Menstruation: Absent Periods (Amenorrhea)
DescriptionAn in-depth report on the causes and treatment of absent periods.
Alternative NamesMenstrual Disorders
According to some evidence, the four major causes of primary amenorrhea (in which a woman has never had a period) are the following: ovarian failure (48.5% of cases of amenorrhea); born with no uterus and vagina (15.2%); deficiencies in reproductive hormones, such as in hypogonadotropic hypogonadism (8.3%); and delayed puberty (6%). Until recently, the great majority of these women were unable to become pregnant. Advances in reproductive techniques, however, are enabling many to have children.
There are many causes of secondary amenorrhea, including eating disorders, polycystic ovarian syndrome, and a number of medications and medical conditions.
The most common cause of primary amenorrhea is delayed puberty due to some genetic factor that delays physical development. Being short is the most common sign of this, although sometimes a family history of delayed menstruation can indicate this situation. Time usually resolves the problem.
Functional Hypothalamic Amenorrhea (FHA) and Eating Disorders
Functional hypothalamic amenorrhea (FHA) is the absence of menstruation due to disturbances in the thyroid gland and hypothalamus-pituitary-adrenal (HPA) system, which regulates reproduction and other important functions. The eating disorders anorexia and bulimia are most often associated with FHA. FHA may be due to other different factors, most unknown.
Severe weight loss, changes of appetite, or both appear to cause hormonal abnormalities that can cause FHA. How this occurs is not entirely clear. Some observations include the following:
Treatments for Functional Hypothalamus Amenorrhea. In one small 2002 study, 70% of women with FHA recovered with no therapy at all after an average of eight years. The important factors associated with recovery were weight gain or maintenance of normal weight, lowering stress hormone levels, and restoring normal estrogen levels. If anorexia is the cause of FHA, it should be treated immediately and aggressively, since severe anorexia can be life threatening.An important goal is to reduce or prevent bone mass depletion, which occurs in almost 90% of women with anorexia. Estrogen replacement is usually not useful, but there are many available bone protective agents, such as calcium and vitamin D supplements and bisphosphonate, such as alendronate (Fosamax). Other agents showing promise for improving bone density and other symptoms of anorexia include dehydroepiandrosterone (DHEA), a weak male hormone, and recombinant human IGF-I (rhIGF-I), which is a growth hormone. Other supplements that might be required, particularly in women with the female athlete triad, include B vitamins, zinc, and iron.
[For more information, see Well-Connected Report # 49, Eating Disorders.]
Polycystic Ovarian Syndrome (PCOS)
Polycystic ovarian syndrome (PCOS) is a condition in which the ovaries produce high amounts of androgens (male hormones), particularly testosterone. PCOS occurs in about 6% of women, and amenorrhea or oligomenorrhea (infrequent menses) is quite common. According to a 2002 study, nearly 30% of obese women with PCOS had amenorrhea. (The rate was lower--4.7%--in women with normal weight.)
In PCOS, increased androgen production produces high LH levels and low FSH levels, so that follicles are prevented from producing a mature egg. Without egg production, the follicles swell with fluid and form into cysts. Every time an egg is trapped within the follicle, another cyst forms, so the ovary swells, sometimes reaching the size of a grapefruit. Without ovulation, progesterone is no longer produced, whereas estrogen levels remain normal.
The elevated levels of androgens (hyperandrogenism) can cause obesity, facial hair, and acne, although not all women with PCOS have such symptoms. Other male characteristics, such as deepening voice and clitoral enlargement, are rare.
PCOS also poses a high risk for insulin resistance, particularly in women who are also obese. Insulin resistance is associated with diabetes type 2, in which insulin levels are normal or high but the body cannot use this hormone efficiently. About half of PCOS patients, in fact, also have diabetes.
The drug valproate (used to treat seizures and bipolar disease) has been associated with PCOS. In most cases, the cause of PCOS is unknown.
Treating Polycystic Ovary Syndrome. Treatments for PCOS include the following:
Elevated Prolactin Levels (Hyperprolactinemia)
Prolactin is a hormone produced in the pituitary gland that stimulates breast development and milk production in association with pregnancy. High levels of prolactin (hyperprolactinemia) in women who are not pregnant or nursing can reduce gonadotropin hormones and inhibit ovulation, thus causing amenorrhea. It is the cause of between 10% and 40% of cases of secondary amenorrhea. Secretions from the breast not related to pregnancy or nursing (called galactorrhea) is a telltale symptom of high prolactin levels and should be investigated.
Hyperprolactinemia can be caused by hypothyroidism or pituitary adenomas. (These are benign tumors that secrete prolactin. They can cause headache and visual problems as well as breast secretions.) Some drugs, including oral contraceptives and some antipsychotic drugs, can also elevate levels of prolactin.
