorrhea as a symptom. In addition, the Branch supports studies on neuroendocrine regulation of menstruation in women with and without related conditions, such as PCOS; on the regulation of pubertal onset and factors, including lifestyle issues such as caloric restriction or excessive exercise or stress, that influence menstruation initiation or cycling; and on physiological processes beyond pregnancy, breastfeeding, and menopause that may cause or contribute to amenorrhea.
The National Centers for Translational Research in Reproduction and Infertility (NCTRI) (Formerly the Specialized Cooperative Centers Program in Reproduction and Infertility Research [SCCPIR]) is a national network of research-based centers, supported through the FI Branch, that promote interactions between basic and clinical scientists, with the goal of improving reproductive health. Several NCTRI sites study amenorrhea as a condition and as a symptom of other conditions such as polycystic ovary syndrome (PCOS).
The FI Branch also supports the Fertility Preservation Research Program, which funds research on several areas. These include the incidence and prevalence of infertility in women who have undergone chemotherapy or radiation therapy, which can cause short- and long-term amenorrhea, and the development of biomarkers and clinical parameters to better predict ovarian reserve and thus the potential success of in vitro fertilization (IVF).
Through the NCTRI, NICHD also supports the Human Endometrial Tissue and DNA Bank. The Tissue Bank stores donated human endometrial tissue, blood, and DNA as a resource for researchers to use in in vitro and in situ studies and experiments. Specimens are catalogued according to histology and clinical parameters.
Citations
Sjaarda, L. A., Mumford, S. L., Kissell, K., Schliep, K. C., Hammoud, A. O., Perkins, N. J., et al. (2014). Increased androgen, anti-Müllerian hormone, and sporadic anovulation in healthy, eumenorrheic women: a mild PCOS-like phenotype? Journal of Clinical Endocrinology and Metabolism, 99(6), 2208–2216. Retrieved November 7, 2016, from https://www.ncbi.nlm.nih.gov/pubmed/24606085
Mumford, S. L., Schisterman, E. F., Siega-Riz, A. M., Gaskins, A. J., Steiner, A. Z., Daniels, J. L., et al. (2011). Cholesterol, endocrine and metabolic disturbances in sporadic anovulatory women with regular menstruation. Human Reproduction, 26(2), 423–430. Retrieved November 7, 2016, from https://www.ncbi.nlm.nih.gov/pubmed/21115506
Hambridge, H. L., Mumford, S. L., Mattison, D. R., Ye, A., Pollack, A. Z., Bloom, M. S., et al. (2013). The influence of sporadic anovulation on hormone levels in ovulatory cycles. Human Reproduction, 28(6), 1687–1694. Retrieved November 7, 2016, from https://www.ncbi.nlm.nih.gov/pubmed/23589536