amenorrhea

Amenorrhea

Index of the post

  • Overview
  • Causes
  • Causes of amenorrhea based on the classification
  • Risk factors
  • Symptoms
  • Diagnosis
  • Investigations
  • Treatment
  • Complications
  • References and further reading

Overview

Amenorrhea is the absence of menstrual periods.

  • Some women never go through puberty.
  • So periods never start.
  • This disorder is called primary amenorrhea.
  • In other women, periods start at puberty, then stops.
  • Amenorrhea is normal only before puberty, during pregnancy, while breastfeeding and menopause.

Causes

  • Primary amenorrhea may be caused by a birth defect in which the uterus or fallopian tubes do not develop normally or by a chromosomal disorder, such as Turner syndrome.
  • Primary amenorrhea can also result from malfunction of the hypothalamus, pituitary gland or ovaries.
  • Sometimes it results from the malfunction of the thyroid gland.
  • Young women who are very thin, particularly who have anorexia nervosa, may never menstruate.
  • Secondary amenorrhea may result from malfunction of the hypothalamus, pituitary gland, ovaries, thyroid gland, adrenal glands, or almost any part of the reproductive tract.
  • Malfunction of these organs may result from a tumor, an autoimmune disorder or use of certain drugs. This includes hallucinogenic drugs, chemotherapeutic drugs and antidepressant drugs.
  • Cushing’s syndrome and polycystic ovarian syndrome may cause periods to stop or be irregular.
  • Other causes of secondary amenorrhea include a hydatidiform mole and Asherman’s syndrome.
  • Stress due to internal or situational concerns may cause secondary amenorrhea because stress interferes with the brain’s control of the ovaries.
  • Exercising too much or too little may also affect the brain’s control of ovaries.
  • Either behavior can cause the brain to signal the pituitary gland to decrease its production of hormones that stimulate the ovaries.
  • As a result, ovaries produce less estrogen and periods stop.

Causes of amenorrhea based on classification

Primary amenorrhea

  • Primary amenorrhea is the complete absence of menstrual bleeding or periods by the age of 16.
  • Female children by the age of 14 who have not reached menarche and who shows no signs of secondary sexual characteristics – in general, those who do not show the initiation of puberty are also considered to be suffering from primary amenorrhea.

Causes of primary amenorrhea due to outflow tract anomalies or obstruction

  • Uterine causes
    • Mullerian agenesis
      • It is the second most common cause of primary amenorrhea, affecting 15% of the women.
      • It is also known as Mayer Rokitansky Kuster Hauser syndrome or vaginal agenesis.
      • It is characterized by the failure of the Mullerian duct to develop, leading to a missing uterus and a variable degree of vaginal hypoplasia of its upper portion.
  • Vaginal causes
    • Vaginal atresia
      • This is a condition in which the vagina is abnormally closed or absent.
    • Cryptomenorrhea
      • In this condition, menstrual bleeding occurs, but it is not visible due to the obstruction of the outflow tract.
      • The endometrium is shed in this condition, but the menstrual flow is retained by the vaginal septum or by a part of the hymen due to congenital defects.
    • Imperforate hymen
      • This is a congenital disorder in which a hymen which lacks an opening, completely blocks the vagina.

Causes of primary amenorrhea due to Gonadal disorders or end-organ disorders

  • The most common cause is gonadal dysgenesis including the Turner syndrome.
  • Androgen insensitivity syndrome
    • This is an intersex condition which results due to complete or partial inability of the cell to respond to androgens.
  • Specific forms of congenital adrenal hyperplasia.
  • Receptor abnormalities for hormones (FSH and LH).
  • Galactosemia
    • This is a rare genetic metabolic disorder which affects a person’s ability to metabolize galactose.
  • Swyer syndrome
    • This is a condition in which a person is female from outside with streak gonads – a form of aplasia, resulting in hormonal failure that manifests as sexual infantism and infertility, with no initiation of puberty and secondary sex characteristics.
  • Aromatase deficiency
    • Aromatase is an enzyme which plays an important role in the biosynthesis of estrogens.
  • Prader – Willi syndrome
    • This is a genetic disorder which occurs due to the loss of function of specific genes.
  • Certain intersexed conditions
    • Intersex people are those who are born with variations in sex characteristics including genitals, gonads, sex hormones and chromosomes. These people do not fit in the classical definition of a male or a female, as defined by the UN Office of the High Commissioner for Human Rights.
  • Male pseudohermaphroditism
    • This disorder occurs in 1 in every 1,50,000 childbirths.

Causes of primary amenorrhea due to pituitary and hypothalamic disorders or central regulatory disorders

  • Kallmann syndrome
    • This is a genetic disorder which inhibits a person from starting or fully completing puberty.

