primery amenorrhea

Amenorrhea
Amenorrhea, or the absence of menses, is a common symptom of several pathophysiologic states. This condition traditionally has been divided into primary amen¬orrhea, in which menarche (the first menses) has not occurred, and secondary amenorrhea, in which men¬ses has been absent for 6 months or more. A more functional or clinical division of menstrual disorders based on initial history and physical examination would be as follows:
1\primary amenorrhea with sexual infantalism,
2\ primary amenorrhea with breast development and mullerian anomalies (normal secondary sexual character),
3\amenorrhea and oligomen¬orrhea with breast development and normal mullerian structures. this group includes disorders causing primary as well as secondary amenorrhea, oligomeno-rrhea, and the hyperandrogenic states.


Primary Amenorrhea
The diagnosis of primary amenorrhea is made when no spontaneous uterine bleeding has occurred by the age of 16 years. The workup should be initiated earlier if there is no evidence of breast development (thelarche) by age 14 years. The presence of normal breast development confirms gonadal secretion of estrogen but not necessarily the presence of ovarian tissue. The presence of normal amounts of pubic and axillary hair confirms gonadal or adrenal secretion of androgens as well as the presence of functional androgen receptors.




1\PRIMARY AMENORRHEA WITH SEXUAL INFANTILISM

Patients with primary amenorrhea and no secondary sexual characteristics (sexual infantalism) display the absence of gonadal hormone secretion. The differential diagnosis is based on whether the defect is the result of a lack of gonadotropin secretion (hypogonadotropic hypogonadism) or an inability of the ovaries to respond to gonadotropin (hypergonadotropic hypogonadism due to gonadal agenesis or dysgenesis). The distinc¬tion can be made by the measurement of a basal serum follicle-stimulating hormone (FSH).

A\Hypogonadotropic Primary Amenorrhea and Sexual Infantilism

Patients with hypogonadotropic hypogonadism have low FSH levels, whereas patients with hypergonado¬tropic hypogonadism (e.g., gonadal dysgenesis) have elevated FSH levels in the menopausal range (>40 mIU/L).
Hypogonadotropic hypogonadism may be caused by lesions of the hypothalamus like craniopharyngioma or other central nervous system tumor or by functional disorders that result in inadequate gonadotropin-releasing hormone (GnRH) synthesis and release., Kallman s syndrome is a rare genetic condition that is characterized by a failure to start or a failure to complete puberty. It is also accompanied by a lack of sense of smell (anosmia) Kallmann syndrome occurs due to a failure of the hypothalamus to release GnRH
magnetic resonance imaging (MRI) or comput¬erized tomography (CT) of the hypothalamic-pituitary area is recommended.


Hypogonadotropic hypogonadism resulting in primary amenorrhea and sexual infantilism may also be the result of lesions of the pituitary, including prolactin-secreting adenomas, or a general process of pituitary failure. These patients should be screened for other pituitary hormonal deficiencies by testing for thyroid-stimulating hormone (TSH), growth hormone, and adrenocorticotropic hormone (ACTH).
Finally, apparent hypogonadotropic hypogonad¬ism may actually represent constitutionally delayed puberty. This delay in the normal onset of puberty is generally attributed to undefined hereditary factors because there is commonly a history of late puberty in family members. Constitutional delay of puberty is a diagnosis of exclusion.



B\Hypergonadotropic Primary Amenorrhea and Sexual Infantilism

Patients with hypergonadotropic hypogonadism have some form of failed gonadal development or prema¬ture gonadal failure and will have elevated FSH levels.
These patients may have gonadal agenesis (the absence or early disappearance of the normal gonad). Examples in males who may appear to be female in some cases are pure gonadal dysgenesis, or the testicular regres¬sion syndrome. These patients have an apparently normal 46 XY karyotype but lack testicular develop-ment. If fetal testicular regression occurs between 8 and 10 weeks of gestation, they may have female ex¬ternal genitalia with or without ambiguity in addition to a lack of gonads, a hypoplastic uterus (secondary to absent secretion of antimullerian hormone), and rudi¬mentary genital ducts .
Other individuals with hypergonadotropic primary amenorrhea and sexual infantilism may have gonadal dysgenesis, the presence of an abnormally developed gonad due to chromosomal defects. The differential diagnosis includes 45 XO (Turner syndrome) , and pure gonadal dysgenesis (46 XX and 46 XY). Although most affected patients show no signs of secondary sexual character¬istics, occasionally an individual with mosaicism or Turner syndrome will have sufficient ovarian follicular activity and secrete enough estrogen to cause breast development, menstruation, ovulation, and rarely even pregnancy.
In individuals with the presence of a Y chromo¬some, there is a risk for developing a gonadoblastoma (a benign germ cell tumor of the gonad) All patients with hypergonadotropic hypogo¬nadism should have a karyotype performed. Because it is important to identify mosaicism,.
Patients with sexual infantilism may be treated to stimulate breast development by very gradually increasing estrogen doses. One commonly used regi¬men is to start with 0.3 mg conjugated estrogen every other day and slowly increase over 3- to 6-month in¬tervals.
Individuals with persistent hypogonadotropic hy-pogonadism who seek fertility require either human menopausal gonadotropin injections or pulsatile GnRH administered by an infusion pump. Pa¬tients with gonadal dysgenesis who have a normal uterus and cervix can achieve pregnancy only by in vitro fertilization using donor oocytes. \]

