Estetrol drospirenone effective as firstline endometriosis treatment: Study
Endometriosis is a chronic inflammatory condition affecting women of reproductive age that worsens their quality of life (QoL) because of various chronic pelvic pain symptoms, including dysmenorrhea, intermenstrual lower abdominal and back pain, defecation pain, and dyspareunia. Guidelines recommend combination estrogen and progestin drugs as the first-line therapy. Ethinyl estradiol (EE), a widely used estrogen in combined oral contraceptives (OCs), affects the vascular endothelium and liver protein synthesis related to hemostasis and blood pressure, increasing the risk of cardiovascular complications. Estetrol (E4) is a native estrogen produced in fetal liver that specifically binds to estrogen receptors (ERs) a and b. Estradiol activates both nuclear and membrane ERa equally, whereas E4 acts as an agonist of nuclear ERa and an ERa-dependent membrane-initiated steroid signaling antagonist. Therefore, E4 was termed the first native estrogen with selective tissue activity and was classified differently from selective ER modulators. The combination of E4 (15 mg)/drospirenone (DRSP) (3 mg) achieved sufficient ovulation suppression, with a low frequency of unscheduled bleeding and minimal effects on lipid and glucose metabolism and hemostasis.
Estetrol/drospirenone has lower estrogenic activity than EE-based OCs, possibly with decreased thromboembolic risk. To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis, a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was carried across Twenty-five study centers in Japan. A total of 162 Japanese women were diagnosed with endometriosis. Participants were randomly allocated to the E4/DRSP group or the placebo group. In the E4/DRSP group, participants were orally administered one tablet containing E4 (15 mg) and DRSP (3 mg) daily for 24 days, followed by one placebo tablet for 4 days for a hormone-free interval, constituting a 1-cycle regimen. One placebo tablet was administered once daily for 28 days to participants in the placebo group. The treatments were continued for six cycles (24 weeks) throughout the confirmatory period. Changes in visual analogue scale (VAS) scores for the most severe pelvic pain (lower abdominal and back pain) from baseline to six treatment cycles at the end of the confirmatory study period were studied.
Estetrol/drospirenone showed changes in the mean VAS scores for the most severe pelvic pain from baseline to the end of the 6-cycle treatment. The between-group difference was significant, showing superiority to placebo. The responder rates, R30% and R50% reductions in the VAS scores from baseline, were higher in the E4/DRSP group than in the placebo group: 53.2% vs. 29.6% and 36.4% vs. 12.3%. Objective gynecological findings (induration of the cul-de-sac, pelvic tenderness, and limited uterine mobility) were significantly improved by E4/DRSP treatment, and the proportions of stable and worsened participants were significantly lower than in the placebo group.
Estetrol/drospirenone decreased the size of endometriomas and improved quality of life, on the basis of quality of life–related questionnaires and global impression scores. No safety concerns were observed with E4/DRSP treatment. Few differences were observed in the proportion of participants with hemostasis parameters outside the reference range between the E4/DRSP and placebo groups.
Endometriosis and its associated symptoms negatively affect educational attainment, work productivity, career choices and success, social life and activities, family choices, personal relationships, mental and emotional health, and QoL (21), which may alter women’s life course trajectories. Furthermore, there is often a prolonged delay from symptom onset to diagnosis and treatment of endometriosis, increasing the impact on the life course. Therefore, early diagnosis, effective intervention, and comprehensive care are required to minimize the impact of endometriosis.
This study demonstrated that E4/DRSP is clinically effective for EAPP treatment, with improved objective gynecological findings, QoL, and global impressions in patients with endometriosis. Estetrol/drospirenone should be considered a firstline endometriosis treatment.
Source: Tasuku Harada, M.D., Ph.D.,a Takao Kobayashi, M.D., Ph.D.,b Akihiro Hirakawa; Fertil Steril® Vol. 122, No. 5, November 2024 https://doi.org/10.1016/j.fertnstert.2024.07.011