Secondary amenorrhea

  • A woman is considered to be suffering from secondary amenorrhea if:
    • An established menstrual bleeding has stopped for 3 months in a woman with a history of regular menstruation.
    • An established menstrual bleeding has stopped for 9 months in a woman with a history of irregular periods.

Causes of primary amenorrhea due to central regulatory disorders or hypothalamic and pituitary disorders

  • Hypothalamic causes
    • Stress
    • Physical exercise
    • Eating disorders
    • Weight loss and low body weight
      • About 10% less than the normal body weight interrupts many hormonal functions in the body, potentially halting ovulation.
      • Weight loss causes elevated levels of ghrelin – a hormone which inhibits hypothalamic-pituitary-ovarial axis. This elevated release of ghrelin causes a diminished release of LH and FSH from the pituitary gland.
      • Females with low body weight also have lower levels of leptin – a hormone which signals energy balance and fat stores to the reproductive axis.
    • Obesity
    • Anorexia nervosa
      • This is an eating disorder in which a person suffers from a fear of gaining weight and has a strong desire to remain thin, leading to restriction in eating.
      • Women suffering from this disorder often stop having periods due to abnormal hormonal changes attributed to low body weight.
    • Bulimia nervosa
      • This is an eating disorder which is characterized by binge eating followed by purging.
      • Binge eating refers to eating a large amount of food in a short span of time.
      • Purging refers to the attempts of getting rid of the eaten food either by vomiting or by consuming laxatives.
      • Just like anorexia nervosa, women suffering from this disorder often stop having periods due to abnormal hormonal changes attributed to low body weight.
  • Pituitary causes
    • Sheehan syndrome
      • In this condition, the functioning of the pituitary gland is decreased due to ischemic necrosis due to blood loss and due to hypovolemic shock during and after childbirth
    • Hyperprolactinemia
      • This condition refers to the presence of abnormally high levels of prolactin in the blood.
      • Prolactin plays an important role in females to produce milk.
    • Hemochromatosis
      • This condition refers to the accumulation of iron in the body due to any cause.
  • Other central regulatory disorders
    • Hyperthyroidism
    • Hypothyroidism
    • Arrhenoblastoma of the ovary
      • This is an ovarian tumor that releases male hormone testosterone or other hormones. This is commonly known as Sertoli-Leydig cell tumor.

Causes of primary amenorrhea due to Gonadal disorders or end-organ disorders

  • Anovulation
    • In this condition, ovaries do not release an oocyte during a menstrual cycle.
  • Menopause
  • Pregnancy
    • This is the most common cause.
  • Premature menopause
    • This condition refers to the loss of functions of ovaries before the age of 40. Under normal circumstances, menopause begins around the age of 50.
  • PCOS (Polycystic Ovarian Syndrome)
    • Unlike normal menstrual bleeding in which hormonal levels keep fluctuating, PCOS causes relatively high and sustained levels of hormones.
  • Pituitary tumor
  •  Medications
    • Antipsychotics
    • Cancer chemotherapy
    • Antidepressants
    • Blood pressure drugs
    • Allergy medications
  • Drug addiction
    • Addiction to opioids is also known to cause amenorrhea in long-term users.
  •  Contraceptives
    • Women who take contraceptive pills or contraceptive devices which are injected or implanted or women who use intrauterine contraceptive devices may not have periods.
    • Even after stopping oral contraceptives, it may take some time before regular ovulation and menstruation to return.
  • Breastfeeding
  • Celiac disease
    • This is an autoimmune disorder which affects the small intestine.

Natural causes of amenorrhea

  • Pregnancy
  • Breastfeeding
  • Menopause

Causes of primary amenorrhea due to outflow tract anomalies or obstruction

  • Intrauterine adhesions like Asherman’s syndrome
    • This is an acquired uterine condition which occurs when adhesion or a scar tissue forms inside the uterus and/or the cervix.
    • The buildup of scar tissue in the lining of the uterus can occur due to D&C (dilation and curettage), cesarean section or treatment of uterine fibroids.
    • The normal buildup and shredding of the uterine lining is prevented by uterine scarring.

Risk factors

  • Rigorous athletic training
  • Family history
  • Eating disorders
    • Anorexia nervosa
    • Bulimia nervosa

Symptoms

  • The primary symptom of amenorrhea is the complete absence of menstrual bleeding or periods.
  • Serious back pain near the pelvis and spine, which is relieved only after taking a short course of progesterone to trigger menstrual bleeding is a characteristic of amenorrhea.
  • Elevated levels of testosterone caused by amenorrhea may lead to decreased breast size and body hair growth.
  • This elevated levels of testosterone may also lead to the formation of ovarian cysts.
  • Loss of self-esteem may also be observed in amenorrhoeic athletes.
  • Amenorrhea may or may not be accompanied by other symptoms, depending on the cause.

