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Amenorrhea: What’s Causing Your Missed Periods?


It can be concerning when your regularly scheduled period doesn't begin. A missed period is called amenorrhea. It is normal for this to occur during natural amenorrhea, which includes pregnancy, breastfeeding, and menopause. There is no cause for concern when natural amenorrhea occurs; however, if you are late to start your period for the first time or miss a period for at least 3 months in a row, it’s a good idea to speak with your doctor.

Symptoms

Along with a lack of menstrual flow, other signs or symptoms that may accompany amenorrhea include:

  • Milky nipple discharge
  • Hair loss
  • Headache
  • Vision changes
  • Excess facial hair
  • Pelvic pain
  • Acne

Types

There are two types of amenorrhea, which include:

  1. Primary amenorrhea: Lack of menstruation by age 16 for someone who has normal growth and secondary sexual characteristics. However, if a girl has not developed any sexual characteristics by age 13 or has had her first menses, a doctor will likely perform an exam. Primary amenorrhea can be genetic, related to a malfunction of disease of the reproductive organs, systemic, drug or radiation-induced, among others.
  2. Secondary amenorrhea: This occurs when a woman's menstrual flow begins during puberty but then later stops. For it to be considered amenorrhea, the time frame is generally 6 months with no menstrual flow, but most doctors will perform an exam if your period has been absent for 3 months.

FSH levels help determine what's causing amenorrhea.

  • Low or normal FSH levels account for 66% of cases, and includes weight loss and anorexia, PCOS, low thyroid, Cushing syndrome, and pituitary diseases.
  • High FSH levels account for 12% of cases and are often due to chromosomal abnormalities, gonadal dysgenesis, or premature ovarian failure. A scarred uterine lining accounts for 7% of cases.

Classifications

Amenorrhea is often classified by the organ causing the issue. Often, this can be the hypothalamus, pituitary, ovaries, or uterus. Systemic diseases can also adversely impact all of these organs, either separately or as combined effects.

Hypogonadotropic hypogonadism (HH)

This condition results when the hypothalamus or pituitary glands do not produce hormones that signal the secretion of sex hormones, preventing women from menstruating.

Causes of HH include:

  • Congenital abnormalities

- Isolated GnRH deficiency

- Forms of hypopituitarism

- Congenital central nervous system (CNS) defects

- Constitutional delay

  • Endocrine disorders

- Congenital adrenal hyperplasia (CAH)

- Cushing syndrome

- Pseudohypoparathyroidism

- Hyperprolacitinemia

- Excess or lack of thyroid hormones

  • A tumor

- Unclassified pituitary adenoma

- Craniopharyngioma

- Unclassified malignant tumor

  • Systemic illnesses

- Sarcoidosis

- Drug abuse

  • Eating disorders

- Anorexia nervosa

Pituitary amenorrhea

The loss of luteinizing hormone and follicle-stimulating hormones lead to pituitary amenorrhea. Possible causes include:

  • Mutations or excess prolactin from the pituitary, often from a benign tumor, prolactinoma.
  • Trauma and radiation to the pituitary

The pituitary gland can affect other organs, such as the adrenal glands, which affect the whole system called the hypothalamic-pituitary-ovarian (HPO) axis.

Ovarian causes of primary amenorrhea

Ovarian dysgenesis is the loss or underdevelopment of the ovaries. Conditions and causes of this include:

  • Turner syndrome is a congenital developmental disorder of the reproductive system.
  • Primary ovarian insufficiency (POI): Depletion of ovarian follicles from POI or premature menopause causes amenorrhea. Premature menopause affects 1 in 10,000 women by age 20 years, 1 in 1000 women by age 30 years, 1 in 250 women by age 35 years, and 1 in 100 women by age 40 years.
  • The fragile X syndrome accounts for approximately 6% of POI. Autoimmune destruction of the ovaries occurs in 3 to 4% of POI cases.
  • Polycystic ovarian syndrome (PCOS) usually presents as secondary amenorrhea, but in some cases may be primary.

Anatomical abnormalities

A uterus and open vaginal tract are needed for normal menstruation to occur. Female reproductive tract abnormalities account for about one-fifth of primary amenorrhea cases.

Abnormalities include:

  • Cyclic pelvic pain is common in girls with disorders of the reproductive tract involving an obstructed vagina, cervix, or uterine malformation.
  • Intact hymen obstructs menstrual flow. These patients have menstrual blood in the vagina that collects and can result in a perirectal mass.
  • The absence of the uterus and portions of the vagina can result in amenorrhea.
  • The uterus lining can become scarred after a surgical procedure such as suction and curettage performed for miscarriages or abortions, leading to amenorrhea.

Enzyme and receptor defects

Congenital adrenal hyperplasia causes an excess production of the hormone deoxycortisone and a deficiency of cortisol and adrenal and gonadal sex steroids, leading to:

  • Complete androgen insensitivity syndrome: Caused by a defective androgen receptor, it results in female genitalia and male genes.
  • Aromatase deficiency: A disorder in which estrogen synthesis cannot occur, leading to increased levels of testosterone that makes the female genital appear more like a male.

Risk factors

Characteristics that may increase your risk of amenorrhea include:

  • Family history: Have any other women in your family had amenorrhea?
  • Eating disorders: Have you suffered from an eating disorder, such as anorexia nervosa or bulimia?
  • Excessive exercise: Do you participate in intense and prolonged exercise?
  • A history of gynecologic procedures: Have you had to have tissue removed from your uterus or had a loop electrodiathermy excision procedure done?

Problems

In addition to a loss of menstrual flow, amenorrhea can cause the following complications:

  • Pregnancy issues and infertility: You can't become pregnant if you are not ovulating due to missed periods. If your hormones are imbalanced, this can also lead to problems with a pregnancy, such as miscarriage.
  • Psychological stress: A lack of a period can cause excessive worries regarding what's wrong.
  • Osteoporosis: A condition that leads to weak bones, it can be caused by a lack of estrogen.
  • Cardiovascular disease: A lack of estrogen can cause several heart conditions, including high blood pressure.
  • Pelvic pain: Anatomical abnormalities may cause pain in the pelvic area.

References:

Bakalov V.K., Vanderhoof V.H., Bondy C.A., Nelson L.M (2002). Adrenal antibodies detect asymptomatic auto-immune adrenal insufficiency in young women with spontaneous premature ovarian failure. Hum Reprod.

Committee on Adolescent Health Care (2017). Committee Opinion No.702: Female Athlete Triad. Obstet Gynecol.

Coulam C.B., Adamson S.C., & Annegers J.F. (1986). Incidence of premature ovarian failure. Obstet Gynecol.

Crosignani P.G. (2006). Current treatment issues in female hyperprolactinemia. Eur J Obstet Gynecol Reprod Biol.

De Souza M.J., Toombs R.J., Scheid J.L., O'Donnell E., West S.L.,& Williams N.I. (2009) High prevalence of subtle and severe menstrual disturbances in exercising women: confirmation using daily hormone measures. Hum Reprod.

Gardner D.G., & Shoback D. (2011). Greenspan's Basic and Clinical Endocrinology. 9th ed. New York: McGraw-Hill.

Hughes I.A., & Deeb A. (2006). Androgen resistance. Best Pract Res Clin Endocrinol Metab.

Jones M.E., Boon W.C., McInnes K., Maffei L., Carani C., & Simpson E.R. (2007) Recognizing rare disorders: aromatase deficiency. Nat Clin Pract Endocrinol Metab.

Kawano Y., Kamihigashi S., & Nakamura S. et al. (2000). Delayed puberty associated with hyperprolactinemia caused by pituitary microadenoma. Arch Gynecol Obstet.

Mayo Clinic. Amenorrhea.

Morcel K., Camborieux L., & Guerrier D. (2007). Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Orphanet J Rare Dis.

Practice Committee of the American Society for Reproductive Medicine (2004). Current evaluation of amenorrhea. Fertil Steril. 9.

Professional Guide to Diseases (Professional Guide Series). 8th ed. Lippincott Williams & Wilkins; 2005.

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