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Premature Menopause

(Premature Ovarian Failure; Primary Ovarian Insufficiency)

By JoAnn V. Pinkerton, MD, University of Virginia Health System

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Premature menopause is the permanent end of menstrual periods before age 40. It occurs because the ovaries no longer release eggs (ovulation) and become less able to produce hormones.

  • Some women have no symptoms except being unable to become pregnant, and others have the same symptoms as those of natural menopause (such as hot flashes or night sweats).

  • Blood tests can confirm the diagnosis, and other tests are done to identify the cause.

  • Various measures, including estrogen (typically taken until about age 51, when menopause occurs on average), can relieve or reduce symptoms.

  • To become pregnant, women with premature menopause can have eggs from another woman implanted in their uterus.

Hormonally, premature menopause resembles natural menopause. The ovaries produce very little estrogen. Ovulation stops. However, sometimes the ovaries start functioning for a short time and can release an egg, making pregnancy possible. The ovaries still contain thousands of eggs.

Causes

Premature menopause has many causes:

  • Genetic abnormalities: Chromosomes, including the sex chromosomes, may be abnormal. Sex chromosome abnormalities include Turner syndrome, disorders that confer a Y chromosome (which normally occurs only in males), and Fragile X syndrome.

  • Autoimmune disorders: The body produces abnormal antibodies that attack the body’s tissues, including the ovaries. Examples are thyroiditis, vitiligo, and myasthenia gravis.

  • Metabolic disorders: Addison disease and diabetes are examples.

  • Viral infections: Mumps is an example.

  • Chemotherapy for cancer

  • Radiation therapy

  • Surgical removal of the ovaries: Surgery to remove both ovaries (bilateral oophorectomy) ends menstrual periods and causes menopause.

  • Surgical removal of the uterus: Surgery to remove the uterus (hysterectomy) ends menstrual periods but does not cause most of the other symptoms of menopause as long as the ovaries are functioning.

  • Toxins: Tobacco is an example.

Symptoms

Some women may have no symptoms, except that they cannot become pregnant. Other women develop the same symptoms that are associated with normal menopause (which occurs at about age 51), such as hot flashes, night sweats, or mood swings. Menstrual periods may become lighter or irregular, or they may stop.

The lack of estrogen may lead to decreased bone density (osteoporosis) and thinning and drying of the lining of the vagina (vaginal atrophy). If women with premature menopause do not take estrogen therapy, the risk of mood disorders, Parkinson disease, dementia, and coronary artery disease is increased.

If the cause is a disorder that confers a Y chromosome, the risk of cancer of the ovaries is increased.

Women may have symptoms of the disorder causing premature menopause. For example, if Turner syndrome is the cause, they may be short and have a webbed neck and learning disabilities.

Diagnosis

  • A pregnancy test

  • Measurement of hormone levels

  • Additional tests to identify the cause

  • Sometimes chromosome analysis

Doctors suspect premature menopause when women younger than 40 have menopausal symptoms or cannot become pregnant.

A pregnancy test is done, and levels of estrogen and follicle-stimulating hormone (which stimulates the ovaries to produce estrogen and progesterone) are measured weekly for several weeks to confirm the diagnosis of premature menopause.

Additional tests may be done to help doctors identify the cause of premature menopause and thus evaluate a woman’s health risks and recommend treatment for premature menopause. A new blood test for a substance called anti-mullerian factor (which is produced in the ovaries) can be done to evaluate how well the ovaries are functioning and to estimate the chances that a woman will be able to become pregnant.

For women younger than 35, a chromosome analysis may be done. If a chromosomal abnormality is detected, additional procedures and treatment may be required.

Treatment

  • Oral contraceptives or hormone therapy

  • If pregnancy is desired, in vitro fertilization

If women with premature menopause do not wish to become pregnant, they are given one of the following:

  • Birth control pills that contains estrogen and a progestin (combination oral contraceptives)

  • Hormone therapy that contains a higher dose of estrogen, taken every day, and a progestin or progesterone, taken for 12 to 14 days each month (cyclical hormone therapy)

These treatments are typically taken until the usual time of menopause (on average, until age 51). Then, doctors decide whether to continue the treatments based on the woman's individual circumstances.

Estrogen helps relieve symptoms and helps prevent other effects of menopause (such as vaginal dryness, and mood swings). The higher dose of estrogen in hormone therapy helps maintain bone density. Because taking estrogen alone increases the risk of cancer of the uterine lining (endometrial cancer), most women also take a progestin or progesterone with the estrogen to help protect against this cancer. Women who no longer have a uterus may take estrogen alone.

If women with premature menopause wish to become pregnant, doctors recommend in vitro (test tube) fertilization. Another woman’s eggs (donor eggs) are implanted in the uterus after they have been fertilized in the laboratory. Estrogen and a progestin or progesterone are also given to enable the uterus to support the pregnancy. This technique gives women up to a 50% chance of becoming pregnant. Otherwise the chance of becoming pregnant is less than 10%.

Women who have a Y chromosome need to have their ovaries removed to decrease the risk of developing ovarian cancer. Hormone therapy is usually also recommended for these women until they reach the average age of menopause or longer to prevent the effects of the lack of estrogen.

Drugs Mentioned In This Article

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  • CRINONE

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