Epidemiology and causes of secondary amenorrhea
- Corrine K Welt, MD
Corrine K Welt, MD
- Professor of Medicine
- University of Utah School of Medicine
- Robert L Barbieri, MD
Robert L Barbieri, MD
- Editor-in-Chief — Obstetrics, Gynecology and Women's Health
- Section Editor — General Gynecology and Female Reproductive Endocrinology
- Kate Macy Ladd Professor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
- Section Editors
- William F Crowley, Jr, MD
William F Crowley, Jr, MD
- Section Editor — Female Reproductive Endocrinology
- Daniel K Podolsky Professor of Medicine
- Harvard Medical School
- Mitchell E Geffner, MD
Mitchell E Geffner, MD
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Keck School of Medicine, University of Southern California
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). 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 epidemiology and causes of secondary amenorrhea are reviewed here. The evaluation and management of secondary amenorrhea and the causes, evaluation, and management of primary amenorrhea are discussed separately. (See "Evaluation and management of secondary amenorrhea" and "Causes of primary amenorrhea" and "Evaluation and management of primary amenorrhea".)
The most common causes of secondary amenorrhea, based upon a series of 262 patients with amenorrhea of adult onset, include :
●Hypothalamus – 35 percent (almost all functional hypothalamic amenorrhea) (see 'Functional hypothalamic amenorrhea' below)
●Pituitary – 17 percent (13 percent hyperprolactinemia, 1.5 percent “empty sella,” 1.5 percent Sheehan syndrome, 1 percent Cushing’s syndrome) (see 'Pituitary disease' below)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Reindollar RH, Novak M, Tho SP, McDonough PG. Adult-onset amenorrhea: a study of 262 patients. Am J Obstet Gynecol 1986; 155:531.
- Practice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil Steril 2006; 86:S148.
- Laufer MR, Floor AE, Parsons KE, et al. Hormone testing in women with adult-onset amenorrhea. Gynecol Obstet Invest 1995; 40:200.
- Rosenfield RL. Clinical review: Adolescent anovulation: maturational mechanisms and implications. J Clin Endocrinol Metab 2013; 98:3572.
- de Roux N, Young J, Misrahi M, et al. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N Engl J Med 1997; 337:1597.
- Santoro N, Filicori M, Crowley WF Jr. Hypogonadotropic disorders in men and women: diagnosis and therapy with pulsatile gonadotropin-releasing hormone. Endocr Rev 1986; 7:11.
- Gordon CM. Clinical practice. Functional hypothalamic amenorrhea. N Engl J Med 2010; 363:365.
- Perkins RB, Hall JE, Martin KA. Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability, and response to neurotransmitter modulation. J Clin Endocrinol Metab 1999; 84:1905.
- Constantini NW, Warren MP. Menstrual dysfunction in swimmers: a distinct entity. J Clin Endocrinol Metab 1995; 80:2740.
- Warren MP. Clinical review 40: Amenorrhea in endurance runners. J Clin Endocrinol Metab 1992; 75:1393.
- Warren MP, Brooks-Gunn J, Fox RP, et al. Osteopenia in exercise-associated amenorrhea using ballet dancers as a model: a longitudinal study. J Clin Endocrinol Metab 2002; 87:3162.
- Couzinet B, Young J, Brailly S, et al. Functional hypothalamic amenorrhoea: a partial and reversible gonadotrophin deficiency of nutritional origin. Clin Endocrinol (Oxf) 1999; 50:229.
- Laughlin GA, Dominguez CE, Yen SS. Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1998; 83:25.
- Warren MP, Voussoughian F, Geer EB, et al. Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating. J Clin Endocrinol Metab 1999; 84:873.
- Miller KK, Grinspoon S, Gleysteen S, et al. Preservation of neuroendocrine control of reproductive function despite severe undernutrition. J Clin Endocrinol Metab 2004; 89:4434.
- Berga SL, Daniels TL, Giles DE. Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations. Fertil Steril 1997; 67:1024.
- Caronia LM, Martin C, Welt CK, et al. A genetic basis for functional hypothalamic amenorrhea. N Engl J Med 2011; 364:215.
- Perkins RB, Hall JE, Martin KA. Aetiology, previous menstrual function and patterns of neuro-endocrine disturbance as prognostic indicators in hypothalamic amenorrhoea. Hum Reprod 2001; 16:2198.
- Falsetti L, Gambera A, Barbetti L, Specchia C. Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors. J Clin Endocrinol Metab 2002; 87:500.
- Gaete X, Vivanco M, Eyzaguirre FC, et al. Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus. Fertil Steril 2010; 94:1822.
- Codner E, Merino PM, Tena-Sempere M. Female reproduction and type 1 diabetes: from mechanisms to clinical findings. Hum Reprod Update 2012; 18:568.
- Molteni N, Bardella MT, Bianchi PA. Obstetric and gynecological problems in women with untreated celiac sprue. J Clin Gastroenterol 1990; 12:37.
- Kooy A, de Greef WJ, Vreeburg JT, et al. Evidence for the involvement of corticotropin-releasing factor in the inhibition of gonadotropin release induced by hyperprolactinemia. Neuroendocrinology 1990; 51:261.
- Kakuno Y, Amino N, Kanoh M, et al. Menstrual disturbances in various thyroid diseases. Endocr J 2010; 57:1017.
- Krassas GE, Pontikides N, Kaltsas T, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf) 1999; 50:655.
- Groff TR, Shulkin BL, Utiger RD, Talbert LM. Amenorrhea-galactorrhea, hyperprolactinemia, and suprasellar pituitary enlargement as presenting features of primary hypothyroidism. Obstet Gynecol 1984; 63:86S.
- Grubb MR, Chakeres D, Malarkey WB. Patients with primary hypothyroidism presenting as prolactinomas. Am J Med 1987; 83:765.
- Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19:41.
- Burgers JA, Fong SL, Louwers YV, et al. Oligoovulatory and anovulatory cycles in women with polycystic ovary syndrome (PCOS): what's the difference? J Clin Endocrinol Metab 2010; 95:E485.
- Grynberg M, Fanchin R, Dubost G, et al. Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population. Reprod Biomed Online 2010; 20:553.
- van Liempt SW, van Rheenen-Flach LE, van Waesberghe JH, et al. Solely inhibin B producing ovarian tumour as a cause of secondary amenorrhoea with hot flushes: case report and review of literature. Hum Reprod 2012; 27:1144.
- Hypothalamic dysfunction
- - Functional hypothalamic amenorrhea
- Risk factors
- Role of leptin deficiency
- Genetic basis
- - Hypothalamic tumors and infiltrative lesions
- - Systemic illness
- Type 1 diabetes mellitus
- Celiac disease
- Pituitary disease
- - Hyperprolactinemia
- - Other sellar masses
- - Other diseases of the pituitary
- Thyroid disease
- Polycystic ovary syndrome
- - Other hyperandrogenic disorders
- Ovarian disorders
- - Primary ovarian insufficiency (premature ovarian failure)
- - Ovarian tumors
- Uterine disorders