gynecology and obstetrics
Amenorrhea
Etiology of Amenorrhea
Amenorrhea can be classified based on a number of different criteria, such as Primary or secondary Gonadal dysgenesis, anatomic, or endocrinologic Gonadal dysgenesis and congenital reproductive tract anomalies cause primary amenorrhea. Secondary amenorrhea may be caused by acquired anatomic reproductive tract abnormalities that interfere with menstrual function or obstruct the menstrual flow. Primary or secondary amenorrhea may be due to endocrinologic disorders. Gonadal dysgenesisdue to genetic or chromosomal abnormalities (which can cause primary ovarian insufficiency) include Turner Syndrome None 46,XY gonadal dysgenesis Anatomic causesof amenorrhea include Vaginal Anomalies (eg, vaginal agenesis, imperforate hymen) Acquired abnormalities (eg, Asherman syndrome or cervical stenosis) Common endocrinologic causesinclude Constitutional delay of puberty Pregnancy (the most common cause in women of reproductive age) Polycystic Ovary Syndrome (PCOS) None Prolactinoma (eg, due to pituitary adenoma, lactational amenorrhea during breastfeeding, or use of antipsychotics) Functional hypothalamic amenorrhea (eg, due to excessive exercise, eating disorders, or stress [ Etiology references ) Primary Ovarian Insufficiency (premature ovarian failure) Hormonal medications (eg, oral contraceptives, depotmedroxyprogesterone) Progestin-only contraceptives often cause amenorrhea. Combined estrogen/progestin contraceptives can cause amenorrhea if they are used continuously (without placebo pills or no medication every few weeks) or for a long time (if the endometrium becomes atrophic). Other endocrinologic causes are receptor or enzyme disorders (eg, complete androgen insensitivity syndrome, 5-alpha-reductase deficiency). Amenorrhea due to ovulatory dysfunction is usually secondary but may be primary if ovulation never begins—eg, because of a genetic disorder. If ovulation never begins, Delayed Puberty usually results, and development of secondary sexual characteristics is abnormal. Genetic disorders that confer a Y chromosome increase the risk of ovarian germ cell cancer. most common Some Causes of Anovulatory Amenorrhea None Hypothalamic dysfunction (particularly functional hypothalamic amenorrhea) Pituitary dysfunction Primary ovarian insufficiency (premature ovarian failure) Endocrine disorders that cause androgen excess (particularly Polycystic Ovary Syndrome (PCOS) ) Hypothalamic dysfunction may result in decreased GnRH production, which in turn may cause decreased gonadotropin production. A common cause is insufficient energy intake due to dietary restriction or strenuous exercise. Women with amenorrhea due to hypothalamic dysfunction have lower levels of serum leptin (an anorectic hormone produced by fat cells); lower levels may contribute to decreased gonadotropin production ( Etiology references ). Ovarian hormones have direct and indirect effects on other tissues (eg, bone, skin, muscle). FSH=follicle-stimulating hormone; GnRH=gonadotropin-releasing hormone; LH=luteinizing hormone. Amenorrhea may also occur if patients have abnormalities that affect menstrual function or obstruct menstrual flow. Many patients with these conditions have normal reproductive endocrine function and may have ovulatory menstrual cycles. most common Some Causes of Ovulatory Amenorrhea None Congenital anatomic genital abnormalities that obstruct menstrual flow Acquired abnormalities of female reproductive tract (eg, Asherman syndrome, cervical stenosis) Obstructive abnormalities cause primary amenorrhea and are usually accompanied by normal hormonal function. Such obstruction may result in Hematocolpos (accumulation of menstrual blood in the vagina), which can cause the vagina to bulge Hematometra (accumulation of blood in the uterus), which can cause uterine distention that may be noted as a pelvic mass or bulging of the cervix Because ovarian function is normal, external genital organs and other secondary sexual characteristics develop normally. Some congenital disorders (eg, those accompanied by vaginal aplasia or a vaginal septum) also cause urinary tract and skeletal abnormalities. Some acquired anatomic abnormalities, such as endometrial scarring after uterine instrumentation (Asherman syndrome), cause secondary ovulatory amenorrhea. 1.Gordon CM, Ackerman KE, Berga SL, et al: Functional hypothalamic amenorrhea: An Endocrine Society Clinical Practice Guideline.J Clin Endocrinol Metab102 (5):1413–1439, 2017. doi: 10.1210/jc.2017-00131 2.Bouzoni E, Perakakis N, Mantzoros CS: Circulating profile of activin-follistatin-inhibin axis in women with hypothalamic amenorrhea in response to leptin treatment.Metabolism113:154392, 2020. doi: 10.1016/j.metabol.2020.154392 Epub 2020 Oct 10. 