Amenorrhea

For patient information on primary amenorrhea, click here

For patient information on secondary amenorrhea, click here

Overview
Amenorrhoea (British English), amenorrhea (American English), or amenorrhœa, is the absence of a menstrual period in a woman of reproductive age. Physiologic states of amenorrhoea are seen during pregnancy and lactation (breastfeeding), the latter also forming the basis of a form of contraception known as the lactational amenorrhea method. Outside of the reproductive years there is absence of menses during childhood and after menopause. Amenorrhea can be transient, intermittent, or permanentAmenorrhoea is a symptom with many potential causes.

Primary amenorrhea
In primary amenorrhea there is absence of menarche by the age of 16.

Menstruation cycles never begin.

There will be a delay of menses one year beyond the family history of first menses.

There is no defining sexual characteristics by age 14. Primary amenorrhea may be caused by developmental problems such as the congenital absence of the uterus, or failure of the ovary to receive or maintain egg cells. Also, delay in pubertal development will lead to primary amenorrhoea.

Secondary amenorrhea
Secondary amenorrhea is defined as absence of menses in a woman who had previously menstruated for at least 3 cycles or 6 months. Secondary amenorrhea is more common than primary Amenorrhea.

Secondary amenorrhea is often caused by hormonal disturbances from the hypothalamus and the pituitary gland or from premature menopause, or intrauterine scar formation.

Oligomenorrhea
Oligomenorrhea is a condition in which menses are infrequent. This condition is not the same as Amenorrhea.

Etymology and history
The term is derived from Greek: a = negative, men = month, rhoia = flow. Derived adjectives are amenorrheal and amenorrheic. The opposite is the normal menstrual period.

Historically, the term amenorrhea has often been used as a euphemism for "unwanted pregnancy" and many folk treatments for this condition are in fact abortifacients.

Pregnancy, as noted, is only one potential cause for amenorrhea; sometimes pseudo-pregnancy can be a cause for this as well.

Complete Differential Diagnosis of Amenorrhea
Causes include:In alphabetical order.

Primary Amenorrhea

 * 17 beta-hydroxysteroid dehydrogenase deficiency
 * Agonadism
 * After trauma
 * Anorexia Nervosa
 * Anovulation
 * Complete androgen insenstivity syndrome
 * Constitutional bradygenesis
 * Constitutional delay of puberty
 * Diabetes Mellitus
 * Early infantile brain damage
 * Gonadal dysgenesis
 * Homozygous adrenogenital syndrome
 * Hymenal atresia
 * Hyperandrogenism
 * Hypothalamic and pituitary tumors
 * Hyperprolactinemia / Prolactin-secreting tumors
 * Dysgerminoma
 * Craniopharyngioma
 * Idiopathic gonadotropin deficiency
 * Kallmann's Syndrome
 * Mayer-Rokitansky-Hauser Syndrome
 * Mullerian dysgenesis
 * Outflow tract disorders
 * Pituitary insufficiency
 * Pituitary schistosomiasis
 * Pituitary tuberculosis
 * Empty Sella Syndrome
 * Polycystic Ovary Syndrome
 * Post-hormonal contraceptive Amenorrhea
 * Severe systemic diseases
 * Swyer's Syndrome
 * Testicular feminization
 * Turner's Syndrome
 * Uterine atresia
 * Uterine hypoplasia
 * Vaginal atresia / gynatresia

Secondary Amenorrhea

 * 5-alpha-reductase deficiency
 * Addiction
 * Addison's Disease
 * Adrenocortical insuffiency
 * After curettage
 * After hysterectomy
 * After radiation (can be reversed)
 * Adrenal tumors
 * Anovulation
 * Asherman's Syndrome
 * Autoimmune diseases
 * Body building (and use of androgens)
 * Castration (radiation or surgical)
 * Central nervous system tumor (CNS)
 * Cervical stenosis
 * Change of environment
 * Complete and incomplete androgen insensitivity
 * Congenital adrenal hyperplasia
 * Craniocerebral trauma
 * Cushing's Syndrome
 * Depression
 * Diabetes Mellitus
 * Encephalitis
 * Enzymatic defects in testosterone biosynthesis
 * Exposure to maternal androgens in utero
 * Extreme obesity
 * During chemotherapy
 * Functional hypothalalmic Amenorrhea due to:
 * Stress
 * Eating disorders
 * Excessive exercise
 * Weight loss
 * Gonadotropin deficiency in tumors
 * Hormone-active ovarian tumor
 * Hermaphroditism
 * Heterozygous adrenogenital syndrome
 * Hyperprolactinemia
 * Hyperthyroidism
 * Hypothyroidism
 * Hysterectomy
 * Imprisonment
 * Meningitis
 * Mullerian anomalies
 * Myotonic dystrophy
 * Pituitary insufficiency
 * Polycystic ovary syndrome
 * Post-hormonal contraception
 * Post-infection (mumps, severe pelvic inflammatory disease)
 * Postoerative gonadotropin deficiency
 * Pregnancy
 * Premature menopause
 * Prolactinoma
 * Sheehan's Syndrome
 * Stress
 * Testicular feminization
 * Transsexuality when taking androgens
 * Turner's Syndrome
 * Uterine cavity sclerosis
 * Uterine Schistosomiasis
 * Abortion
 * Severe generalized infections of the pelvis
 * Post uterine surgery
 * Overzealous or repeated uterine curettage
 * Tuberculosis endometritis

Differential Diagnosis Organized by Category of Causes

 * Physiologic
 * Pregnancy
 * Lactation
 * Menopause
 * Hypothalamic
 * Structural
 * Craniopharyngioma
 * Lymphoma
 * Sarcoidosis
 * Hemochromatosis
 * Functional
 * Anorexia/bulimia
 * Excessive exercise/weight loss
 * Stress
 *  Pituitary 
 * Secretory tumors
 * Prolactinoma
 * Cushing’s disease
 * Acromegaly
 * Destructive lesions
 * Non-functional tumors
 * Sheehan's syndrome
 * Hemochromatosis
 *  Ovarian 
 * Premature ovarian failure
 * Hyperandrogenic disorders
 * polycystic ovary syndrome (PCOS)
 * Nonclassical congenital adrenal hyperplasia (NCCAH)
 * Adrenal/ovarian androgen-secreting tumors
 *  Anatomic 
 * Destruction of uterine cavity
 * Asherman’s syndrome
 * Tuberculosis (TB)
 *  Other 
 * Hyperthyroidism/hypothyroidism
 * Cushing’s syndrome

Hormonal involvement
Hypogonadotropic amenorrhoea refers to conditions where there are very low levels of serum FSH and LH. Generally, inadequate levels of these hormones lead to inadequately stimulated ovaries who then fail to produce enough estrogen to stimulate the endometrium (uterine lining), hence amenorrhoea. This is typical for conditions of pubertal delay, hypothalamic or pituitary dysfunction. In general, women with hypogonadotropic amenorrhoea are potentially fertile.

Hypergonadotropic amenorrhoea refers to conditions with high levels of FSH (and LH). FSH levels are typically in the menopausal range. This implies that the ovary or gonad does not respond to pituitary stimulation. Gonadal dysgenesis or premature menopause are possible causes. Chromosome testing is usually indicated in younger individuals with hypergonadotropic amenorrhoea.

In normogonadotropic amenorrhoea, FSH levels are in the normal range. This would suggest that the hypothalamic-pituitary-ovarian axis is functional. Amenorrhoea may be due to outflow obstruction, or abnormal ovarian regulation or excess androgens as seen in polycystic ovary syndrome.

Cushing's Disease/Syndrome can also cause amenorrhoea due to excessive amounts of cortisol in the blood stream.

