Amenorrhea

Definition

Description

Amenorrhea, or the absence of menstrual periods, can be classified into two categories—primary and secondary. Primary refers to late onset of menstruation and includes girls who have not had a period by age 15 or 16. Secondary amenorrhea is the cessation of menstruation for three or more months. It is important to note that the absence of menstrual periods, in these cases of amenorrhea, is a symptom, not a disease. Missing three or more periods can also be sign of pregnancy, which also is labeled physiological amenorrhea.

Demographics

Primary amenorrhea occurs in less than 1% of women in the United States. Secondary amenorrhea is much more common, and occurs in approximately 5%-7% of women annually in the United States. Secondary amenorrhea might be more common in areas of the world where malnutrition is common, as malnutrition and low weight can lead to secondary amenorrhea. Ethnicity, however, does not appear to be a factor affecting the development of amenorrhea. Amenorrhea may affect as many as 20% of women seeking treatment for infertility.

Primary amenorrhea

Menarche, or a woman's first menstrual period, occurs on average between ages 12 and 13 years in the United States. Based on Tanner's stages of puberty for females, menarche typically occurs 2.3 years after breast development begins. Worldwide, the average age of menarche ranges from 12-16 years.

Primary amenorrhea is defined as any one of three conditions:

Secondary amenorrhea

Secondary amenorrhea is the absence of menstruation in a woman of reproductive age after menarche has taken place. Although it is common for menstrual periods to be irregular during early adolescence, menstruation usually becomes regular within 18 months after the first menstrual cycle. After regular periods are established, it is considered abnormal for a woman to miss three or more consecutive periods, except in the case of pregnancy.

Risk factors

Poor nutrition, low body weight, and strenuous physical training increase the risk of developing amenorrhea. Secondary amenorrhea is one of the symptoms of a condition called the female athlete triad, which includes an eating disorder, amenorrhea, and osteoporosis (thinning bones). This group of conditions is so common among young competitive female athletes that the National College Athletic Association has produced a handbook for coaches on how to recognize and manage this syndrome. Female athletes who participate in rowing, distance running, and cycling are especially prone to missing periods. Women athletes at particular risk for developing prolonged amenorrhea include ballerinas, gymnasts, and female jockeys who typically exercise strenuously and must maintain a low body weight. Individuals with eating disorders and hormonal imbalances are also at risk for developing amenorrhea.

Causes and symptoms

Normal menstrual bleeding occurs between menarche and menopause on average every 28 days, although timing varies somewhat from woman to woman. A normal menstrual cycle depends on cyclic changes in estrogen and progesterone levels, as well as the integrity of the clotting system and the ability of the arteries in the uterus to constrict. Abnormalities in any of these functions can cause bleeding to stop or increase.

Primary amenorrhea

The main cause of primary amenorrhea is a delay in the beginning of puberty either from natural reasons, such as heredity or poor nutrition, or because of a problem in the endocrine system, such as a pituitary tumor or hypothyroidism. An obstructed flow tract or inflammation in the uterus might indicate an underlying metabolic, endocrine, congenital, or gynecological disorder.

Typical causes of primary amenorrhea include:

Gonadal failure (a nonfunctioning sex gland) is the most common cause of primary amenorrhea, accounting for almost half the patients with this syndrome. The second most common cause is uterovaginal agenesis (absence of a uterus and/or vagina), with an incidence of about 15% of individuals with primary amenorrhea.

Secondary amenorrhea

EATING DISORDERS. One of the most important and common causes of amenorrhea in adolescent girls is anorexia nervosa, occurring in about four in 100 Caucasian females. As many as one-third of female athletes are at risk for anorexia, based on their attitudes about weight and their symptoms. Most girls with anorexia are white, and about three-fourths of them come from households at the middle-income level or above. In the 2010s, however, the number of African American and Hispanic females diagnosed with anorexia has increased. Competitive athletes of all races have an increased risk of developing anorexia nervosa, especially in sports where weight is tied to performance such as gymnastics, figure skating, and cheerleading. When weight loss drops below 75% of ideal body weight, pituitary gonadotropin function (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) levels can also become abnormal.

STRESS. Psychological stress is a common cause of missed periods, particularly in adolescents. It is common for a woman's period to be delayed when she is having problems with school, work, or relationships. A change in environment (e.g., the start of college, moving to a new job) can cause enough stress to inhibit menstruation or cause a period to be late. Amenorrhea caused by stress usually resolves on its own. Physical stress from heavy training combined with the psychological stress of competition make female athletes especially prone to amenorrhea.

