Causes of Amenorrhea

 Causes of Amenorrhea

 

When endocrine function along the hypothalamic– pituitary–ovarian axis is disrupted or an abnormality devel-ops in the genital outflow tract (obstruction of the uterus, cervix, or vagina or scarring of the endometrium), menstru-ation ceases. Causes of amenorrhea are divided into those arising from (1) pregnancy, (2) hypothalamic–pituitary dys-function, (3) ovarian dysfunction, and (4) alteration of the genital outflow tract.

 

PREGNANCY

Because pregnancy is the most common cause of amenorrhea, it is essential to exclude pregnancy in the evaluation of amenorrhea.

A history of breast fullness, weight gain, and nausea suggest the diagnosis of pregnancy, which is confirmed by a positive human chorionic gonadotropin (hCG) assay. It is important to rule out pregnancy to allay the patient’s anxiety and to avoid unnecessary testing. Also, some treatments for other causes of amenorrhea can be harmful to an ongoing pregnancy. Lastly, the diag-nosis of ectopic pregnancy should be entertained in the presence of abnormal menses and a positive preg-nancy test, as this would necessitate medical or surgical intervention.

 

Box 35.1

Types of Abnormal Uterine Bleeding

Polymenorrhea—frequent menstrual bleeding

(frequency, 21 days or less) Menorrhagia—prolonged or excessive uterine

bleeding that occurs at regular intervals (the loss of 80 mL or more of blood that lasts for more than 7 days)

Metrorrhagia—irregular menstrual bleeding or bleeding between periods

Menometrorrhagia—frequent menstrual bleeding that is excessive and irregular in amount and duration

American College of Obstetricians and Gynecologists. Manage-ment of anovulatory bleeding. ACOG Practice Bulletin 14. Washington, DC: American College of Obstetricians and Gyne-cologists; 2000.

 

HYPOTHALAMIC–PITUITARY DYSFUNCTION

 

Release of hypothalamic gonadotropin-releasing hor-mone (GnRH) occurs in a pulsatile fashion, modulated by catecholamine secretion from the central nervous system and by feedback of sex steroids from the ovaries. When this pulsatile secretion of GnRH is disrupted or altered, the anterior pituitary gland is not stimulated to secrete follicle-stimulating hormone (FSH) and luteinizing hor-mone (LH). The result is an absence of folliculogenesis despite estrogen production, no ovulation, and lack of corpus luteum with its usual production of estrogen and progesterone. Because of the lack of sex hormone produc-tion with no stimulation of the endometrium, there is no menstruation.

 

Alterations in catecholamine secretion and metabo-lism in sex steroid hormone feedback or an alteration of blood flow through the hypothalamic–pituitary portal plexus can disrupt the signaling process that leads to ovu-lation. This latter disruption can be caused by tumors or infiltrative processes that impinge on the pituitary stalk and alter blood flow.

 

The most common causes of hypothalamic–pituitary dysfunction are presented in Box 35.2. Most hypothalamic– pituitary amenorrhea is of functional origin and can be corrected by modifying causal behavior, by stimulating gonadotropin secretion, or by giving exogenous human menopausal gonadotropins.

 

The physician cannot differentiate hypothalamic– pituitary causes of amenorrhea from ovarian or genital outflow causes by medical history or even physical exam-ination alone. However, there are some clues in the med-ical history and physical examination that would suggest a hypothalamic–pituitary etiology for amenorrhea. A his tory of any condition listed in Box 35.2 should cause the physician to consider hypothalamic–pituitary dysfunction. 

 

Box 35.2

Causes of Hypothalamic–Pituitary Amenorrhea

Functional Causes

Weight loss

Excessive exercise

Obesity

Drug-Induced Causes

Marijuana

Psychoactive drugs, including antidepressants

Neoplastic Causes

Prolactin-secreting pituitary adenomas Craniopharyngioma Hypothalamic hamartoma

Psychogenic Causes

Chronic anxiety

Pseudocyesis

Anorexia nervosa

Other Causes

Head injury

Chronic medical illness

 

The definitive method to identify hypothalamic–pituitary dysfunction is to measure FSH, LH, and prolactin levels in the blood. In these conditions, FSH and LH levels are in the low range. The prolactin level is normal in most conditions, but is elevated in prolactin-secreting pituitary adenomas. 

 

OVARIAN DYSFUNCTION

 

In ovarian failure, the ovarian follicles are either exhausted or are resistant to stimulation by pituitary FSH and LH. Asthe ovaries cease functioning, blood concentrations of FSH and LH increase. Women with ovarian failure experience thesymptoms and signs of estrogen deficiency. A summary of causes is presented in Box 35.3.

 

ALTERATION OF THE GENITAL OUTFLOW TRACT

 

Obstruction of the genital outflow tract prevents overt menstrual bleeding even if ovulation occurs.

 

Box 35.3

Causes of Ovarian Failure

Chromosomal Causes

Turner syndrome (45,X gonadal dysgenesis)

X chromosome long-arm deletion (46,XX q5)

Other Causes

Gonadotropin-resistant ovary syndrome (Savage syndrome)

Premature natural menopause

Autoimmune ovarian failure (Blizzard syndrome)

 

Most cases ofoutflow obstruction result from congenital abnormalities in the  development and canalization of the müllerian ducts. Imperforatehymen and no uterus or vagina are the most common anomalies that result in primary amenorrhea. Surgical cor-rection of an imperforate hymen allows for menstruation and fertility. Less-commonly encountered anomalies, such as a transverse vaginal septum, are more difficult to correct, and even with attempted surgical correction, menstruation and fertility are often not restored.

 

Scarring of the uterine cavity (Asherman syndrome) is the most frequent anatomic cause of secondary amenorrhea (Fig. 35.1). Women who undergo dilation and curettage (D&C) for retained products of pregnancy (especially when infection is present) are at risk for developing scar-ring of the endometrium. Cases of mild scarring can be corrected by surgical lysis of the adhesions performed by hysteroscopy and D&C. However, severe cases are often refractory to therapy. Estrogen therapy should be added to the surgical treatment postoperatively to stimulate endometrial regeneration of the denuded areas. In some cases, a balloon or intrauterine (contraceptive) device may be placed in the uterine cavity to help keep the uterine walls apart during healing.




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