Atlas of pathophysiology, 2 Edition

Part II - Disorders

Genital Diseases


Amenorrhea is the abnormal absence of menstruation. Absence of menstruation is normal before puberty, after menopause, or during pregnancy and lactation; it's pathologic at any other time. Primary amenorrhea is the absence of menarche in an adolescent by age 14 without the development of secondary sex characteristics or by age 16 with normal development of secondary sex characteristics. Secondary amenorrhea is the absence of menstruation for at least 6 months after the normal onset of menarche. Primary amenorrhea occurs in 0.3% of women; secondary amenorrhea, in about 4% of women. Prognosis is variable, depending on the specific cause. Surgical correction of outflow tract obstruction is usually curative.


·   Anovulation due to deficient secretion of:

§  estrogen

§  gonadotropins

§  luteinizing hormone

§  follicle-stimulating hormone (FSH)

·   Lack of ovarian response to gonadotropins

·   Constant presence of progesterone or other endocrine abnormalities

·   Endometrial adhesions (Asherman syndrome)

·   Ovarian, adrenal, or pituitary tumor

·   Emotional disorders—common in patients with depression or anorexia nervosa:

·   mild emotional disturbances tend to distort the ovulatory cycle

·   severe psychic trauma may abruptly change the bleeding pattern or completely suppress one or more full ovulatory cycles

·   Malnutrition or intense exercise—suppresses hormonal changes initiated by the hypothalamus

·   Pregnancy

·   Weight loss

·   Thyroid disorder

·   Ovarian or adrenal tumor

·   Anatomic defects


The mechanism varies depending on the cause and whether the defect is structural, hormonal, or both. Women who have adequate estrogen levels but a progesterone deficiency don't ovulate and are thus infertile. In primary amenorrhea, the hypothalamic-pituitary-ovarian axis is dysfunctional. Because of anatomic defects of the central nervous system, the ovary doesn't receive the hormonal signals that normally initiate the development of secondary sex characteristics and the beginning of menstruation.

Secondary amenorrhea can result from any of several mechanisms, including:

·   central—hypogonadotropic hypoestrogenic anovulation

·   uterine—such as Asherman syndrome, in which severe scarring has replaced functional endometrium

·   premature ovarian failure.

Signs and symptoms

·   Absence of menstruation

·   Vasomotor flushes

·   Vaginal atrophy

·   Hirsutism

·   Acne (secondary amenorrhea)

·   Infertility

Diagnostic test results

·   Physical and pelvic examination and sensitive pregnancy test rule out pregnancy, as well as anatomic abnormalities (such as cervical stenosis) that may cause false amenorrhea (cryptomenorrhea), in which menstruation occurs without external bleeding.

·   Onset of menstruation (spotting) within 1 week after giving pure progestational agents such as medroxyprogesterone (Provera) indicate enough estrogen to stimulate the lining of the uterus (if menstruation doesn't occur, special diagnostic studies such as gonadotropin levels are indicated).

·   Blood and urine studies show hormonal imbalances, such as elevated pituitary gonadotropin levels. low pituitary gonadotropin levels, and abnormal thyroid levels (without suspicion of premature ovarian failure or central hypogonadotropism, gonadotropin levels aren't clinically meaningful because they're released in a pulsatile fashion).

·   Complete medical workup, including appropriate X-rays, computed tomography scans, or magnetic resonance imaging; laparoscopy; and a biopsy, identify ovarian, adrenal, and pituitary tumors.

·   Tests to identify dominant or missing hormones include:

§  “ferning” of cervical mucus on microscopic examination (an estrogen effect)

§  vaginal cytologic examination

§  endometrial biopsy

§  serum progesterone level

§  serum androgen levels

§  elevated urinary 17-ketosteroid levels with excessive androgen secretions

§  plasma FSH level more than 50 IU/L, depending on the laboratory (suggests primary ovarian failure); or normal or low FSH level (possible hypothalamic or pituitary abnormality, depending on the clinical situation).


·   Appropriate hormone replacement to reestablish menstruation

·   Treatment of the cause of amenorrhea not related to hormone deficiency—for example, surgery for amenorrhea due to a tumor

·   Inducing ovulation—for example, with clomiphene citrate in women with intact pituitary gland and amenorrhea secondary to gonadotropin deficiency, polycystic ovarian disease, or excessive weight loss or gain

·   FSH and human menopausal gonadotropins for women with pituitary disease

·   Reassurance and emotional support (psychiatric counseling if amenorrhea results from emotional disturbances)

·   Teaching the patient how to keep an accurate record of her menstrual cycles






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