Diagnosis

  • Primary amenorrhea is diagnosed when periods have not started by the age of 16.
  • Girls who have no signs of puberty by the age of 13 or who have not started having periods within 5 years of starting puberty are evaluated for possible problems.
  • Secondary amenorrhea is diagnosed when a woman of reproductive age has had no menstrual periods for at least 3 months.
  • A physical examination can help doctors determine whether puberty occurred normally and may provide evidence of the cause of amenorrhea.
  • Other procedures may be needed to confirm or identify the cause.
  • Hormone levels in the blood may be measured.
  • X – Rays of the skull may be taken to look for a pituitary tumor.
  • Computed tomography, magnetic resonance imaging or Ultrasonography may be used to look for a tumor in the ovaries or adrenal glands.

Investigations

  • Pregnancy test
    • Since pregnancy is the leading cause of amenorrhea, this is the first test that is done to confirm whether a woman is pregnant or not.
    • If a pregnancy is confirmed, no further tests for amenorrhea are required.
  • Thyroid function test
    • Measuring the amounts of TSH (thyroid stimulating hormone) in blood is done to confirm the proper functioning of the thyroid.
    • If required form the results of TSH levels, T3 and T4 levels are also evaluated.
  • Measuring FSH levels
    • Levels of FSH (follicle stimulating hormone) is checked to determine whether the ovaries are functioning properly or not.
  • Determination of prolactin levels
    • Low levels of prolactin may be indicative of a tumor of the pituitary gland.
  • Test for male hormones
    • Male hormones are tested if a woman is experiencing increased facial hairs and a lowered voice.
    • Slightly elevated levels of testosterone can be seen in women suffering from PCOS.
    • A raised testosterone level may indicate an androgen-secreting tumor or late onset of CAH. This requires further investigations before reaching conclusion.
  • In this test, a woman has to take hormones (estrogen-progesterone combination) for 7 to 10 days.
  • This is done to trigger menstrual bleeding.
  • This will confirm the doctor that the cause of amenorrhea was lack of estrogen or not.
  • Sonography or Ultrasound scan
    • This is done to detect the presence of abnormalities if any in a woman’s reproductive system.
    • This is particularly recommended to a woman who has never experienced menstruation.
  • CT (Computerized Tomography) scan
    • This test is done to check the presence or absence of any congenital or acquired abnormalities of the kidneys, uterus, and ovaries.
  • MRI (Magnetic Resonance Imaging)
    • This test is done to confirm the presence or absence of a pituitary tumor.
  • In this test, a thin, lighted camera is passed through a woman’s vagina and the cervix to inspect the uterus.
  • This is done to inspect the uterine lining and the openings of the fallopian tubes.
  • This is done to confirm the presence or absence of:
    • Turner syndrome
    • Testicular feminization
    • Rare conditions such as XXX
  • It should be performed in women suffering from primary amenorrhea with the absence of secondary sexual characteristics.
  • It is also useful in early primary ovarian failure.

Treatment

  • The underlying disorder is treated if possible. For example, a tumor is removed if it is the cause.
  • Some disorders such as Turner syndrome and other genetic disorders cannot be cured.
  • If a girl’s periods have never started and all test results are normal, she is examined every 3 to 6 months to monitor the progression of puberty.
  • Progestin and sometimes estrogen may be given to start her periods and to stimulate the development of secondary sexual characteristics, such as breasts.
  • Drug-induced amenorrhea
    • Addition of metformin to antipsychotic treatment can restore menstruation.
    • Metformin decreases the resistance to insulin, prolactin, testosterone and luteinizing hormone.
    • Metformin also decreases the ratio of LH/FSH ratio.
  • Oestrogen therapy
    • This is employed if oestrogen levels are low.
  • If the underlying cause of amenorrhea is not life-threatening in women who do not plan to have biological children, treatment may be unnecessary.
  • Athletic amenorrhea
    • This is treated by decreasing the amount and intensity of exercise and increasing the quantity and frequency of food intake.
    • Rest and frequent breaks are recommended.
  • Hypothalamic amenorrhea
    • Treatment with selective serotonin reuptake inhibitor is recommended.
  • Stress-induced amenorrhea
    • Seek professional help to identify the areas of stress in your life.
    • These professionals will also assist you in the ways of relieving stress and improving your overall mental health.

Complications

  • Osteoporosis
    • Estrogen plays an important role in regulating calcium loss after the age of 25 to 30.
    • When a woman’s ovaries no longer produce estrogen due to amenorrhea, she is more likely to suffer rapid calcium loss, which leads to osteoporosis.
  • Infertility
    • If a woman doesn’t ovulate and hence don’t have menstrual bleeding or periods, she can’t get pregnant.

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By |2018-08-27T13:37:54+00:00November 24th, 2017|Disease/pathological condition, Women's health|0 Comments

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B. Pharm (K.L.E. society's S.V.V. Patil College of Pharmacy, Bengaluru) M. Pharm (Maharishi Arvind Institute of Pharmacy, Jaipur)

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