Medications Used to Treat Hyperprolactemia. Agents known as dopamine agonists are used for women with hyperprolactinemia caused by tumors in the pituitary gland.
Surgery. Surgery may be needed for women who do not respond to medications or whose tumors are large, but recurrence occurs in as many as 40% of patients within five years.
Premature Ovarian Failure (POF)
Premature ovarian failure (POF) is the early depletion of follicles before age 40, which, in most cases, leads to premature menopause. It affects about 1% of women and is typically preceded by irregular periods, which might continue for years. In this condition, follicle-stimulating hormones (FSH) are elevated, as they are during perimenopause. Premature ovarian failure is a significant cause of infertility and women who have this condition have only a 5% to 10% chance to conceive without fertility treatments.
Causes of Premature Ovarian Failure. There are a number of causes of POF. Often the cause of this disorder or other causes of POF is unknown. In some cases, it may represent an acceleration of the aging process.
The following may conditions may produce POF:
Managing Premature Ovarian Failure. There is no treatment available that will restore ovarian function in women with premature ovarian failure. Women who wish to be pregnant usually will require in vitro fertilization with donor eggs. Hormone replacement therapy may be used to prevent bone loss and reduce menopause symptoms. Freezing ovarian tissue is under investigation for women who are at risk for premature ovarian failure, such as young women with a genetic history of this condition or those who need to undergo cancer treatments.
Idiopathic Hypogonadotropic Hypogonadism
Idiopathic hypogonadotropic hypogonadism is a rare condition in which follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are underproduced and prevent the development of functional ovaries. There are no other abnormalities in the hypothalamus-pituitary axis (such as tumors or abnormal stress hormones or prolactin). In most cases, the causes of hypergonadotropic hypogonadism are unknown. Genetic factors, including Kallman's syndrome, have been identified in about 20% of these cases.
Structural Problems Causing Obstruction
In some cases, structure problems or scarring in the uterus may prevent menstrual flow. Inborn genital tract abnormalities may also cause primary amenorrhea. Ashermans syndrome, for example, is scarring in the uterus that can cause obstructions and secondary amenorrhea. It may be caused by surgery, repeated injury, or unknown factors. A specific malformation called Mullerian agenesis, in which no vagina or uterus develops, is rare but still causes about 16% of primary amenorrhea cases.
Medical Conditions That Cause Secondary Amenorrhea
Epilepsy. Epilepsy is associated with a number of reproductive disorders that cause amenorrhea, including polycystic ovary syndrome, functional hypothalamic amenorrhea, hyperprolactinemia, and high levels of male hormones. Evidence suggests that any of the following conditions may account for such associations:
Thyroid Problems. Thyroid problems, either too much thyroid hormone (hyperthyroidism) or too little (hypothyroidism), can interrupt cycles. Hypothyroidism can result in excess prolactin. Most women with hypothyroidism fail to produce eggs, and they may receive a diagnosis of hypothyroidism for the first time during a fertility evaluation. [SeeWell-Connected Report #38 Hypothyroidism.]
Celiac Sprue. Celiac sprue is an inability to tolerate gluten, a protein found in wheat, rye, oats, barley, and other grains. Exposure to gluten damages the lining of the intestinal tract. It is also associated with late puberty, early menopause, and amenorrhea. This disorder is now considered more common than previously believed and may even be linked to non-intestinal symptoms, such as depression, discolored teeth, and neurologic problems.
Metabolic Syndrome. A set of conditions referred to metabolic syndrome (also called syndrome X) consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease. A 2002 study also reported that, as with PCOS, women with metabolic syndrome have higher levels of male hormones and are, therefore, at risk for irregular periods and infertility. A 2002 study estimated that 24% of the population now has this condition.
Other Conditions. Cushing's disease, which is a disorder of the adrenal gland, can cause amenorrhea. Other medical conditions associated with delayed puberty and amenorrhea include Crohn's disease, sickle cell disease, HIV, kidney disease, and diabetes.
Other Factors That May Cause or Contribute to Amenorrhea
Stress. Physical and emotional stress may block the release of luteinizing hormone, causing temporary amenorrhea.
Obesity. Obesity is a significant risk factor for amenorrhea, independent of its association with polycystic ovarian syndrome (PCOS). In one 2003 study, overweight women without PCOS were classified in one of five grades, depending on the severity of the obesity. The risk for irregular or absent periods increased two fold with each increase in grade. In this group, amenorrhea was also highly associated with type 2 diabetes and other blood sugar abnormalities.