Amenorrhoea
Encyclopedia
Amenorrhoea amenorrhea (AmE
American English
American English is a set of dialects of the English language used mostly in the United States. Approximately two-thirds of the world's native speakers of English live in the United States....

), or amenorrhœa, is the absence of a menstrual period
Menstrual cycle
The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....

 in a woman of reproductive age. Physiological states of amenorrhoea are seen during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

 and lactation
Breastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...

 (breastfeeding), the latter also forming the basis of a form of contraception known as the lactational amenorrhoea method
Lactational Amenorrhea Method
The lactational amenorrhea method is a method of avoiding pregnancies which is based on the natural postnatal infertility that occurs when a woman is amenorrheic and fully breastfeeding...

. Outside of the reproductive years there is absence of menses during childhood and after menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...

.

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
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...

 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
Secondary sex characteristic
Secondary sex characteristics are features that distinguish the two sexes of a species, but that are not directly part of the reproductive system. They are believed to be the product of sexual selection for traits which give an individual an advantage over its rivals in courtship and aggressive...

 by age 14 with no menarche
Menarche
Menarche is the first menstrual cycle, or first menstrual bleeding, in female human beings. From both social and medical perspectives it is often considered the central event of female puberty, as it signals the possibility of fertility....

 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
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 and the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

, from premature menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...

 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 oligomenorrhoea
Oligomenorrhea
Oligomenorrhea is infrequent menstruation. More strictly, it is menstrual periods occurring at intervals of greater than 35 days, with only four to nine periods in a year. Also, menstrual periods should have been regularly established previously before the development of infrequent flow...

.

Classification

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
    Menarche
    Menarche is the first menstrual cycle, or first menstrual bleeding, in female human beings. From both social and medical perspectives it is often considered the central event of female puberty, as it signals the possibility of fertility....

    , women by the age of 14 who still have not reached menarche, plus having no sign of secondary sexual characteristics such as thelarche
    Thelarche
    Thelarche is the onset of secondary breast development, usually occurring at the beginning of puberty in girls. Its etymology is from Greek θηλή [tʰelḗ], “nipple” and ἀρχή [arkʰḗ], “beginning, onset”. Thelarche is usually noticed as a firm, tender lump directly under the centre of the nipple...

     or pubarche
    Pubarche
    Pubarche refers to the first appearance of pubic hair in a child. Pubarche is one of the physical changes of puberty but should not be equated with it since it may occur independently of complete puberty...

    —thus are without evidence of initiation of puberty
    Puberty
    Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...

    —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 The hypothalamic-pituitary-ovarian axis is functional. The ovary
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...

 or gonad
Gonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...

 does not respond to pituitary stimulation. Gonadal dysgenesis or premature menopause are possible causes. Chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 testing is usually indicated in younger individuals with hypergonadotropic amenorrhoea. Low oestrogen levels are seen in these patients and the hypo-oestrogenism
Hypoestrogenism
Hypoestrogenism refers to a lower than normal level of estrogen, the primary sex hormone for women. In general, lower levels of estrogen may cause differences in the breasts, genitals, urinary tract and skin....

 may require treatment.
Generally, inadequate levels of FSH lead to inadequately stimulated ovaries which then fail to produce enough oestrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

 to stimulate the endometrium
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...

 (uterine lining), hence amenorrhoea. In general, women with hypogonadotropic amenorrhoea are potentially fertile.
FSH
FSH
FSH may refer to:* Follicle-stimulating hormone* Fox Sports Houston, a regional Fox Sports Net affiliate station for the Houston, Texas area* Facioscapulohumeral muscular dystrophy* International Civil Aviation Organisation code for Flash Airlines...

