Objective To assess differences in gynecologic history and lightheadedness during menstrual cycle phases among patients with POTS and healthy control women. Methods In a prospective, questionnaire‐based study carried out at Paden Autonomic Dysfunction Center, Vanderbilt University, between April 2005 and January 2009, a custom‐designed questionnaire was administered to patients with POTS (n = 65) and healthy individuals (n = 95). The results were analyzed via Fisher exact test and Mann–Whitney U test. Results Patients with POTS reported increased lightheadedness through all phases of the menstrual cycle phases as compared with healthy controls. Both groups experienced the greatest lightheadedness during menses, and a decrease in lightheadedness during the follicular phase. Patients with POTS reported a higher incidence of gynecologic diseases as compared with healthy controls. Conclusion The severity of lightheadedness was found to vary during the menstrual cycle, which may relate to changes in estrogen levels. Patients with POTS also reported an increase in estrogen‐related gynecologic disease.