Amenorrhea overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Amenorrhea, 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 permanent. Amenorrhoea is a symptom with many potential causes.
Historical Perspective
The Egyptian ancient belief honored menstrual blood as a life-giving nature. The Mesopotamian mother goddess, named Ninhursag, believed to create mankind from loam and her "blood of life". The first descriptions about disturbances in menstrual cycle are found in Papyrus Ebres [named after the Egyptologist Georg M. Ebers (1837-1898)], from New Kingdom period (1450-1550 B.C.E). They described the patients as a "women who suffers from the side of her pubic region as an irregularity of her menstruation". In 1907, British Medical Journal, released an article about different types of treatments (mostly herbal and conservative) for amenorrhea. In 1911, some researchers evaluate the therapeutic methods presented 4 years ago and make some suggestions to manage amenorrhea better. The term amenorrhea is derived from Greek language [a = negative, men = month, rhoia = flow], means lack of menstruation cycle in a woman.
Classification
Amenorrhea may be classified according to etiology into three subtypes, including primary amenorrhea, secondary amenorrhea, and functional amenorrhea. Primary amenorrhea is basically referred to a young girl that has not experienced menarche, at all, classified as hypergonadotropic hypogonadism, hypogonadotropic hypogonadism, and eugonadotropic state. Secondary amenorrhea reflects a woman that has ordinary menstruation cycles, experiencing at least 3 months of menstruation cycle absence, classified as polycystic ovary syndrome, hypothalamic-pituitary dysfunction, hypothalamic-pituitary failure, and ovarian failure. Functional amenorrhea is a subtype of the amenorrhea caused by exaggerated different lifestyles, classified as stress, weight loss, and exercise related groups.
Pathophysiology
It is thought that amenorrhea is absence of menstrual cycle, from the beginning of puberty (primary amenorrhea) or after many normal cycles (secondary amenorrhea). Distinguishing between primary and secondary amenorrhea is based on history, solely; because upon every cause of secondary amenorrhea can be a cause of primary amenorhea, indeed. Mainly the pathophysiology of amenorrhea is described in many categories, include hypothalamic, pituitary, thyroid, adrenal, ovarian, uterine, and vaginal pathogenesis. About 25 various genes, in 3 different group of Kallmann syndrome related genes, hypothalamus-pituitary-gonadal (HPG) axis related genes, and obesity related genes, play roles in amenorrhea. On gross pathology, normal endometrium in proliferative or luteal phases are characteristic findings of amenorrhea. Craniopharyngioma gross pathology is cystic mass filled with motor oil-like fluid. On microscopic histopathological analysis, trabecular squamous epithelium surrounded by palisaded columnar epithelium, small-to-medium sized cells with moderate amount of basophilic cytoplasm, bland nuclei, and calcifications are characteristic findings of craniopharyngioma. On microscopic histopathological analysis, loss of fibrous stroma and nested cells of normal anterior pituitary (based on the type of adenoma) are characteristic findings of pituitary adenoma.
Causes
Common causes of amenorrhea include breastfeeding, pregnancy, menopause, and stress. Causes of amenorrhea can be divided upon the classification of the disease, include primary amenorrhea (craniopharyngioma, idiopathic gonadotropin deficiency, Kallmann's Syndrome, Mayer-Rokitansky-Hauser Syndrome, Mullerian dysgenesis, and outflow tract disorders), secondaary amenorrhea (craniocerebral trauma, curettage, Cushing's Syndrome, depression, diabetes mellitus, and drug side effects), and functional amenorrhea (stress, rapid weight loss, and excessive exercise).
Differentiating Amenorrhea from Other Diseases
As amenorrhea manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. Primary amenorrhea must be differentiated from other diseases that cause lack of menstrual cycle, such as Mullerian agenesis, 3-beta-hydroxysteroid dehydrogenase type 2 deficiency, androgen insensitivity syndrome, Kallmann syndrome, Turner syndrome, and 17-alpha-hydroxylase deficiency. In contrast, secondary amenorrhea must be differentiated from other diseases that cause menstrual cycle arrest, such as primary ovarian insufficiency, hypothyroidism, hyperprolactinemia, polycystic ovary syndrome, and Asherman's syndrome.
Epidemiology and Demographics
The incidence of primary amenorrhea is approximately 3,000 per 100,000 individuals, mostly due to hypothalamic amenorrhea. The incidence of secondary amenorrhea is approximately 3,300 per 100,000 individuals in Sweden. The prevalence of amenorrhea is approximately 3,000 to 4,000 per 100,000 individuals worldwide. The prevalence of amenorrhea was estimated to be 13,400 cases per 100,000 female athletes. The case-fatality rate/mortality rate of amenorrhea is approximately below 1%, due to pituitary macroadenomas or generally brain lesions which cause amenorrhea. Primary amenorrhea is usually first diagnosed among adolescence, 16 years of age. There is no racial predilection to amenorrhea. Commonly, it seems that girls from developed countries experience the puberty and menarche earlier than developing countries, due to nutritional and socioeconomic situation. But, since the diagnosis age of primary amenorrhea is based on the society mean age of puberty onset and menarche, therefore there is not any difference between developing and developed countries in prevalence of amenorrhea.
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