Outflow tract abnormalities tend to be normogonadotropic and FSH levels are in the normal range. Gonadal, usually ovarian, abnormalities tend to be linked to elevated FSH levels or hypergonadotropic amenorrhoea. FSH levels are typically in the menopausal range. Both hypothalamic and pituitary disorders are linked to low FSH levels leading to hypogonadotropic amenorrhoea.
Primary
  • Uterine: Mullerian agenesis
    Mullerian agenesis
    Müllerian agenesis is a congenital malformation in women characterised by a failure of the müllerian ducts to develop, resulting in a missing uterus and fallopian tubes and variable malformations of the upper portion of the vagina. It is the second most common cause of primary amenorrhea after...

     (Second most common cause, 15% of primary amenorrhoea)
  • Vaginal: Vaginal atresia
    Vaginal atresia
    Vaginal Atresia is a birth defect or congenital abnormality of the female genitourinary system that manifests itself in the absence of a vagina , or a deformed and nonfunctional vagina ....

    , cryptomenorrhoea
    Cryptomenorrhea
    Cryptomenorrhea or cryptomenorrhoea, also known as hematocolpos, is a condition where menstruation occurs but is not visible due to an obstruction of the outflow tract. Specifically the endometrium is shed, but a congenital obstruction such as a vaginal septum or on part of the hymen retains the...

    , imperforate hymen.
  • Gonadal dysgenesis, including Turner Syndrome
    Turner syndrome
    Turner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...

    . Most common cause.
  • Androgen insensitivity syndrome
    Androgen insensitivity syndrome
    Androgen insensitivity syndrome is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as...

     (Testicular feminization syndrome).
  • Receptor abnormalities for hormones FSH
    FSH
    FSH may refer to:* Follicle-stimulating hormone* Fox Sports Houston, a regional Fox Sports Net affiliate station for the Houston, Texas area* Facioscapulohumeral muscular dystrophy* International Civil Aviation Organisation code for Flash Airlines...

     and LH
    Luteinizing hormone
    Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

    .
  • Specific forms of congenital adrenal hyperplasia
    Congenital adrenal hyperplasia
    Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....

  • Swyer syndrome
    Swyer syndrome
    Swyer syndrome, or XY gonadal dysgenesis, is a type of hypogonadism in a person whose karyotype is 46,XY. The person is externally female with streak gonads, and left untreated, will not experience puberty...

  • Galactosaemia
    Galactosemia
    Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Although the sugar lactose can metabolize to galactose, galactosemia is not related to and should not be confused with lactose intolerance...

  • Aromatase
    Aromatase
    Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...

     deficiency
  • Prader-Willi syndrome
    Prader-Willi syndrome
    Prader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...

  • Male pseudo-hermaphroditism (about 1 in every 150,000 births)
  • Other intersexed conditions
  • Hypothalamic: Kallmann syndrome
    Kallmann syndrome
    Kallmann syndrome is a genetic disorder marked by anosmia and hypogonadism - the decreased functioning of the glands that produce sex hormones. Abnormalities in various genes may cause a defect in the hypothalamus, causing a deficiency of gonadotropin-releasing hormone ; this in turn causes...

    .
  • Secondary
  • Intrauterine adhesions (Asherman's Syndrome
    Asherman's syndrome
    Asherman's syndrome , also called "uterine synechiae" or intrauterine adhesions , presents a condition characterized by the presence of adhesions and/or fibrosis within the uterine cavity due to scars...

    )
  • Pregnancy
    Pregnancy
    Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

     (most common cause)
  • Anovulation
    Anovulation
    An anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause...

  • Menopause
    Menopause
    Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...

  • Premature menopause
  • Polycystic ovary syndrome
    Polycystic ovary syndrome
    Polycystic ovary syndrome is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease....

     (PCO-S)
  • Drug-induced
  • Hypothalamic: Exercise amenorrhoea, related to physical exercise
    Physical exercise
    Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...

    , Stress
    Stress (medicine)
    Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...

     amenorrhoea, Eating disorders and weight loss (obesity, anorexia nervosa
    Anorexia nervosa
    Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...

    , or bulimia
  • Pituitary: Sheehan syndrome, Hyperprolactinaemia
    Hyperprolactinaemia
    Hyperprolactinaemia or hyperprolactinemia is the presence of abnormally-high levels of prolactin in the blood. Normal levels are less than 500 mIU/L for women, and less than 450 mIU/L for men....

    , Haemochromatosis
    Haemochromatosis
    Haemochromatosis type 1 is a hereditary disease characterized by excessive intestinal absorption of dietary iron resulting in a pathological increase in total body iron stores. Humans, like most animals, have no means to excrete excess iron...

  • Other central regulatory: hypothyroidism
    Hypothyroidism
    Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

    , hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

    , arrhenoblastoma

  • Hypothalamic

    Women who go through significant weight loss, dieting, or perform considerable amounts of exercise on a regular basis are at risk of developing hypothalamic (or '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 oestrogen and progesterone. However, recent studies have shown that there are no differences in the body composition, or hormonal levels in amenorrhoeic athletes as compared to regularly cycling athletes. Instead, amenorrhoea has been shown to be directly attributable to a low energy availability. Many women who diet or 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 amenorrhoea is severe bone loss sometimes resulting in osteoporosis
    Osteoporosis
    Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...

     and osteopenia
    Osteopenia
    Osteopenia is a condition where bone mineral density is lower than normal. It is considered by many doctors to be a precursor to osteoporosis. However, not every person diagnosed with osteopenia will develop osteoporosis...

    . It is the third component of an increasingly common disease known as female athlete triad
    Female athlete triad
    Female Athlete Triad is a syndrome in which eating disorders , amenorrhoea/oligomenorrhoea and decreased bone mineral density are present. Also know simply as the Triad, this condition is seen in females participating in sports that emphasize leanness or low body weight...

     syndrome. The other two components of this syndrome are osteoporosis
    Osteoporosis
    Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...

     and disordered eating
    Disordered eating
    Disordered eating is a classification to describe a wide range of irregular eating behaviors that do not warrant a diagnosis of a specific eating disorder such as anorexia nervosa or bulimia nervosa. Affected people may be diagnosed with an eating disorder not otherwise specified...

    . Awareness
    Awareness
    Awareness is the state or ability to perceive, to feel, or to be conscious of events, objects or sensory patterns. In this level of consciousness, sense data can be confirmed by an observer without necessarily implying understanding. More broadly, it is the state or quality of being aware of...

     and intervention can usually prevent this occurrence in most female athletes. Many doctors simply prescribe the combined oral contraceptive pill to women with hypothalamic amenorrhoea, and these women continue in their patterns of under-eating and over-exercising. Often, they do not realize that they have a problem until they are trying to conceive, when their amenorrhoea leads them to seek the treatment of a reproductive endocrinologist.

    Drug-induced

    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
    Depo Provera
    Depo-Provera is a branded progestogen-only contraceptive, depot medroxyprogesterone acetate long acting reversible hormonal contraceptive birth control drug that is injected every 3 months...

     commonly induce this side-effect
    Adverse effect
    In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...

    . Extended cycle use of combined hormonal contraceptives also allow suppression of menstruation.
    The use of opiates (such as heroin) on a regular basis has also been known to cause amenorrhoea in longer term users.

    Treatments

    Treatments vary based on the underlying condition. Key issues are problems of surgical correction if appropriate and oestrogen therapy if oestrogen 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 their health.

    Unless receiving eggs from an egg donor
    Egg donor
    Egg donation is the process by which a woman provides one or several eggs for purposes of assisted reproduction or biomedical research. For assisted reproduction purposes, egg donation involves the process of in vitro fertilization as the eggs are fertilized in the laboratory. After the eggs...

     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.

    Etymology

    The term is derived from Greek
    Greek language
    Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...

    : a = negative, men = month, rhoia = flow. Derived adjectives are amenorrhoeal and amenorrhoeic. The opposite is the normal menstrual period (eumenorrhoea).

    History

    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 than they did under the conditions prevalent for most of human evolutionary history.

    External links

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