Impact of secondary amenorrhea on cardiovascular disease risk in physically active women: a systematic review and meta‐analysis

Background: Exercise‐associated secondary amenorrhea results in estrogen deficiency, which may lead to dysfunction in estrogen's normal cardioprotective pathways. Estrogen may be essential in a woman's endothelial adaptations to exercise. The objective of this review was to assess the association between secondary amenorrhea in physically active women and cardiovascular disease (CVD) risk. 

Methods and Results: A literature search was performed in January 2023 and updated in August 2023 of the Cumulative Index to Nursing and Allied Health Literature (EBSCOhost), Cochrane Library, Embase (Ovid), MEDLINE (Ovid), SPORTDiscus (EBSCOhost), and Scopus from inception to present with no date or language limitations. Citation chaining was done to screen for additional studies. Eight sources were searched for gray literature. Studies that compared physically active women with amenorrhea to physically active women with eumenorrhea aged 18 to 35 years with evidence of CVD, alterations to cardiovascular physiology, or CVD risks were included. Eighteen observational studies from 3 countries were included. Overall, the quality of evidence was good. A meta‐analysis was performed. Physically active women with secondary amenorrhea had significantly lower estradiol, flow‐mediated dilation, resting heart rate, systolic blood pressure, and diastolic blood pressure and higher total cholesterol, triglycerides, high‐density lipoprotein, and low‐density lipoprotein cholesterol. 

Conclusions: Estrogen deficiency resulting from exercise‐associated secondary amenorrhea in physically active women may impact cardiovascular physiology and certain CVD risk factors. The research in this area is observational; therefore, findings should be interpreted cautiously. However, as exercise‐associated secondary amenorrhea is reversible and the primary prevention of CVD is important for public health, it may be important to treat secondary amenorrhea and restore estrogen levels.