Effects of Progestins in Combination with EE on Endothelial Function, Lipid Levels, and Oxidative Stress in Women with Endometriosis

Methodology and Study Course, Monitored Population

A total of 40 women with endometriosis of at least grade 3 were included in the prospective clinical study. All participants were indicated for laparoscopic surgical treatment with histopathological confirmation of the diagnosis due to infertility, pain, and/or menorrhagia. Prior to the surgery, the study participants were divided into 2 groups and used combined hormonal contraception for 3 months:

• The "EE + DRSP" group (n = 20) used 20 μg ethinylestradiol + 3 mg drospirenone (DRSP; a progestin without androgenic properties) in a 24+4 regimen.
• The remaining 20 patients in the "EE + NET" group used 35 μg EE + 1 mg norethisterone (NET; a progestin with androgenic properties) in a 21+7 regimen.

None of the patients had a personal history of smoking, caffeine or alcohol abuse, arterial hypertension, thyroid disease, diabetes mellitus, cardiovascular, hepatic, or infectious diseases, or hormonal therapy.

Before and after the treatment, plasma concentrations of sex hormone-binding globulin (SHBG), lipids, copper, and ceruloplasmin (antioxidants), derivatives of reactive oxygen metabolites (d-ROM), nitrites/nitrates (vasodilators), endothelin 1 (vasoconstrictor), asymmetric dimethylarginine (ADMA, an independent risk factor for acute coronary events and cardiovascular mortality), and biological antioxidant potential were measured. Flow-mediated dilation of the brachialis artery was evaluated sonographically after 5 minutes of cuff compression.

Results

Both groups showed a significant decrease in plasma concentrations of estradiol, follicle-stimulating hormone (FSH), and CA-125.

In the EE + DRSP group, an increase in flow-mediated dilation of the brachialis artery and plasma concentrations of nitrites/nitrates was observed. In contrast, a decrease in endothelin 1 concentrations was noted. In the EE + NET group, no significant changes in these parameters were observed.

A decrease in ADMA concentration was observed in both groups.

The EE + NET group showed a significant decrease in plasma concentrations of total cholesterol, HDL-c, and LDL-c. In contrast, the EE + DRSP group showed an increase in HDL-c and a decrease in LDL-c. Both groups also showed an increase in plasma concentrations of triglycerides, copper, ceruloplasmin, SHBG, and d-ROM, but not in biological antioxidant potential.

Changes in triglyceride concentrations positively correlated with changes in SHBG concentrations (r = 0.57; p < 0.001). A similar trend was observed for plasma concentrations of copper and d-ROM (r = 0.87; p < 0.001).

Conclusion

Progestins with androgenic properties (norethisterone) inhibit the beneficial effects of ethinylestradiol on endothelial function and the increase in plasma HDL concentration, as well as the unfavorable effects on increasing LDL-c. In contrast, progestins without androgenic properties (drospirenone) used with EE orally in a 24+4 regimen within combined hormonal contraception have positive effects on endothelial function and HDL-c levels. Further clinical studies are needed to evaluate the impact on cardiovascular risk.

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Source: Sakurada T., Matsushita H., Noguchi Y. et al. Effects of androgenic properties of progestin combined with ethinylestradiol on vascular endothelial reactivity, plasma lipids and free radical production in women with endometriosis. J Obstet Gynaecol Res 2021; 47 (3): 941–948, doi: 10.1111.jog.14620.