Quality of life and use of hormonal treatment following surgical menopause in BRCA-carriers and ovarian cancer survivors

<p dir="ltr"><i>Background and objectives</i></p><p dir="ltr">Removal of both ovaries before natural menopause will induce surgical menopause with a negative impact on short- and long-term health. Bilateral salpingo-oophorectomy before menopause is performed to treat ovarian cancer or, in some cases, as a preventive measure. For women treated for ovarian cancer, postoperative Menopausal Hormone Therapy (MHT) may improve quality of life and long-term health. The extent of MHT use and its safety in terms of overall survival after ovarian cancer treatment in premenopausal women is unclear. Women with a BRCA1/2 pathogenic variant have an inherited risk of developing ovarian cancer and are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at a fertile age. Studies on the sexual and psychological consequences following RRSO are needed to improve guidance and care.</p><p dir="ltr">The objective was to investigate the proportion of postoperative MHT use in premenopausal women treated with bilateral salpingo-oophorectomy due to ovarian cancer. Second, to prospectively assess sexual function and psychological well-being in women before and after RRSO, as well as to compare with healthy women of the same age. Further, to determine whether serum testosterone levels correlate with sexual functioning and psychological well- being after RRSO. Finally, to evaluate whether postoperative MHT use following bilateral salpingo-oophorectomy due to treatment for ovarian cancer affects overall survival.</p><p dir="ltr"><i>Methods and Main Results</i></p><p dir="ltr"><b>Studies I and IV</b> are nationwide retrospective register and population-based cohort studies. In <b>Study I</b>, 664 women in Sweden aged 18-50, who underwent bilateral salpingo-oophorectomy as part of treatment for epithelial ovarian cancer, non-epithelial ovarian cancer, or a borderline ovarian tumor diagnosis from January 2008 to December 2014, were identified in the Swedish Quality Register of Gynecologic Cancer. For <b>study IV</b>, the inclusion criterion was identical but extended until December 2015, and a total of 779 women were identified. Dispensing of MHT was obtained by linkage to the National Prescription Drug Register.</p><p dir="ltr"><b>In </b><b>study I</b>, the proportion of women who dispensed MHT post-surgery and factors associated with its use were analyzed. Within the first year after surgery 62 % of the total cohort did not dispense MHT. Among women aged 44 or younger, 54% did not receive MHT within the first year. Factors associated with MHT dispensing included younger age (<40 years, 40-44 years) and a borderline ovarian tumor diagnosis. <b>In Study IV</b>, the safety of postoperative MHT use was evaluated in relation to overall survival using flexible parametric survival models, adjusting for covariates, with separate analyses for epithelial ovarian cancer, non-epithelial ovarian cancer, and borderline ovarian tumors. Among 472 women with epithelial ovarian cancer, there was no difference in 10-year overall survival between the postoperative MHT users and the non-users. For the subgroup with epithelial ovarian cancer and no residual disease at surgery (n=363), overall survival was similar regardless of postoperative MHT use. Borderline ovarian tumors were diagnosed in 239 women, with no survival differences related to MHT use.</p><p dir="ltr"><b>In studies II and III</b>, 43 women with a known BRCA1/2 pathogenic variant, opting for RRSO at Karolinska University Hospital during 2011-2014, and 73 women of the same age with their ovaries preserved, were included. Sexual function and psychological well-being were assessed using the validated questionnaires Female Sexual Function Index, Hospital Anxiety and Depression Scale, and Psychological General Well-Being Index. Blood samples were collected, and serum testosterone was measured by tandem mass spectrometry. Free Androgen Index was also calculated. Data were collected at two time-points in the RRSO group: before and one year after surgery. The comparison group was assessed only at inclusion.</p><p dir="ltr">After RRSO, areas of sexual function deteriorated, and anxiety levels decreased, while levels of depression and psychological well-being remained unchanged. Women with RRSO reported higher rates of sexual dysfunction and greater anxiety symptoms as opposed to the comparison group, whereas no differences in symptom levels of depression or well-being were found. Serum testosterone levels were unchanged, and the Free Androgen Index was significantly higher among the comparison group. No correlations were observed between testosterone levels and sexual function or psychological health.</p><p dir="ltr"><i>Conclusions</i></p><p dir="ltr">The rate of postoperative MHT dispensing after ovarian cancer surgery in women 50 years or younger was low. Risk-reducing salpingo-oophorectomy was linked to a deterioration in sexual function but did not negatively affect psychological well-being. Following RRSO, more sexual dysfunction was reported than among women with retained ovaries; however, endogenous testosterone levels did not relate to sexual or psychological health. Postoperative MHT did not reduce overall survival, supporting its oncological safety. Postoperative MHT use should be discussed with young ovarian cancer survivors to promote short and long-term health.</p><h3>List of scientific papers</h3><p dir="ltr">I. Hormone replacement in premenopausal women treated with bilateral oophorectomy for ovarian cancer - A nationwide population-based study. von <b>Kartaschew ÅE</b>, Dahm-Kähler P, Rodriguez-Wallberg KA, Holmberg E, Rådestad AF. Gynecol Oncol. 2022 Dec;167(3):476-482. <a href="https://doi.org/10.1016/j.ygyno.2022.09.027" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.ygyno.2022.09.027</a></p><p dir="ltr">II. Sexual function following risk-reducing salpingo-oophorectomy: a prospective cohort study. von <b>Kartaschew ÅE</b>, Hirschberg AL, Gemzell-Danielsson K, Flöter Rådestad A. Sex Med. 2024 .Nov 19;12(5):qfae078. <a href="https://doi.org/10.1093/sexmed/qfae078" target="_blank">https://doi.org/10.1093/sexmed/qfae078</a></p><p dir="ltr">III. Psychological quality of life in BRCA1/2- carriers following risk-reducing salpingo-oophorectomy: a preliminary report.<b> </b><b>Ehlin von Kartaschew Å,</b> Lindén Hirschberg A, Gemzell-Danielsson K, Flöter Rådestad A. Menopause. September 2025; 32(9):p 849-857. <a href="https://doi.org/10.1097/gme.0000000000002571" rel="noreferrer" target="_blank">https://doi.org/10.1097/gme.0000000000002571</a></p><p dir="ltr">IV. Menopausal Hormone Therapy After Ovarian Cancer: A 10-Year Survival Analysis in Premenopausal Women.<b> </b><b>Åsa Ehlin von Kartaschew</b>, Pernilla Dahm-Kähler, Kenny Rodriguez Wallberg, Erik Holmberg, Angelique Flöter Rådestad [Manuscript]</p>