Sie sind auf Seite 1von 16

\n'); } if ( plugin ) { document.write(' (navigator.appName && navigator.appName.



Home | Specialties | Resource Centers | CME | PDA | Contributor Recruitment | Patien Education

Janua Articles Images CME Advanced Search Consumer Health Quick Find Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography Link

You are in: eMedicine Specialties > Pediatrics > Gynecology

Rate this Article

Last Updated: December 9, 2005

Email to a Colleague Get CME/CE for article

Synonyms and related keywords: menstrual cycle, menarche, menstrual bleeding, absence of menstrual bleeding, menstrual dysfunction, menses, absent menses, lack of menstruation, absent menstruation, abnormal menstrual cycle, primary amenorrhea, secondary amenorrhea, Turner syndrome, delayed puberty, dietary amenorrhea, emotional amenorrhea, jogger's amenorrhea, ovarian amenorrhea, pathologic amenorrhea, period, missed period, absent period, physiology of menstruation, gonadotropin-releasing hormone, GnRH, follicle-stimulating hormone, FSH, luteinizing-hormone, LH, estrogen, progesterone, follicular phase, ovulatory phase, ovulation, corpus luteum, luteal phase, human chorionic gonadotropin hormone, hCG, dehydroepiandrostenedione, adrenarche, pituitary tumor, polycystic ovary syndrome, inflammatory bowel disease, gonadal dysgenesis, galactorrhea, hyperandrogenism, androgen insensitivity syndrome, adrenal tumors, ovarian tumors, imperforate hymen, Rokitansky-Hauser syndrome

Click for related images.

Continuing Education


Section 1 of 10

Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty

CME available for this topic. Click here to take this

Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

Patient Education

Author: Kenneth M Bielak, MD, Clinic Director of Family Practice Center, Associate Professor, Department of Family Medicine, University of Tennessee at Knoxville Coauthor(s): Gayla S Harris, MD, Assistant Professor, Department of Obstetrics and Gynecology, University of Tennessee Medical Center Kenneth M Bielak, MD, is a member of the following medical societies: American Academy of Family Physicians, American College of Sports Medicine, American Medical Association, and American Medical Society for Sports Medicine Editor(s): Elizabeth M Alderman, MD, Clinical Professor of Pediatrics, Albert Einstein College of Medicine, Yeshiva University; Consulting Staff, Montefiore Medical Center, Director of Fellowship Training, Division of Adolescent Medicine, Albert Einstein College of Medicine, Children's Hospital at Montefiore; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor,, Inc; Wayne Wolfram, MD, MPH, Clinical Associate Professor, Departments of Pediatrics, Children's Hospital and University of Cincinnati; Paul D Petry, DO, FACOP, Assistant Professor, Department of Pediatrics, Division of Maternal Child Health, Northeast Regional Medical Center; and Maureen Strafford, MD, Arnold P Gold Foundation Associate Professor, Departments of Anesthesiology and Pediatrics, Tufts University and Tufts-New England Medical Center Disclosure

Women's Health Center Eating Disorders Center Pregnancy and Reproduction Center Amenorrhea Overview Amenorrhea Causes Amenorrhea Symptoms Amenorrhea Treatment Anorexia Nervosa Overview Birth Control Overview Birth Control FAQs


Section 2 of 10

Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

Background Amenorrhea is the absence of menstrual bleeding.

Amenorrhea is a normal feature in prepubertal, pregnant, and postmenopausal females. In females of reproductive age, diagnosing amenorrhea is a matter of first determining whether pregnancy is the etiology. In the absence of pregnancy, the challenge is to determine the exact cause of absent menses. This article reviews the physiologic aspects of menstruation and presents an approach for ascertaining the etiology of amenorrhea. Only the main components of amenorrhea are highlighted. Many minor components of physiology are important but cannot be discussed in the context of this overview. Pathophysiology The menstrual cycle is an orderly progression of hormonal events in the female body that results in the release of an egg. Menstruation occurs when an egg released by the ovary remains unfertilized; subsequently, the soggy decidua of the endometrium (which was primed to receive a fertilized egg) is sloughed in a flow of menses in preparation for another cycle. The menstrual cycle can be divided into 3 physiologic phases: follicular, ovulatory, and luteal. Each phase has a distinct hormonal secretory milieu. When one diagnoses the disease processes responsible for amenorrhea, consideration of the target organs of these reproductive hormones (hypothalamus, pituitary, ovary, uterus) is helpful. MENSTRUAL CYCLE
Section 3 of 10

Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

Follicular phase In physiologic terms, the first day of menses is considered the first day of the menstrual cycle. The following 13 days of the cycle are designated the follicular phase. The hypothalamus is the initiator of the follicular phase. The gonadotropin-releasing hormone (GnRH) pump located in the hypothalamus releases GnRH in a pulsatile fashion into the portal vessel system surrounding the anterior pituitary gland. GnRH interacts with the anterior pituitary gland to release follicle-stimulating hormone (FSH) in the follicular

phase. FSH is secreted into the circulation and interacts with the granulosa cells surrounding the developing oocytes. As levels of progesterone, estradiol, and inhibin decline 2-3 days before menses, the hypothalamus begins to release higher levels of FSH, which recruits oocytes for the next menstrual cycle. As FSH increases during the early portion of the follicular phase, it interacts with granulosa cells to stimulate the aromatization of androgens into estradiol. Early in the follicular phase, both estradiol and FSH increase the FSH-receptor content of the developing follicles. Over the next several days, the steady increase of estradiol (E 2) levels exerts a progressively greater suppressive influence on pituitary FSH release. Only one selected lead follicle, with the largest reservoir of estrogen, can withstand the declining FSH environment. The remaining oocytes that initially were recruited with the lead follicle undergo atresia. Immediately prior to ovulation, the combination of E2 and FSH leads to the production of luteinizing-hormone (LH) receptors on the granulosa cells surrounding the lead follicle. During the late follicular phase, estrogen positively influences LH secretion, instead of suppressing pituitary LH secretion as it does early in the follicular phase. To have this positive effect, the E2 level must achieve a sustained elevation for several days. The LH surge promotes maturation of the dominant oocyte, the release of the oocyte and then the luteinization of the granulosa cells and the surrounding theca cells of the dominant follicle resulting in progesterone production. The appropriate level of progesterone arising from the maturing dominant follicle contributes to the precise timing of the mid-cycle surge of LH. E2 promotes uterine endometrial gland growth, which allows for future implantation. Ovulatory phase Ovulation occurs approximately 34-36 hours after the onset of the LH surge or 10-12 hours after the LH peak and 24-36 hours after peak E2 levels. The rise in progesterone increases the distensibility of the follicular wall and enhances proteolytic enzymatic activity, which eventually breaks down the collagenous follicular wall.

After the ovum is released, the granulosa cells increase in size and take on a yellowish pigmentation characteristic of lutein. The corpus luteum then produces estrogen, progesterone, and androgens and becomes increasingly vascularized. Luteal phase The lifespan and steroidogenic capacity of the corpus luteum depend on continued tonic LH secretion from the pituitary gland. The corpus luteum secretes progesterone that interacts with the endometrium of the uterus to prepare it for implantation. This process is termed endometrial decidualization. In the normal ovulatory menstrual cycle, the corpus luteum declines in function 9-11 days after ovulation. If the corpus luteum is not rescued by human chorionic gonadotropin (hCG) hormone from the developing placenta, menstruation reliably occurs 14 days after ovulation. If conception occurs, placental hCG maintains luteal function until placental production of progesterone is well established. The menstrual cycle is a complex but coordinated system of hormonal changes and organ responses. The main directive of the menstrual cycle is to stimulate growth of a follicle to release an egg and prepare a site for implantation if fertilization should occur. Absence of fertilization results in the timely release of the prepared endometrium, which is termed menses. At birth, female infants have a predetermined number of primordial follicles that are arrested in the diplotene stage of meiotic prophase until stimulation at puberty. Until puberty, the hypothalamus is in a quiescent state. At age approximately 8 years, GnRH is synthesized in the hypothalamus and released. The adrenal cortex begins to produce dehydroepiandrostenedione to initiate the start of adrenarche (ie, the development of sexual hair). The orderly progression of puberty begins with breast budding (thelarche) then continues with the growth of pubic hair (pubarche), accelerated growth, and menses (menarche). In the United States, the average age of girls at menarche is 12.8 years, with a range of 9-16 years. CLINICAL DETAILS
Section 4 of 10

Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary

Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

The differential diagnosis of amenorrhea is broad and can range from genetic abnormalities to endocrine disorders and psychological, environmental, and structural anomalies. To facilitate prompt and accurate diagnostic workup, obtaining a thorough history and preforming detailed physical examination is essential. In the differential diagnosis of primary or secondary amenorrhea, the most important step in diagnosis is to exclude pregnancy. Always consider pregnancy first. After pregnancy is excluded, an algorithmic approach is followed to narrow the diagnostic possibilities. Causes of primary and secondary amenorrhea overlap considerably; therefore, ascertaining the patient's sexual development is the key to differentiating these conditions. See the Algorithms for Evaluation of Amenorrhea below to determine the most logical course leading to a specific diagnosis. History An adequate history comprises childhood growth and development, among other areas, including height and weight charts and age at thelarche and menarche. Ascertaining the age at menarche of the patient's mother and sisters is advisable because the age at menarche in family members can occur within a year of the age in others. The duration and flow of menses, cycle days, day and date of last menstrual period, presence or absence of molimina (breast soreness and mood change immediately before menses) are necessary pieces of information. Any history of chronic illness, trauma, surgery, and medications is also important. A sexual history should be obtained in a confidential manner. Information regarding substance use, exercise, diet, home and school situations, and psychosocial issues should be elicited. A comprehensive review of symptoms should include vasomotor symptoms, hot flashes, virilizing changes, galactorrhea, headache, fatigue, palpitations, nervousness, hearing loss, and visual changes. Physical examination Physical examination begins with vital signs, including height and weight, and with sexual maturity ratings. Physical

examination findings are as follows:

Generalized findings o Anorexia - Cachexia, bradycardia, hypotension, and hypothermia o Pituitary tumor - Funduscopic changes, visual field impairment, and cranial nerve signs o Polycystic ovary (PCO) syndrome - Acne, acanthosis nigricans, and obesity o Inflammatory bowel disease - Fissure, skin tags, and occult blood found on rectal examination o Gonadal dysgenesis (eg, Turner syndrome) Webbed neck, increased carrying angle, and lack of breast development Breast findings o Galactorrhea - Breast palpation o Delayed puberty - Underdeveloped with sparse pubic hair o Gonadal dysgenesis (eg, Turner syndrome) Undeveloped breasts with normal growth of pubic hair Pubic hair and external genitalia findings o Hyperandrogenism - Pubic hair distribution and excess facial hair o Androgen insensitivity syndrome - Absent or sparse axillary and pubic hair with breast development o Delayed puberty - Without breast development o Adrenal or ovarian tumors - Clitoromegaly and virilization o Pelvic fullness - Pregnancy, ovarian mass, and genital anomalies Vaginal findings o Imperforate hymen - Distension or bulging of the external vagina o Agenesis (Rokitansky-Hauser syndrome) Foreshortened vagina without uterus and normal pubic hair o Androgen insensitivity syndrome Foreshortened vagina without uterus and absent pubic hair Uterine findings: If the uterus is enlarged, pregnancy must be excluded. Cervical findings

o o

o o

Assess the vaginal canal, the effect of estrogen on the vaginal mucosa, and mucus secretion. The presence of mucus suggests that the ovaries are producing estradiol (E2) (unopposed by progesterone). Clear, abundant mucus after cycle day 20 suggests anovulation. Lack of mucus and a dry, pale vagina suggest that no current production of E2.

Laboratory evaluation The history and physical findings help in selecting tests in a female patient with amenorrhea. Possible tests include endocrinologic and chemical tests to detect chronic disease processes. If the history and physical findings suggest an ovarian-axis problem with normal puberty, TSH, prolactin, folliclestimulating hormone (FSH), and LH measurements are the first line of testing. If hirsutism is predominant on examination, include androgen testing of testosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and 17-OH progesterone to determine the organ of cause (eg, adrenal gland vs ovary). If the history or physical findings suggest a chronic disease process, the following may be indicated including measurement of the erythrocyte sedimentation rate (ESR), liver function tests, BUN determination, creatinine determination, and urinalysis. Bone age is important in differentiating pubertal delays as a cause. To evaluate the CNS, a coned view of the sella turcica or MRI of the pituitary is indicated. Many specialists prefer MRI. PRIMARY AND SECONDARY AMENORRHEA
Section 5 of 10

Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

Primary amenorrhea is defined either as absence of menses by age 14 years with the absence of growth or development of secondary sexual characteristics (eg,

breast development) or as absence of menses by age 16 years with normal development of secondary sexual characteristics. Secondary amenorrhea is defined as the cessation of menstruation for at least 6 months or for at least 3 of the previous 3 cycle intervals. Since only 3 diagnoses are unique to primary amenorrhea and never cause secondary amenorrhea, differentiating primary from secondary amenorrhea does little to enhance the clinician's understanding of the etiology. Diagnoses unique to primary amenorrhea include vaginal agenesis, androgen insensitivity syndrome, and Turner syndrome (45,XO). The remaining diagnoses should be considered in patients with both primary and secondary amenorrhea. The causes of amenorrhea are listed below. Organize clinical evaluation on the basis of sexual development and basic developmental physiology. With such a vast differential diagnosis, one way to organize and memorize the causes of amenorrhea can be in its relationships with generalized pubertal delay, normal pubertal development, or abnormalities of the genital tract. Causes of amenorrhea

Generalized pubertal delay o Constitutional delay o Hypergonadotropic hypogonadism Turner syndrome Gonadal dysgenesis with mosaic karyotype Pure gonadal dysgenesis (Perrault syndrome, Swyer syndrome) Gonadotropin-resistant ovary syndrome Acquired causes (eg, high-dose alkylating chemotherapy, pelvic radiation, autoimmune oophoritis) o Hypogonadotropic hypogonadism Chronic conditions (eg, starvation, excessive exercise, depression, psychological stress, marijuana use, Crohn disease, cystic fibrosis, sickle cell disease, thalassemia major, HIV infection, renal disease, thyroid disease, diabetes mellitus, anorexia nervosa) Slow-growing CNS tumors (eg, adenomas, craniopharyngiomas, meningiomas, pituitary microadenomas) Abnormal hypothalamic development (eg, Kallmann syndrome, Prader-Willi syndrome, and Laurence-Moon-Biedl syndrome) Acquired miscellaneous disorders (eg, infiltration disorders [sarcoidosis, Langerhans cell histiocytosis, syphilis, tuberculomas], ischemia disorders [caused by trauma, aneurysm, obstruction of the aqueduct of Sylvius] and

destruction [concentrated, high-dose exposure to radiation]) Normal puberty o Associated with hyperandrogenicity (eg, PCO syndrome, late-onset 21-hydroxylase deficiency [nonclassic congenital adrenal hyperplasia], immaturity of the hypothalamic-pituitary-ovarian axis, Cushing disease, androgen-producing ovarian or adrenal tumors, ovarian stromal hypertrophy) o Associated with absence of hirsutism or virilization (eg, immaturity of the hypothalamic-pituitary-ovarian axis, pregnancy) o Hypergonadotropic hypogonadism (eg, ovarian failure, high-dose alkylating chemotherapy, pelvic radiation, autoimmune oophoritis) Anomalies of the genital tract o Mllerian agenesis (eg, Mayer-Rokitansky-Kuster-Hauser syndrome) breast present o Congenital or acquired anatomic obstruction (eg, imperforate hymen, transverse vaginal septum, Asherman syndrome, endometrial destruction due to severe infection or surgery) o Androgen insensitive syndrome-absent uterus with normal breast development
Section 6 of 10


Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

Hypergonadotropic hypogonadism Puberty is considered delayed when no breast development is evident at 13.5 years, pubic hair is absent at 14 years, and menarche is absent at 16 years. The most common cause of delayed puberty is constitutional delay. Another common reason for delayed puberty is ovarian failure, which is also termed hypergonadotropic hypogonadism. Elevated levels of follicle-stimulating hormone (FSH) and luteinizing-hormone (LH) characterize hypergonadotropic hypogonadism with low estrogen production. The most common example of hypergonadotropic hypogonadism is found in Turner syndrome, which is caused by a 45,X karyotype. Clinical manifestations of Turner syndrome include a webbed neck, short stature, broad shieldlike chest, anomalous auricles, and hypoestrogenemia resulting in sexual immaturity. Gonadal dysgenesis fits the same pattern of high FSH and LH and low estradiol (E 2) levels. Gonadal dysgenesis is caused by a mosaic karyotype with an abnormal X chromosome or with a normal karyotype (46,XX) and streak ovaries. Individuals with Perrault syndrome have gonadal dysgenesis, a normal karyotype, and neurosensory deafness. Sawyer syndrome is illustrated by a phenotypically immature female with a 46,XY karyotype without testis-determining factor on the Y chromosome. Another rare cause of hypergonadotropic hypogonadism is gonadotropin-resistant ovary

