What Are the Causes of Secondary Amenorrhea?

Patient Presentation
A 12-year-old female came to clinic for her health maintenance examination. She and her mother were concerned because she had had irregular menses for 1 year. They had seemed to stop after she had begun training and during her cross-country season which she was currently participating in. She was eating a fairly well-balanced diet but both stated that with her changed schedule for practice she was now missing an afternoon snack. She denied any eating disorder behavior, liked the way her body looked and felt and denied any sexual activity.

The past medical history showed breast budding at her 10 year visit, menarche at 11 years, and she had had 6 menstruations since that time but none for ~6 weeks coinciding with her increased exercise. The review of systems was negative for hair or skin changes, elimination problems, bruising/bleeding, changes in her voice or increased muscle mass, and balance or neurological problems including no difficulty with mentation. She was doing well with her friends and in school. There were no behavior or sleep changes and her energy was good. She denied taking any medications.

The pertinent physical exam showed normal vital signs. Her height between years 10-12 years was at the 75%. At her 10 year examination her weight was 32.3 kg (at 50%), at 11 year visit it was 34.1 kg (between 25-50%) and her current weight was 37.2 kg (between 25-50% but close to 25%). Her mother thought that the patient was 5 pounds heavier before running (still between 25-50%) HEENT had no abnormalities in her oral cavity or thyroid masses. Skin and neurological examinations were normal as was the rest of her examination. She was Tanner stage III for breast and pubic hair. Her genitalia showed a pink intact hymen.

The diagnosis of a healthy female with irregular menses was made. Her history fit the chronology of normal anovulatory menstrual cycles, probably complicated by increased exercise and mild weight loss. Pregnancy, chronic disease or brain tumor seemed unlikely. The laboratory evaluation at that time included doing a complete blood count and lipid panel for her health maintenance examination. Thyroid testing was also ordered. All eventually returned normal. The patient’s clinical course revealed that the pediatrician recommended to increase her overall calories by increasing nutritious food by a small amount during meals and re-instituting one snack at night. “I think this is a combination of your body learning to have periods and the exercise. If you don’t have another period in 6 weeks I want you to call me,” the pediatrician recommended. Within the week she had a normal 4 day menstrual period.

The first sign of puberty in females is breast budding (Tanner stage II) which normally occurs from 8-13 years. Menarche usually occurs within 2 years of breast budding occurring usually at Tanner stage III-IV breast development. Menarche occurs for most girls from 10-15 years. Most cycles range between 21-45 days.

Age > 13 years without acquisition of secondary sexual characteristics, > 15 years before menarche or 5 years after acquisition of secondary sexual characteristics or cycles longer than 45 days are indications for evaluation. After menarche is it not uncommon to have anovulatory cycles that are irregular but generally they still occur within 45 days.

Primary amenorrhea is the absence of menses. Secondary amenorrhea is defined as no menses for 3 or more cycles or irregular menses for 6 months or more after regular menses are established. Secondary amenorrhea occurs in about 2-5% of college women but is more common in certain populations such as dancers and distance runners (65-69%).

First characterized in 1992, female athlete triad (FAT) includes “…low energy availability, menstrual dysfunction, and low bone mineral density.” Prevalence is 1-14% with highest frequency in professional ballet dancers. The cause of menstrual dysfunction in FAT is functional hypothalamic amenorrhea (FHA). A review of FAT can be found here.

FHA is caused by suppression of the gonadotropin-releasing hormone pulsatility in an otherwise normal (anatomically and organically) hypothalamic-pituitary-ovarian axis. The most common causes for FHA are excessive stress, exercise, or weight loss (including eating disorders). There also is a genetic disposition. FHA is the most common cause of primary and secondary amenorrhea in adolescent girls. It accounts for ~25-35% of secondary amenorrhea in adolescents. It is considered a non-organic cause of secondary amenorrhea and is a diagnosis of exclusion. Generally, short-term there are few complications. But long-term there can be increased risk of cardiovascular disease, and low bone mineral abnormalities, breast and vaginal atrophy and sexual dysfunction and fertility problems. Bone density accrual is the greatest in the teenage years and requires calcium, Vitamin D and phosphorus but also requires regular exercise and estrogen for optimal mineralization. Interestingly, if weight loss is the cause, the patient usually will have resumption of menses at an average of 2 kg more than the weight she became amenorrheic at.

Learning Point
Common causes of secondary amenorrhea and initial evaluation for these causes include:

  • Pregnancy
    • Pregnancy test
  • Thyroid dysfunction
    • Thyroid test
  • Functional hypothalamic amenorrhea (FHA)
  • Polycystic ovarian syndrome
    • Follicle stimulating hormone and leuteinizing hormone to evaluate for ovarian insufficiency and/or failure
    • Testosterone and DHEA if signs of masculinization
  • Causes of primary amenorrhea
  • Chronic disease
    • CBC
    • Complete metabolic panel
    • Tissue transgulatminease
  • Hormone based contraceptives
  • Prolactinoma
    • MRI of pituitary
  • Turner’s syndrome or other genetic problem
    • Karyotype

Questions for Further Discussion
1. What causes primary amenorrhea?
2. What causes dysfunctional uterine bleeding? A review can be found here
3. What potential health problems are associated with polycystic ovarian syndrome? A review can be found here
4. What are potential complications of teenage pregnancy? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Menstruation

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Berz K, McCambridge T. Amenorrhea in the Female Athlete: What to Do and When to Worry. Pediatr Ann. 2016;45(3):e97-e102. doi:10.3928/00904481-20160210-03

Sophie Gibson ME, Fleming N, Zuijdwijk C, Dumont T. Where Have the Periods Gone? The Evaluation and Management of Functional Hypothalamic Amenorrhea. J Clin Res Pediatr Endocrinol. 2020;12(Suppl 1):18-27. doi:10.4274/jcrpe.galenos.2019.2019.S0178

Huhmann K. Menses Requires Energy: A Review of How Disordered Eating, Excessive Exercise, and High Stress Lead to Menstrual Irregularities. Clin Ther. 2020;42(3):401-407. doi:10.1016/j.clinthera.2020.01.016

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa