Amenorrhea

Amenorrhoea (BE), amenorrhea (AmE), 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.

Amenorrhoea is a symptom with many potential causes. Primary amenorrhoea (menstruation cycles never starting) 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 amenorrhoea (menstruation cycles ceasing) is often caused by hormonal disturbances from the hypothalamus and the pituitary gland or from premature menopause, or intrauterine scar formation.

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

Historically, the term amenorrhoea 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.

Classification of amenorrhoea
Types of amenorrhoea is diagnosed based on several factors which include the age of onset, and level of hormonal involvement.

Age of onset
There are two types of amenorrhea: primary and secondary amenorrhea. Primary amenorrhoea is the absence of menstruation in a woman by the age of 16. Also, as pubertal changes precede the first period, menarche, women who have no sign of thelarche or pubarche and thus are without evidence of initiation of puberty by the age of 14 have primary amenorrhoea. (Reference: Speroff L et al, Clinical Gynecologic Endocrinology and Infertility, 1999)

Secondary amenorrhoea is where an established menstruation has ceased - for three months in a woman with a history of regular cyclic bleeding, or six months in a woman with a history of irregular periods.

Primary amenorrhoea

 * 1) Gonadal dysgenesis, including Turner Syndrome.
 * 2) Mullerian agenesis (Mayer-von-Rokitansky-Küster-Hauser syndrome (MRKH)).
 * 3) Androgen insensitivity syndrome.
 * 4) Delay in hypothalamic-pituitary maturation.
 * 5) Olfacto-genital dysplasia, Kallmann syndrome.
 * 6) Vaginal obstruction, cryptomenorrhea, imperforate hymen.
 * 7) Receptor abnormalities for FSH, LH.
 * 8) Specific forms of congenital adrenal hyperplasia
 * 9) Swyer syndrome
 * 10) Galactosemia
 * 11) Aromatase deficiency
 * 12) Prader-Willi syndrome
 * 13)  Male pseudo-hermaphroditism (about 1 in every 150,000 births)

Secondary amenorrhoea

 * 1) Pregnancy
 * 2) Anovulation
 * 3) Menopause
 * 4) Premature menopause
 * 5) Hypothalamic-pituitary dysfunction, including
 * 6) Exercise amenorrhoea, related to excessive physical exercise
 * 7) Stress amenorrhoea,
 * 8) Eating disorders and weight loss (obesity, anorexia nervosa, or bulimia)
 * 9) Hyperprolactinemia (elevated prolactin levels)
 * 10) Polycystic ovary syndrome (PCO-S)
 * 11) Androgen producing tumor (i.e arrhenoblastoma)
 * 12) Intrauterine adhesions (Asherman's Syndrome)
 * 13) Thyroid dysfunction
 * 14) Hemochromatosis
 * 15) Drug-induced

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

 * 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.

Treatments
Treatments vary based on the underlying condition. Key issues are problems of surgical correction if appropriate and estrogen therapy if estrogen levels are low.

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 her health.

Unless receiving eggs from an egg donor, 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. The best way to treat 'athletic' amenorrhoea is to decrease the amount and intensity of exercise. Similarly, to treat drug-induced amenorrhoea, stopping the medication on the advice of a doctor is a usual course of action.