syndrome, which is characterized by FSH-resistant ovaries. Acquired causes of hypergonadotropic hypogonadism can result from high-dose alkylating chemotherapy and radiation treatments to the pelvis. Elevated ESR and anti-ovarian antibody levels may suggest autoimmune oophoritis, but such tests are rarely needed. Autoimmune oophoritis is an exclusionary diagnosis. Like all forms of hyperandrogenic hypogonadotropic amenorrhea, these conditions are not reversible. Hypogonadotropic hypogonadism Hypogonadotropic hypogonadism occurs when FSH and LH levels are low. The most common causes of hypogonadotropic hypogonadism include chronic illness, starvation, excessive exercise, anorexia nervosa, depression, stress, and marijuana use. Hypogonadotropic hypogonadism involves slowed GnRH release caused by multifactorial components of decreased body fat and increased beta endorphins. Chronic illness can affect pubertal development adversely by interfering with metabolism through malabsorption and poor nutrition (eg, Crohn disease, diabetes mellitus, hypothyroidism and hyperthyroidism, cystic fibrosis, anorexia nervosa, excessive exercise). Tumors in the CNS can compress the portal vessels and impede the flow of GnRH from the hypothalamus to the pituitary gland. Pituitary adenomas, craniopharyngiomas, and meningiomas are examples of slow-growing nonmetastatic tumors that are uncommon causes of hypogonadotropic hypogonadism. Anterior pituitary prolactinomas releasing prolactin hormone are the most common pituitary tumors to cause hypogonadotropic hypogonadism. Other acquired disorders can disrupt pituitary function by destructive means, such as ischemia, infiltration, and obstruction. Head trauma, cranial aneurysms, and infiltrative processes (eg, sarcoidosis, syphilis, tuberculomas) are examples of conditions that can disrupt pituitary function. Abnormal development of the hypothalamus can result in hypogonadotropic hypogonadism. Kallmann syndrome manifests with anosmia, pubertal delay, and a normal response to exogenous gonadotropins from an embryonic lack of protein coded for by the gene KAL1, which prevents GnRH-producing cells from migrating from the olfactory area to the hypothalamus. Other syndromes associated with hypothalamic dysfunction include Prader-Willi syndrome and Laurence-Moon-Biedl syndrome. AMENORRHEA WITH NORMAL PUBERTY
Section 7 of 10

Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With

Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

Frequently, amenorrhea with normal puberty is associated with hirsutism. The most common cause in this setting is PCO syndrome. PCO syndrome is characterized by anovulation, hirsutism, and obesity. Other than anovulation, the other characteristics may not always be present. Ovarian hyperthecosis results in hyperandrogenicity, which is evident by signs of hirsutism, acne, and obesity and can be associated with type 2 diabetes mellitus and acanthosis nigricans. Hyperthecosis can also cause virilization, as seen in clitoromegaly, temporal balding, and deepened voice change. See Polycystic Ovarian Syndrome for an indepth discussion of this entity. Another cause of hirsutism is the rare late-onset 21-hydroxylase deficiency, which is caused by mutations in the 21-hydroxylase gene resulting in excessive 17hydroxyprogesterone levels. This deficiency is also termed nonclassic congenital adrenal hyperplasia and can occur in 1-10% of women with hirsutism. Other causes of hyperandrogenism include Cushing disease, ovarian stromal hypertrophy, and androgen-producing tumors of the ovary and adrenal glands. Exogenous anabolic steroid use should be considered in the differential for hyperandrogenic amenorrhea. Anovulation remains the most common cause of amenorrhea in the setting of nonvirilization. Anovulation is caused by immaturity of the hypothalamic-pituitaryovarian axis, which can be apparent after discontinuation of various hormonal contraception medications and can result in loss of menses for several months. Idiopathic premature menopause occurs in 1% of women younger than 40 years. Premature ovarian failure can be idiopathic, secondary to chemotherapy or radiation therapy, or autoimmune in origin. Hyperprolactinemia is a pituitary cause of amenorrhea in the presence of normal puberty. Hyperprolactinemia can occur as a consequence of breastfeeding, microadenomas of the pituitary, and use of psychoactive medications (eg, haloperidol, phenothiazines, amitriptyline, benzodiazepines, cocaine, marijuana). Amenorrhea may be caused by thyroid disorders, including hyperthyroidism and hypothyroidism. Hypogonadotropic hypogonadism can occur from the same causes as delayed puberty (see Amenorrhea with Delayed Puberty). In addition, Sheehan syndrome, which results from panhypopituitarism after pituitary infarction from postpartum hemorrhage or shock, can manifest as pubertal amenorrhea. Amenorrhea resulting from genital tract anomalies can arise from the absence of reproductive organs. Mayer-Rokitansky-Hauser syndrome is an anomaly of the genital tract characterized by vaginal agenesis. The uterus is usually absent, and the vagina is foreshortened. Because the ovaries function normally and produce estradiol (E2), breasts are normal in shape and contour. Pubarche is also normal in this patient population; therefore, pubic hair remains normal. Mayer-Rokitansky-

