Evaluation of primary amenorrhea

Last reviewed: March 2019

Last updated: July 2018

Summary

Amenorrhea is the transient or permanent absence of menstrual flow and may be subdivided into primary and secondary presentations, relative to menarche. [1]

Primary amenorrhea: lack of menses by age 15 years in a patient with appropriate development of secondary sexual characteristics, or absent menses by age 13 years and no other pubertal maturation.
Secondary amenorrhea: lack of menses in a non-pregnant female for at least 3 cycles of her previous interval, or lack of menses for 6 months in a patient who was previously menstruating.

Although overlapping attributes exist between the two groups, the diagnostic approaches vary significantly. The prevalence of primary amenorrhea in the US is <0.1%, compared with 4% for secondary amenorrhea. [2] [3] Even when causes of primary and secondary amenorrhea overlap, the relative likelihoods for these etiologies may differ. For example, polycystic ovary syndrome may cause either primary or secondary amenorrhea, but much more commonly causes secondary amenorrhea. Many causes of primary amenorrhea are rare in the general population (e.g., Kallman syndrome). Conditions that may seem to be rare events generally may appear more commonly in this subgroup of adolescent girls presenting with primary amenorrhea.

Despite the low prevalence of primary amenorrhea, a prompt, comprehensive assessment by a specialist in reproductive medicine is warranted, as amenorrhea is often the presenting sign of an underlying reproductive disorder. A delay in diagnosis and treatment may adversely impact the long-term future of such patients. For example, an adolescent with androgen insensitivity syndrome requires counseling for eventual removal of gonads because these patients carry up to about a 30% risk of gonadal neoplasms. In polycystic ovary syndrome and hyperinsulinemia, behavioral and dietary modifications may prevent subsequent cardiovascular disease. [4] [5] [6]

Differentials

Common

Primary hypothalamic amenorrhea
Emotional/physical stress or female athlete triad
Constitutional delay
Malnutrition or chronic disease state
Kallman syndrome (hypogonadotropic hypogonadism)
Hyperprolactinemia
Polycystic ovary syndrome
Non-classic congenital adrenal hyperplasia
Turner syndrome or mixed gonadal dysgenesis
Mayer-Rokitansky-Kuster-Hauser syndrome (Mullerian agenesis)
Outflow tract obstruction, including imperforate hymen or transverse vaginal septum

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Uncommon

Craniopharyngioma
GnRH receptor deficiency
Post-encephalitis
Androgen-producing ovarian tumor
Androgen-producing adrenal tumor
Bilateral agenesis testes (Swyer syndrome)
5-alpha-reductase deficiency
17-alpha-hydroxylase (CYP17) deficiency
Androgen insensitivity syndrome

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Contributors

Authors VIEW ALL 

Meir Jonathon Solnik, MD

Associate Professor

Director

Division of Urogynecology

Director

Center for Minimally Invasive Gynecologic Surgery

Cedars-Sinai Medical Center

Los Angeles

Disclosures

MJS is a consultant for Medtronic, serves on the advisory boards of Abbvie and Allergan, and has been a moderator for Bayer.

Acknowledgements

MJS would like to gratefully acknowledge Jessica Papillon-Smith, a previous contributor to this topic. JP-S declares that she has no competing interests.