Impacts of endometrioma on ovarian aging from basic science to clinical management

Abstract

Endometriosis is a common reproductive disorder characterized by the presence of endometrial implants outside of the uterus. It affects ~1 in 10 women of reproductive age. Endometriosis in the ovary, also known as endometrioma (OMA), is the most frequent implantation site and the leading cause of reproductive failure in affected women. Ovarian aging is one of the characteristic features of OMA, however its underlying mechanism yet to be determined. Accumulated evidence has shown that pelvic and local microenvironments in women with OMA are manifested, causing detrimental effects on ovarian development and functions. Whilst clinical associations of OMA with poor ovarian reserve, premature ovarian insufficiency, and early menopause have been reported. Moreover, surgical ablation, fenestration, and cystectomy of OMA can further damage the normal ovarian reservoir, and trigger hyperactivation of primordial follicles, subsequently resulting in the undesired deterioration of ovarian functions. Nevertheless, there is no effective treatment to delay or restore ovarian aging. This review comprehensively summarised the pathogenesis and study hypothesis of ovarian aging caused by OMA in order to propose potential therapeutic targets and interventions for future studies.

Endometriosis risk is associated with shorter anogenital distance by meta-analysis

“…Significantly shorter AGDs (for AGD-AF, AGD-AC, or both) have also been associated with four correlates of endometriosis: premature ovarian insufficiency [34,35], dysmenorrhea [36,37], reduced responses to ovarian stimulation in IVF [29,38], and relatively regular menstrual cycles [39]. These findings support the hypothesis of causal links between lower prenatal testosterone and higher risk of endometriosis, as does evidence suggesting that women with endometriosis exhibit a higher level of sexual difference from males than do healthy women for a suite of sexually dimorphic traits [40].…”

“…Significantly shorter AGDs (for AGD-AF, AGD-AC, or both) have also been associated with four correlates of endometriosis: premature ovarian insufficiency [34,35], dysmenorrhea [36,37],…”

Polygenic risk score phenome-wide association study reveals an association between endometriosis and testosterone

“…One study reported an increased risk of early natural menopause (< 45 years) in endometriosis patients [ 40 ]. Potential mechanisms include effects of endometrioma (endometriosis on the ovary) on ovarian function, effects of surgical excision of endometrioma [ 41 ] and effects of endometriosis-related traits such as reduced body mass index [ 39 ]. The attenuation of the effect of endometriosis PRS on age at menopause when endometriosis cases were excluded may point to effects of lesion presence on age at menopause, but further validation is needed.…”

Diminished Ovarian Reserve in Endometriosis: Insights from In Vitro, In Vivo, and Human Studies—A Systematic Review

“…Normally, a single follicle achieves full maturation to release an oocyte during each menstrual cycle, and this is regulated meticulously using hormones such as gonadotropins [6]. The importance of OR extends into various facets of reproductive medicine [7,8]. It not only informs the biological timeline for a woman's fertility, but it also serves as a critical parameter in assessing and planning the management of infertility.…”

“…However, it is well documented that certain pathological conditions, including endometriosis, disrupt normal follicular activation and maturation, thereby contributing to ovarian dysfunction and a consequential decline in OR. Women with endometriosis, particularly those of advanced age, are at a heightened risk of reduced OR compared to their younger, healthy counterparts [7,8]. The mechanisms instigating this decline-particularly in the context of endometriosis-are not yet fully elucidated, and they continue to be the subject of comprehensive scientific inquiry.…”