Exercise amenorrhoea
Female athletes or women who perform considerable amounts of exercise on a regular basis are at risk of developing 'athletic' amenorrhoea. It was thought for many years that low body fat levels and exercise related chemicals (such as beta endorphins and catecholamines) disrupt the interplay of the sex hormones estrogen and progesterone. However recent studies have shown that there are no differences in the body composition, or hormonal levels in amenorrheic athletes. Instead, amenorrhea has been shown to be directly attributable to a low energy availability. Many women who exercise at a high level do not take in enough calories to expend on their exercise as well as to maintain their normal menstrual cycles. 

A second serious risk factor of amenorrhea is severe bone loss sometimes resulting in osteoporosis and osteopenia. It is the third component of an increasingly common disease known as female athlete triad syndrome. The other two components of this syndrome are osteoporosis and disordered eating. Awareness and intervention can usually prevent this occurrence in most female athletes.

High risk sports

 * Cross country
 * Ballet
 * Track and Field
 * Swimming
 * Cycling
 * Rowing
 * Diving
 * Figure skating
 * Gymnastics
 * all other intense and strenuous sports

Drug-induced amenorrhea
Certain medications, particularly contraceptive medications, can induce amenorrhoea in a healthy woman. The lack of menstruation usually begins shortly after beginning the medication and can take up to a year to resume after stopping a medication. Hormonal contraceptives that contain only progestogen like the oral contraceptive Micronor, and especially higher-dose formulations like the injectable Depo Provera commonly induce this side-effect. Recently, an extended cycle combined oral contraceptive pill which aims to purposefully induce amenorrhea (Lybrel), has been approved by the FDA.

Laboratory Studies
Any woman of child bearing potential should have a pregnancy test ordered to rule out pregnancy.

Otherwise, consideration should be given to the following laboratory studies based upon clinical suspicion:
 * Estradiol
 * Prolactin
 * Thyroid stimulating hormone (TSH)
 * Follicle stimulating hormone (FSH)
 * Luteinizing hormone (LH)
 * Testosterone
 * 17-hydroxyprogesterone
 * Dehydroepiandrosterone-sulfate (DHEA-S)

Imaging Studies
If a pituitary cause of amenorrhea is thought to be present, then MRI or a CT of the head should be obtained. Signs and symptoms of pituitary involvement include headache, visual field cuts, and elevated prolactin levels.

Public ultrasound will reveal abnormalities of the mullerian structures such as uterine hypoplasia.

Treatment
Treatmentment varies depending upon the underlying condition. For those who do not plan to have biological children, treatment may be unnecessary if the underlying cause of the amenorrhoea is not threatening to the patient's health.

Lifestyle Changes
The best way to treat 'athletic' amenorrhoea is to decrease the amount and intensity of exercise. Weight gain may be helpful as well. To prevent osteoporosis, consider oral contraceptives. Pulsatile gonadotropin-releasing hormone (GnRH) or exogenous gonadotropins may be necessary.

Pharmacotherapy
Hormone replacement therapy should be considered for ovarian failure. Unless receiving eggs from an egg donor or invetro fertilization, a woman is unable to conceive while she is amenorrhoeic. On the other hand, 'athletic' and drug-induced amenorrhoea has no effect on long term fertility as long as menstruation can recommence. Similarly, to treat drug-induced amenorrhea, stopping the medication on the advice of a doctor is the usual course of action.

In polycystic ovarian disease the following may be helpful:
 * To decrease peripheral estrogen, reduce weight
 * To decrease ovarian androgen secretion, consider oral contraceptives
 * Clomiphene enhances fertility
 * Endometrial hyperplasia is prevented by cyclic progesterone

Surgical Treatment
Surgical correction may be required if an imperforate hymen is the cause.

Psychological Counseling
Psychological counseling may be helpful if there is the presence of a Y chromosome or absent mullerian organs.

Prognosis
Among patients with androgen insensitivity syndrome there is an increased risk of testicular cancer, and surveillance should be encouraged.