Amenorrhea (Absence of Menstrual Bleeding)

Amenorrhea is a symptom of an underlying disorder rather than a condition in and of itself.

Amenorrhea is the absence of menstrual bleeding and may be primary or secondary.

• Primary amenorrhea is the absence of menstrual bleeding and secondary sexual characteristics (for example, breast development and pubic hair) in a girl by age 14 years or the absence of menstrual bleeding with normal development of secondary sexual characteristics in a girl by age 16 years.
• Secondary amenorrhea is the absence of menstrual bleeding in a woman who had been menstruating but later stops menstruating for three or more months in the absence of pregnancy, lactation (production of breast milk), cycle suppression with systemic hormonal contraceptive (birth control) pills, or menopause.

For a woman to have regular menstrual cycles, her hypothalamus, pituitary gland, ovaries, and uterus should all be functioning normally. The hypothalamus stimulates the pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH cause the ovaries to produce the hormones estrogen and progesterone. Estrogen and progesterone are responsible for the cyclical changes in the endometrium (uterine lining), including menstruation. In addition, a woman’s genital tract should be free of any abnormalities to allow the passage of menstrual blood.

Amenorrhea can result because of an abnormality in the hypothalamic-pituitary-ovarian axis, anatomical abnormalities of the genital tract, or functional causes.

Hypothalamic causes

• Craniopharyngioma (a brain tumor near the pituitary gland)
• Kallmann syndrome (deficiency of gonadotropins, which are hormones capable of promoting growth and function of reproductive organs)
• Nutritional deficiency
• Low body weight or growth delay

Pituitary causes

• Prolactinoma (high blood levels of prolactin, a hormone that stimulates secretion of milk from the breasts during breastfeeding) - is possibly caused by prolactinoma (a tumor of the pituitary gland secreting the hormone prolactin)
• Disorders related to other pituitary tumors (for example, Cushing syndrome, acromegaly, or thyroid-stimulating hormone)
• Postpartum pituitary necrosis (death of pituitary cells after a woman delivers a baby)
• Autoimmune hypophysitis (cells of the pituitary gland destroyed by the body’s own defense system)
• Craniopharyngioma (a tumor within the pituitary gland)
• Pituitary radiation
• Sarcoidosis (a generalized disease that may affect the pituitary)

Ovarian causes

• Anovulation (lack of the release of an egg)
• Hyperandrogenemia (high blood levels of male hormones)
• Polycystic ovary syndrome (hormonal disorder affecting women of reproductive age)
• Premature ovarian failure
• Turner syndrome (a genetic disorder characterized by underdeveloped ovaries, failure to menstruate, and short stature)
• Pure gonadal dysgenesis (defective development of the ovary)
• Autoimmune oophoritis (cells of the ovaries destroyed by the body’s own defense system)
• Fragile X premutation
• Radiation or chemotherapy
• Galactosemia (an inherited disorder in which galactose, a type of sugar, accumulates in the blood)
• Anatomical abnormalities of the genital tract
• Intrauterine adhesions
• Imperforate hymen (a hymen in which there is no opening, the membrane completely closes off the vagina)
• Transverse vaginal septum (a dividing wall or membrane in the vagina)
• Aplasia (absence of an organ or tissue) of the vagina, the cervix, or the uterus

Functional causes

• Anorexia/bulimia
• Chronic diseases (for example, tuberculosis)
• Excessive weight gain or weight loss
• Malnutrition
• Depression or other psychiatric disorders
• Recreational drug abuse
• Psychotropic drug use (drugs prescribed to stabilize or improve mood, mental status, or behavior)
• Excessive stress
• Excessive exercise
• Cycle suppression with systemic hormonal contraceptive (birth control) pills

Amenorrhea is a symptom of an underlying disorder rather than a condition in and of itself. Additional symptoms may be present depending on the associated condition.