Hauser syndrome accounts for 15% of primary amenorrhea cases and is second to Turner syndrome as the most common cause of primary amenorrhea. Androgen insensitivity syndrome (previously termed testicular feminization) accounts for 10% of patients with amenorrhea. Androgen insensitivity syndrome is caused by an abnormality of the androgen receptor. The gonads are testicles producing testosterone; however, testosterone has no effect because the androgen receptor is nonfunctional. The phenotypic appearance in patients with this condition is female, but the circulating hormonal pattern is male. Androgen insensitivity syndrome is a maternal X-linked recessive disease in which the testes remain intraabdominal or partially descended, and pubic hair is sparse. Spontaneous testicular regression is a rare disorder of genetic males that results in a female phenotype with an absent uterus. In addition, certain enzyme deficiencies affecting androgen production can result in male pseudohermaphrodites. All disorders that are phenotypically female but chromosomally male (XY) require that the gonads be removed to avert cancerous changes. Primary amenorrhea can result from an imperforate hymen, which presents as a boggy uterus and cyclic abdominal pain. Asherman syndrome occurs after an overzealous curettage of the endometrial lining, which results in adhesions or synechiae that prevent the endometrium from responding to E 2. Clinically significant infections that destroy the endometrial lining can also result in primary or secondary amenorrhea. ALGORITHMS FOR EVALUATION OF AMENORRHEA
Section 8 of 10

Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

Algorithm for evaluation of amenorrhea with delayed puberty Obtain the following laboratory results: thyroid function; bone age; and luteinizinghormone (LH), follicle-stimulating hormone (FSH), and prolactin levels.

If TSH levels are elevated and thyroxine (T4) levels are low, the cause is hypothyroidism. If the bone age is delayed, the cause is constitutional delay. If the bone age is normal, obtain LH, FSH, and prolactin levels. If LH and FSH levels are elevated, obtain a karyotype. o If the karyotype is 45,XO, the cause is gonadal dysgenesis (ie, Turner syndrome). Amenorrhea can also occur when 1 of the 2 X chromosomes is abnormal, such as a ring chromosome, or if a partial loss of the p or q arm of the X chromosome is occurs.

If the karyotype is 46,XX, the primary cause is ovarian failure. Perform an autoimmune workup. Consider an etiology of autoimmune oophoritis, effects of radiation therapy or chemotherapy, 17-alphahydroxylase deficiency, or resistant ovary syndrome. If LH and FSH levels are low or within the reference range, obtain a head MRI. o If head MRI findings are abnormal, the cause is pituitary tumor, pituitary destruction, or hypothalamic disease. o If prolactin levels are elevated, obtain a head MRI. If head MRI findings are abnormal, the cause is pituitary tumor or a brain lesion disrupting the pituitary stalk. If the MRI finding is normal, the cause may be marijuana use or psychiatric medicine, specifically dopamine antagonist medications, which lead to a decrease in prolactin inhibiting factor and a subsequent increase in serum prolactin levels. If head MRI findings are normal with normal history and physical examination findings, the etiology may be drug use, an eating disorder, athleticism, or psychosocial stress. If head MRI findings are normal but clinical evaluation and screening study findings are abnormal, chronic disease can be excluded.

Algorithm for evaluation of amenorrhea with normal puberty with uterus present Obtain a pregnancy test.