HORMONAL DISORDERS. The hypothalamus secretes gonadotropin-releasing hormone (GnRH), a hormone that helps regulate the normal menstrual cycle. This hormone is part of a complex feedback mechanism with the female hormones estrogen and progesterone. Hypothalamic function can be altered because of a lesion or mass in the hypothalamus or central nervous system, resulting in low circulating levels of GnRH. Stress, strenuous exercise, and significant weight loss all provoke a drop in GnRH and subsequent decline in estrogen levels resulting in amenorrhea. Amenorrhea due to extreme dieting and exercise is a warning sign for anorexia nervosa or bulimia nervosa. Regular menstruation typically resumes with a gain in body weight.

The pituitary gland secretes two hormones, LH and FSH. In a healthy menstrual cycle, FSH stimulates maturation of an egg, or ovum, in the ovary. This occurs at the beginning, or follicular phase, of the cycle. During the follicular phase, ovarian production of estrogen rises and peaks, dropping off just before ovulation. Ovulation is the release of the fully mature ovum, and is prompted by a spike in LH, which rises, peaks, and drops off. In the second half of the menstrual cycle, known as the luteal phase, progesterone is secreted by a gland formed from the sac in the ovary that once held the ripening ovum, now called the corpus luteum. Progesterone is the dominant hormone of the luteal phase of the menstrual cycle, accompanied by a gradual rise in estrogen as the cycle prepares to begin again.

Disorders of the pituitary gland leading to amenorrhea include tumors, most often benign tumors known as adenomas. These tumors tend to produce hormones such as prolactin, adrenocorticotropic hormone (ACTH), or thyroid-stimulating hormone (TSH), all of which can disrupt the menstrual cycle. Of these, prolactin-secreting tumors are the most common. Prolactin inhibits GnRH and thus disrupts menstruation cycles. A common symptom of elevated prolactin is galactorrhea, or milky discharge from the nipples. Because thyroid function closely affects female hormones and the menstrual cycle, thyroid function should be assessed by measuring TSH. Additional abnormalities of the pituitary gland are Sheehan syndrome, which often presents in the postpartum period as an inability to lactate (produce milk), and empty sella syndrome, an abnormality of the pituitary gland that can be present at birth or a result of radiation or surgery.

KEY TERMS
Anovulation—
The absence of ovulation in the menstrual cycle.
Autoimmune disease—
A condition in which the body's immune system produces antibodies to destroy its own tissues or blood components.
Estrogen—
Any of several steroid hormones, produced mainly in the ovaries, that stimulate estrus (sexual receptivity and fertility) and the development of female secondary sexual characteristics.
Fragile X syndrome—
A genetic condition that causes an intellectual disability.
Hymen—
Membrane that stretches across the opening of the vagina.
Hyperprolactinemia—
The production of too much prolactin, a hormone that normally stimulates the production of breast milk.
Hypothalamus—
The hypothalamus regulates many functions of the autonomic nervous system as well as communicates with the endocrine system via the pituitary gland.
Hypothyroidism—
Underactive thyroid gland.
Hysterectomy—
Surgical removal of the uterus.
Imperforate hymen—
The lack of an opening in the membranous fold partly or completely closing the opening to the vagina.
Insulin—
A hormone made by the pancreas that controls blood glucose (sugar) levels by moving excess glucose into muscle, liver, and other cells for storage.
Luteinizing hormone—
A hormone that acts with follicle-stimulating hormone (FSH) to cause ovulation of mature follicles and secretion of estrogen from the ovary.
Menopause—
The stage of life during which a woman passes from the reproductive to the nonreproductive stage, accompanied by the cessation of menstruation.
Osteoporosis—
A condition found in older individuals in which bones decrease in density and become fragile and more likely to break. It can be caused by lack of vitamin D and/or calcium in the diet.
Ovulation—
The release of a fully mature ovum from the ovary as part of a normal menstrual cycle.
Pituitary gland—
Often referred to as the “master gland,” the pituitary is an endocrine gland that secretes several hormones that regulate growth, reproduction, and metabolic processes.
Phytoestrogen—
Phytoestrogens are compounds found in many plants and have mild estrogenic and anti-estrogenic activity. They are known as hormone modulators for their ability to regulate either excess or deficient estrogen states.
Tanner stages—
Stages of physical development in childhood, adolescence, and adulthood, first described by Drs. Marshall and Tanner in 1969; also referred to as pubertal stages 1 through 5.
Turner syndrome—
A rare disorder in which a female, at birth, has only one X chromosome.