• Galactorrhea (breasts produce milk in a woman who is not pregnant or breastfeeding), headache, or reduced peripheral vision can be a sign of an intracranial tumor.
• Increased hair growth in a male pattern (hirsutism) may be caused by excess androgen (a hormone that encourages the development of male sex characteristics).
• Vaginal dryness, hot flashes, night sweats, or disordered sleep may be a sign of ovarian insufficiency or premature ovarian failure.
• Noticeable weight gain or weight loss may be present.
• Excessive anxiety may be present in women with associated psychiatric abnormalities.

Consult a health care professional if a girl is 14 years old and her secondary sexual characteristics (for example, breast development and pubic hair) have not started to develop, or a girl is 16 years old and has not had her first menstrual period.

For women who have already begun menstruating, they should see a health care professional if they have missed three consecutive menstrual periods.

A doctor may perform the following tests to determine the cause of the amenorrhea:

• Blood tests may be performed to determine the levels of hormones secreted by the pituitary gland (FSH, LH, TSH, and prolactin) and the ovaries (estrogen).
• Ultrasonography of the pelvis may be performed to assess the abnormalities of the genital tract or to look for polycystic ovaries.
• CT scan or MRI of the head may be performed to exclude pituitary and hypothalamic causes of amenorrhea.

If the above tests are inconclusive, additional tests may be performed including:

• Thyroid function tests
• Determination of prolactin levels
• Hysterosalpingogram (X-ray test) or saline infusion sonography (SIS), both of which examine the uterus
• Hysteroscopy (visual inspection of the uterine cavity)

• In some women, nutritional deficiencies induced by dieting can cause amenorrhea. Such women should eat a properly balanced diet.
• In some women, excessive body weight can be the cause of amenorrhea. These women should restrict the amount of fat in their diet, and they should exercise moderately to maintain ideal body weight.
• More than 8 hours of vigorous exercise a week may cause amenorrhea. A moderate exercise program may restore normal menstruation.
• In women with anorexia nervosa or excessive weight loss, normal menstrual cycles can often be restored by undergoing treatment to restore and maintain healthy body weight.
• If amenorrhea is caused by emotional stress, finding ways to deal with stress and conflicts may help.
• Maintaining a healthy lifestyle by avoiding alcohol consumption and cigarette smoking is also helpful.

Treatment depends on the cause of amenorrhea. Once the cause is determined, treatment is directed at correcting the underlying disease, which should restore menstruation. In case of anatomical abnormalities of the genital tract, surgery may be indicated.

Some causes of amenorrhea can be managed by medical (drug) therapy. Examples include the following:

• Dopamine agonists such as bromocriptine (Parlodel) or pergolide (Permax), are effective in treating hyperprolactinemia. In most women, treatment with dopamine agonist medications restores normal ovarian endocrine function and ovulation.
• Hormone replacement therapy consisting of estrogen and progestin can be used for women in whom estrogen deficiency remains because the ovarian function cannot be restored.
• Metformin (Glucophage) is a drug that has been successfully used in women with polycystic ovary syndrome to induce ovulation.
• In some cases, oral contraceptives may be prescribed to restore the menstrual cycle and to provide estrogen replacement to women with amenorrhea who do not wish to become pregnant. Before administering oral contraceptives, withdrawal bleeding is induced with an injection of progesterone or oral administration of 5-10 mg of medroxyprogesterone (Provera) for 10 days.

• Some pituitary and hypothalamic tumors may require surgery and, in some cases, radiation therapy.
• Women with intrauterine adhesions require the dissolution of the scar tissue.
• Surgical procedures required for other genital tract abnormalities depend on the specific clinical situation.

Follow-up is required for women with amenorrhea caused by ovarian insufficiency. The follow-up is performed to monitor ovarian hormone replacement and to detect the development of associated conditions.

By maintaining a normal weight, girls can prevent primary amenorrhea caused by excessive weight loss or weight gain.

Amenorrhea is typically not a life-threatening condition. The prognosis for amenorrhea depends upon the underlying cause and the type of treatment that is available. For most women, medications, lifestyle changes, or surgery can correct amenorrhea.

Amenorrhea has been associated with reduced bone density and increased fracture rates.