If the pregnancy test result is positive, refer the patient to the appropriate specialist. If the pregnancy test result is negative, obtain TSH, prolactin, FSH and LH levels. If the TSH level is elevated, the diagnosis is hypothyroidism. If the prolactin level is elevated, hyperprolactinemia is the diagnosis. Causes include prolactinoma, CNS tumors and medications. If the FSH level is low, obtain MRI of the head. If the MRI is abnormal, consider hypothalamic disease, pituitary disease or pituitary tumor. If MRI is normal, proceed with clinical evaluation to exclude chronic disease, anorexia nervosa, marijuana or cocaine use, and social or psychological stresses. If FSH is elevated, ovarian failure is the diagnosis. Obtain a karyotype. o If the karyotype is abnormal, consider pure gonadal dysgenesis, such as Turner syndrome or mosaic or mixed gonadal dysgenesis. o If the karyotype is normal (46 XX), the cause is ovarian failure. o Consider premature ovarian failure, autoimmune oophoritis, exposure to radiation or chemotherapy, resistant ovary syndrome or multiple endocrine neoplasm (MEN) syndrome. If TSH, prolactin, and FSH levels are within reference range, perform a

progestin challenge test. o If withdrawal bleeding occurs, consider anovulation secondary to PCO syndrome. o If no withdrawal bleed occurs, proceed with estradiol priming followed by a progestin challenge. o If the challenge does not induce menses, consider Asherman syndrome or outlet obstruction. If hirsutism is present, check testosterone, DHEAS, and 17-OH progesterone level. o If the testosterone and DHEAS levels are within the reference range or moderately elevated, perform a progesterone challenge. o If withdrawal bleeding occurs, the diagnosis is PCOS. o If the 17-OH progesterone level is elevated, the diagnosis is adult onset adrenal hyperplasia. o If the testosterone level or DHEAS is 2 or more times higher than the reference range, consider PCO syndrome, hyperthecosis or an androgen secreting tumor of the ovary or adrenal gland

Algorithm for evaluation of genital tract abnormalities Obtain a pelvic sonography. If the uterus is absent, obtain a karyotype.

If the karyotype is 46,XY, obtain testosterone levels. o If testosterone levels are within reference range or are high (male range), the cause is androgen insensitivity. o If testosterone levels are within reference range or are low (female range), the cause is testicular regression or gonadal enzyme deficiency. If the karyotype is 46,XX, the cause is mllerian agenesis (ie, RokitanskyKuster-Hauser syndrome).
Section 9 of 10


Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

Other than pregnancy, constitutional delay, anovulation, and chronic illness, most of the other disorders causing amenorrhea may require referral to a subspecialist for treatment. Many of the treatment methods require surgery or specific therapies. For the adolescent with constitutional delay and anovulation, the goal should be the restoration of ovulatory cycles. If ovulatory cycles are not restored spontaneously, estrogen-progestin therapy is indicated. Reassure patients because the diagnosis of amenorrhea can cause tremendous anxiety. For excellent patient education resources, visit eMedicine's Women's Health Center, Eating Disorders Center, and Pregnancy and Reproduction Center. Also,

see eMedicine's patient education articles Amenorrhea, Anorexia Nervosa, Birth Control Overview, and Birth Control FAQs. BIBLIOGRAPHY
Section 10 of 10

Author Information Introduction Menstrual Cycle Clinical Details Primary And Secondary Amenorrhea Amenorrhea With Delayed Puberty Amenorrhea With Normal Puberty Algorithms For Evaluation Of Amenorrhea Management Of Amenorrhea Bibliography

Aloi JA: Evaluation of amenorrhea. Compr Ther 1995 Oct; 21(10): 5758[Medline]. ASRM: Practice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil Steril 2004 Sep; 82 Suppl 1: S33-9[Medline]. Braverman PK, Sondheimer SJ: Menstrual disorders. Pediatr Rev 1997 Jan; 18(1): 17-25; quiz 26[Medline]. Gidwani GP: Amenorrhea in the athlete. Adolesc Med 1999 Jun; 10(2): 27590, vii[Medline]. Iglesias EA, Coupey SM: Menstrual cycle abnormalities: diagnosis and management. Adolesc Med 1999 Jun; 10(2): 255-73[Medline]. Pletcher JR, Slap GB: Menstrual disorders. Amenorrhea. Pediatr Clin North Am 1999 Jun; 46(3): 505-18[Medline]. Reyftmann L, Dechaud H, Ovtchnikoff S, et al: Amenorrhoea revealing an arteriovenous uterine malformation, and recovery of menses after embolization. Reprod Biomed Online 2003 Oct; 7(3): 327-9[Medline].

Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER Amenorrhea excerpt

Copyright 2005,, Inc.

About Us | Privacy | Terms of Use | Contact Us | Advertise | Institutional Subscribers

We subscribe to the HONcode principles of the Health On the Net Foundation

1996-2005 eMedicin All Rights