Amenorrhea & Menstrual Abnormalities in Eating Disorder Patients

Amenorrhea, or the absence of menstruation, affects many individuals with eating disorders due to hormonal disruptions caused by weight loss, malnutrition, and purging. This can lead to complications such as low estrogen, reduced bone density, and fertility concerns, though fertility often normalizes with recovery. Weight restoration and nutritional rehabilitation are key to resuming menstruation.

Amenorrhea & Eating Disorders

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-V. Despite its removal, amenorrhea continues to be a ubiquitous feature of severe weight loss in women.

Amenorrhea Frequency

Many women with a history of eating disorders experience amenorrhea. An estimated 84% of women with anorexia nervosa experience amenorrhea, while up to 11% report oligomenorrhea (infrequent periods). For women with bulimia nervosa, up to 40% experience amenorrhea and up to 64% report infrequent periods.

How Amenorrhea Occurs

Amenorrhea in patients with eating disorders is most often related to loss of body weight and hormonal changes that accompany weight loss, known as hypothalamic amenorrhea, rather than a primary problem with the ovaries or uterus. A combination of factors like negative energy balance, over-exercise and stress 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 not proliferate and no period occurs.

Low levels of leptin contribute to abnormal GnRH secretion and loss of the 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 impairs FSH and LH secretion
• Thyroid hormones

Individuals with a history of purging via vomiting, independent of BMI, are also at risk for menstrual dysfunction. Vomiting as infrequently a 1-3x/month is also associated with a 1.5x increased risk of menstrual irregularity. This is likely related to hormonal changes associated with purging behaviors.

Complications of Amenorrhea

Low estrogen

Low estrogen can lead to symptoms that mimic pre-menopause, like night sweats, sleep disturbances and irritability.

Another serious potential consequence of amenorrhea and low estrogen levels is low bone mineral density. 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.

Pregnancy & fertility

Despite fears about infertility, pregnancy is still possible as ovulation may still occur. These pregnancies are considered at higher risk for adverse outcomes, like delivery, maternal medical complications, and neonatal complications.  However, a history of amenorrhea does not have long-term effects on fertility in patients with eating disorders, with reproduction and fertility normalizing upon cessation of purging behaviors and normalization of body weight.

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.

Treatment of Amenorrhea

There is no clear treatment or preventative measure for hypothalamic amenorrhea, other than weight restoration and adequate nutrition[AR1] . Degree of weight restoration needed to resume menstruation varies in the literature, with some sources citing return at greater than 90% of ideal body weight while others note a stronger correlation with the weight at which periods stopped.

Hormonal contraceptives

It is not advised to use hormonal contraceptives in this setting singularly for the purpose of inducing 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.

While there is no benefit of oral contraceptives in improving bone mineral density, transdermal estrogen is beneficial toward improving bone mineral density, as estrogen supplied via the skin is metabolized differently than estrogen provided orally.

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.
• Austin, S. B., Ziyadeh, N. J., Vohra, S., Forman, S., Gordon, C. M., Prokop, L. A., Keliher, A., & Jacobs, D. (2008). Irregular Menses Linked to Vomiting in a Nonclinical Sample: Findings from the National Eating Disorders Screening Program in High Schools. Journal of Adolescent Health, 42(5), 450–457.
• 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.