February 8, 2021
Secondary Amenorrhea and Associated Risks: A Research Review
By Kelsey Fischer
Editor’s Note: This is a review of research[i] published in 2020 in the Clinical Journal of Sport Medicine titled, “Low Bone Mineral Density in Elite Female Athletes with a History of Secondary Amenorrhea in their Teens.” It was written by Kelsey Fischer during the two-week online elective taught by FACTS cofounder, Dr. Marguerite Duane, at Georgetown University School of Medicine. Secondary amenorrhea in teenage girls can have long term implications. Teaching young girls, including elite athletes, how to chart their cycle could lead to earlier evaluation and diagnosis of possible etiologies at the root of this important symptom.
Many factors play a role in the development of bone mineral density (BMD), including nutrition, exercise, genetics, and hormones. Estradiol, a form of estrogen, is an essential hormone for bone development. Peak bone mass occurs at approximately age 20; therefore, estradiol patterns in the preceding teenage years are of vital importance. A woman’s menstrual cycle reflects estradiol patterns as well as stressors exerting an effect on her body. Low levels of estradiol can cause amenorrhea, which can significantly impact the development of BMD and place girls at risk for osteoporosis later in life.
A known but frequently unrecognized female athlete triad consists of low energy availability, menstrual dysfunction, and low BMD. This triad is common among female athletes and is often screened for as part of preparticipation physical evaluations. Studies have shown a 4-fold increased risk of low BMD in female athletes who have late menarche or primary amenorrhea compared to those without menstrual abnormalities. This study by Nose-Ogura et al examines the relationship between secondary amenorrhea, specifically during the teenage years, and BMD.
The elite female athletes in this study were from the Japan Institute of Sports Science. The study included 210 female athletes older than 20 years of age from a variety of sports. Information about their current and past menstrual history, athletic training, and stress fracture history was used to group the athletes. Of the participants, 58 athletes were determined to have amenorrhea greater than 3 months, and designated as “amenorrhea athletes” (AA). Additionally, 152 athletes with a regular menstrual cycle were designated as “eumenorrheic athletes” (EA).
Blood samples were collected to measure luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels. The study used dual-energy x-ray absorptiometry (DEXA) to measure the BMD and body fat to ultimately compare the results between athlete groups. Low BMD was determined to be a Z score <-1 in the lumbar spine, which is considered a weight-bearing area of the body.
The average age of participants was 23.6 +/- 3.5 years. Of the 210 athletes, 39 (18.6%) had low BMD, 29 (13.8%) had secondary amenorrhea in their teens, and 39 (18.6%) had a BMI of less than 18.5.
Many factors for low BMD were analyzed to look for correlations. Considering all variables, factors that increased the odds for low BMD included (1) secondary amenorrhea for greater than 1 year in their teens or at present, (2) increased duration of amenorrhea, (3) more training days per week, and (4) later age of menarche. Furthermore, lower hormone levels, less body fat, lower body weight, and lower BMI indicated increased odds for developing low BMD. When examining factors individually, secondary amenorrhea as a teen and lower BMI correlated with low BMD. In addition, a positive correlation was established between BMI and BMD.
When comparing BMD of athletes with and without amenorrhea in their teens, three groups were established: (1) athletes with secondary amenorrhea in their teens > 1 year and amenorrhea in their 20’s, (2) athletes with regular menstruation in their teens and secondary amenorrhea in their 20’s, and (3) athletes with regular menstruation as teens and in their 20’s. Notably, athletes with secondary amenorrhea as teens and in their 20’s demonstrated the lowest BMD. Athletes with secondary amenorrhea in their 20’s still showed a significantly lower BMD than those with regular menstruation.
Regarding hormone levels, estradiol and LH levels within the amenorrheic group were significantly lower than the eumenorrheic group. BMD values were also lower in athletes with amenorrhea compared to athletes with regular menstruation.
This study was the first to look at the role that secondary amenorrhea may play in the development of BMD in athletes. At least 1 year of amenorrhea during a female athlete’s teenage years increased her risk for low BMD in her twenties 23-fold. This significant finding highlights the importance of early diagnosis of menstrual dysfunction in these patients to prevent long term complications. Other factors thought or known to influence BMD were also investigated. This is a key consideration for elite female athletes, since low BMD increases their risk for bone fractures and injuries, which can have a lasting effect throughout a woman’s life.
Thankfully, if the female athlete triad is diagnosed promptly, modification of energy intake and expenditure can improve body weight and menstruation. However, this has not been found to consistently improve BMD.
Early detection of secondary amenorrhea is vital to prevent low Bone Mineral Density (BMD) in young athletes.
This study also suggests a need for further guidance and screening measures to evaluate female athletes in their teenage years. Additional evaluation of female athletes in their 20’s with DEXA testing should also be considered.
This study is limited by the lack of availability of estradiol levels from the participants’ teenage years, the lack of assessment of BMD for athletes engaged in impact versus non-impact sports, and the measurement of BMD strictly from a weight-bearing site (lumbar spine).
This study reaffirms that the diagnosis of amenorrhea from a variety of etiologies and its impact on a woman’s health can follow her for a lifetime.
Although amenorrhea is seen more frequently in athletes, there are many other reasons why females have amenorrhea. Future research should focus on broadening the study to include elite athletes from other nationalities to apply these findings to a greater population. Other research should also consider the effect of secondary amenorrhea on other groups, such as non-elite athletes and non-athletes. What if low BMI or menstrual irregularities impact BMD in other groups of women as much as in elite athletes? This could translate to a need for additional screening recommendations for a broader female patient population and, potentially, at a younger age.
Editor’s Note: Teaching girls and young women to chart the female cycle is an important aspect of preventive health care that empowers women with information for a lifetime. This practice has increased relevance in the setting of amenorrhea and other forms of menstrual dysfunction, which can alert patients and physicians about the need for further evaluation.
In 2015, the American College of Obstetricians and Gynecologists (ACOG) recommended that menstrual history serve as a vital sign in the care of girls and teens, and then reaffirmed this recommendation in 2017. The American Academy of Pediatrics has also endorsed the ACOG guidance. Within a few months of charting, patients can learn their normal patterns, which enables them to identify abnormal patterns before the root cause of amenorrhea or menstrual changes begins to cause other symptoms. Charting the female cycle is an inexpensive and indispensable tool, and it is time for it to become a routine part of women’s health care.
[i] Nose-Ogura S, Yoshino O, Dohi M, Kigawa M, Harada M, Kawahara T, Osuga Y, Saito S. Low Bone Mineral Density in Elite Female Athletes With a History of Secondary Amenorrhea in Their Teens. Clin J Sport Med. 2020 May;30(3):245-250. doi: 10.1097/JSM.0000000000000571.
About the Author
Kelsey Fischer is a fourth-year medical student interested in internal medicine and obstetrics and gynecology with a passion for oncology. As a student trying to navigate medical education during the COVID-19 pandemic, she was grateful for the opportunity to participate in the FACTS elective. As a woman, it opened her eyes to aspects of fertility and family planning that were new to her. As a future physician, she knows this information gives her an extra tool to serve her patients better.
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