Information on the following diseases can be found in the Related Disorders section of this report:

• Amenorrhea

The sole symptom of primary amenorrhea is absence of the first menstruation and the lack of a regular monthly cycle of menstruation. Other features may include lack of secondary sexual characteristics (i.e., the development of axillary hair and pubic hair), and incomplete or underdeveloped sexual organs (external genitalia) and breasts. Laboratory tests may reveal a deficiency in the functioning of the ovaries or an underactive pituitary gland. The hymen may completely cover the opening of the vagina (imperforate hymen).

Primary amenorrhea is usually caused by an excess or a deficiency of a hormone called gonadotropic-releasing hormone (GnRH), which is produced in the hypothalamus. Severe eating disorders (i.e., anorexia nervosa), crash dieting, emotional stress (i.e., depression), and obesity can cause amenorrhea. Tuberculosis or lymphoma can alter the function of the hypothalamus gland resulting in primary amenorrhea. (For more information, choose "Anorexia Nervosa," "Tuberculosis," and "Lymphoma" as your search terms in the Rare Disease Database.)

Some chromosomal disorders (e.g., Turner syndrome) may cause primary ovarian failure. It is possible that autoimmune disease or menopause before the first menstrual flow (premenarchal menopause) may also cause primary amenorrhea.

Primary amenorrhea may also be caused by abnormalities of the anatomy including the absence at birth of the vagina, uterus, and/or ovaries. Other abnormalities include the underdevelopment of the lining of the uterus (atrophic endometrium) and a rare condition in which both ovaries and testes are present in one individual (hermaphroditism). Menstrual flow may also be obstructed by the complete closure of the vaginal opening by the hymen (imperforate hymen) or the presence of a membranous partition across the vaginal canal (transverse vaginal septum). (For more information, choose "Hermaphroditism" as your search term in the Rare Disease Database.)

A variety of drugs can cause secondary amenorrhea including barbiturates, opiates, corticosteroids, chlordiazepoxide, phenothiazines, and progesterone.

For some women with primary amenorrhea, functioning that is normal for that person (simple physiologic delay) may explain why a female as old as 18 years of age has not menstruated. In these cases, secondary sexual characteristics are usually present and the external sexual organs appear normal.

Disorders of menstruation are among the most common forms of disease affecting females that result from the abnormal function of glands and tissues that secrete hormones (endocrinopathy).

Symptoms of the following disorders can be similar to those of primary amenorrhea. Comparisons may be useful for a differential diagnosis:

Amenorrhea can be a symptom of many disorders and the absence of menstruation may occur for many different reasons. These disorders include acromegaly, Stein-Levanthal syndrome (polycystic ovary disease), congenital adrenal hyperplasia, hypogonadotropic hypogonadism, Cushing disease, hyperthyroidism, hypothyroidism, and tumors of the pituitary gland. (For more information on these disorders, choose "Acromegaly," "Stein-Levanthal," "Adrenal Hyperplasia, Congenital," "Cushing," and "Hypothyroidism" as your search terms in the Rare Disease Database.)

Women with primary amenorrhea should be examined by a physician who specializes in treating disorders related to women's health (gynecologist) or dysfunctioning glands (endocrinologist). If the primary amenorrhea is a result of a normal delay (physiologic delay), generally no therapy is indicated before age 16. If secondary sexual development (breast development, distribution of body hair, etc.) is lacking by age 14, then a thorough investigation is warranted.

The treatment of primary amenorrhea depends on the cause. The administration of hormones such as progesterone and estrogen and/or corticosteroid drugs may be effective in the treatment of some types of amenorrhea. The patient may also benefit from emotional support and counseling. Imperforate hymen, other anatomical malformations, and tumors may require surgery.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

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JOURNAL ARTICLES

Liang HY, Chang HL, Chen CY, Chang PY, Lo FS, Lee LW. Psychiatric manifestations in young females with congenital adrenal hyperplasia in Taiwan. Chang Gung Med J. 2008 Jan-Feb;31(1):66-73.


Kossack N, Simoni M, Richter-Unruh A, Themmen AP, Gromoll J.
Mutations in a Novel, Cryptic Exon of the Luteinizing Hormone/Chorionic Gonadotropin Receptor Gene Cause Male Pseudohermaphroditism. PLoS Med. 2008 Apr 22;5(4)

Bry-Gauillard H, Meduri G, Abirached F, Constancis E, Brailly S, Chanson P, Young J.
Primary amenorrhea revealing an occult progesterone-secreting ovarian tumor. Fertil Steril. 2008 Feb 25;

Swenne I. Weight and growth requirements for menarche in teenage girls with eating disorders, weight loss and primary amenorrhea.
Horm Res. 2008;69(3):146-51.

Slopien R, et al., [Primary amenorrhea in patient with persisting communicating hydrocephalus]. Ginekol Pol. 1999;70:389-91. Polish.

Ben-Skowronek I, et al. [Prolactinoma as a cause of primary amenorrhea in a 16-year-old girl]. Ginekol Pol. 1999;70:367-69. Polish.

De Roux N, et al., The same molecular defects of the gonadotropin-releasing hormone receptor determine a varying degree of hypogonadism in affected kindred. J Clin Endocrinol Metab. 1999;84:567-72.

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