Turner Syndrome
The disorder is characterized by partial or complete loss (monosomy) of one of the X chromosomes
Individuals with Turner syndrome may benefit from growth hormone (GH) therapy, which can help to normalize height Estrogen and progesterone replacement therapy will generally promote puberty and the development of secondary sexual characteristics. Hormone replacement therapy is usually begun around 12-14 years of age. Replacement therapy must be continued until menopause.
Most individuals with Turner syndrome remain unable to conceive children. In vitro fertilization (IVF) with a donor egg and an implanted pregnancy is sometimes possible.




2\PRIMARY AMENORRHEA WITH BREAST DEVELOPMENT AND MULLERIAN ANOMALIES (normal secondary sexual charecters)

Patients with primary amenorrhea, breast develop¬ment, and some defect of mullerian structures fall into two categories: those with complete androgen in¬sensitivity syndrome (AIS), formerly called testicular feminization, and those with mullerian dysgenesis or agenesis. The distinction between these two diagnoses can be made by the measurement of a serum testoste¬rone level and determination of the karyotype.


A\Androgen Insensitivity Syndrome

Patients with complete androgen insensitivity syn¬drome have a defect in the androgen receptor. Their karyotype is 46 XY, and they demonstrate male levels of testosterone, although usually on the lower side of normal, their testes are located within the abdominal wall or cavity (cryptorchic). This loca¬tion, with greater body heat, typically does not allow for normal male hormonal secretion. Breast develop¬ment (with smaller nipples and areolae than normal genotypical females) is caused by the testicular secre¬tion of estrogens and by the conversion of circulat¬ing androgen to estrogens in the liver and elsewhere. The testicles of individuals with AIS secrete normal male amounts of antimullerian hormone; therefore, patients have only a vaginal dimple and no uterus. Treatment should consist of gonadal resection to avoid neoplasia (i.e., gonadoblastomas and dysgerminomas) once puberty is complete. The creation of a neovagina when the patient is prepared for sexual activity is pos-sible. Psychologi¬cal counseling is an important component in the care of these patients.
B\Mullerian Dysgenesis or Agenesis

Patients with primary amenorrhea, breast develop¬ment, and a 46 XX karyotype have levels of testoster¬one appropriate for females. This clinical diagnosis may be caused by mullerian defects that cause de¬struction of the vaginal canal (e.g., imperforate hymen or a transverse vaginal septum) or by the absence of a normal cervix or uterus and normal fallopian tube . An imperforate hymen should be suspected in adolescents who report monthly dysmenorrhea in the absence of vaginal bleeding. Clinical these patients often present with a vaginal bulge and a midline cystic mass on rectal examination. Ultrasonog¬raphy confirms the presence of a normal uterus and ovaries with a hematocolpos. These patients should be treated with hymenectomy.
Alternatively, women may present with similar symptoms BUT without a vaginal bulge. When ultra sonography confirms a normal uterus and ovaries a transverse, obstructing vaginal septum or cervical agenesis should be sus¬pected. MRI is the diagnostic procedure of choice in these patients. If the MRI scan confirms a transverse septum, surgical correction is indicated.
Finally; rectal examination and ultrasonography may be a sign of the absence of a uterus indicating mullerian agenesis or Meyer-Rokitansky-Kuster- Hauser syndrome. This syndrome is characterized by a failure of the mullerian ducts to fuse distally and to form the upper genital tract. These patients may have unilateral or bilateral rudimentary uterine tis¬sues ,fallopian tubes, and ovaries. It is un¬common to have functional endometrial tissue.
Congenital anatomic abnormalities of the uterus or vagina, or both, are often associated with renal abnor¬malities such as a unilateral solitary kidney or a dou¬ble renal collecting system, among others. Therefore, these patients should have an intravenous pyelogram or other diagnostic study to confirm a normal urinary system.






Diagnosis of Primary Amenorrhea

A diagnostic approach to primary amenorrhea. (FSH = follicle-stimulating hormone; LH = luteinizing hormone; TSH = thyroid-stimulating hormone.)