Another common ovarian cause of amenorrhea is polycystic ovary syndrome (PCOS). PCOS, also known as Stein-Leventhal syndrome, is a collection of symptoms that often includes menstrual irregularity, excess growth of facial or chest hair, and obesity. Women with PCOS might have irregular, anovulatory cycles and multiple follicular cysts on their ovaries. They also might have insulin resistance. Some women have increased masculine features such as excess body hair from the higher male hormones produced by the ovaries.

PREGNANCY AND CONTRACEPTION. The most common cause of secondary amenorrhea is pregnancy, also called physiological amenorrhea. In addition, some newer oral contraceptives (birth control pills) inhibit menstruation along with preventing ovulation. A woman's periods also can halt temporarily after she stops taking birth control pills. This temporary halt usually lasts for a month or two, although in some cases it can last for a year or more. Some intrauterine devices (IUDs) that release hormones can cause menstruation to stop. Breastfeeding also can inhibit the return to normal menstruation after a pregnancy. The cessation of menstruation occurs permanently after menopause or a hysterectomy.

Premenopausal women receiving single or multiagent chemotherapy are at risk for short-term amenorrhea, as well as ovarian damage. Even young women who resume menstruation following chemotherapy are at risk for early menopause; therefore, those treated in childhood and adolescence should be counseled regarding the chance of early menopause in order to plan ahead for childbearing.

Diagnosis

A complete reproductive and medical history, and physical and pelvic exam are normally performed as a starting point for diagnosing amenorrhea. A pregnancy test should be performed; pregnancy needs to be ruled out whenever a woman's period is two to three weeks overdue.

Because successful management of amenorrhea requires an accurate diagnosis of its cause, a full workup is necessary. Amenorrhea, either primary or secondary, is evaluated by the following strategy: first, laboratory analysis of TSH and prolactin is done to rule out hypothyroidism or hyperprolactinemia. If prolactin is elevated, magnetic resonance imaging (MRI) may be indicated to rule out a pituitary adenoma or other pituitary tumor.

If TSH and prolactin levels are normal, the next step in diagnosis is testing of progesterone levels. This diagnostic procedure involves administering oral or injected progesterone that should prompt uterine bleeding within two to seven days. This is done to mimic the luteal phase of the menstrual cycle, where a rise and drop in progesterone is followed by menstruation. The presence of estrogen in the follicular phase builds the lining of uterus, and the effect of progesterone in the luteal phase is to slough off that lining, prompting menstrual bleeding. If bleeding occurs after a progesterone challenge, a diagnosis of anovulation can be made.

If withdrawal bleeding does not occur, there may be an abnormality of the anatomy of the uterus or vagina, or too little estrogen for the uterus to build up an endometrial lining. At this point, oral estrogen is administered for 21 days, followed by 5 days of oral progesterone to provoke menstruation. Alternatively, one cycle of oral contraceptive pills can be used. If no withdrawal bleed occurs, a problem with anatomy might be the origin of the amenorrhea. If a withdrawal bleed does occur, doctors continue studying the problem until they can pinpoint a cause.

Additional tests include FSH and LH levels. Elevated levels suggest premature ovarian failure, as the ovaries are not responding to high levels of stimulating hormones. Normal or low levels of FSH and LH require further assessment of the pituitary gland via imaging techniques.

Treatment

Traditional

Treatment of amenorrhea depends on the cause. Primary amenorrhea often requires no treatment, but it is always important to discover the cause of the problem. Not all conditions can be treated, but when amenorrhea is caused by a treatable condition, doctors treat it first. Individuals with eating disorders should be evaluated for, and treated with, appropriate psychiatric intervention and nutritional counseling. In rare cases, surgery may be needed for women with ovarian or uterine cysts.

For women who exercise and train strenuously, amenorrhea often can be treated by temporarily reducing the amount of strenuous exercise in which the woman is engaged. Professional athletes and dancers should work closely with their doctors to make changes in their exercise routines that are both effective and realistic given the demands of their careers.

Drugs

If a hormonal imbalance is diagnosed, hormone supplements might be given to correct the imbalance. For example, with PCOS, birth control pills are often prescribed. A pituitary tumor may be treated with a drug that reduces prolactin secretions.

Alternative

Holistic approaches to treatment of amenorrhea are tailored to address the cause of the imbalance. After appropriate diagnostic measures are taken to identify the cause, a holistic treatment plan will account for the whole person by addressing nutrition, exercise, sleep, and stress management in addition to therapies to balance the menstrual cycle.

