Atherosclerosis-related biomarkers in women with endometriosis: The effects of dienogest and oral contraceptive therapy

Abstract

Objective Chronic inflammation in endometriosis is associated with increased risk of future cardiovascular disease; however, no studies have investigated the cardiovascular risk of women who have undergone hormonal therapy for endometriosis. We investigated atherosclerosis-related biomarkers in women with and without endometriosis and the effects of dienogest (DNG) and oral contraceptive (OC) therapies. Study design In this cross-sectional study, 109 women with endometriosis and 42 control women without endometriosis were enrolled. The endometriosis group was divided into the untreated (n = 34), DNG therapy (n = 33), and OC therapy (n = 42) groups. Lipid profile serum levels, inflammatory marker such as high-sensitivity C-reactive protein, oxidative stress markers such as oxidized low-density lipoprotein and diacron-reactive oxygen metabolites, and atherosclerosis indicators (cardio-ankle vascular index [CAVI] and ankle-brachial pressure index [ABI]) were measured. Results The median treatment duration was 28 months in the DNG group and 32.5 months in the OC group. Triglyceride levels were higher in the OC group than in the other three groups ( P < 0.05). Regarding markers of inflammation and oxidative stress, log high-sensitivity C-reactive protein and diacron-reactive oxygen metabolites levels were higher in the untreated group than in the control group ( P < 0.05), and these markers were further increased in the OC group (log high-sensitivity C-reactive protein: P < 0.05; diacron-reactive oxygen metabolites: P < 0.01), but not in the DNG group. There was no difference in the CAVI and ABI among all groups. Spearman correlation revealed a positive correlation between duration of OC therapy and CAVI (ρ = +0.49; P = 0.002), but no correlation between the duration of DNG therapy and CAVI (ρ = –0.04; P = 0.81). Conclusions Inflammation and oxidative stress markers are increased in women with untreated endometriosis. Treatment with OC, but not with DNG, further increases these levels. There was a positive association between the duration of OC administration and atherosclerosis risk for women with endometriosis. Our results suggest that DNG could be administered to endometriosis without the increased atherosclerosis risk and short-term OC administration for endometriosis is not harmful, however, atherosclerosis risk should be strictly observed.

Association between endometriosis and increased arterial stiffness

“…In the abovementioned study, Santoro et al failed to show a difference in carotid IMT, despite increased levels of several inflammatory markers and decreased FMD [22]. In a recent study, there was no difference in the mean CAVI when adjusted for age and ankle brachial index amongst groups [25]. On the contrary, Tani higher total cholesterol, LDL and triglycerides [7,27], whereas other studies found similar levels [19,21,22].…”

Establishing a Comprehensive Framework for Future Explorations: An Endometriosis and Cardiovascular Disease Literature Review

“…Maeda et al, 2020, found cIMT levels were significantly increased in women with endometriosis using oral contraceptives for an extended period. This is representative of arterial wall thickening, indicating an elevated risk for atherosclerosis [31]. As mentioned, the administration of hormonal therapy as part of a treatment plan for women with endometriosis for extended periods increases the risk of developing atherosclerosis and by extension cardiovascular disease due to the consequential increase in oxidative stress.…”

“…For example, a 2020 study by Maeda et al investigated atherosclerosis-related biomarkers in women with endometriosis, where they used a VaSera VS-1000 vascular screen system. Using this equipment, they measure the SBP of the upper (brachial arterial) and lower (tibial arterial) SBP, dividing ankle SBP by brachial SBP to calculate the ABI index value [31]. It is often recommended that repeated measures of the ABI should be taken, preferably over an extended period prior to diagnosis.…”

“…Dienogest (DNG) and oral contraceptives are two of the most common hormone therapies prescribed by clinicians for women suffering from endometriosis. Maeda et al tested for various biomarkers to determine the impact of these two hormone therapies on the development of atherosclerosis [31]. The biomarkers hs-CRP and diacron-reactive oxygen metabolites levels were the highest in women on oral contraceptive therapy.…”

“…Numerous studies in the past have arrived at a consensus that a longer duration of oral contraceptive administration increases oxidative stress in healthy women [31]. Although the mechanism through which oral contraceptive use increases oxidative stress is unknown, this is one of the potential mechanisms linking endometriosis and atherosclerosis.…”