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Amenorrhea

Amenorrhea Overview Definition Etiology Risk Factors Signs and Symptoms Differential Diagnosis Diagnosis Physical Examination Laboratory Tests Pathology/Pathophysiology Imaging Other Diagnostic Procedures Treatment Options Treatment Strategy Drug Therapies Complementary and Alternative Therapies Patient Monitoring Other Considerations Prevention Complications/Sequelae Prognosis Pregnancy References
Overview Definition

Amenorrhea is the absence of menses. Primary amenorrhea is defined as the failure of menses to begin once a woman reaches 16 years of age, whether or not other pubertal changes such as breast development/pubic or axillary hair are present. Secondary amenorrhea is the absence of menses for the length of time equal to three consecutive normal menstrual cycles in a woman who has previously experienced cyclical menses. Interference with hypothalamic/pituitary functioning plays a major role in the disorder, and the resultant "hypoestrogenemic amenorrhea" may play a role in the development of cardiovascular disease, osteoporosis, and infertility. Amenorrhea may be present with other conditions or abnormalities, including hirsutism, obesity, and galactorrhea. Incidence of primary amenorrhea in U.S. is 2.5% of female population.

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Etiology

Generally, the causes of amenorrhea include certain genetic defects, anatomic abnormalities, ovarian failure, or hypothalamic, pituitary, or other endocrine dysfunction.

  • Pregnancy—high hCG: (Primary—even in denial of intercourse/Secondary)
  • Hypothalamic/pituitary dysfunction—low-normal follicle-stimulating hormone (FSH): Interferes with GnRH production, therefore pituitary gonadotropin secretion (Primary/Secondary)
  • Ovarian—high FSH: Dysfunction/dysgenesis of ovaries (Primary); premature ovarian failure (before the age of 40) (Secondary)
  • Hyperandrogenism—low-normal FSH: Secretion of excessive testosterone (Primary/Secondary)
  • Pseudohermaphroditism—high luteinizing hormone (LH): Defective testosterone synthesis with excessive testosterone levels (Primary)
  • Uterine—normal FSH: Absent or malformed uterus (Primary); intrauterine infection, endometritis (Secondary)
  • Menopause—high FSH: Beginning as early as age 40 (Secondary)
  • Normal delayed onset (Primary)

Related causes:

  • Breast-feeding
  • After stopping oral contraceptive use
  • Diabetes mellitus
  • Tuberculosis
  • Stress
  • Psychological disorders
  • Brain disease
  • Genetic defect
  • Testicular Feminization Syndrome
  • Malnutrition/extreme weight loss (anorexia)
  • Strenuous exercise of long duration
  • Extreme obesity
  • Drug abuse
  • Cyanotic congenital heart disease
  • Drug therapies—steroids, danazol
  • Turner's Syndrome

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Risk Factors
  • Genetic deficiencies
  • Endocrine system disorders
  • Extreme athletic training
  • Psychological stresses

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Signs and Symptoms

In addition to the obvious absence of menses, there may be other symptoms related to the particular cause of the amenorrhea. They include:

  • Primary: Headaches, blood pressure/visual field abnormalities, acne, short stature (Turner's syndrome), tall stature (eunuchoidism/gigantism)
  • Secondary: Nausea, breast enlargement, hot flushes, headaches, visual field abnormalities, thirst, polyuria, goiter, skin darkening, anorexia, alcoholism, Cushing's syndrome, cirrhosis, renal failure

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Differential Diagnosis
  • Primary and/or sexual infantilism: Differentiate between gonadal dysgenesis and hypopituitarism.
  • Rule out pregnancy.
  • Anatomical variants or tumor mass through examination

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Diagnosis Physical Examination
  • Breasts may or may not be developed; pubic and axillary hair may or may not be present; external genitalia/reproductive organs may be abnormal or absent.
  • History and physical examination should determine the cause of amenorrhea.

