Amenorrhea (Absence of Menstruation) in Eating Disorder Patients

What is Amenorrhea?

Amenorrhea is the absence of menstruation, often defined as missing one or more menstrual periods, in women of childbearing age. Amenorrhea is divided into two subtypes:

• Primary amenorrhea: the absence of menstruation in someone who has not had a period by age 15
• Secondary amenorrhea: the absence of three or more periods in a row by someone who has had periods in the past.

Amenorrhea was previously considered a diagnostic criterion for anorexia nervosa, but it was removed with the publication of the DSM-5. Despite its removal, amenorrhea continues to be a ubiquitous feature of severe weight loss in women.

Amenorrhea & Anorexia Nervosa

Many women with a history of anorexia nervosa experience amenorrhea. Typically, this is secondary amenorrhea, with an estimated 66-84% of women with anorexia nervosa experiencing amenorrhea (6-11% reporting oligomenorrhea, or infrequent periods), and 7-40% of women with bulimia nervosa experiencing amenorrhea (36-64% reporting oligomenorrhea).

Amenorrhea in patients with eating disorders is related to loss of body weight and hormonal changes that accompany the weight loss, rather than a primary problem with the ovaries or uterus. This type of amenorrhea is referred to as hypothalamic amenorrhea. It is related to a combination of factors including a negative energy balance, over-exercise and stress. This leads to dysfunction of the hypothalamus, a structure in the brain that is important in hormone function. Typically, the hypothalamus releases a hormone called gonadotropin-releasing hormone (GnRH) which regulates menstrual cycle hormones including luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol. However, in hypothalamic amenorrhea, the GnRH pulses become dysregulated, leading to reduced LH and FSH secretion from the pituitary gland, ultimately contributing to reduced estradiol production from the ovaries. Without adequate estradiol, the lining of the uterus does no proliferate and therefore no shedding (i.e. menses) occurs.

Leptin (a hormone that is secreted by adipocytes and functions as a mediator in the adaptation to energy deprivation) may also play a role in hypothalamic amenorrhea, with low levels contributing to abnormal GnRH secretion and loss of menstrual cycle. Other hormones which tend to be dysregulated with the negative energy balance of eating disorders may also contribute. These hormones may include:

• Ghrelin: an appetite-stimulating hormone secreted from the stomach. This hormone is elevated in anorexia nervosa and also impairs FSH and LH secretion
• Thyroid hormones

Female Athlete Triad

The female triad is defined as the combination of negative energy balance, menstrual dysfunction, and low bone mineral density. Historically, disordered eating was included in the definition but this has since been removed with later definitions.

Amenorrhea & Low Estrogen

Low estrogen can lead to symptoms that mimic pre-menopause:

• Night sweats
• Loss of sleep
• Frequent awakening
• Irritable mood

Another serious potential consequence of amenorrhea and low estrogen levels is decreased bone mineral density, also known as osteopenia, with the more severe form being osteoporosis. Decreased bone mineral density can lead to chronic pain, loss of height and increased risk of fractures. Because bone accrual is an ongoing process that peaks during adolescence, reduced bone mineral density is more common in those who developed their eating disorder at a younger age and may be an irreversible complication of anorexia nervosa.

Amenorrhea & Pregnancy

It is still possible, despite being rare, for women with anorexia nervosa to become pregnant. These pregnancies are considered higher risk for bad outcomes. While hormonal contraceptives should not be used to induce withdrawal bleeding, contraception may still be necessary to prevent pregnancy in sexually active patients. Regular obstetrician-gynecologist (OB-GYN) visits are also recommended to keep patient informed about possible pregnancy. Ultimately, it seems that reproduction and fertility normalize upon recovery from an eating disorder.

Treatment of Amenorrhea

There is no clear treatment or preventative measure for this amenorrhea, other than weight restoration and adequate nutrition. There is variability in the literature regarding the degree of weight restoration needed for resumption of menses, with some sources citing return at greater than 90% of ideal body weight, and others seeing a stronger correlation with the weight at which cessation of menses was observed.

It is not advised to use hormonal contraceptives in this setting singularly for the purpose of inducing a withdrawal bleeding for patients with anorexia nervosa. The induction of withdrawal bleeding can give a false sense of wellness to patients, which could decrease motivation for nutritional rehabilitation and weight restoration.

Depending on the severity of the eating disorder, malnutrition or other medical complications, it may be necessary for the patient to be admitted to a specialized medical stabilization unit for severe eating disorders.

References

• Ante, Z., Luu, T. M., Healy-Profitos, J., et al. (2020). Pregnancy outcomes in women with anorexia nervosa. International Journal of Eating Disorders, 53, 673-82.
• Bulik, C. M., Hoffman, E. R., von Holle, A., Torgersen, L., Stoltenberg, C., & Reichborn-Kjennerud, T. (2010). Unplanned Pregnancy in Women With Anorexia Nervosa. Obstetrics & Gynecology, 116(5), 1136–1140.
• Chou, S. H., Chamberland, J. P., Liu, X., Matarese, G., Gao, C., Stefanakis, R., Brinkoetter, M. T., Gong, H., Arampatzi, K., & Mantzoros, C. S. (2011). Leptin is an effective treatment for hypothalamic amenorrhea. Proceedings of the National Academy of Sciences, 108(16), 6585–6590.
• Hoffman, E. R., Zerwas, S. C., & Bulik, C. M. (2011). Reproductive issues in anorexia nervosa. Expert Review of Obstetrics & Gynecology, 6(4), 403–414.
• Kimmel, M., Ferguson, E., Zerwas, S., Bulik, C., & Meltzer-Brody, S. (2015). Obstetric and gynecologic problems associated with eating disorders. International Journal of Eating Disorders, 49(3), 260–275.
• Mountjoy, M., Sundgot-Borgen, J., Burke, L., et al. (2014). The IOC consensus statement: beyond the Female Athlete Triad—Relative energy deficiency in sport (RED-S). British Journal of Sports Medicine, 48, 491-7.

Last Reviewed: December 2023 by Dennis Gibson, MD, FACP, CEDS