Preventive health strategies for women at increased hereditary risk of ovarian cancer include gynecologic screening (GS) and/or prophylactic oophorectomy (PBSO). Hormone replacement therapy (HRT) is often prescribed to compensate for postsurgical endocrine deficiencies. This study examined the impact of HRT use on levels of endocrine symptoms and sexual functioning among premenopausal women who have undergone PBSO. Comparisons were made with similar women undergoing GS. Questionnaire data on endocrine symptoms and sexual functioning were obtained from 450 premenopausal, high-risk women who had participated in this nationwide, cross-sectional, observational study. Thirty-six percent of women had undergone PBSO and 64% had opted for GS. In the PBSO group, 47% of the women were current HRT users. They reported significantly fewer vasomotor symptoms than nonusers (P < .05). However, compared with premenopausal women undergoing GS, oophorectomized HRT users were more likely to report vasomotor symptoms (P < .01). HRT users and nonusers reported comparable levels of sexual functioning. Compared with women in the GS group, oophorectomized HRT users reported significantly more sexual discomfort due to vaginal dryness and dyspareunia (P < .01). Although HRT has a positive impact on surgically induced vasomotor symptoms, it may be less effective than is often assumed. Symptom levels remain well above those of premenopausal women undergoing screening, and sexual discomfort is not alleviated by HRT. Physicians need to provide younger high-risk women considering PBSO with realistic information about both benefits and drawbacks of this preventive strategy, including information about premature menopause and HRT.