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Laboratory Tests
  • Pregnancy test (serum or urine hCG)
  • Cervical mucus/endometrium analysis
  • Serum analysis: GnRH, LH, FSH, thyroid-stimulating hormone (TSH), T3, T4, prolactin, estrogen, testosterone levels
  • Renal/hepatic function
  • Plasma potassium

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Pathology/Pathophysiology
  • Dependent upon underlying disorder

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Imaging

Frequently not necessary. Imaging studies could include:

  • CT/MRI of head for brain/pituitary disease
  • MRI of hypothalamus if high prolactin levels
  • Pelvic ultrasound

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Other Diagnostic Procedures
  • Detailed medical history, including prior menstrual cycles
  • Physical examination to determine degree of breast development; presence of pubic and axillary hair in pubescent girls
  • Examine external genitalia/reproductive organs: presence of uterus
  • Chromosome analysis
  • Trial period—usually 10 days—with progesterone and/or MPA or estrogen. If bleeding follows withdrawal, reproductive system is functional.

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Treatment Options Treatment Strategy

Treat according to underlying cause.

  • Pituitary tumors: Bromocriptine to inhibit prolactin secretion; surgical removal; radiation therapy
  • Developmental abnormalities: Hormone therapy; surgery; psychosocial counseling and support
  • Oral contraceptives or hormones to artificially induce menses
  • Estrogen replacement therapy for hypogonadism/hysterectomy/post menopause

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Drug Therapies
  • Estrogen replacement therapy: Greatly reduces risk of cardiovascular disease and inhibits osteoporosis. Conjugated estrogens 0.625 to 1.25 mg/day; or on days 1 to 25 of calendar month (0.3 mg/day prevents bone loss). Women with intact uterus should receive progestin to reduce risk of estrogen-induced endometrial carcinoma.
  • Medroxyprogesterone acetate (MPA)—progestin of choice—is given at 5 to 10 mg/day on days 16 to 25 of calendar month
  • Alternative estrogen replacement: Includes ethinyl estradiol (20 or 50 mcg); estradiol (0.5, 1, 2 mg); Selective Estrogen Receptor Modulators (SERMs) such as raloxifene and Evista for patients refusing estrogen but at-risk for osteoporosis
  • Progesterone: For ovarian cysts or some intrauterine disorders (if no pregnancy desired)
  • Pulsatile GnRH: To stimulate reproductive function
  • Long-acting GnRH analogs: To suppress reproductive function
  • Specific drugs to treat underlying disorders

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Complementary and Alternative Therapies

Treating amenorrhea with alternative therapies may be effective in aiding the body to metabolize hormones efficiently while ensuring that the nutritional requirements for hormone production are met. Begin with nutritional support, vitamins and minerals, and essential fatty acids. Herbal treatment should begin with Vitex alone. Other herbs may be added according to underlying etiology. Minimum length of treatment is three months.

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Nutrition

Minimize refined foods, as they deplete the body of magnesium and other essential nutrients which are needed for normal hormone production. Limit animal products, as they are a source of saturated fats and exogenous estrogens. Limit the Brassica family of vegetables (cabbage, broccoli, brussel sprouts, cauliflower, kale) because they inhibit thyroid function. Eliminate methylxanthines (coffee, chocolate), as they place a burden on the liver and may compromise appropriate hormone ratios. Include whole grains, organic vegetables, and omega-3 fats (cold-water fish, nuts, and seeds).

  • Calcium (1,000 mg/day), magnesium (600 mg/day), vitamin D (200 to 400 IU/day), vitamin K (1 mg/day), and boron (1 to 3 mg/day) help to optimize bone density and are needed for hormone production.
  • Iodine (up to 600 mcg/day), tyrosine (200 mg one to two times/day), zinc (30 mg/day), vitamin E (800 IU/day), vitamin A (10,000 to 15,000 IU/day), vitamin C (1,000 mg tid), and selenium (200 mcg/day) are needed for thyroid health and hormone balance.
  • B6 (200 mg/day) is a specific therapy which may reduce high prolactin levels caused by pituitary tumors.
  • Essential fatty acids: Flaxseed, evening primrose, or borage oil (1,000 to 1,500 mg one to two times/day) to enhance hormone production

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Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, it is important to ascertain a diagnosis before pursuing treatment. Herbs may be used as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, teas should be made with 1 tsp. herb per cup of hot water. Steep covered 5 to 10 minutes for leaf or flowers, and 10 to 20 minutes for roots. Drink 2 to 4 cups/day. Tinctures may be used singly or in combination as noted.

Amenorrhea needs to be treated with a well-balanced formula that supports pituitary function and hormone activity, as well as addressing the underlying cause. Balancing hormones should be undertaken with the supervision of a qualified practitioner.

