Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Evaluation and management of secondary amenorrhea

Corrine K Welt, MD
Robert L Barbieri, MD
Section Editors
William F Crowley, Jr, MD
Mitchell E Geffner, MD
Deputy Editor
Kathryn A Martin, MD


Amenorrhea (absence of menses) can be a transient, intermittent, or permanent condition resulting from dysfunction of the hypothalamus, pituitary, ovaries, uterus, or vagina (table 1 and table 2). It is often classified as either primary (absence of menarche by age 15 years) or secondary (absence of menses for more than three months in girls or women who previously had regular menstrual cycles or six months in girls or women who had irregular menses [1]). Missing a single menstrual period may not be important to assess, but amenorrhea lasting three months or more and oligomenorrhea (fewer than nine menstrual cycles per year or cycle length greater than 35 days) require investigation. The etiologic and diagnostic considerations for oligomenorrhea are the same as for secondary amenorrhea.

The evaluation of secondary amenorrhea and a brief summary of treatment options are reviewed here. The epidemiology and causes of secondary amenorrhea, and overviews of primary amenorrhea and abnormal uterine bleeding in adolescents, are discussed separately. (See "Epidemiology and causes of secondary amenorrhea" and "Evaluation and management of primary amenorrhea" and "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis".)


Once pregnancy has been ruled out, a logical approach to women with either primary or secondary amenorrhea is to consider disorders based upon the levels of control of the menstrual cycle: hypothalamus, pituitary, ovary, and uterus. Determining the site of the defect is important because it determines the appropriate therapeutic regimen. While the most common causes of secondary amenorrhea are likely to be functional hypothalamic amenorrhea or polycystic ovary syndrome (PCOS), disorders with an anatomic or pathologic cause must be ruled out (algorithm 1) [2,3].

Rule out pregnancy — A pregnancy test is recommended as a first step in evaluating any woman with secondary amenorrhea. Measurement of serum beta subunit of human chorionic gonadotropin (hCG) is the most sensitive test. Commercially available home kits for measurement of hCG in urine are improving, but the clinician who suspects pregnancy should order a serum hCG measurement, even if the woman had a negative home test.

History — The woman should be asked about any past medical history, risk factors, or symptoms that might suggest any of the major causes of secondary amenorrhea or oligomenorrhea (algorithm 1 and table 1). The history should include the following questions:


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Aug 30 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Deligeoroglou E, Athanasopoulos N, Tsimaris P, et al. Evaluation and management of adolescent amenorrhea. Ann N Y Acad Sci 2010; 1205:23.
  2. Reindollar RH, Novak M, Tho SP, McDonough PG. Adult-onset amenorrhea: a study of 262 patients. Am J Obstet Gynecol 1986; 155:531.
  3. Practice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil Steril 2006; 86:S148.
  4. Laufer MR, Floor AE, Parsons KE, et al. Hormone testing in women with adult-onset amenorrhea. Gynecol Obstet Invest 1995; 40:200.
  5. Nakamura S, Douchi T, Oki T, et al. Relationship between sonographic endometrial thickness and progestin-induced withdrawal bleeding. Obstet Gynecol 1996; 87:722.
  6. Rebar RW, Connolly HV. Clinical features of young women with hypergonadotropic amenorrhea. Fertil Steril 1990; 53:804.
  7. Sum M, Warren MP. Hypothalamic amenorrhea in young women with underlying polycystic ovary syndrome. Fertil Steril 2009; 92:2106.
  8. Wang JG, Lobo RA. The complex relationship between hypothalamic amenorrhea and polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93:1394.
  9. Goel P, Narang S, Gupta BK, et al. Evaluation of serum prolactin level in patients of subclinical and overt hypothyroidism. J Clin Diagn Res 2015; 9:BC15.
  10. Berga SL, Marcus MD, Loucks TL, et al. Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy. Fertil Steril 2003; 80:976.
  11. Welt CK, Chan JL, Bullen J, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004; 351:987.
  12. Chou SH, Chamberland JP, Liu X, et al. Leptin is an effective treatment for hypothalamic amenorrhea. Proc Natl Acad Sci U S A 2011; 108:6585.
  13. Broome JD, Vancaillie TG. Fluoroscopically guided hysteroscopic division of adhesions in severe Asherman syndrome. Obstet Gynecol 1999; 93:1041.