What is amenorrhea?

Amenorrhea is the medical term for the absence of menstrual periods, either on a permanent or temporary basis. Amenorrhea can be classified as primary or secondary. In primary amenorrhea, menstrual periods have never begun (by age 16), whereas secondary amenorrhea is defined as the absence of menstrual periods for three consecutive cycles or a time period of more than six months in a woman who was previously menstruating.

The menstrual cycle can be influenced by many internal factors such as transient changes in hormonal levels, stress, and illness, as well as external or environmental factors. Missing one menstrual period is rarely a sign of a serious problem or an underlying medical condition, but amenorrhea of longer duration may signal the presence of a disease or chronic condition.

What causes amenorrhea?

The normal menstrual cycle occurs because of changing levels of hormones made and secreted by the ovaries. The ovaries respond to hormonal signals from the pituitary gland located at the base of the brain, which is, in turn, controlled by hormones produced in the hypothalamus of the brain. Disorders that affect any component of this regulatory cycle can lead to amenorrhea. However, a common cause of amenorrhea in young females sometimes overlooked or misunderstood by the individual and others, is an undiagnosed pregnancy. Amenorrhea in pregnancy is a normal physiological function. Occasionally, the same underlying problem can cause or contribute to either primary or secondary amenorrhea. For example, hypothalamic problems, anorexia or extreme exercise can play a major role in causing amenorrhea depending on the age of the person and if she has experienced menarche.

Primary amenorrhea
Primary amenorrhea is typically the result of a genetic or anatomic condition in young females that never develop menstrual periods (by age 16) and is not pregnant. Many genetic conditions that are characterized by amenorrhea are conditions in which some or all of the normal internal female organs either fail to form normally during fetal development or fail to function properly. Diseases of the pituitary gland and hypothalamus (a region of the brain important for the control of hormone production) can also cause primary amenorrhea since these areas play a critical role in the regulation of ovarian hormones.

Gonadal dysgenesis is the name of a condition in which the ovaries are prematurely depleted of follicles and oocytes (egg cells) leading to premature failure of the ovaries. It is one of the most common cases of primary amenorrhea in young women.

Another genetic cause is Turner syndrome, in which women are lacking all or part of one of the two X chromosomes normally present in the female. In Turner syndrome, the ovaries are replaced by scar tissue and estrogen production is minimal, resulting in amenorrhea. Estrogen-induced maturation of the external female genitalia and sex characteristics also fails to occur in Turner syndrome.

Other conditions that may be causes of primary amenorrhea include androgen insensitivity (in which individuals have XY (male) chromosomes but do not develop the external characteristics of males due to a lack of response to testosterone and its effects), congenital adrenal hyperplasia, and polycystic ovary syndrome (PCOS).

Secondary amenorrhea
Pregnancy is an obvious cause of amenorrhea and is the most common reason for secondary amenorrhea. Further causes are varied and may include conditions that affect the ovaries, uterus, hypothalamus, or pituitary gland.

Hypothalamic amenorrhea is defined as amenorrhea that is due to a disruption in the regulator hormones produced by the hypothalamus in the brain. These hormones influence the pituitary gland, which in turn sends signals to the ovaries to produce the characteristic cyclic hormones. A number of conditions can affect the hypothalamus and lead to hypothalamic amenorrhea, such as:

extreme weight loss,

emotional or physical stress,

rigorous exercise, and

severe illness.
Other types of medical conditions can cause secondary amenorrhea:

tumors or other diseases of the pituitary gland that lead to elevated levels of the hormone prolactin (which is involved in milk production) also cause amenorrhea due to the elevated prolactin levels;

hypothyroidism;

elevated levels of androgens (male hormones), either from outside sources or from disorders that cause the body to produce too high levels of male hormones;

ovarian failure (premature ovarian failure or early menopause);

polycystic ovary syndrome; and

Asherman’s syndrome is an example of uterine disease that causes amenorrhea. It results from scarring of the uterine lining following instrumentation (such as dilation and curettage) of the uterine cavity to manage postpartum bleeding or infection.

Post-pill amenorrhea
Women who have stopped taking oral contraceptive pills should experience the return of menstruation within three months after discontinuing pill use. Previously, it was believed that birth control pills increased a woman’s risk of amenorrhea following use of the pill, but this has been proven not to be the case. Women who do not resume menstruation after three months have passed since oral contraceptive pills were stopped should be evaluated for causes of secondary amenorrhea.

What are the symptoms of amenorrhea?

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 biological-determined child bearing years) should be further investigated to rule out serious conditions that may result in amenorrhea.

How is amenorrhea diagnosed?

The diagnosis of amenorrhea requires a careful medical history to document the presence of amenorrhea as well as any other coexisting medical conditions that may be the cause of amenorrhea. A physical examination, including a pelvic examination is also performed.

Depending upon the results of the history and physical examination further diagnostic tests may be ordered. Blood tests may be ordered to examine the levels of ovarian, pituitary, and thyroid hormones. These tests may include measurements of prolactin, follicle-stimulating hormone (FSA), estrogen, thyrotropin, dehydroepiandrosterone sulfate (DHEA-S), and testosterone. For some individuals, a pregnancy test is the first test performed.