  • Chaste tree (Vitex agnus cactus) helps to normalize pituitary function but must be taken long term (12 to 18 months) for maximum effectiveness. To be used only under physician supervision with hormone therapy.
  • Black cohosh (Cimicifuga racemosa), licorice (Glycyrrhiza glabra), and squaw vine (Mitchella repens) help to balance estrogen levels. Licorice is contraindicated in hypertension.
  • Chaste tree, wild yam (Dioscorea villosa), and lady's mantle (Alchemilla vulgaris) help to balance progesterone levels.
  • Kelp (Laminaria hyperborea), bladderwrack (Fucus vesiculosus), oatstraw (Avena sativa), and horsetail (Equisetum arvense) are rich in minerals that support the thyroid.
  • Milk thistle (Silybum marianum), dandelion root (Taraxacum officinale), and vervain (Verbena hastata) support the liver and may help restore hormone ratios.
  • Sage (Salvia officinalis) is a specific herb for reducing high prolactin levels due to pituitary tumors.

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Homeopathy

Constitutional homeopathic support can be very effective in addressing underlying causes of amenorrhea. This should be done by an experienced homeopathic practitioner.

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Physical Medicine

The following methods help to increase circulation and relieve pelvic congestion.

  • Castor oil pack. Used externally, castor oil is a powerful anti-inflammatory. Apply oil directly to skin, cover with a clean soft cloth (e.g., flannel) and plastic wrap. Place a heat source (hot water bottle or heating pad) over the pack and let sit for 30 to 60 minutes. For best results, use for three consecutive days.
  • Contrast sitz baths. Use two basins that can be comfortably sat in. Fill one with hot water, one with cold water. Sit in hot water for three minutes, then in cold water for one minute. Repeat this three times to complete one set. Do one to two sets per day three to four days per week.

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Acupuncture

Treatment of amenorrhea with acupuncture may be beneficial for normalizing hormone production and endocrine function. In some cases it may restore regular menstrual cycles.

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Massage

Therapeutic massage may be helpful in relieving the effects of stress and improving endocrine function.

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Patient Monitoring

Track progress of therapy.

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Other Considerations

Although the mechanism is not known, the fat cell hormone, "leptin," is necessary for a healthy reproductive system.

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Prevention
  • When cause is unknown, prevention is not possible
  • Attention to nutrition/appropriate body weight/alcohol and drug abuse
  • Stress-relieving techniques
  • Avoid extreme exercise regimens

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Complications/Sequelae
  • Emotional and psychological distress, particularly in congenital defects and if pregnancy is desired and unattainable
  • Hot flushes, mood changes, depression, and vaginal dryness in estrogen deficiency
  • Long-term estrogen replacement increases risk of breast cancer, melanoma, seizures; 10-fold increased risk of endometrial carcinoma if unopposed with progestin. May cause weight gain, tender breasts, edema, and—rarely—venous thrombosis, and hypertriglyceridemia

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Prognosis
  • Not detrimental to overall health
  • Prognosis is good where underlying disorders are correctly diagnosed and treated (normal delay of onset, weight issues, chronic illnesses, benign tumors, ovarian cysts, hormone imbalances, and similar causes; poor for congenital abnormalities, testicular feminization syndrome, true hermaphroditism, cystic fibrosis, Prader-Willi syndrome, and similar disorders
  • After pregnancy and breast-feeding cease: Menses usually return spontaneously
  • Discontinuation of oral contraceptives: Menses usually rectify spontaneously within 24 months
  • Post-menopause/hysterectomy: Menses cease
  • Irreversible amenorrhea: Where this causes emotional distress, induction of pseudo-menstruation may be possible through drug therapy if uterus is present

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Pregnancy
  • Impossible in certain congenital abnormalities
  • Fertility may be affected
  • Complications such as incomplete spontaneous abortion, ectopic pregnancy, trophoblastic disease

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References

Mowrey DB. The Scientific Validation of Herbal Medicine. New Canaan, Conn: Keats Publishing; 1988.

National Institutes of Health: Accessed at www.nih.gov on January 16, 1999.

Tierney LM, McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment 1999. 38th ed. Stamford, Conn: Appleton & Lange; 1999.

Tyler VE. Herbs of Choice: The Therapeutic Use of Phytomedicinals. Binghamton, NY: Pharmaceutical Products Press; 1994.

Ullman D. Discovering Homeopathy. Berkeley, Calif: North Atlantic Books; 1991.

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