Evaluation of primary amenorrhea

Amenorrhea is the transient or permanent absence of menstrual flow and may be subdivided into primary and secondary presentations, relative to menarche.[1]Practice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea: a committee opinion. Fertil Steril. 2024 Jul;122(1):52-61. https://www.fertstert.org/article/S0015-0282(24)00082-7/fulltext http://www.ncbi.nlm.nih.gov/pubmed/38456861?tool=bestpractice.com ​​

• 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. See Evaluation of secondary amenorrhea.

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]Timmreck LS, Reindollar RH. Contemporary issues in primary amenorrhea. Obstet Gynecol Clin North Am. 2003;30:287-302. http://www.ncbi.nlm.nih.gov/pubmed/12836721?tool=bestpractice.com [3]Pettersson F, Fries H, Nillius SJ. Epidemiology of secondary amenorrhea: incidence and prevalence rates. Am J Obstet Gynecol. 1973;117:80-86. http://www.ncbi.nlm.nih.gov/pubmed/4722382?tool=bestpractice.com Even when causes of primary and secondary amenorrhea overlap, the relative likelihoods for these etiologies may differ. For example, polycystic ovary syndrome (PCOS) may cause either primary or secondary amenorrhea, but presents usually as 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 and comprehensive assessment by a specialist in reproductive medicine, or a clinician well-versed in adolescent development 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:[1]Practice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea: a committee opinion. Fertil Steril. 2024 Jul;122(1):52-61. https://www.fertstert.org/article/S0015-0282(24)00082-7/fulltext http://www.ncbi.nlm.nih.gov/pubmed/38456861?tool=bestpractice.com [4]Weidler EM, Linnaus ME, Baratz AB, et al. A management protocol for gonad preservation in patients with androgen insensitivity syndrome. J Pediatr Adolesc Gynecol. 2019 Dec;32(6):605-11. https://pmc.ncbi.nlm.nih.gov/articles/PMC6917890 http://www.ncbi.nlm.nih.gov/pubmed/31233832?tool=bestpractice.com [5]Tack LJW, Maris E, Looijenga LHJ, et al. Management of gonads in adults with androgen insensitivity: an international survey. Horm Res Paediatr. 2018;90(4):236-46. https://eprints.gla.ac.uk/172615 http://www.ncbi.nlm.nih.gov/pubmed/30336477?tool=bestpractice.com [6]Hughes IA, Davies JD, Bunch TI, et al. Androgen insensitivity syndrome. Lancet. 2012 Oct 20;380(9851):1419-28. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60071-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/22698698?tool=bestpractice.com [7]American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Gynecology. ACOG Committee Opinion No. 605: primary ovarian insufficiency in adolescents and young women. Obstet Gynecol. 2014 Jul;124(1):193-7. https://journals.lww.com/greenjournal/fulltext/2014/07000/committee_opinion_no__605__primary_ovarian.36.aspx http://www.ncbi.nlm.nih.gov/pubmed/24945456?tool=bestpractice.com [8]Shroff R, Kerchner A, Maifeld M, et al. Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. J Clin Endocrinol Metab. 2007;92:4609-4614. https://academic.oup.com/jcem/article/92/12/4609/2597028?login=false http://www.ncbi.nlm.nih.gov/pubmed/17848406?tool=bestpractice.com [9]Lass N, Kleber M, Winkel K, et al. Effect of lifestyle intervention on features of polycystic ovarian syndrome, metabolic syndrome, and intima-media thickness in obese adolescent girls. J Clin Endocrinol Metab. 2011 Nov;96(11):3533-40. https://academic.oup.com/jcem/article-abstract/96/11/3533/2834697 http://www.ncbi.nlm.nih.gov/pubmed/21880803?tool=bestpractice.com ​​

• An adolescent with complete androgen insensitivity requires counseling about the eventual removal of gonads, because these patients carry a 14% to 22% risk of gonadal neoplasms, although malignancy is rare before the age of 20 years.​ Removal needs to be weighed up against preserving hormone function during puberty and considerations of any fertility potential.​​​​​​

• Premature ovarian insufficiency occurring at an early age affects bone density during a critical period for bone development.

• In young teens presenting with PCOS, obesity, and hyperinsulinemia; behavioral and dietary modifications may prevent subsequent metabolic syndrome.​