Imaging studies, such as ultrasound, X-ray, and CT or MRI scanning may also be recommended in certain individuals to help establish the cause of amenorrhea.

What is the treatment for amenorrhea?

Treatment of both primary and secondary amenorrhea is determined by the precise cause of the amenorrhea. Treatment goals can be to relieve symptoms of hormonal imbalance, to establish menstruation, prevent complications associated with amenorrhea, and/or to achieve fertility, although not all of these goals can be achieved in every case.

In cases in which genetic or anatomical abnormalities are the cause of amenorrhea (typically primary amenorrhea), surgery may be recommended to correct anatomical abnormalities.

Hypothalamic amenorrhea that is related to weight loss, excessive exercise, physical illness, or emotional stress can typically be corrected by addressing the underlying cause. For example, weight gain and reduction in intensity of exercise can usually restore menstrual periods in women who have developed amenorrhea due to weight loss or overly intensive exercise, respectively, who do not have additional causes of amenorrhea. In some cases, nutritional counseling may be of benefit.

In premature ovarian failure, hormone therapy may be recommended both to avoid the unpleasant symptoms of estrogen depletion as well as prevent complications (see below) of low estrogen level such as osteoporosis. This may consist of oral contraceptive pills for those women who do not desire pregnancy or alternative estrogen and progesterone medications. While postmenopausal hormone therapy has been associated with certain health risks in older women, younger women with premature ovarian failure can benefit from this therapy to prevent bone loss.

Women with PCOS (polycystic ovary syndrome) may benefit from treatments that reduce the level or activity of male hormones, or androgens.

Dopamine agonist medications such as bromocriptine (Parlodel) can reduce elevated prolactin levels, which may be responsible for amenorrhea. Consequently, medication levels may be adjusted by the person’s physician if appropriate.

Assisted reproductive technologies and the administration of gonadotropin medications (drugs that stimulate follicle maturation in the ovaries) can be appropriate for women with some types of amenorrhea who wish to attempt to become pregnant.

While many companies and individuals have marketed herbal therapies as a treatment for amenorrhea, none of these have been conclusively proved to be of benefit. Herbal therapies are not regulated by the U.S. FDA and the quality of herbal preparations is not tested. Herbal remedies have been associated with serious and even fatal side effects in rare cases, and some preparations have been shown to contain high levels of toxins. Before deciding to take a natural or alternative remedy for amenorrhea, it is wise to seek the advice of your health care practitioner.

What are the complications of amenorrhea?

Infertility is a significant complication of amenorrhea for women who desire to become pregnant. Osteopenia (a reduction in bone density) or osteoporosis is a complication of low estrogen levels, which may occur with prolonged amenorrhea. Other complications of amenorrhea depend upon the underlying cause of the amenorrhea.

Can amenorrhea be prevented?

Amenorrhea is a symptom and not a disease in itself. Therefore, amenorrhea can be prevented only to the extent that the underlying cause can be prevented. For example, amenorrhea that results from genetic or inborn conditions cannot be prevented. On the other hand, amenorrhea that results from self-imposed stringent dieting or intensive exercise is typically preventable.

What is the outlook for a woman suffering from amenorrhea?

The outlook for amenorrhea varies widely and is dependent upon the cause of the amenorrhea. Hypothalamic amenorrhea that is a result of stress, exercise, or weight loss generally can be corrected if the responsible factors can be corrected. Medical and hormonal therapies can be of great benefit in preventing unpleasant side effects or complications of amenorrhea in many women.

Amenorrhea At A Glance

Amenorrhea refers to the absence of menstrual periods; it may be either primary (meaning a woman never developed menstrual periods) or secondary (absence of menstrual periods in a woman who was previously menstruating).

Genetic or inborn conditions are the most common causes of primary amenorrhea.

Amenorrhea may result from disorders of the ovaries, pituitary gland, or hypothalamus.

Intensive exercising, extreme weight loss, physical illness, and stress can all result in amenorrhea.

Amenorrhea is a symptom and not a disease in itself, so amenorrhea can be prevented only to the extent that the underlying cause can be prevented.

Infertility and bone loss (osteoporosis) are complications of amenorrhea.

Treatments may include surgical correction of anatomical abnormalities, medications or hormone therapies, and treatment of any underlying conditions responsible for amenorrhea.

The outlook for amenorrhea varies according to the cause of the amenorrhea.
REFERENCES:

Current evaluation of amenorrhea. Fertil Steril. 2006 Nov;86(5 Suppl):S148-55.

Davis AR; Kroll R; Soltes B; Zhang N; Grubb GS; Constantine GD. Occurrence of menses or pregnancy after cessation of a continuous oral contraceptive. Fertil Steril. 2008 May;89(5):1059-63.

eMedicine.com; “Amenorrhea, Secondary.”

eMedicine.com; “Amenorrhea, Primary.”

Last Editorial Review: 10/21/2009 2:44:58 PM

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