Short summary

Early menopause occurs spontanously or is iatrogenic induced. Early menopause increases the risk of cardiovascular diseases and osteoporosis. The possible protective effect of hormone replacement therapy on these risks is still not well understood. Additionally, a subgroup of early menopause is due to surgical removal of the ovaries due to hereditary risk of cancer. Through retrospective cohort studies we aim to analyze this group of women and assess risk and protective factors.

Rationale

After the discovery of hereditary ovarian cancer (HOC) syndromes and the protective benefits of risk-reducing bilateral salpingo-oophorectomy (RRBSO) an increasing number of premenopausal women at risk undergo this procedure[1, 2]. Bilateral salpingo-oophorectomy (BSO) was also once a common practice at benign hysterectomy and for managing benign ovarian tumors in premenopausal women to reduce the risk of ovarian cancer. Current clinical trends and guidelines have introduced more focus on the endocrine effects of ovarian hormones, also in late pre- and early postmenopausal women, and the importance of ovarian preservation when possible[3, 4]. Numerous studies have investigated the benefits and drawbacks of RRBSO, primarily in the context of pathogenic variants in BRCA1 and BRCA2, reporting reduced overall mortality and a lower risk of developing breast cancer[5-7]. However, these studies and meta-analyses do not include comparisons to the general population and fail to account for other risks associated with premenopausal BSO, such as an increased risk of cardiovascular disease and osteoporosis[8, 9]. One study observed higher mortality rates in women who underwent BSO before age 45 compared to a reference group without premenopausal BSO[10]. It is unclear whether the increased mortality is attributable to underlying morbidity, such as HOC, among women undergoing premenopausal BSO. Additionally, there is a lack of studies assessing the possible mitigating effect of hormone replacement therapy (HRT) regarding overall mortality and breast cancer risk. While evidence finds that HRT increases the risk of breast cancer[11], all six international and national guidelines consistently recommend HRT for healthy women with HOC following RRBSO[12]. It is reasonable to hypothesize that women at high risk of developing breast cancer due to hereditary breast and ovarian cancer may be hesitant or unwilling to follow these recommendations after undergoing RRBSO.

Description of the cohort

Registry based cohort study: Women from 1972-2024 Retrospective nested cohort study: Women in the Region of Southern Denmark 2000-2024.

Data and biological material

None

Collaborating researchers and departments

Department of clinical genetics, Vejle Hospital

• Karina Rønlund