Amenorrhea caused by extremes of body mass: pathophysiology and sequelae

Key Points

Amenorrhea is defined as the abnormal absence of menstrual periods. The term literally means "no monthly flow," originating from the Greek words a, men, and rhoia. Abnormal or pathologic amenorrhea should be distinguished from absence of menses because of physiologic causes such as pregnancy, lactation, and menopause. Conventionally, amenorrhea can be categorized into primary amenorrhea, defined as a state of never having had menstrual bleeding, and secondary amenorrhea, defined as cessation of previously established menstrual periods. Nongestational secondary amenorrhea is a common condition of reproductive-aged women, with prevalence estimated at 3% to 4% in the general population.¹ The American Society for Reproductive Medicine recommends an evaluation for patients with oligomenorrhea, defined as fewer than 9 cycles a year, and secondary amenorrhea lasting at least 3 months.² However, the seminal work by Treloar et al is still relevant, and it should be noted that amenorrhea with no period for 90 days is statistically uncommon even in the first reproductively competent year after menarche.³

This review will be limited to discussion of secondary amenorrhea that is related to extremes of body mass. Although a comprehensive discussion of the relationship of body mass to other critical health outcomes is beyond the scope of this review, other relevant adverse consequences of excesses of body mass will be mentioned.

Low body weight

Epidemiology

The most common causes for low body weight-related amenorrhea include eating disorders, strenuous exercise (such as ballet, gymnastics, swimming, marathon running, etc), and stress. It has been estimated that up to 1% of the population suffers from restrictive eating disorders.¹⁰ However, the true prevalence of these conditions is probably underestimated because the data are notoriously fraught with methodologic problems related to the changing diagnostic criteria and inherent difficulties of self-report.¹¹ These disorders can take several forms and appear to have varying relationships to amenorrhea. The DSM-IV defines 3 eating disorders as: anorexia nervosa, bulimia nervosa, and "eating disorder not otherwise specified."⁵ The next edition of the DSM (DSM-V) is in the works, and according to some experts, amenorrhea may not be included as a prima facie diagnostic criterion because it may not add to the specificity of diagnosis.¹² Additionally, although bulimia may not necessarily be linked with excessively low body weight, it is associated with menstrual dysfunction in some reports.¹³ Of note, craniopharyngiomas or other brain tumors may present as hypothalamic amenorrhea with characteristic low gonadotropins; however, these entities are not typically linked with abnormally low body mass.