Clinical nutrition for amenorrhea is aimed at restoring balance to overall health. For example, for underweight women the goal is to increase calories, dietary protein and high quality fats. Women experiencing amenorrhea who are overweight with an elevated body mass index may benefit from a diet low in refined carbohydrates and high in fiber and lean proteins to help reduce weight and manage insulin resistance. In all cases, an emphasis on whole foods, complex carbohydrates, legumes, nuts, and seeds is preferred. Increasing cold-water fish is beneficial for their essential fatty acid content. Soy foods that are weakly estrogenic are helpful in situations where estrogen is low.

Botanical medicine can be of help in restoring balance to the menstrual cycle by regulating sex hormones.

QUESTIONS TO ASK YOUR DOCTOR
Home remedies

Weight loss can restore menstruation in a severely obese woman. Optimizing digestion will benefit overall health, as will incorporating routine in mealtimes. Easing up on strenuous exercise and eating a proper diet can restore periods in athletes.

Prognosis

The outcome of treatment depends on the cause of amenorrhea. Prolonged amenorrhea can lead to infertility and other medical problems such as osteoporosis. If the halt in the normal period is caused by stress or illness, periods normally begin again when the stress is resolved or the illness is treated. Amenorrhea that occurs with discontinuing birth control pills usually resolves within six to eight weeks, although it can take up to a year.

The prognosis for PCOS depends on the severity of the symptoms and the treatment plan. If a woman wishes to become pregnant, treatment with fertility drugs may be required or, on rare occasions, surgery on the ovaries may be necessary.

Prevention

Many cases of amenorrhea cannot be prevented. However, eating a balanced diet; maintaining a healthy body weight; getting plenty of moderate-intensity exercise; and avoiding smoking, drugs, and excessive alcohol consumption can help prevent many problems that can increase the risk of amenorrhea. Avoiding excessive stress and participating in relaxing activities, such as yoga, can help reduce the risk of amenorrhea caused by stress.

See also Eating disorders .

Resources

BOOKS

Rinaldi, Nicola J., Stephanie G. Buckler, and Lisa Sanfilippo Waddell. No Period. Now What? A Guide to Regaining Your Cycles and Improving Your Fertility. Waltham: Antica Press, 2016.

Santoro, Nanette F., and Genevieve Neal-Perry, eds. Amenorrhea: A Case-Based Clinical Guide. New York: Springer, 2010.

PERIODICALS

American College of Obstetricians and Gynecologists. “Menstruation in Girls and Adolescents: Using the Menstrual Cycle as a Vital Sign.” Obstetrics and Gynecology 126 (2015): e143–6.

Jacobson, M. H., et al. “Menses Resumption after Cancer-Induced Amenorrhea Occurs Early or Not at All.” Fertility and Sterility 105, no. 3 (March 2016): 765–72.

Peric, M., et al. “Disordered Eating, Amenorrhea, and Substance Use and Misuse among Professional Ballet Dancers: Preliminary Analysis.” Medcyna Pracy 67, no. 1 (2016): 21–7.

WEBSITES

Bielak, Kenneth M. “Amenorrhea Treatment and Management.” Medscape. http://emedicine.medscape.com/article/252928-treatment#d8 (accessed February 26, 2017).

Mayo Clinic Staff. “Amenorrhea.” Mayo Foundation for Medical Education and Research. http://www.mayoclinic.com/health/amenorrhea/DS00581 (accessed February 26, 2017).

MedlinePlus. “Absent Menstrual Periods, Primary.” US National Library of Medicine. http://www.nlm.nih.gov/medlineplus/ency/article/001218.htm (accessed February 26, 2017).

NEDA. “Athletes and Eating Disorders. What Coaches, Trainers, Parents and Teammates Need to Know.” National Eating Disorders Association. https://www.nationaleatingdisorders.org/athletes-and-eating-disorders (accessed February 26, 2017).

Sherman, Roberta, and Ron Thompson. Managing the Female Athlete Triad. NCAA. http://www.femaleathletetriad.org/wp-content/uploads/2008/10/NCAA-Managing-the-Female-Athlete-Triad.pdf (accessed February 26, 2017).

ORGANIZATIONS

American Academy of Family Physicians, PO Box 11210, Shawnee Mission, KS, 66207-1210, (913) 906-6075, Fax: (913) 906-6075, http://www.aafp.org .

American College of Obstetricians and Gynecologists, PO Box 70620, Washington, DC, 20024, (202) 638-5577, http://www.acog.org .

National Athletic Trainers' Association, 21620 Valwood Pkwy., Suite 115, Carrollton, TX, 75006, (214) 637-6282, Fax: (214) 637-2206, (800) 879-6282, http://www.nata.org .

Carol A. Turkington
Tish Davidson, AM
Revised by Teresa Odle, BA, ELS

  This information is not a tool for self-diagnosis or a substitute for professional care.