Human (Female) Reproduction - Amenorrhoea

Amenorrhoea , is the absence of a menstrual period in a woman of reproductive age. Physiological 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. It is defined as an absence of secondary sexual characteristics by age 14 with no menarche or normal secondary sexual characteristics but no menarche by 16 years of age.

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. It is defined as the absence of menses for three months in a woman with previously normal menstruation or nine months for women with a history of oligomenorrhea.

Etymology and history

The term is derived from Greek: a = negative, men = month, rhoia = flow. Derived adjectives are amenorrhoeal andamenorrheic. The opposite is the normal menstrual period (eumenorrhea). In preindustrial societies, menarche typically occurred later than in current industrial societies. After menarche, menstruation was suppressed during much of a woman`s reproductive life by either pregnancy or nursing. Reductions in age of menarche and lower fertility rates mean that modern women menstruate far more often.

Classification of amenorrhoea

There are two primary ways to classify amenorrhoea. Types of amenorrhoea are classified as primary or secondary, or based on functional compartments (Speroff). The latter classification relates to the hormonal state of the patient that could be hypo-, eu-, or hypergonadotropic (meaning FSH levels are either low, normal or high).

By primary vs. secondary: Primary amenorrhoea is the absence of menstruation in a woman by the age of 16. As pubertal changes precede the first period, or menarche, women by the age of 14 who still have not reached menarche, plus having no sign of secondary sexual characteristics such as thelarche or pubarche -thus are without evidence of initiation of puberty- are also considered as having primary amenorrhoea. Secondary amenorrhoea is where an established menstruation has ceased for three months in a woman with a history of regular cyclic bleeding, or nine months in a woman with a history of irregular periods. This usually happens to women aged 40 55. Amenorrhoea may cause serious pain in the back near the pelvis and spine. This pain has no cure but can be relieved by a short course of progesterone to trigger menstrual bleeding.
By compartent: The reproductive axis can be viewed as having four compartments: 1. outflow tract (uterus,cervix, vagina), 2.ovaries, 3. pituitary gland, and 4. hypothalamus. Pituitary and hypothalamic causes are often grouped together.

P/S	Outflow tract anomalies/obstruction	Gonadal/end-organ disorders	Pituitary and hypothalamic/central regulatory disorders
Overview	Outflow tract abnormalities tend to be normogonadotropic and FSH levels are in the normal range. This would suggest that the hypothalamic-pituitary-ovarian axis is functional. Causes for outflow tract abnormalities include uterine absence and obstructions of the reproductive tract.	Gonadal, usually ovarian, abnomalities tend to be linked to elevated FSH levels or hypergonadotropic amenorrhoea. 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. Low estrogen levels are seen in these patients and the hypoestrogenism may require treatment.	Both hypothalamic and pituitary disoders are linked to low FSH levels leading to hypogonadotropic amenorrhoea. Generally, inadequate levels of these hormones lead to inadequately stimulated ovaries which then fail to produce enough estrogen to stimulate the endometrium (uterine lining), hence amenorrhoea. In general, women with hypogonadotropic amenorrhoea are potentially fertile.
Primary	Uterine: Mullerian agenesis (Second most common cause, 15% of primary amenorrhea)^[6] Vaginal: Vaginal atresia, cryptomenorrhea, imperforate hymen.	Gonadal dysgenesis, including Turner Syndrome. Most common cause. Androgen insensitivity syndrome. Receptor abnormalities for hormones FSH and LH. Specific forms of congenital adrenal hyperplasia Swyer syndrome Galactosemia Aromatase deficiency Prader-Willi syndrome Male pseudo-hermaphroditism (about 1 in every 150,000 births) Other intersexed conditions	Hypothalamic: Kallmann syndrome.
Secondary	Intrauterine adhesions (Asherman`s Syndrome)	Pregnancy (most common cause) Anovulation Menopause Premature menopause Polycystic ovary syndrome (PCO-S) Drug-induced	Hypothalamic: Exercise amenorrhoea, related to physical exercise, Stress amenorrhoea, Eating disorders and weight loss (obesity, anorexia nervosa, or bulimia Pituitary: Sheehan syndrome, Hyperprolactinemia, Hemochromatosis Other central regulatory: hypothyroidism, hyperthyroidism, arrhenoblastoma

Specific types of amenorrhoea

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.

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. Extended cycle use of combined hormonal contraceptives also allow suppression of menstruation.

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 or in vitro 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. 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.